MDedge Emergency Medicine

The US Food and Drug Administration has removed two senior public relations employees, one of whom advised the agency against unbridled promotion of convalescent blood plasma as a treatment for people with COVID-19, multiple media outlets reported Aug. 28.

Officials claim the dismissals are coincidental and are not related to a controversy about whether claims regarding convalescent plasma therapy that were put forth by President Donald Trump and FDA Commissioner Stephen M. Hahn, MD, were exaggerated, according to reports from The New York Times , CNN, and elsewhere.

One of the PR employees, Emily Miller, was on the job less than 2 weeks. The White House named her FDA chief spokeswoman 11 days ago, but Hahn removed her from that post Aug. 28.

On Aug. 27, the US Department of Health and Human Services terminated the contract for Wayne L. Pines, a PR consultant to the FDA. Pines reportedly advised Hahn to apologize for making misleading claims about the therapeutic benefits of convalescent plasma therapy for COVID-19.

The FDA did not respond to multiple requests for comment.

The controversy stems from comments Hahn made about the announcement of the emergency use authorization for convalescent plasma for patients with COVID-19. He said that plasma had been found to save the lives of 35 out of every 100 people who were treated. That statement was later found to be erroneous because he presented a relative risk reduction as an absolute decrease in risk. He later apologized via Twitter.

Researchers running clinical trials to evaluate the efficacy of convalescent plasma for COVID-19 are concerned that the emergency use authorization could thwart efforts to recruit participants for their studies.

This article first appeared on Medscape.com.

The US Food and Drug Administration has removed two senior public relations employees, one of whom advised the agency against unbridled promotion of convalescent blood plasma as a treatment for people with COVID-19, multiple media outlets reported Aug. 28.

Officials claim the dismissals are coincidental and are not related to a controversy about whether claims regarding convalescent plasma therapy that were put forth by President Donald Trump and FDA Commissioner Stephen M. Hahn, MD, were exaggerated, according to reports from The New York Times , CNN, and elsewhere.

One of the PR employees, Emily Miller, was on the job less than 2 weeks. The White House named her FDA chief spokeswoman 11 days ago, but Hahn removed her from that post Aug. 28.

On Aug. 27, the US Department of Health and Human Services terminated the contract for Wayne L. Pines, a PR consultant to the FDA. Pines reportedly advised Hahn to apologize for making misleading claims about the therapeutic benefits of convalescent plasma therapy for COVID-19.

The FDA did not respond to multiple requests for comment.

The controversy stems from comments Hahn made about the announcement of the emergency use authorization for convalescent plasma for patients with COVID-19. He said that plasma had been found to save the lives of 35 out of every 100 people who were treated. That statement was later found to be erroneous because he presented a relative risk reduction as an absolute decrease in risk. He later apologized via Twitter.

Researchers running clinical trials to evaluate the efficacy of convalescent plasma for COVID-19 are concerned that the emergency use authorization could thwart efforts to recruit participants for their studies.

This article first appeared on Medscape.com.

The US Food and Drug Administration has removed two senior public relations employees, one of whom advised the agency against unbridled promotion of convalescent blood plasma as a treatment for people with COVID-19, multiple media outlets reported Aug. 28.

Officials claim the dismissals are coincidental and are not related to a controversy about whether claims regarding convalescent plasma therapy that were put forth by President Donald Trump and FDA Commissioner Stephen M. Hahn, MD, were exaggerated, according to reports from The New York Times , CNN, and elsewhere.

One of the PR employees, Emily Miller, was on the job less than 2 weeks. The White House named her FDA chief spokeswoman 11 days ago, but Hahn removed her from that post Aug. 28.

On Aug. 27, the US Department of Health and Human Services terminated the contract for Wayne L. Pines, a PR consultant to the FDA. Pines reportedly advised Hahn to apologize for making misleading claims about the therapeutic benefits of convalescent plasma therapy for COVID-19.

The FDA did not respond to multiple requests for comment.

The controversy stems from comments Hahn made about the announcement of the emergency use authorization for convalescent plasma for patients with COVID-19. He said that plasma had been found to save the lives of 35 out of every 100 people who were treated. That statement was later found to be erroneous because he presented a relative risk reduction as an absolute decrease in risk. He later apologized via Twitter.

Researchers running clinical trials to evaluate the efficacy of convalescent plasma for COVID-19 are concerned that the emergency use authorization could thwart efforts to recruit participants for their studies.

This article first appeared on Medscape.com.

New York City Health + Hospitals (NYCH+H), the country’s largest public health care system, encompasses 11 hospitals with 4,354 staffed acute beds during normal times. It serves as the safety net for 1.1 million of the 8.4 million residents of the most populous city in the United States, many of them uninsured, undocumented, covered by Medicaid, or otherwise disadvantaged.

At the very epicenter in the early days of the historic COVID-19 pandemic, NYCH+H transferred patients between its facilities, added medical and ICU beds by the hundreds, mobilized palliative care volunteers, harnessed telemedicine and a clinician hotline, and made other sweeping changes to ensure that the city’s public health system would be able to respond to demand at the peak of the surge. That peak hit in April, when an average of 9,000 new COVID-19 cases were being reported in the city every day.

Through it all, hospitalists have played critical roles in both planning for the system’s response and caring for severely ill COVID-19 patients. Their stories reflect both the unprecedented demands on the system and the dedication of frontline clinicians.

One of those, Carla Saladini-Aponte, MD, who just finished her residency in June 2019, found herself on the firing line in March 2020 as an attending physician at 457-bed NYCH+H/Jacobi Hospital in the Bronx. “I have experienced so much in my first year on the job, dealing with a disease that we’ve never seen before,” she said. “We didn’t grasp the extent of the COVID crisis in the beginning, so we were emotionally unprepared when it first hit.”

Starting on March 30, NYCH+H administration mobilized a centralized incident command structure to coordinate response systemwide to a rapidly changing situation.

Two weeks later Jacobi was a COVID-19 hospital, top to bottom, with its medical ICU beds increased from 12 to more than 100. By mid-April, Dr. Saladini-Aponte’s team, one of 11 medical teams in the hospital, had 26 patients, all of them with COVID-19. There was not a consensus in the early days on how to manage patients with severe respiratory distress. “But by the time the surge came, we had a better understanding of the scope of the situation,” she said.

Learning to be an attending

“They don’t teach you how to be an attending during residency,” Dr. Saladini-Aponte said. “At the beginning I wasn’t such a good teacher. I just wanted to prove myself and stay one step ahead of the residents. But as an academic hospitalist you have to listen to others. I learned to ask questions of the residents every morning, including how they were doing personally.”

Sometimes a visiting consultant would ask on the floor: “‘Where’s your attending?’” not recognizing Dr. Saladini-Aponte, fresh out of residency, filling that role. At times, she felt like a PGY-4 (postgraduate year 4). But she quickly grew into the attending role and was asked to be site coordinator for the mobilization of palliative medicine volunteers at Jacobi.

“We found ourselves having to make tough ethical decisions. Some patients, even if we provided a ventilator and maximum oxygen therapy, would still die. There were difficult discussions when we didn’t know if we had enough dialysis machines, or how to manage other limited resources. The hospital was saying: You decide, if there’s a high degree of certainty about the outcome. But we had never practiced medicine this way before,” she said.

“That’s why our hospital provided daily ethics meetings with our ethics council. There would be eight people sitting 6 feet apart in a conference room, all wearing masks. We’d talk about situations that were giving us trouble. Their role wasn’t to provide answers but to help us see the scope of the situation and the complexities,” she explained.

Dr. Saladini-Aponte said she has had many sleepless nights since the pandemic began. “Sometimes, I would come home from work and lie down on the floor and cry,” she said. “But we had so much support from volunteers helping our little hospitalist service of seven.” It was also important to keep up with the clinical information, and one of her coworkers created “cheat sheets” for the clinicians, regularly updated with the latest essential information on antibiotics, testing, and the like.

“At the peak, I was trying to read everything I could about the virus. I was just pulling myself in too many directions. I asked for help from my boyfriend to remind me not to log onto my computer when I came home from work,” she said. “One of my techniques for preventing burnout was just to avoid social media. I couldn’t deal with what was going on in the news. It just angered me. Even now, seeing people without masks makes me very uncomfortable.”
 

Organizing the crisis response

As chief value officer for NYCH+H, Hyung (Harry) Cho, MD, FACP, SFHM, typically focuses on issues of patient safety and overuse of medical treatments in the health system. But in the COVID-19 crisis, he found himself at the forefront of organizing its response. “We tried to provide support centrally and to standardize practice in how we test and treat,” he said.

“We were truly at the epicenter of the pandemic,” Dr. Cho said. “All of our hospitals had different experiences, and unique responses. But the system worked well.” Patients were transferred from the more overtaxed hospitals to Bellevue and other NYCH+H hospitals with spare beds. An emergency medical response structure was put in place, and every morning the system’s Tiger Team, with multidisciplinary personnel from administration, operations, logistics, and medical/technical specialists, would gather virtually to discuss needs across the system.

“It was a very open atmosphere and we asked people to report what was happening on the ground,” Dr. Cho said. “We started rapidly reviewing batches of 20 patients at a time for transfer in order to alleviate pressure in the most overtaxed ERs.”

NYCH+H also had to work through concerns about PPE, just like other U.S. hospitals. Treatment guidelines were changing by the day. Medical concerns were relayed at a rapid pace. Another priority was trying to limit unnecessary exposure for staff through a recommendation that only one clinician from a team would go into the room of an infected patient, unless another was absolutely needed.

The reality of public health

NYCH+H was created by the New York State Legislature in 1969 and rebranded in 2015. It includes a low- to no-cost health insurance plan called MetroPlus, along with outpatient centers, comprehensive case management, and social supports in the home.

“What people know about public health systems is that we typically are underresourced. That’s just the reality of public health,” Dr. Cho said. “We help the community, the underserved. The people who truly needed our help are also the ones who have been disproportionately affected by COVID-19. And that is where we really shine as a system.”

Dr. Cho lauded the performance of the health system’s frontline staff. “Watching them come together during the entire pandemic, and do their best every day, was truly inspiring,” he said. “But when they got to the peak, it really took an emotional toll on them.”

NYCH+H’s in-house staff support program, called Helping Healers Heal, was mobilized with specially trained teams at each of its 11 hospitals to provide peer-to-peer support, mental health expertise, and team-debriefing sessions to staff members following traumatic events. Support is provided both over the phone and in person on the floors, Dr. Cho said. “During the surge, everything was happening so quickly, there was no time to take a pause. Now, as we are able to catch our breath, that’s when they most need support.”

The hospitalists at NYCH+H hospitals intended to have goals-of-care conversations with all patients, but everyone was very busy – so having these conversations became harder and harder, Dr. Cho said. Recognizing limited staffing for the quadrupling of patients who needed palliative care at NYCH+H hospitals, he asked the medicine chairs about their palliative care needs and then used social media outreach to ask for help. The message went viral, attracting 413 volunteers from across the country. Sixty-seven telepalliative volunteers were put to work doing goals-of-care conversations remotely with inpatients and their families.¹

Expediting transfers

For Ian Fagan, MD, a hospitalist and associate medical director for general internal medicine Inpatient Services at Bellevue Hospital in Manhattan, hospitalist shifts are a normal part of his job. But he had to give them up during the surge to focus on planning, management, and especially scheduling other doctors, with sufficient backups needed to cover last minute changes. Dr. Fagan did that by using the existing pool of hospitalist staff, physicians who were reassigned from other specialties, agency staff, military medical personnel, and volunteer doctors who flew in from around the country to help. He also worked 10- to 12-hour days for 36 consecutive days.

The impact of disparities in access to care in New York City was reflected in the greater demand for care in the hospitals in Brooklyn, Queens, and the Bronx. “With fewer patients and more hospital beds in Manhattan, we had the capacity to share our beds,” Dr. Fagan said. “It was so amazing to me how quickly we could move patients from one hospital to another. We started accepting up to 40 transfers a day. But hey, we were still really busy.”

Bellevue is the nation’s oldest public hospital. “We care for the homeless, for immigrants, and we don’t ask questions. That’s our mission. I’m so proud to work here, and so grateful,” Dr. Fagan said. “If someone is undocumented or without insurance, I will give them exactly the same care. We stepped up in a big way to care for people of New York, but we’ve always been there for them – and we were there for them during the COVID surge.”

The hospitals in the system also worked together in ways Dr. Fagan had never seen. “It helped to have a central command structure with a bird’s eye view from above the level of individual hospitals, to organize and see which hospitals could step up. It’s good to have the data to put it in perspective,” he said. The system also utilized a temporary low-acuity medical center set up by NYCH+H on Roosevelt Island, as well as field hospitals organized at the Jacob K. Javits Convention Center and the USTA Billie Jean King National Tennis Center.

“At Bellevue we tried to stay ready, with the ability to turn former hospital units that were being used as offices back to beds. We always had three units lined up that were fully ready to convert. For example, I was medical director of the preop clinic and one day they gave us 24 hours to pack everything and move out. Three days later, it was a 24-bed unit. We also built a more robust rapid response and code team,” he said.

“It was hard for me not to take hospitalist shifts, because my identity is being a doctor. I eventually came to terms with the importance of the role that I was doing every day. I felt I could protect my colleagues, and if they were having an emotional day, to give them the opportunity to talk to someone. I also did the onboarding, one-on-one, of the new doctors.”

As the crisis in New York City has ebbed, Dr. Fagan was recently able to again take a week of clinical service. “The first day back on the floor I felt that I had forgotten everything. But by the end of the day, I thought, ‘Okay, I do know how to do this, after all.’ Census is down here. It’s quiet. That’s good. We need it now,” he said.

“I think the hardest moment for me was when the head nurse on our trauma unit, Ernesto DeLeon, known to everybody here, died of COVID in our ICU in April,” Dr. Fagan said. When Mr. DeLeon died, 100 hospital personnel gathered in the halls outside the room to pay their respects. “There had been a palpable fear in our lives – and this showed us that the fear was real. Ernesto was the first person I knew well who died, who acquired COVID at work doing what we’re all doing. We haven’t lost any doctors yet, but when this nurse died, we allowed ourselves to realize that this is personal. In that moment, we needed to allow ourselves to be human.”

Joan Curcio, MD, associate director of medicine at Elmhurst Hospital, said Elmhurst was where the story started for New York City and for NYCH+H. “I trained here and have spent my entire career at this hospital. It came to feel like what a battleground must be like, with things coming at you from every direction,” she said. “It was overwhelming in ways I could not have foreseen. I had seen videos from Italy [an early COVID-19 epicenter], but until it happened here, it was just hard to process.”

Things started slowly, with a few patients with severe acute respiratory distress syndrome and a 5- to 7-day turnaround to get results of their viral infection tests. “By week 2, a greater number of patients from our clinics and testing sites were filtering through the emergency department. Then hundreds.”

The normal occupancy rate for the department of medicine at Elmhurst is 110-115%, which typically means full beds plus patients in the emergency department. “We started to grow to 160, then 180, and then a peak of 250% of occupancy. We took over a rehab surgery floor, then a 35-bed surgery and hospice floor, which went to full capacity just like that,” she said. The number of non–critical care service teams increased to 20, working with redeployed staff, volunteers, military, and agency personnel, while ICU beds increased from 20 to 105.

“We were dealing with a much higher acuity level and enduring emotional turmoil with families, trying to carve out time to call them after our shift was over,” Dr. Curcio explained. Elmhurst developed a call-in hotline and a daily call-out service for families. Technology was mobilized to provide video visits and new systems were designed for isolation and for PPE distribution and use.

“I just felt that I couldn’t get everything done. I felt continually overwhelmed, and it didn’t matter how much time I took. I never felt I was able to give enough to anybody in any area, which was hard to take,” Dr. Curcio said. “But I still felt a sense of purpose and that I was making a difference – thanks to lots of support from the central office.”

Patient volume at Elmhurst is now down, lower than Dr. Curcio has ever seen it. “One of the main issues right now, moving forward, is ‘how do we function in a post-crisis mode?’” she said. The process of transitioning back to non-COVID-19 care will be complex. “When we clear a floor and clean it to go back to being a cold [COVID-19-negative] unit, it’s a whole different level of cleaning that takes 7 days.”

One moment that was particularly jarring for Dr. Curcio occurred while she was giving a tour of the hospital to visiting military medical personnel. “We went into the emergency department and I turned around and looked into a shower room, which was full of body bags. They were all full.”

But the experience has also been inspiring. “People gave their all without complaint. We hospitalists, and all those recruited to act as hospitalists, essentially took responsibility for the COVID response,” she said. “This was, hopefully, the experience of a lifetime as a medical professional. I wouldn’t want to ever experience something as daunting as this again.”
 

Reference

1. Israilov S et al. National outreach of telepalliative medicine volunteers for a New York City safety net system COVID-19 pandemic response. J Pain Symptom Manag. 2020 May 29. doi: 10.1016/j.jpainsymman.2020.05.026.

New York City Health + Hospitals (NYCH+H), the country’s largest public health care system, encompasses 11 hospitals with 4,354 staffed acute beds during normal times. It serves as the safety net for 1.1 million of the 8.4 million residents of the most populous city in the United States, many of them uninsured, undocumented, covered by Medicaid, or otherwise disadvantaged.

At the very epicenter in the early days of the historic COVID-19 pandemic, NYCH+H transferred patients between its facilities, added medical and ICU beds by the hundreds, mobilized palliative care volunteers, harnessed telemedicine and a clinician hotline, and made other sweeping changes to ensure that the city’s public health system would be able to respond to demand at the peak of the surge. That peak hit in April, when an average of 9,000 new COVID-19 cases were being reported in the city every day.

Through it all, hospitalists have played critical roles in both planning for the system’s response and caring for severely ill COVID-19 patients. Their stories reflect both the unprecedented demands on the system and the dedication of frontline clinicians.

One of those, Carla Saladini-Aponte, MD, who just finished her residency in June 2019, found herself on the firing line in March 2020 as an attending physician at 457-bed NYCH+H/Jacobi Hospital in the Bronx. “I have experienced so much in my first year on the job, dealing with a disease that we’ve never seen before,” she said. “We didn’t grasp the extent of the COVID crisis in the beginning, so we were emotionally unprepared when it first hit.”

Starting on March 30, NYCH+H administration mobilized a centralized incident command structure to coordinate response systemwide to a rapidly changing situation.

Two weeks later Jacobi was a COVID-19 hospital, top to bottom, with its medical ICU beds increased from 12 to more than 100. By mid-April, Dr. Saladini-Aponte’s team, one of 11 medical teams in the hospital, had 26 patients, all of them with COVID-19. There was not a consensus in the early days on how to manage patients with severe respiratory distress. “But by the time the surge came, we had a better understanding of the scope of the situation,” she said.

Learning to be an attending

“They don’t teach you how to be an attending during residency,” Dr. Saladini-Aponte said. “At the beginning I wasn’t such a good teacher. I just wanted to prove myself and stay one step ahead of the residents. But as an academic hospitalist you have to listen to others. I learned to ask questions of the residents every morning, including how they were doing personally.”

Sometimes a visiting consultant would ask on the floor: “‘Where’s your attending?’” not recognizing Dr. Saladini-Aponte, fresh out of residency, filling that role. At times, she felt like a PGY-4 (postgraduate year 4). But she quickly grew into the attending role and was asked to be site coordinator for the mobilization of palliative medicine volunteers at Jacobi.

“We found ourselves having to make tough ethical decisions. Some patients, even if we provided a ventilator and maximum oxygen therapy, would still die. There were difficult discussions when we didn’t know if we had enough dialysis machines, or how to manage other limited resources. The hospital was saying: You decide, if there’s a high degree of certainty about the outcome. But we had never practiced medicine this way before,” she said.

“That’s why our hospital provided daily ethics meetings with our ethics council. There would be eight people sitting 6 feet apart in a conference room, all wearing masks. We’d talk about situations that were giving us trouble. Their role wasn’t to provide answers but to help us see the scope of the situation and the complexities,” she explained.

Dr. Saladini-Aponte said she has had many sleepless nights since the pandemic began. “Sometimes, I would come home from work and lie down on the floor and cry,” she said. “But we had so much support from volunteers helping our little hospitalist service of seven.” It was also important to keep up with the clinical information, and one of her coworkers created “cheat sheets” for the clinicians, regularly updated with the latest essential information on antibiotics, testing, and the like.

“At the peak, I was trying to read everything I could about the virus. I was just pulling myself in too many directions. I asked for help from my boyfriend to remind me not to log onto my computer when I came home from work,” she said. “One of my techniques for preventing burnout was just to avoid social media. I couldn’t deal with what was going on in the news. It just angered me. Even now, seeing people without masks makes me very uncomfortable.”
 

Organizing the crisis response

As chief value officer for NYCH+H, Hyung (Harry) Cho, MD, FACP, SFHM, typically focuses on issues of patient safety and overuse of medical treatments in the health system. But in the COVID-19 crisis, he found himself at the forefront of organizing its response. “We tried to provide support centrally and to standardize practice in how we test and treat,” he said.

“We were truly at the epicenter of the pandemic,” Dr. Cho said. “All of our hospitals had different experiences, and unique responses. But the system worked well.” Patients were transferred from the more overtaxed hospitals to Bellevue and other NYCH+H hospitals with spare beds. An emergency medical response structure was put in place, and every morning the system’s Tiger Team, with multidisciplinary personnel from administration, operations, logistics, and medical/technical specialists, would gather virtually to discuss needs across the system.

“It was a very open atmosphere and we asked people to report what was happening on the ground,” Dr. Cho said. “We started rapidly reviewing batches of 20 patients at a time for transfer in order to alleviate pressure in the most overtaxed ERs.”

NYCH+H also had to work through concerns about PPE, just like other U.S. hospitals. Treatment guidelines were changing by the day. Medical concerns were relayed at a rapid pace. Another priority was trying to limit unnecessary exposure for staff through a recommendation that only one clinician from a team would go into the room of an infected patient, unless another was absolutely needed.

The reality of public health

NYCH+H was created by the New York State Legislature in 1969 and rebranded in 2015. It includes a low- to no-cost health insurance plan called MetroPlus, along with outpatient centers, comprehensive case management, and social supports in the home.

“What people know about public health systems is that we typically are underresourced. That’s just the reality of public health,” Dr. Cho said. “We help the community, the underserved. The people who truly needed our help are also the ones who have been disproportionately affected by COVID-19. And that is where we really shine as a system.”

Dr. Cho lauded the performance of the health system’s frontline staff. “Watching them come together during the entire pandemic, and do their best every day, was truly inspiring,” he said. “But when they got to the peak, it really took an emotional toll on them.”

NYCH+H’s in-house staff support program, called Helping Healers Heal, was mobilized with specially trained teams at each of its 11 hospitals to provide peer-to-peer support, mental health expertise, and team-debriefing sessions to staff members following traumatic events. Support is provided both over the phone and in person on the floors, Dr. Cho said. “During the surge, everything was happening so quickly, there was no time to take a pause. Now, as we are able to catch our breath, that’s when they most need support.”

The hospitalists at NYCH+H hospitals intended to have goals-of-care conversations with all patients, but everyone was very busy – so having these conversations became harder and harder, Dr. Cho said. Recognizing limited staffing for the quadrupling of patients who needed palliative care at NYCH+H hospitals, he asked the medicine chairs about their palliative care needs and then used social media outreach to ask for help. The message went viral, attracting 413 volunteers from across the country. Sixty-seven telepalliative volunteers were put to work doing goals-of-care conversations remotely with inpatients and their families.¹

Expediting transfers

For Ian Fagan, MD, a hospitalist and associate medical director for general internal medicine Inpatient Services at Bellevue Hospital in Manhattan, hospitalist shifts are a normal part of his job. But he had to give them up during the surge to focus on planning, management, and especially scheduling other doctors, with sufficient backups needed to cover last minute changes. Dr. Fagan did that by using the existing pool of hospitalist staff, physicians who were reassigned from other specialties, agency staff, military medical personnel, and volunteer doctors who flew in from around the country to help. He also worked 10- to 12-hour days for 36 consecutive days.

The impact of disparities in access to care in New York City was reflected in the greater demand for care in the hospitals in Brooklyn, Queens, and the Bronx. “With fewer patients and more hospital beds in Manhattan, we had the capacity to share our beds,” Dr. Fagan said. “It was so amazing to me how quickly we could move patients from one hospital to another. We started accepting up to 40 transfers a day. But hey, we were still really busy.”

Bellevue is the nation’s oldest public hospital. “We care for the homeless, for immigrants, and we don’t ask questions. That’s our mission. I’m so proud to work here, and so grateful,” Dr. Fagan said. “If someone is undocumented or without insurance, I will give them exactly the same care. We stepped up in a big way to care for people of New York, but we’ve always been there for them – and we were there for them during the COVID surge.”

The hospitals in the system also worked together in ways Dr. Fagan had never seen. “It helped to have a central command structure with a bird’s eye view from above the level of individual hospitals, to organize and see which hospitals could step up. It’s good to have the data to put it in perspective,” he said. The system also utilized a temporary low-acuity medical center set up by NYCH+H on Roosevelt Island, as well as field hospitals organized at the Jacob K. Javits Convention Center and the USTA Billie Jean King National Tennis Center.

“At Bellevue we tried to stay ready, with the ability to turn former hospital units that were being used as offices back to beds. We always had three units lined up that were fully ready to convert. For example, I was medical director of the preop clinic and one day they gave us 24 hours to pack everything and move out. Three days later, it was a 24-bed unit. We also built a more robust rapid response and code team,” he said.

“It was hard for me not to take hospitalist shifts, because my identity is being a doctor. I eventually came to terms with the importance of the role that I was doing every day. I felt I could protect my colleagues, and if they were having an emotional day, to give them the opportunity to talk to someone. I also did the onboarding, one-on-one, of the new doctors.”

As the crisis in New York City has ebbed, Dr. Fagan was recently able to again take a week of clinical service. “The first day back on the floor I felt that I had forgotten everything. But by the end of the day, I thought, ‘Okay, I do know how to do this, after all.’ Census is down here. It’s quiet. That’s good. We need it now,” he said.

“I think the hardest moment for me was when the head nurse on our trauma unit, Ernesto DeLeon, known to everybody here, died of COVID in our ICU in April,” Dr. Fagan said. When Mr. DeLeon died, 100 hospital personnel gathered in the halls outside the room to pay their respects. “There had been a palpable fear in our lives – and this showed us that the fear was real. Ernesto was the first person I knew well who died, who acquired COVID at work doing what we’re all doing. We haven’t lost any doctors yet, but when this nurse died, we allowed ourselves to realize that this is personal. In that moment, we needed to allow ourselves to be human.”

Joan Curcio, MD, associate director of medicine at Elmhurst Hospital, said Elmhurst was where the story started for New York City and for NYCH+H. “I trained here and have spent my entire career at this hospital. It came to feel like what a battleground must be like, with things coming at you from every direction,” she said. “It was overwhelming in ways I could not have foreseen. I had seen videos from Italy [an early COVID-19 epicenter], but until it happened here, it was just hard to process.”

Things started slowly, with a few patients with severe acute respiratory distress syndrome and a 5- to 7-day turnaround to get results of their viral infection tests. “By week 2, a greater number of patients from our clinics and testing sites were filtering through the emergency department. Then hundreds.”

The normal occupancy rate for the department of medicine at Elmhurst is 110-115%, which typically means full beds plus patients in the emergency department. “We started to grow to 160, then 180, and then a peak of 250% of occupancy. We took over a rehab surgery floor, then a 35-bed surgery and hospice floor, which went to full capacity just like that,” she said. The number of non–critical care service teams increased to 20, working with redeployed staff, volunteers, military, and agency personnel, while ICU beds increased from 20 to 105.

“We were dealing with a much higher acuity level and enduring emotional turmoil with families, trying to carve out time to call them after our shift was over,” Dr. Curcio explained. Elmhurst developed a call-in hotline and a daily call-out service for families. Technology was mobilized to provide video visits and new systems were designed for isolation and for PPE distribution and use.

“I just felt that I couldn’t get everything done. I felt continually overwhelmed, and it didn’t matter how much time I took. I never felt I was able to give enough to anybody in any area, which was hard to take,” Dr. Curcio said. “But I still felt a sense of purpose and that I was making a difference – thanks to lots of support from the central office.”

Patient volume at Elmhurst is now down, lower than Dr. Curcio has ever seen it. “One of the main issues right now, moving forward, is ‘how do we function in a post-crisis mode?’” she said. The process of transitioning back to non-COVID-19 care will be complex. “When we clear a floor and clean it to go back to being a cold [COVID-19-negative] unit, it’s a whole different level of cleaning that takes 7 days.”

One moment that was particularly jarring for Dr. Curcio occurred while she was giving a tour of the hospital to visiting military medical personnel. “We went into the emergency department and I turned around and looked into a shower room, which was full of body bags. They were all full.”

But the experience has also been inspiring. “People gave their all without complaint. We hospitalists, and all those recruited to act as hospitalists, essentially took responsibility for the COVID response,” she said. “This was, hopefully, the experience of a lifetime as a medical professional. I wouldn’t want to ever experience something as daunting as this again.”
 

Reference

1. Israilov S et al. National outreach of telepalliative medicine volunteers for a New York City safety net system COVID-19 pandemic response. J Pain Symptom Manag. 2020 May 29. doi: 10.1016/j.jpainsymman.2020.05.026.

New York City Health + Hospitals (NYCH+H), the country’s largest public health care system, encompasses 11 hospitals with 4,354 staffed acute beds during normal times. It serves as the safety net for 1.1 million of the 8.4 million residents of the most populous city in the United States, many of them uninsured, undocumented, covered by Medicaid, or otherwise disadvantaged.

At the very epicenter in the early days of the historic COVID-19 pandemic, NYCH+H transferred patients between its facilities, added medical and ICU beds by the hundreds, mobilized palliative care volunteers, harnessed telemedicine and a clinician hotline, and made other sweeping changes to ensure that the city’s public health system would be able to respond to demand at the peak of the surge. That peak hit in April, when an average of 9,000 new COVID-19 cases were being reported in the city every day.

Through it all, hospitalists have played critical roles in both planning for the system’s response and caring for severely ill COVID-19 patients. Their stories reflect both the unprecedented demands on the system and the dedication of frontline clinicians.

One of those, Carla Saladini-Aponte, MD, who just finished her residency in June 2019, found herself on the firing line in March 2020 as an attending physician at 457-bed NYCH+H/Jacobi Hospital in the Bronx. “I have experienced so much in my first year on the job, dealing with a disease that we’ve never seen before,” she said. “We didn’t grasp the extent of the COVID crisis in the beginning, so we were emotionally unprepared when it first hit.”

Starting on March 30, NYCH+H administration mobilized a centralized incident command structure to coordinate response systemwide to a rapidly changing situation.

Two weeks later Jacobi was a COVID-19 hospital, top to bottom, with its medical ICU beds increased from 12 to more than 100. By mid-April, Dr. Saladini-Aponte’s team, one of 11 medical teams in the hospital, had 26 patients, all of them with COVID-19. There was not a consensus in the early days on how to manage patients with severe respiratory distress. “But by the time the surge came, we had a better understanding of the scope of the situation,” she said.

Learning to be an attending

“They don’t teach you how to be an attending during residency,” Dr. Saladini-Aponte said. “At the beginning I wasn’t such a good teacher. I just wanted to prove myself and stay one step ahead of the residents. But as an academic hospitalist you have to listen to others. I learned to ask questions of the residents every morning, including how they were doing personally.”

Sometimes a visiting consultant would ask on the floor: “‘Where’s your attending?’” not recognizing Dr. Saladini-Aponte, fresh out of residency, filling that role. At times, she felt like a PGY-4 (postgraduate year 4). But she quickly grew into the attending role and was asked to be site coordinator for the mobilization of palliative medicine volunteers at Jacobi.

“We found ourselves having to make tough ethical decisions. Some patients, even if we provided a ventilator and maximum oxygen therapy, would still die. There were difficult discussions when we didn’t know if we had enough dialysis machines, or how to manage other limited resources. The hospital was saying: You decide, if there’s a high degree of certainty about the outcome. But we had never practiced medicine this way before,” she said.

“That’s why our hospital provided daily ethics meetings with our ethics council. There would be eight people sitting 6 feet apart in a conference room, all wearing masks. We’d talk about situations that were giving us trouble. Their role wasn’t to provide answers but to help us see the scope of the situation and the complexities,” she explained.

Dr. Saladini-Aponte said she has had many sleepless nights since the pandemic began. “Sometimes, I would come home from work and lie down on the floor and cry,” she said. “But we had so much support from volunteers helping our little hospitalist service of seven.” It was also important to keep up with the clinical information, and one of her coworkers created “cheat sheets” for the clinicians, regularly updated with the latest essential information on antibiotics, testing, and the like.

“At the peak, I was trying to read everything I could about the virus. I was just pulling myself in too many directions. I asked for help from my boyfriend to remind me not to log onto my computer when I came home from work,” she said. “One of my techniques for preventing burnout was just to avoid social media. I couldn’t deal with what was going on in the news. It just angered me. Even now, seeing people without masks makes me very uncomfortable.”
 

Organizing the crisis response

As chief value officer for NYCH+H, Hyung (Harry) Cho, MD, FACP, SFHM, typically focuses on issues of patient safety and overuse of medical treatments in the health system. But in the COVID-19 crisis, he found himself at the forefront of organizing its response. “We tried to provide support centrally and to standardize practice in how we test and treat,” he said.

“We were truly at the epicenter of the pandemic,” Dr. Cho said. “All of our hospitals had different experiences, and unique responses. But the system worked well.” Patients were transferred from the more overtaxed hospitals to Bellevue and other NYCH+H hospitals with spare beds. An emergency medical response structure was put in place, and every morning the system’s Tiger Team, with multidisciplinary personnel from administration, operations, logistics, and medical/technical specialists, would gather virtually to discuss needs across the system.

“It was a very open atmosphere and we asked people to report what was happening on the ground,” Dr. Cho said. “We started rapidly reviewing batches of 20 patients at a time for transfer in order to alleviate pressure in the most overtaxed ERs.”

NYCH+H also had to work through concerns about PPE, just like other U.S. hospitals. Treatment guidelines were changing by the day. Medical concerns were relayed at a rapid pace. Another priority was trying to limit unnecessary exposure for staff through a recommendation that only one clinician from a team would go into the room of an infected patient, unless another was absolutely needed.

The reality of public health

NYCH+H was created by the New York State Legislature in 1969 and rebranded in 2015. It includes a low- to no-cost health insurance plan called MetroPlus, along with outpatient centers, comprehensive case management, and social supports in the home.

“What people know about public health systems is that we typically are underresourced. That’s just the reality of public health,” Dr. Cho said. “We help the community, the underserved. The people who truly needed our help are also the ones who have been disproportionately affected by COVID-19. And that is where we really shine as a system.”

Dr. Cho lauded the performance of the health system’s frontline staff. “Watching them come together during the entire pandemic, and do their best every day, was truly inspiring,” he said. “But when they got to the peak, it really took an emotional toll on them.”

NYCH+H’s in-house staff support program, called Helping Healers Heal, was mobilized with specially trained teams at each of its 11 hospitals to provide peer-to-peer support, mental health expertise, and team-debriefing sessions to staff members following traumatic events. Support is provided both over the phone and in person on the floors, Dr. Cho said. “During the surge, everything was happening so quickly, there was no time to take a pause. Now, as we are able to catch our breath, that’s when they most need support.”

The hospitalists at NYCH+H hospitals intended to have goals-of-care conversations with all patients, but everyone was very busy – so having these conversations became harder and harder, Dr. Cho said. Recognizing limited staffing for the quadrupling of patients who needed palliative care at NYCH+H hospitals, he asked the medicine chairs about their palliative care needs and then used social media outreach to ask for help. The message went viral, attracting 413 volunteers from across the country. Sixty-seven telepalliative volunteers were put to work doing goals-of-care conversations remotely with inpatients and their families.¹

Expediting transfers

For Ian Fagan, MD, a hospitalist and associate medical director for general internal medicine Inpatient Services at Bellevue Hospital in Manhattan, hospitalist shifts are a normal part of his job. But he had to give them up during the surge to focus on planning, management, and especially scheduling other doctors, with sufficient backups needed to cover last minute changes. Dr. Fagan did that by using the existing pool of hospitalist staff, physicians who were reassigned from other specialties, agency staff, military medical personnel, and volunteer doctors who flew in from around the country to help. He also worked 10- to 12-hour days for 36 consecutive days.

The impact of disparities in access to care in New York City was reflected in the greater demand for care in the hospitals in Brooklyn, Queens, and the Bronx. “With fewer patients and more hospital beds in Manhattan, we had the capacity to share our beds,” Dr. Fagan said. “It was so amazing to me how quickly we could move patients from one hospital to another. We started accepting up to 40 transfers a day. But hey, we were still really busy.”

Bellevue is the nation’s oldest public hospital. “We care for the homeless, for immigrants, and we don’t ask questions. That’s our mission. I’m so proud to work here, and so grateful,” Dr. Fagan said. “If someone is undocumented or without insurance, I will give them exactly the same care. We stepped up in a big way to care for people of New York, but we’ve always been there for them – and we were there for them during the COVID surge.”

The hospitals in the system also worked together in ways Dr. Fagan had never seen. “It helped to have a central command structure with a bird’s eye view from above the level of individual hospitals, to organize and see which hospitals could step up. It’s good to have the data to put it in perspective,” he said. The system also utilized a temporary low-acuity medical center set up by NYCH+H on Roosevelt Island, as well as field hospitals organized at the Jacob K. Javits Convention Center and the USTA Billie Jean King National Tennis Center.

“At Bellevue we tried to stay ready, with the ability to turn former hospital units that were being used as offices back to beds. We always had three units lined up that were fully ready to convert. For example, I was medical director of the preop clinic and one day they gave us 24 hours to pack everything and move out. Three days later, it was a 24-bed unit. We also built a more robust rapid response and code team,” he said.

“It was hard for me not to take hospitalist shifts, because my identity is being a doctor. I eventually came to terms with the importance of the role that I was doing every day. I felt I could protect my colleagues, and if they were having an emotional day, to give them the opportunity to talk to someone. I also did the onboarding, one-on-one, of the new doctors.”

As the crisis in New York City has ebbed, Dr. Fagan was recently able to again take a week of clinical service. “The first day back on the floor I felt that I had forgotten everything. But by the end of the day, I thought, ‘Okay, I do know how to do this, after all.’ Census is down here. It’s quiet. That’s good. We need it now,” he said.

“I think the hardest moment for me was when the head nurse on our trauma unit, Ernesto DeLeon, known to everybody here, died of COVID in our ICU in April,” Dr. Fagan said. When Mr. DeLeon died, 100 hospital personnel gathered in the halls outside the room to pay their respects. “There had been a palpable fear in our lives – and this showed us that the fear was real. Ernesto was the first person I knew well who died, who acquired COVID at work doing what we’re all doing. We haven’t lost any doctors yet, but when this nurse died, we allowed ourselves to realize that this is personal. In that moment, we needed to allow ourselves to be human.”

Joan Curcio, MD, associate director of medicine at Elmhurst Hospital, said Elmhurst was where the story started for New York City and for NYCH+H. “I trained here and have spent my entire career at this hospital. It came to feel like what a battleground must be like, with things coming at you from every direction,” she said. “It was overwhelming in ways I could not have foreseen. I had seen videos from Italy [an early COVID-19 epicenter], but until it happened here, it was just hard to process.”

Things started slowly, with a few patients with severe acute respiratory distress syndrome and a 5- to 7-day turnaround to get results of their viral infection tests. “By week 2, a greater number of patients from our clinics and testing sites were filtering through the emergency department. Then hundreds.”

The normal occupancy rate for the department of medicine at Elmhurst is 110-115%, which typically means full beds plus patients in the emergency department. “We started to grow to 160, then 180, and then a peak of 250% of occupancy. We took over a rehab surgery floor, then a 35-bed surgery and hospice floor, which went to full capacity just like that,” she said. The number of non–critical care service teams increased to 20, working with redeployed staff, volunteers, military, and agency personnel, while ICU beds increased from 20 to 105.

“We were dealing with a much higher acuity level and enduring emotional turmoil with families, trying to carve out time to call them after our shift was over,” Dr. Curcio explained. Elmhurst developed a call-in hotline and a daily call-out service for families. Technology was mobilized to provide video visits and new systems were designed for isolation and for PPE distribution and use.

“I just felt that I couldn’t get everything done. I felt continually overwhelmed, and it didn’t matter how much time I took. I never felt I was able to give enough to anybody in any area, which was hard to take,” Dr. Curcio said. “But I still felt a sense of purpose and that I was making a difference – thanks to lots of support from the central office.”

Patient volume at Elmhurst is now down, lower than Dr. Curcio has ever seen it. “One of the main issues right now, moving forward, is ‘how do we function in a post-crisis mode?’” she said. The process of transitioning back to non-COVID-19 care will be complex. “When we clear a floor and clean it to go back to being a cold [COVID-19-negative] unit, it’s a whole different level of cleaning that takes 7 days.”

One moment that was particularly jarring for Dr. Curcio occurred while she was giving a tour of the hospital to visiting military medical personnel. “We went into the emergency department and I turned around and looked into a shower room, which was full of body bags. They were all full.”

But the experience has also been inspiring. “People gave their all without complaint. We hospitalists, and all those recruited to act as hospitalists, essentially took responsibility for the COVID response,” she said. “This was, hopefully, the experience of a lifetime as a medical professional. I wouldn’t want to ever experience something as daunting as this again.”
 

Reference

1. Israilov S et al. National outreach of telepalliative medicine volunteers for a New York City safety net system COVID-19 pandemic response. J Pain Symptom Manag. 2020 May 29. doi: 10.1016/j.jpainsymman.2020.05.026.

Add patients with chronic kidney disease with or without diabetes to the growing list of people who get proven benefit from treatment with an SGLT2 inhibitor.

Courtesy European Society of Cardiology

In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga) cut the incidence of substantially worsened chronic kidney disease by an average of 39% compared with placebo when added to standard treatment, with a number needed to treat of 19 to prevent one primary outcome event after a median of 2.4 years.

The level of benefit was similar in both the one-third of enrolled patients without diabetes and in the two-thirds with diabetes, showing a statistically significant 50% cut in the primary endpoint among patients without diabetes, Hiddo J.L. Heerspink, MD, reported at the virtual annual congress of the European Society of Cardiology.

“We found that dapagliflozin delayed the initiation of dialysis, and reduced the number of deaths,” regardless of diabetes status, Dr. Heerspink, of University Medical Centre Groningen, the Netherlands, said during a press conference. “DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment for patients with chronic kidney disease.”

This finding ushers in a “completely new era in chronic kidney disease management,” said Janani Rangaswami, MD, a nephrologist and cardiorenal syndrome specialist at Einstein Medical Center in Philadelphia. “It’s good news” for these patients.

The results showed that dapagliflozin is the first “game changing” drug for chronic kidney disease in 2 decades, following the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, she said in an interview. And given the consistency of the findings with the results from several other studies that documented meaningful renal protection by several different SGLT2 inhibitors, the results from this single trial also convincingly establish dapagliflozin as a standard-of-care agent to use on the types of patients the study enrolled, she said in an interview.
 

Representing many real-world patients

The DAPA-CKD trial enrolled 4,304 patients with albuminuria based on having a urinary albumin-to-creatinine ratio of at least 200 mg/g, and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m² (with 90% of patients having an eGFR of less than 60 mL/min per 1.73 m²), and 97% were on treatment with a renin-angiotensin system–blocking drug. The primary endpoint was the combined rate of a drop in eGFR of at least 50% from baseline, progression to end stage renal disease, or renal or cardiovascular death; the between-group difference in this composite was driven primarily by both preserved eGFR and by prevention of end stage renal disease.

This represents both an appropriate target population, and meaningful endpoints, Dr. Rangaswami said. The study was “very representative of who we see in real-world practice,” a group that likely includes “hundreds of thousands” of U.S. patients with nondiabetic chronic kidney disease, she estimated.

Another notable finding was that 14% of the enrolled patients had eGFR values at baseline of 25-29 mL/min per 1.73 m², pegging them as having stage 4 chronic kidney disease, and the median baseline eGFR was 43 mL/min per 1.73 m², but dapagliflozin treatment was as safe and effective in these patients as it was in enrolled patients with a higher level of retained renal activity. This experience should give clinicians greater confidence about using dapagliflozin and other drugs in the sodium-glucose cotransporter (SGLT) 2 inhibitor class in patients with substantially depressed renal function, Dr. Rangaswami said.

“We now need to be more proactive about treating patients with more advanced kidney disease who can still benefit” from dapagliflozin treatment. “The sooner you intervene the better,” to slow further progression, but the new findings show “benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis.”

A heart-kidney connection

Dapagliflozin treatment also cut all-cause mortality by a statistically significant, relative 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization, a benefit seen consistently in several prior studies of SGLT2 inhibitors, but possibly unexpected here because enrolled patients underwent no selection for a history of heart failure or any other cardiovascular disease. But the finding shouldn’t surprise, because “chronic kidney disease is an independent risk factor for cardiovascular disease across the board, and especially for heart failure,” noted Dr. Rangaswami.

“Heart and kidney disease is one big spectrum,” and the collected experience of several trials that have now proven the efficacy of SGLT2 inhibitors among patients with heart failure with reduced ejection fraction or with chronic kidney disease, regardless of their glycemic control, shows how broadly this drug class can benefit patients across the breadth of this spectrum, she said.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Heerspink has been a consultant to and received research funding from AstraZeneca and from several other companies. Dr. Rangaswami had no disclosures.

[email protected]

Add patients with chronic kidney disease with or without diabetes to the growing list of people who get proven benefit from treatment with an SGLT2 inhibitor.

Courtesy European Society of Cardiology

In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga) cut the incidence of substantially worsened chronic kidney disease by an average of 39% compared with placebo when added to standard treatment, with a number needed to treat of 19 to prevent one primary outcome event after a median of 2.4 years.

The level of benefit was similar in both the one-third of enrolled patients without diabetes and in the two-thirds with diabetes, showing a statistically significant 50% cut in the primary endpoint among patients without diabetes, Hiddo J.L. Heerspink, MD, reported at the virtual annual congress of the European Society of Cardiology.

“We found that dapagliflozin delayed the initiation of dialysis, and reduced the number of deaths,” regardless of diabetes status, Dr. Heerspink, of University Medical Centre Groningen, the Netherlands, said during a press conference. “DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment for patients with chronic kidney disease.”

This finding ushers in a “completely new era in chronic kidney disease management,” said Janani Rangaswami, MD, a nephrologist and cardiorenal syndrome specialist at Einstein Medical Center in Philadelphia. “It’s good news” for these patients.

The results showed that dapagliflozin is the first “game changing” drug for chronic kidney disease in 2 decades, following the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, she said in an interview. And given the consistency of the findings with the results from several other studies that documented meaningful renal protection by several different SGLT2 inhibitors, the results from this single trial also convincingly establish dapagliflozin as a standard-of-care agent to use on the types of patients the study enrolled, she said in an interview.
 

Representing many real-world patients

The DAPA-CKD trial enrolled 4,304 patients with albuminuria based on having a urinary albumin-to-creatinine ratio of at least 200 mg/g, and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m² (with 90% of patients having an eGFR of less than 60 mL/min per 1.73 m²), and 97% were on treatment with a renin-angiotensin system–blocking drug. The primary endpoint was the combined rate of a drop in eGFR of at least 50% from baseline, progression to end stage renal disease, or renal or cardiovascular death; the between-group difference in this composite was driven primarily by both preserved eGFR and by prevention of end stage renal disease.

This represents both an appropriate target population, and meaningful endpoints, Dr. Rangaswami said. The study was “very representative of who we see in real-world practice,” a group that likely includes “hundreds of thousands” of U.S. patients with nondiabetic chronic kidney disease, she estimated.

Another notable finding was that 14% of the enrolled patients had eGFR values at baseline of 25-29 mL/min per 1.73 m², pegging them as having stage 4 chronic kidney disease, and the median baseline eGFR was 43 mL/min per 1.73 m², but dapagliflozin treatment was as safe and effective in these patients as it was in enrolled patients with a higher level of retained renal activity. This experience should give clinicians greater confidence about using dapagliflozin and other drugs in the sodium-glucose cotransporter (SGLT) 2 inhibitor class in patients with substantially depressed renal function, Dr. Rangaswami said.

“We now need to be more proactive about treating patients with more advanced kidney disease who can still benefit” from dapagliflozin treatment. “The sooner you intervene the better,” to slow further progression, but the new findings show “benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis.”

A heart-kidney connection

Dapagliflozin treatment also cut all-cause mortality by a statistically significant, relative 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization, a benefit seen consistently in several prior studies of SGLT2 inhibitors, but possibly unexpected here because enrolled patients underwent no selection for a history of heart failure or any other cardiovascular disease. But the finding shouldn’t surprise, because “chronic kidney disease is an independent risk factor for cardiovascular disease across the board, and especially for heart failure,” noted Dr. Rangaswami.

“Heart and kidney disease is one big spectrum,” and the collected experience of several trials that have now proven the efficacy of SGLT2 inhibitors among patients with heart failure with reduced ejection fraction or with chronic kidney disease, regardless of their glycemic control, shows how broadly this drug class can benefit patients across the breadth of this spectrum, she said.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Heerspink has been a consultant to and received research funding from AstraZeneca and from several other companies. Dr. Rangaswami had no disclosures.

[email protected]

Add patients with chronic kidney disease with or without diabetes to the growing list of people who get proven benefit from treatment with an SGLT2 inhibitor.

Courtesy European Society of Cardiology

In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga) cut the incidence of substantially worsened chronic kidney disease by an average of 39% compared with placebo when added to standard treatment, with a number needed to treat of 19 to prevent one primary outcome event after a median of 2.4 years.

The level of benefit was similar in both the one-third of enrolled patients without diabetes and in the two-thirds with diabetes, showing a statistically significant 50% cut in the primary endpoint among patients without diabetes, Hiddo J.L. Heerspink, MD, reported at the virtual annual congress of the European Society of Cardiology.

“We found that dapagliflozin delayed the initiation of dialysis, and reduced the number of deaths,” regardless of diabetes status, Dr. Heerspink, of University Medical Centre Groningen, the Netherlands, said during a press conference. “DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment for patients with chronic kidney disease.”

This finding ushers in a “completely new era in chronic kidney disease management,” said Janani Rangaswami, MD, a nephrologist and cardiorenal syndrome specialist at Einstein Medical Center in Philadelphia. “It’s good news” for these patients.

The results showed that dapagliflozin is the first “game changing” drug for chronic kidney disease in 2 decades, following the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, she said in an interview. And given the consistency of the findings with the results from several other studies that documented meaningful renal protection by several different SGLT2 inhibitors, the results from this single trial also convincingly establish dapagliflozin as a standard-of-care agent to use on the types of patients the study enrolled, she said in an interview.
 

Representing many real-world patients

The DAPA-CKD trial enrolled 4,304 patients with albuminuria based on having a urinary albumin-to-creatinine ratio of at least 200 mg/g, and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m² (with 90% of patients having an eGFR of less than 60 mL/min per 1.73 m²), and 97% were on treatment with a renin-angiotensin system–blocking drug. The primary endpoint was the combined rate of a drop in eGFR of at least 50% from baseline, progression to end stage renal disease, or renal or cardiovascular death; the between-group difference in this composite was driven primarily by both preserved eGFR and by prevention of end stage renal disease.

This represents both an appropriate target population, and meaningful endpoints, Dr. Rangaswami said. The study was “very representative of who we see in real-world practice,” a group that likely includes “hundreds of thousands” of U.S. patients with nondiabetic chronic kidney disease, she estimated.

Another notable finding was that 14% of the enrolled patients had eGFR values at baseline of 25-29 mL/min per 1.73 m², pegging them as having stage 4 chronic kidney disease, and the median baseline eGFR was 43 mL/min per 1.73 m², but dapagliflozin treatment was as safe and effective in these patients as it was in enrolled patients with a higher level of retained renal activity. This experience should give clinicians greater confidence about using dapagliflozin and other drugs in the sodium-glucose cotransporter (SGLT) 2 inhibitor class in patients with substantially depressed renal function, Dr. Rangaswami said.

“We now need to be more proactive about treating patients with more advanced kidney disease who can still benefit” from dapagliflozin treatment. “The sooner you intervene the better,” to slow further progression, but the new findings show “benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis.”

A heart-kidney connection

Dapagliflozin treatment also cut all-cause mortality by a statistically significant, relative 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization, a benefit seen consistently in several prior studies of SGLT2 inhibitors, but possibly unexpected here because enrolled patients underwent no selection for a history of heart failure or any other cardiovascular disease. But the finding shouldn’t surprise, because “chronic kidney disease is an independent risk factor for cardiovascular disease across the board, and especially for heart failure,” noted Dr. Rangaswami.

“Heart and kidney disease is one big spectrum,” and the collected experience of several trials that have now proven the efficacy of SGLT2 inhibitors among patients with heart failure with reduced ejection fraction or with chronic kidney disease, regardless of their glycemic control, shows how broadly this drug class can benefit patients across the breadth of this spectrum, she said.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Heerspink has been a consultant to and received research funding from AstraZeneca and from several other companies. Dr. Rangaswami had no disclosures.

[email protected]

Digoxin now deserves to be considered first-line therapy for long-term heart rate control in older patients with permanent atrial fibrillation and symptoms of heart failure, Dipak Kotecha, MBChB, PhD, MSc, declared at the virtual annual congress of the European Society of Cardiology.

He presented the 12-month results of RATE-AF (Rate Control Therapy Evaluation in Permanent Atrial Fibrillation), in which 160 seniors (mean age, 76 years) with moderate or severe symptoms caused by permanent atrial fibrillation (AFib) as well as heart failure symptoms were randomized to low-dose digoxin or the beta-blocker bisoprolol for rate control.

The open-label trial was designed to address a centuries-old unmet need: “Although digoxin has been in use since 1785, we have no longer-term clinical trials of digoxin in patients with AFib or AFib with heart failure,” noted Dr. Kotecha, professor of cardiology at the University of Birmingham (England).

Not only is digoxin greatly understudied in AFib, but permanent AFib – the most common form of the arrhythmia – has received only a tiny fraction of the research attention that’s been devoted to paroxysmal or persistent AFib, he added.

In RATE-AF, digoxin and bisoprolol proved similarly effective at reducing heart rate, from about 100 bpm at baseline to the mid-70s at 6 and 12 months. Notably, only a handful of study participants required an additional rate control drug during the 12-month study. Nor did the two drugs differ in terms of their impact on patient-reported quality of life at 6 months as reflected by their Short Form–36 physical component score, the primary study endpoint. And both drugs were well tolerated, with 96% of patients in the digoxin group still on the drug at a mean of 161 mcg/day at 6 months, and 89% still on their beta-blocker.

But that’s pretty much where the similarities in outcomes ended.

For example, at 12 months, the digoxin group scored significantly higher than the beta-blocker group on several domains of the Short Form–36 physical component score, including vitality, physical function, and global health. More than half of the digoxin group had a two-class improvement in modified European Heart Rhythm Association AFib-related symptoms at 6 months, compared with 10% of the beta-blocker group. At 12 months, nearly 70% of the digoxin group had a two-class improvement, as did 30% on bisoprolol.

Heart failure symptoms in the digoxin group improved from a mean baseline New York Heart Association class of 2.4 to 1.5 at both 6 and 12 months; the improvement was more modest in the beta-blocker group, going from NYHA 2.4 at baseline to 2.0 at both 6 and 12 months. And while N-terminal of the prohormone brain natriuretic peptide levels improved in the digoxin group from a baseline of 1,095 pg/mL to 1,058 at 6 months and 960 at 12 months, NT-proBNP actually went up in the beta-blocker group, from 1,041 to 1,209-1,250 pg/mL at 12 months.

Moreover, Dr. Kotecha continued, while RATE-AF was underpowered to assess clinical events, it’s nevertheless noteworthy that a total of 29 adverse events occurred in 12 months in the digoxin group, compared with 142 with beta-blocker therapy. There were 12 unplanned hospital admissions in the digoxin group and 28 in the beta-blocker group, and 22 primary care visits for either AFib or cardiovascular symptoms in patients on digoxin versus 64 in the beta-blocker group.

“Our results suggest a wider use of digoxin for stable patients with permanent AFib,” Dr. Kotecha concluded. However, in an interview, Jonathan Piccini, MD, had a different take on the study results.

“I don’t think this study should widely impact clinical practice in the U.S.,” according to Dr. Piccini, director of cardiac electrophysiology at Duke University, Durham, N.C.

His reservations included RATE-AF’s modest sample size as well as uncertainty as to the trial’s generalizability, given that bisoprolol isn’t much used in the United States. Also, these were elderly patients with shortness of breath, and it’s unclear how effective digoxin would be for rate control in patients with permanent AFib who are more active.

“The classic teaching is that digoxin is great for rate control at rest, but when people are active it’s not nearly as good as beta-blockers or calcium-channel blockers,” the cardiologist said.

“A beta-blocker is still going to be my first-line rate control agent. But the results of RATE-AF do open my mind that for an older sedentary patient I may very well think twice now about using digoxin, because in that situation it looks like it achieves similar goals as a beta-blocker,” Dr. Piccini added.

On the plus side for RATE-AF: “I am very pleased to see that we have a randomized controlled trial focused on rate control in permanent AFib. It also tickles me pink to see a randomized, controlled study of digoxin. And I’m really excited to see a clinical trial that focuses on quality of life. It should give some confidence to know that from a quality of life perspective clinicians can consider using either digoxin or a beta-blocker for rate control,” he said.

American College of Cardiology vice president Dipti Itchhaporia, MD, said she’d need to see a much larger randomized trial including a calcium-channel blocker as a third-rate control arm before she’d consider digoxin as first-line rate control therapy in patients with AFib with or without heart failure. Also, she has reservations about drawing definitive conclusions from an open, unblinded study in which patient-reported outcomes are the primary endpoint.

“I think these were surprising findings given what we all think about digoxin in this country. In general, digoxin fell out of favor for rate control, mainly because of observational studies showing increased mortality. So most of us choose a beta-blocker,” she observed in an interview.

But of course, a randomized trial, even a 160-patient randomized trial, constitutes a higher level of evidence.

“I don’t think I’m going to convert tomorrow and make digoxin my first-line rate control therapy without more data. But RATE-AF does makes me stop and think about using it more than I did before in some of my permanent AFib patients,” said Dr. Itchhaporia, director of disease management at Hoag Memorial Hospital in Newport Beach, Calif.

Dr. Kotecha reported having no financial conflicts regarding the study, which was funded by the U.K. National Institute for Health Research, the British Heart Foundation, and the European Union.

[email protected]

Digoxin now deserves to be considered first-line therapy for long-term heart rate control in older patients with permanent atrial fibrillation and symptoms of heart failure, Dipak Kotecha, MBChB, PhD, MSc, declared at the virtual annual congress of the European Society of Cardiology.

He presented the 12-month results of RATE-AF (Rate Control Therapy Evaluation in Permanent Atrial Fibrillation), in which 160 seniors (mean age, 76 years) with moderate or severe symptoms caused by permanent atrial fibrillation (AFib) as well as heart failure symptoms were randomized to low-dose digoxin or the beta-blocker bisoprolol for rate control.

The open-label trial was designed to address a centuries-old unmet need: “Although digoxin has been in use since 1785, we have no longer-term clinical trials of digoxin in patients with AFib or AFib with heart failure,” noted Dr. Kotecha, professor of cardiology at the University of Birmingham (England).

Not only is digoxin greatly understudied in AFib, but permanent AFib – the most common form of the arrhythmia – has received only a tiny fraction of the research attention that’s been devoted to paroxysmal or persistent AFib, he added.

In RATE-AF, digoxin and bisoprolol proved similarly effective at reducing heart rate, from about 100 bpm at baseline to the mid-70s at 6 and 12 months. Notably, only a handful of study participants required an additional rate control drug during the 12-month study. Nor did the two drugs differ in terms of their impact on patient-reported quality of life at 6 months as reflected by their Short Form–36 physical component score, the primary study endpoint. And both drugs were well tolerated, with 96% of patients in the digoxin group still on the drug at a mean of 161 mcg/day at 6 months, and 89% still on their beta-blocker.

But that’s pretty much where the similarities in outcomes ended.

For example, at 12 months, the digoxin group scored significantly higher than the beta-blocker group on several domains of the Short Form–36 physical component score, including vitality, physical function, and global health. More than half of the digoxin group had a two-class improvement in modified European Heart Rhythm Association AFib-related symptoms at 6 months, compared with 10% of the beta-blocker group. At 12 months, nearly 70% of the digoxin group had a two-class improvement, as did 30% on bisoprolol.

Heart failure symptoms in the digoxin group improved from a mean baseline New York Heart Association class of 2.4 to 1.5 at both 6 and 12 months; the improvement was more modest in the beta-blocker group, going from NYHA 2.4 at baseline to 2.0 at both 6 and 12 months. And while N-terminal of the prohormone brain natriuretic peptide levels improved in the digoxin group from a baseline of 1,095 pg/mL to 1,058 at 6 months and 960 at 12 months, NT-proBNP actually went up in the beta-blocker group, from 1,041 to 1,209-1,250 pg/mL at 12 months.

Moreover, Dr. Kotecha continued, while RATE-AF was underpowered to assess clinical events, it’s nevertheless noteworthy that a total of 29 adverse events occurred in 12 months in the digoxin group, compared with 142 with beta-blocker therapy. There were 12 unplanned hospital admissions in the digoxin group and 28 in the beta-blocker group, and 22 primary care visits for either AFib or cardiovascular symptoms in patients on digoxin versus 64 in the beta-blocker group.

“Our results suggest a wider use of digoxin for stable patients with permanent AFib,” Dr. Kotecha concluded. However, in an interview, Jonathan Piccini, MD, had a different take on the study results.

“I don’t think this study should widely impact clinical practice in the U.S.,” according to Dr. Piccini, director of cardiac electrophysiology at Duke University, Durham, N.C.

His reservations included RATE-AF’s modest sample size as well as uncertainty as to the trial’s generalizability, given that bisoprolol isn’t much used in the United States. Also, these were elderly patients with shortness of breath, and it’s unclear how effective digoxin would be for rate control in patients with permanent AFib who are more active.

“The classic teaching is that digoxin is great for rate control at rest, but when people are active it’s not nearly as good as beta-blockers or calcium-channel blockers,” the cardiologist said.

“A beta-blocker is still going to be my first-line rate control agent. But the results of RATE-AF do open my mind that for an older sedentary patient I may very well think twice now about using digoxin, because in that situation it looks like it achieves similar goals as a beta-blocker,” Dr. Piccini added.

On the plus side for RATE-AF: “I am very pleased to see that we have a randomized controlled trial focused on rate control in permanent AFib. It also tickles me pink to see a randomized, controlled study of digoxin. And I’m really excited to see a clinical trial that focuses on quality of life. It should give some confidence to know that from a quality of life perspective clinicians can consider using either digoxin or a beta-blocker for rate control,” he said.

American College of Cardiology vice president Dipti Itchhaporia, MD, said she’d need to see a much larger randomized trial including a calcium-channel blocker as a third-rate control arm before she’d consider digoxin as first-line rate control therapy in patients with AFib with or without heart failure. Also, she has reservations about drawing definitive conclusions from an open, unblinded study in which patient-reported outcomes are the primary endpoint.

“I think these were surprising findings given what we all think about digoxin in this country. In general, digoxin fell out of favor for rate control, mainly because of observational studies showing increased mortality. So most of us choose a beta-blocker,” she observed in an interview.

But of course, a randomized trial, even a 160-patient randomized trial, constitutes a higher level of evidence.

“I don’t think I’m going to convert tomorrow and make digoxin my first-line rate control therapy without more data. But RATE-AF does makes me stop and think about using it more than I did before in some of my permanent AFib patients,” said Dr. Itchhaporia, director of disease management at Hoag Memorial Hospital in Newport Beach, Calif.

Dr. Kotecha reported having no financial conflicts regarding the study, which was funded by the U.K. National Institute for Health Research, the British Heart Foundation, and the European Union.

[email protected]

Digoxin now deserves to be considered first-line therapy for long-term heart rate control in older patients with permanent atrial fibrillation and symptoms of heart failure, Dipak Kotecha, MBChB, PhD, MSc, declared at the virtual annual congress of the European Society of Cardiology.

He presented the 12-month results of RATE-AF (Rate Control Therapy Evaluation in Permanent Atrial Fibrillation), in which 160 seniors (mean age, 76 years) with moderate or severe symptoms caused by permanent atrial fibrillation (AFib) as well as heart failure symptoms were randomized to low-dose digoxin or the beta-blocker bisoprolol for rate control.

The open-label trial was designed to address a centuries-old unmet need: “Although digoxin has been in use since 1785, we have no longer-term clinical trials of digoxin in patients with AFib or AFib with heart failure,” noted Dr. Kotecha, professor of cardiology at the University of Birmingham (England).

Not only is digoxin greatly understudied in AFib, but permanent AFib – the most common form of the arrhythmia – has received only a tiny fraction of the research attention that’s been devoted to paroxysmal or persistent AFib, he added.

In RATE-AF, digoxin and bisoprolol proved similarly effective at reducing heart rate, from about 100 bpm at baseline to the mid-70s at 6 and 12 months. Notably, only a handful of study participants required an additional rate control drug during the 12-month study. Nor did the two drugs differ in terms of their impact on patient-reported quality of life at 6 months as reflected by their Short Form–36 physical component score, the primary study endpoint. And both drugs were well tolerated, with 96% of patients in the digoxin group still on the drug at a mean of 161 mcg/day at 6 months, and 89% still on their beta-blocker.

But that’s pretty much where the similarities in outcomes ended.

For example, at 12 months, the digoxin group scored significantly higher than the beta-blocker group on several domains of the Short Form–36 physical component score, including vitality, physical function, and global health. More than half of the digoxin group had a two-class improvement in modified European Heart Rhythm Association AFib-related symptoms at 6 months, compared with 10% of the beta-blocker group. At 12 months, nearly 70% of the digoxin group had a two-class improvement, as did 30% on bisoprolol.

Heart failure symptoms in the digoxin group improved from a mean baseline New York Heart Association class of 2.4 to 1.5 at both 6 and 12 months; the improvement was more modest in the beta-blocker group, going from NYHA 2.4 at baseline to 2.0 at both 6 and 12 months. And while N-terminal of the prohormone brain natriuretic peptide levels improved in the digoxin group from a baseline of 1,095 pg/mL to 1,058 at 6 months and 960 at 12 months, NT-proBNP actually went up in the beta-blocker group, from 1,041 to 1,209-1,250 pg/mL at 12 months.

Moreover, Dr. Kotecha continued, while RATE-AF was underpowered to assess clinical events, it’s nevertheless noteworthy that a total of 29 adverse events occurred in 12 months in the digoxin group, compared with 142 with beta-blocker therapy. There were 12 unplanned hospital admissions in the digoxin group and 28 in the beta-blocker group, and 22 primary care visits for either AFib or cardiovascular symptoms in patients on digoxin versus 64 in the beta-blocker group.

“Our results suggest a wider use of digoxin for stable patients with permanent AFib,” Dr. Kotecha concluded. However, in an interview, Jonathan Piccini, MD, had a different take on the study results.

“I don’t think this study should widely impact clinical practice in the U.S.,” according to Dr. Piccini, director of cardiac electrophysiology at Duke University, Durham, N.C.

His reservations included RATE-AF’s modest sample size as well as uncertainty as to the trial’s generalizability, given that bisoprolol isn’t much used in the United States. Also, these were elderly patients with shortness of breath, and it’s unclear how effective digoxin would be for rate control in patients with permanent AFib who are more active.

“The classic teaching is that digoxin is great for rate control at rest, but when people are active it’s not nearly as good as beta-blockers or calcium-channel blockers,” the cardiologist said.

“A beta-blocker is still going to be my first-line rate control agent. But the results of RATE-AF do open my mind that for an older sedentary patient I may very well think twice now about using digoxin, because in that situation it looks like it achieves similar goals as a beta-blocker,” Dr. Piccini added.

On the plus side for RATE-AF: “I am very pleased to see that we have a randomized controlled trial focused on rate control in permanent AFib. It also tickles me pink to see a randomized, controlled study of digoxin. And I’m really excited to see a clinical trial that focuses on quality of life. It should give some confidence to know that from a quality of life perspective clinicians can consider using either digoxin or a beta-blocker for rate control,” he said.

American College of Cardiology vice president Dipti Itchhaporia, MD, said she’d need to see a much larger randomized trial including a calcium-channel blocker as a third-rate control arm before she’d consider digoxin as first-line rate control therapy in patients with AFib with or without heart failure. Also, she has reservations about drawing definitive conclusions from an open, unblinded study in which patient-reported outcomes are the primary endpoint.

“I think these were surprising findings given what we all think about digoxin in this country. In general, digoxin fell out of favor for rate control, mainly because of observational studies showing increased mortality. So most of us choose a beta-blocker,” she observed in an interview.

But of course, a randomized trial, even a 160-patient randomized trial, constitutes a higher level of evidence.

“I don’t think I’m going to convert tomorrow and make digoxin my first-line rate control therapy without more data. But RATE-AF does makes me stop and think about using it more than I did before in some of my permanent AFib patients,” said Dr. Itchhaporia, director of disease management at Hoag Memorial Hospital in Newport Beach, Calif.

Dr. Kotecha reported having no financial conflicts regarding the study, which was funded by the U.K. National Institute for Health Research, the British Heart Foundation, and the European Union.

[email protected]

Marilyn Stebbins, PharmD, fell ill at the end of February 2020. Initially diagnosed with multifocal pneumonia and treated with antibiotics, she later developed severe gastrointestinal symptoms, fatigue, and shortness of breath. She was hospitalized in early March and was diagnosed with COVID-19.

It was still early in the pandemic, and testing was not available for her husband. After she was discharged, her husband isolated himself as much as possible. But that limited the amount of care he could offer.

“When I came home after 8 days in the ICU, I felt completely alone and terrified of not being able to care for myself and not knowing how much care my husband could provide,” said Dr. Stebbins, professor of clinical pharmacy at the University of California, San Francisco.

“I can’t even imagine what it would have been like if I had been home alone without my husband in the house,” she said. “I think about the people who died at home and understand how that might happen.”

Dr. Stebbins is one of tens of thousands of people who, whether hospitalized and discharged or never admitted for inpatient care, needed to find ways to convalesce at home. Data from the Centers for Medicare & Medicaid Services show that, of 326,674 beneficiaries who tested positive for COVID-19 between May 16 and June 11, 2020, 109,607 were hospitalized, suggesting that two-thirds were outpatients.

Most attention has focused on the sickest patients, leaving less severe cases to fall through the cracks. Despite fever, cough, difficulty breathing, and a surfeit of other symptoms, there are few available resources and all too little support to help patients navigate the physical and emotional struggles of contending with COVID-19 at home.
 

No ‘cookie-cutter’ approach

The speed with which the pandemic progressed caught public health systems off guard, but now, “it is essential to put into place the infrastructure to care for the physical and mental health needs of patients at home because most are in the community and many, if not most, still aren’t receiving sufficient support at home,” said Dr. Stebbins.

Caring for COVID-19 patients at home begins with determining their individual needs, said Gary LeRoy, MD, a family physician in Dayton, Ohio. He emphasized that there is “no cookie-cutter formula” for home care, because every patient’s situation is different.

“I begin by having a detailed conversation with each patient to ascertain whether their home environment is safe and to paint a picture of their circumstances,” Dr. LeRoy, who is the president of the American Academy of Family Physicians, said in an interview.

Dr. LeRoy suggested questions that constitute “not just a ‘medical’ checklist but a ‘whole life’ checklist.”

• Do you have access to food, water, medications, sanitation/cleaning supplies, a thermometer, and other necessities? If not, who might assist in providing those?
• Do you need help with activities of daily living and self-care?
• Who else lives in your household? Do they have signs and symptoms of the virus? Have they been tested?
• Do you have enough physical space between you and other household members?
• Do you have children? How are they being cared for?
• What type of work do you do? What are the implications for your employment if you are unable to work for an extended period?
• Do you have an emotional, social, and spiritual support system (e.g., family, friends, community, church)?
• Do you have concerns I haven’t mentioned?

Patients’ responses will inform the management plan and determine what medical and social resources are needed, he said.
 

Daily check-in

Dr. Stebbins said the nurse case manager from her insurance company called her daily after she came home from the hospital. She was told that a public health nurse would also call, but no one from the health department called for days – a situation she hopes has improved.

One way or another, she said, “health care providers [or their staff] should check in with patients daily, either telephonically or via video.” She noted that video is superior, because “someone who isn’t a family member needs to put eyes on a patient and might be able to detect warning signs that a family member without healthcare training might not notice.”

Dr. LeRoy, who is also an associate professor of medicine at Wright State University, Dayton, Ohio, said that, given his time constraints, a nurse or medical assistant in his practice conducts the daily check-ins and notifies him if the patient has fever or other symptoms.

“Under ordinary circumstances, when a patient comes to see me for some type of medical condition, I get to meet the patient, consider what might be going on, then order a test, wait for the results, and suggest a treatment plan. But these are anything but ordinary circumstances,” said Matthew Exline, MD, a pulmonary and critical care specialist at the Ohio State University Wexner Medical Center, Columbus.

“That traditional structure broke down with COVID-19, when we may have test results without even seeing the patient. And without this interaction, it is harder to know as a physician what course of action to take,” he said in an interview.

Once a diagnosis has been made, the physician has at least some data to help guide next steps, even if there has been no prior meeting with the patient.

For example, a positive test raises a host of issues, not the least of which is the risk of spreading the infection to other household members and questions about whether to go the hospital. Moreover, for patients, positive tests can have serious ramifications.

“Severe shortness of breath at rest is not typical of the flu, nor is loss of taste or smell,” said Dr. Exline. Practitioners must educate patients and families about specific symptoms of COVID-19, including shortness of breath, loss of taste or smell, and gastrointestinal or neurologic symptoms, and when to seek emergency care.

Dr. LeRoy suggests buying a pulse oximeter to gauge blood oxygen levels and pulse rate. Together with a thermometer, a portable blood pressure monitor, and, if indicated, a blood glucose monitor, these devices provide a comprehensive and accurate assessment of vital signs.

Dr. LeRoy also educates patients and their families about when to seek medical attention.

Dr. Stebbins takes a similar approach. “Family members are part of, not apart from, the care of patients with COVID-19, and it’s our responsibility as healthcare providers to consider them in the patient’s care plan.”
 

Keeping family safe

Beyond care, family members need a plan to keep themselves healthy, too.

“A patient with COVID-19 at home should self-quarantine as much as possible to keep other family members safe, if they continue to live in the same house,” Dr. Exline said.

Ideally, uninfected family members should stay with relatives or friends. When that’s not possible, everyone in the household should wear a mask, be vigilant about hand washing, and wipe down all surfaces – including doorknobs, light switches, faucet handles, cellphones, and utensils – regularly with bleach or an alcohol solution.

Caregivers should also minimize the amount of time they are exposed to the patient.

“Set food, water, and medication on the night table and leave the room rather than spending hours at the bedside, since limiting exposure to viral load reduces the chances of contagion,” said Dr. Exline.

The Centers for Disease Control and Prevention offers guidance for household members caring for COVID-19 patients at home. It provides tips on how to help patients follow the doctor’s instructions and ways to ensure adequate hydration and rest, among others.

Patients with COVID-19 who live alone face more formidable challenges.

Dr. LeRoy says physicians can help patients by educating themselves about available social services in their community so they can provide appropriate referrals and connections. Such initiatives can include meal programs, friendly visit and financial assistance programs, as well as childcare and home health agencies.

He noted that Aunt Bertha, a social care network, provides a guide to social services throughout the United States. Additional resources are available on USA.gov.
 

Comfort and support

Patients with COVID-19 need to be as comfortable and as supported as possible, both physically and emotionally.

“While I was sick, my dogs curled up next to me and didn’t leave my side, and they were my saving grace. There’s not enough to be said about emotional support,” Dr. Stebbins said.

Although important, emotional support is not enough. For patients with respiratory disorders, such as chronic obstructive pulmonary disease, asthma, heart failure, or pneumonia, their subjective symptoms of shortness of breath, air hunger, or cough may improve with supplemental oxygen at home. Other measures include repositioning of the patient to lessen the body weight over the lungs or the use of lung percussion, Leroy said.

He added that improvement may also come from drainage of sputum from the airway passages, the use of agents to liquefy thick sputum (mucolytics), or aerosolized bronchodilator medications.

However, Dr. LeRoy cautioned, “one remedy does not work for everyone – an individual can improve gradually by using these home support interventions, or their respiratory status can deteriorate rapidly despite all these interventions.”

For this reason, he says patients should consult their personal physician to determine which, if any, of these home treatments would be best for their particular situation.

Patients who need emotional support, psychotherapy, or psychotropic medications may find teletherapy helpful. Guidance for psychiatrists, psychologists, and social workers regarding the treatment of COVID-19 patients via teletherapy can be found on the American Psychiatric Association, the American Psychological Association, and the National Association of Social Workers websites.

Pharmacists can also help ensure patient safety, Dr. Stebbins said.

If a patient has not picked up their usual medications, Dr. Stebbins said, “they may need a check-in call. Some may be ill and alone and may need encouragement to seek medical attention, and some may have no means of getting to the pharmacy and may need medications delivered.”

A home healthcare agency may also be helpful for homebound patients. David Bersson, director of operations at Synergy Home Care of Bergen County, N.J., has arranged in-home caregivers for patients with COVID-19.

The amount of care that professional caregivers provide can range from several hours per week to full-time, depending on the patient’s needs and budget, and can include companionship, Mr. Bersson said in an interview.

Because patient and caregiver safety are paramount, caregivers are thoroughly trained in protection and decontamination procedures and are regularly tested for COVID-19 prior to being sent into a client’s home.

Health insurance companies do not cover this service, Mr. Bersson noted, but the VetAssist program covers home care for veterans and their spouses who meet income requirements.

Caregiving and companionship are both vital pieces of the at-home care puzzle. “It was the virtual emotional support I got from friends, family, coworkers, and healthcare professionals that meant so much to me, and I know they played an important part in my recovery,” Dr. Stebbins said.

Dr. LeRoy agreed, noting that he calls patients, even if they only have mild symptoms and his nurse has already spoken to them. “The call doesn’t take much time – maybe just a 5-minute conversation – but it makes patients aware that I care.”

Dr. Stebbins, Dr. Exline, and Dr. LeRoy report no relevant financial relationships. Mr. Bersson is the director of operations at Synergy Home Care of Bergen County, New Jersey.

This story first appeared on Medscape.com.

Marilyn Stebbins, PharmD, fell ill at the end of February 2020. Initially diagnosed with multifocal pneumonia and treated with antibiotics, she later developed severe gastrointestinal symptoms, fatigue, and shortness of breath. She was hospitalized in early March and was diagnosed with COVID-19.

It was still early in the pandemic, and testing was not available for her husband. After she was discharged, her husband isolated himself as much as possible. But that limited the amount of care he could offer.

“When I came home after 8 days in the ICU, I felt completely alone and terrified of not being able to care for myself and not knowing how much care my husband could provide,” said Dr. Stebbins, professor of clinical pharmacy at the University of California, San Francisco.

“I can’t even imagine what it would have been like if I had been home alone without my husband in the house,” she said. “I think about the people who died at home and understand how that might happen.”

Dr. Stebbins is one of tens of thousands of people who, whether hospitalized and discharged or never admitted for inpatient care, needed to find ways to convalesce at home. Data from the Centers for Medicare & Medicaid Services show that, of 326,674 beneficiaries who tested positive for COVID-19 between May 16 and June 11, 2020, 109,607 were hospitalized, suggesting that two-thirds were outpatients.

Most attention has focused on the sickest patients, leaving less severe cases to fall through the cracks. Despite fever, cough, difficulty breathing, and a surfeit of other symptoms, there are few available resources and all too little support to help patients navigate the physical and emotional struggles of contending with COVID-19 at home.
 

No ‘cookie-cutter’ approach

The speed with which the pandemic progressed caught public health systems off guard, but now, “it is essential to put into place the infrastructure to care for the physical and mental health needs of patients at home because most are in the community and many, if not most, still aren’t receiving sufficient support at home,” said Dr. Stebbins.

Caring for COVID-19 patients at home begins with determining their individual needs, said Gary LeRoy, MD, a family physician in Dayton, Ohio. He emphasized that there is “no cookie-cutter formula” for home care, because every patient’s situation is different.

“I begin by having a detailed conversation with each patient to ascertain whether their home environment is safe and to paint a picture of their circumstances,” Dr. LeRoy, who is the president of the American Academy of Family Physicians, said in an interview.

Dr. LeRoy suggested questions that constitute “not just a ‘medical’ checklist but a ‘whole life’ checklist.”

• Do you have access to food, water, medications, sanitation/cleaning supplies, a thermometer, and other necessities? If not, who might assist in providing those?
• Do you need help with activities of daily living and self-care?
• Who else lives in your household? Do they have signs and symptoms of the virus? Have they been tested?
• Do you have enough physical space between you and other household members?
• Do you have children? How are they being cared for?
• What type of work do you do? What are the implications for your employment if you are unable to work for an extended period?
• Do you have an emotional, social, and spiritual support system (e.g., family, friends, community, church)?
• Do you have concerns I haven’t mentioned?

Patients’ responses will inform the management plan and determine what medical and social resources are needed, he said.
 

Daily check-in

Dr. Stebbins said the nurse case manager from her insurance company called her daily after she came home from the hospital. She was told that a public health nurse would also call, but no one from the health department called for days – a situation she hopes has improved.

One way or another, she said, “health care providers [or their staff] should check in with patients daily, either telephonically or via video.” She noted that video is superior, because “someone who isn’t a family member needs to put eyes on a patient and might be able to detect warning signs that a family member without healthcare training might not notice.”

Dr. LeRoy, who is also an associate professor of medicine at Wright State University, Dayton, Ohio, said that, given his time constraints, a nurse or medical assistant in his practice conducts the daily check-ins and notifies him if the patient has fever or other symptoms.

“Under ordinary circumstances, when a patient comes to see me for some type of medical condition, I get to meet the patient, consider what might be going on, then order a test, wait for the results, and suggest a treatment plan. But these are anything but ordinary circumstances,” said Matthew Exline, MD, a pulmonary and critical care specialist at the Ohio State University Wexner Medical Center, Columbus.

“That traditional structure broke down with COVID-19, when we may have test results without even seeing the patient. And without this interaction, it is harder to know as a physician what course of action to take,” he said in an interview.

Once a diagnosis has been made, the physician has at least some data to help guide next steps, even if there has been no prior meeting with the patient.

For example, a positive test raises a host of issues, not the least of which is the risk of spreading the infection to other household members and questions about whether to go the hospital. Moreover, for patients, positive tests can have serious ramifications.

“Severe shortness of breath at rest is not typical of the flu, nor is loss of taste or smell,” said Dr. Exline. Practitioners must educate patients and families about specific symptoms of COVID-19, including shortness of breath, loss of taste or smell, and gastrointestinal or neurologic symptoms, and when to seek emergency care.

Dr. LeRoy suggests buying a pulse oximeter to gauge blood oxygen levels and pulse rate. Together with a thermometer, a portable blood pressure monitor, and, if indicated, a blood glucose monitor, these devices provide a comprehensive and accurate assessment of vital signs.

Dr. LeRoy also educates patients and their families about when to seek medical attention.

Dr. Stebbins takes a similar approach. “Family members are part of, not apart from, the care of patients with COVID-19, and it’s our responsibility as healthcare providers to consider them in the patient’s care plan.”
 

Keeping family safe

Beyond care, family members need a plan to keep themselves healthy, too.

“A patient with COVID-19 at home should self-quarantine as much as possible to keep other family members safe, if they continue to live in the same house,” Dr. Exline said.

Ideally, uninfected family members should stay with relatives or friends. When that’s not possible, everyone in the household should wear a mask, be vigilant about hand washing, and wipe down all surfaces – including doorknobs, light switches, faucet handles, cellphones, and utensils – regularly with bleach or an alcohol solution.

Caregivers should also minimize the amount of time they are exposed to the patient.

“Set food, water, and medication on the night table and leave the room rather than spending hours at the bedside, since limiting exposure to viral load reduces the chances of contagion,” said Dr. Exline.

The Centers for Disease Control and Prevention offers guidance for household members caring for COVID-19 patients at home. It provides tips on how to help patients follow the doctor’s instructions and ways to ensure adequate hydration and rest, among others.

Patients with COVID-19 who live alone face more formidable challenges.

Dr. LeRoy says physicians can help patients by educating themselves about available social services in their community so they can provide appropriate referrals and connections. Such initiatives can include meal programs, friendly visit and financial assistance programs, as well as childcare and home health agencies.

He noted that Aunt Bertha, a social care network, provides a guide to social services throughout the United States. Additional resources are available on USA.gov.
 

Comfort and support

Patients with COVID-19 need to be as comfortable and as supported as possible, both physically and emotionally.

“While I was sick, my dogs curled up next to me and didn’t leave my side, and they were my saving grace. There’s not enough to be said about emotional support,” Dr. Stebbins said.

Although important, emotional support is not enough. For patients with respiratory disorders, such as chronic obstructive pulmonary disease, asthma, heart failure, or pneumonia, their subjective symptoms of shortness of breath, air hunger, or cough may improve with supplemental oxygen at home. Other measures include repositioning of the patient to lessen the body weight over the lungs or the use of lung percussion, Leroy said.

He added that improvement may also come from drainage of sputum from the airway passages, the use of agents to liquefy thick sputum (mucolytics), or aerosolized bronchodilator medications.

However, Dr. LeRoy cautioned, “one remedy does not work for everyone – an individual can improve gradually by using these home support interventions, or their respiratory status can deteriorate rapidly despite all these interventions.”

For this reason, he says patients should consult their personal physician to determine which, if any, of these home treatments would be best for their particular situation.

Patients who need emotional support, psychotherapy, or psychotropic medications may find teletherapy helpful. Guidance for psychiatrists, psychologists, and social workers regarding the treatment of COVID-19 patients via teletherapy can be found on the American Psychiatric Association, the American Psychological Association, and the National Association of Social Workers websites.

Pharmacists can also help ensure patient safety, Dr. Stebbins said.

If a patient has not picked up their usual medications, Dr. Stebbins said, “they may need a check-in call. Some may be ill and alone and may need encouragement to seek medical attention, and some may have no means of getting to the pharmacy and may need medications delivered.”

A home healthcare agency may also be helpful for homebound patients. David Bersson, director of operations at Synergy Home Care of Bergen County, N.J., has arranged in-home caregivers for patients with COVID-19.

The amount of care that professional caregivers provide can range from several hours per week to full-time, depending on the patient’s needs and budget, and can include companionship, Mr. Bersson said in an interview.

Because patient and caregiver safety are paramount, caregivers are thoroughly trained in protection and decontamination procedures and are regularly tested for COVID-19 prior to being sent into a client’s home.

Health insurance companies do not cover this service, Mr. Bersson noted, but the VetAssist program covers home care for veterans and their spouses who meet income requirements.

Caregiving and companionship are both vital pieces of the at-home care puzzle. “It was the virtual emotional support I got from friends, family, coworkers, and healthcare professionals that meant so much to me, and I know they played an important part in my recovery,” Dr. Stebbins said.

Dr. LeRoy agreed, noting that he calls patients, even if they only have mild symptoms and his nurse has already spoken to them. “The call doesn’t take much time – maybe just a 5-minute conversation – but it makes patients aware that I care.”

Dr. Stebbins, Dr. Exline, and Dr. LeRoy report no relevant financial relationships. Mr. Bersson is the director of operations at Synergy Home Care of Bergen County, New Jersey.

This story first appeared on Medscape.com.

Marilyn Stebbins, PharmD, fell ill at the end of February 2020. Initially diagnosed with multifocal pneumonia and treated with antibiotics, she later developed severe gastrointestinal symptoms, fatigue, and shortness of breath. She was hospitalized in early March and was diagnosed with COVID-19.

It was still early in the pandemic, and testing was not available for her husband. After she was discharged, her husband isolated himself as much as possible. But that limited the amount of care he could offer.

“When I came home after 8 days in the ICU, I felt completely alone and terrified of not being able to care for myself and not knowing how much care my husband could provide,” said Dr. Stebbins, professor of clinical pharmacy at the University of California, San Francisco.

“I can’t even imagine what it would have been like if I had been home alone without my husband in the house,” she said. “I think about the people who died at home and understand how that might happen.”

Dr. Stebbins is one of tens of thousands of people who, whether hospitalized and discharged or never admitted for inpatient care, needed to find ways to convalesce at home. Data from the Centers for Medicare & Medicaid Services show that, of 326,674 beneficiaries who tested positive for COVID-19 between May 16 and June 11, 2020, 109,607 were hospitalized, suggesting that two-thirds were outpatients.

Most attention has focused on the sickest patients, leaving less severe cases to fall through the cracks. Despite fever, cough, difficulty breathing, and a surfeit of other symptoms, there are few available resources and all too little support to help patients navigate the physical and emotional struggles of contending with COVID-19 at home.
 

No ‘cookie-cutter’ approach

The speed with which the pandemic progressed caught public health systems off guard, but now, “it is essential to put into place the infrastructure to care for the physical and mental health needs of patients at home because most are in the community and many, if not most, still aren’t receiving sufficient support at home,” said Dr. Stebbins.

Caring for COVID-19 patients at home begins with determining their individual needs, said Gary LeRoy, MD, a family physician in Dayton, Ohio. He emphasized that there is “no cookie-cutter formula” for home care, because every patient’s situation is different.

“I begin by having a detailed conversation with each patient to ascertain whether their home environment is safe and to paint a picture of their circumstances,” Dr. LeRoy, who is the president of the American Academy of Family Physicians, said in an interview.

Dr. LeRoy suggested questions that constitute “not just a ‘medical’ checklist but a ‘whole life’ checklist.”

• Do you have access to food, water, medications, sanitation/cleaning supplies, a thermometer, and other necessities? If not, who might assist in providing those?
• Do you need help with activities of daily living and self-care?
• Who else lives in your household? Do they have signs and symptoms of the virus? Have they been tested?
• Do you have enough physical space between you and other household members?
• Do you have children? How are they being cared for?
• What type of work do you do? What are the implications for your employment if you are unable to work for an extended period?
• Do you have an emotional, social, and spiritual support system (e.g., family, friends, community, church)?
• Do you have concerns I haven’t mentioned?

Patients’ responses will inform the management plan and determine what medical and social resources are needed, he said.
 

Daily check-in

Dr. Stebbins said the nurse case manager from her insurance company called her daily after she came home from the hospital. She was told that a public health nurse would also call, but no one from the health department called for days – a situation she hopes has improved.

One way or another, she said, “health care providers [or their staff] should check in with patients daily, either telephonically or via video.” She noted that video is superior, because “someone who isn’t a family member needs to put eyes on a patient and might be able to detect warning signs that a family member without healthcare training might not notice.”

Dr. LeRoy, who is also an associate professor of medicine at Wright State University, Dayton, Ohio, said that, given his time constraints, a nurse or medical assistant in his practice conducts the daily check-ins and notifies him if the patient has fever or other symptoms.

“Under ordinary circumstances, when a patient comes to see me for some type of medical condition, I get to meet the patient, consider what might be going on, then order a test, wait for the results, and suggest a treatment plan. But these are anything but ordinary circumstances,” said Matthew Exline, MD, a pulmonary and critical care specialist at the Ohio State University Wexner Medical Center, Columbus.

“That traditional structure broke down with COVID-19, when we may have test results without even seeing the patient. And without this interaction, it is harder to know as a physician what course of action to take,” he said in an interview.

Once a diagnosis has been made, the physician has at least some data to help guide next steps, even if there has been no prior meeting with the patient.

For example, a positive test raises a host of issues, not the least of which is the risk of spreading the infection to other household members and questions about whether to go the hospital. Moreover, for patients, positive tests can have serious ramifications.

“Severe shortness of breath at rest is not typical of the flu, nor is loss of taste or smell,” said Dr. Exline. Practitioners must educate patients and families about specific symptoms of COVID-19, including shortness of breath, loss of taste or smell, and gastrointestinal or neurologic symptoms, and when to seek emergency care.

Dr. LeRoy suggests buying a pulse oximeter to gauge blood oxygen levels and pulse rate. Together with a thermometer, a portable blood pressure monitor, and, if indicated, a blood glucose monitor, these devices provide a comprehensive and accurate assessment of vital signs.

Dr. LeRoy also educates patients and their families about when to seek medical attention.

Dr. Stebbins takes a similar approach. “Family members are part of, not apart from, the care of patients with COVID-19, and it’s our responsibility as healthcare providers to consider them in the patient’s care plan.”
 

Keeping family safe

Beyond care, family members need a plan to keep themselves healthy, too.

“A patient with COVID-19 at home should self-quarantine as much as possible to keep other family members safe, if they continue to live in the same house,” Dr. Exline said.

Ideally, uninfected family members should stay with relatives or friends. When that’s not possible, everyone in the household should wear a mask, be vigilant about hand washing, and wipe down all surfaces – including doorknobs, light switches, faucet handles, cellphones, and utensils – regularly with bleach or an alcohol solution.

Caregivers should also minimize the amount of time they are exposed to the patient.

“Set food, water, and medication on the night table and leave the room rather than spending hours at the bedside, since limiting exposure to viral load reduces the chances of contagion,” said Dr. Exline.

The Centers for Disease Control and Prevention offers guidance for household members caring for COVID-19 patients at home. It provides tips on how to help patients follow the doctor’s instructions and ways to ensure adequate hydration and rest, among others.

Patients with COVID-19 who live alone face more formidable challenges.

Dr. LeRoy says physicians can help patients by educating themselves about available social services in their community so they can provide appropriate referrals and connections. Such initiatives can include meal programs, friendly visit and financial assistance programs, as well as childcare and home health agencies.

He noted that Aunt Bertha, a social care network, provides a guide to social services throughout the United States. Additional resources are available on USA.gov.
 

Comfort and support

Patients with COVID-19 need to be as comfortable and as supported as possible, both physically and emotionally.

“While I was sick, my dogs curled up next to me and didn’t leave my side, and they were my saving grace. There’s not enough to be said about emotional support,” Dr. Stebbins said.

Although important, emotional support is not enough. For patients with respiratory disorders, such as chronic obstructive pulmonary disease, asthma, heart failure, or pneumonia, their subjective symptoms of shortness of breath, air hunger, or cough may improve with supplemental oxygen at home. Other measures include repositioning of the patient to lessen the body weight over the lungs or the use of lung percussion, Leroy said.

He added that improvement may also come from drainage of sputum from the airway passages, the use of agents to liquefy thick sputum (mucolytics), or aerosolized bronchodilator medications.

However, Dr. LeRoy cautioned, “one remedy does not work for everyone – an individual can improve gradually by using these home support interventions, or their respiratory status can deteriorate rapidly despite all these interventions.”

For this reason, he says patients should consult their personal physician to determine which, if any, of these home treatments would be best for their particular situation.

Patients who need emotional support, psychotherapy, or psychotropic medications may find teletherapy helpful. Guidance for psychiatrists, psychologists, and social workers regarding the treatment of COVID-19 patients via teletherapy can be found on the American Psychiatric Association, the American Psychological Association, and the National Association of Social Workers websites.

Pharmacists can also help ensure patient safety, Dr. Stebbins said.

If a patient has not picked up their usual medications, Dr. Stebbins said, “they may need a check-in call. Some may be ill and alone and may need encouragement to seek medical attention, and some may have no means of getting to the pharmacy and may need medications delivered.”

A home healthcare agency may also be helpful for homebound patients. David Bersson, director of operations at Synergy Home Care of Bergen County, N.J., has arranged in-home caregivers for patients with COVID-19.

The amount of care that professional caregivers provide can range from several hours per week to full-time, depending on the patient’s needs and budget, and can include companionship, Mr. Bersson said in an interview.

Because patient and caregiver safety are paramount, caregivers are thoroughly trained in protection and decontamination procedures and are regularly tested for COVID-19 prior to being sent into a client’s home.

Health insurance companies do not cover this service, Mr. Bersson noted, but the VetAssist program covers home care for veterans and their spouses who meet income requirements.

Caregiving and companionship are both vital pieces of the at-home care puzzle. “It was the virtual emotional support I got from friends, family, coworkers, and healthcare professionals that meant so much to me, and I know they played an important part in my recovery,” Dr. Stebbins said.

Dr. LeRoy agreed, noting that he calls patients, even if they only have mild symptoms and his nurse has already spoken to them. “The call doesn’t take much time – maybe just a 5-minute conversation – but it makes patients aware that I care.”

Dr. Stebbins, Dr. Exline, and Dr. LeRoy report no relevant financial relationships. Mr. Bersson is the director of operations at Synergy Home Care of Bergen County, New Jersey.

This story first appeared on Medscape.com.

New atrial fibrillation (AFib) management guidelines from the European Society of Cardiology (ESC) call for diagnostic confirmation and structured characterization of AFib and the need to streamline integrated care with the Atrial fibrillation Better Care (ABC) pathway.

“It’s as simple as CC to ABC,” quipped one task force member during the virtual unveiling of the guidelines at the ESC Congress 2020.

The guidelines were developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS) and published simultaneously August 29 in the European Heart Journal.

Acknowledging the slew of novel screening tools now available and their reported sensitivity and specificity rates, the document supports opportunistic screening for AFib by pulse taking or electrocardiogram (ECG) rhythm strip in patients at least 65 years of age, with a class 1 recommendation, evidence level B.

Systematic ECG screening should also be considered to detect AFib in individuals at least 75 years of age or in those at high risk for stroke (class IIa, level B).

Other new class I screening recommendations are to inform individuals undergoing screening about the significance and treatment implications of detecting AFib and to have a structured referral platform in place for further physician-led evaluation.

A definite diagnosis of clinical AFib is established only after confirmation by a conventional 12-lead ECG or single-lead ECG strip with at least 30 seconds of AFib.

In line with ESC’s 2016 AFib guidelines, the new iteration classifies AFib as first diagnosed, paroxysmal, persistent, long-standing persistent, and permanent. But it’s also important to classify the clinical profile of AFib, task force member Giuseppe Boriani, MD, PhD, University of Modena, Italy, said in the first of five presentations.

“So the novelty of the 2020 guidelines is related to the proposal of the 4S-AF scheme for a structured characterization of atrial fibrillation that takes into account Stroke risk, severity of Symptoms, Severity of atrial fibrillation burden, and Substrate severity,” he said.

This represents a paradigm shift from a single-domain conventional classification of AFib toward a structured characterization that streamlines assessment, informs treatment decision-making, and facilitates communication among physicians of various specialties, said Tatjana Potpara, MD, PhD, guideline co-chair and head of the Department for Intensive Arrhythmia Care, Clinical Centre of Serbia, Belgrade.

“The beauty of this approach is that, at present, the assessment of the ‘S’ components are performed using available tools, but in the future, the 4S-AF has a great potential to incorporate whatever becomes available for a more precision assessment of substrate or symptoms or arrhythmia burden and so forth,” she said.


 

ABC pathway

The guidelines advocate the previously described ABC pathway for integrated care management, which includes ‘A’ for Anticoagulation/Avoid stroke, ‘B’ for Better symptom control, and ‘C’ for Comorbidity/Cardiovascular risk factor optimization.

The document strengthens support for formal risk score–based assessment of bleeding risk in all patients, including use of the HAS-BLED score to help address modifiable bleeding risk factors and to identify patients at high bleeding risk (HAS-BLED score ≥3) for early and more frequent follow-up.

These assessments should be done regularly, given that both stroke and bleeding risk are dynamic and change over time with aging and comorbidities, Dr. Potpara stressed. In patients with AFib initially at low risk for stroke, the next assessment should be optimally performed at 4-6 months.

The guideline also targets weight loss in patients who are obese and have AFib, particularly those being evaluated for ablation, and good blood pressure control in patients with AFib and hypertension to reduce AFib recurrences and risk for stroke and bleeding (both class I, up from IIa). 

It’s particularly important that these risk factors are addressed, and that modifiable risk factors that go along with increased AFib occurrence and persistence are addressed and communicated to patients, said Gerhard Hindricks, MD, PhD, guideline cochair and medical director of the Rhythmology Department, Heart Centre Leipzig (Germany).

“I have to confess, as an interventional electrophysiologist, there has been a time where I have not appreciated these risk factors intensely enough,” he said. “But we have learned, also in the field of catheter ablation, that weight loss is an essential basis for a good procedure. If we can motivate patients to lose weight and then come to the intervention with better outcome, it’s a true benefit for the patient and addresses patient values. So I’m particularly happy we have introduced that with such intensity in the guidelines.”
 

Rate and rhythm control

The guidelines make no recommendation of one novel oral anticoagulant (NOAC) over another. However, in patients already receiving vitamin K antagonists with low time in the therapeutic range, they recommend switching to a different NOAC but ensuring good adherence and persistence with therapy (class I recommendation) or efforts to improve time in therapeutic range (class IIa).

Catheter ablation takes on a more prominent role for rhythm control and is now recommended after one antiarrhythmic drug therapy fails to improve symptoms of AF recurrence in patients with paroxysmal AFib, or persistent AFib with or without major risk factors for recurrence. The class I recommendation is based on results from the CAPTAF and CABANA trials, said task force member Carina Blomström-Lundqvist, MD, PhD, Uppsala University, Sweden.

Catheter ablation is also now a first-line therapy for patients with AFib who have a high likelihood of tachycardia-induced cardiomyopathy, independent of symptom status. “In this subset of patients, catheter ablation may offer a lot with respect to restoration of left ventricular function,” observed Dr. Hindricks.

Complete electrical isolation of the pulmonary veins is recommended during all AFib catheter ablation procedures (class I).

“Even as a medical conservative, I think it is totally reasonable to move to catheter ablation after a failed drug trial,” commented John Mandrola, MD, Baptist Health, Louisville, Ky., who was not a part of the guideline development. 

Although the chance of a second drug working after one failure is low, he noted that operators in the United States have dofetilide, which is not used much in Europe, and sometimes works surprisingly well.

“That said, the caveat is that moving to catheter ablation after drug failure is only appropriate if we have addressed all the pertinent risk factors: sleep apnea, weight loss, lack of fitness, blood pressure control, and alcohol excess,” he said. 

As for tachycardia-mediated cardiomyopathy, this too can be reasonable, Dr. Mandrola said. “I often get people ‘out of a hole’ with amiodarone plus cardioversion for a few months and then proceed to ablation.”

Notably, the 2020 iteration sharpens its recommendation that amiodarone not be used first-line for long-term rhythm control in all patients with AFib, including those with heart failure with reduced ejection fraction, given its extracardiac toxicity (class I, up from IIa).
 

Quality counts

In response to growing evidence that guideline-adherence is associated with significantly better outcomes in AFib, the 2020 ESC/EACTS guidelines explicitly included a recommendation on the need to measure quality of care to identify opportunities for improvement.

With this framework in mind, a task force with 23 people – including members from ESC and heart rhythm societies in the United States, Asia Pacific, and Latin America, along with patient representatives – was created to develop a list of quality indicators (QIs), ultimately settling on 17 main QIs and 17 secondary ones, said Elena Arbelo, MD, PhD, MSc, University of Barcelona.

The QIs are classified into six domains: patient assessment, anticoagulation, rate control, rhythm control, risk factor modification, and, importantly, outcome measures. A full list is accessible in a paper, simultaneously published in EP EuroPace.

Five patient-reported outcomes fall under the outcomes domain but only one – health-related quality of life – is a main quality indicator. The remaining outcomes are still important but are listed as secondary because of the lack of evidence to sustain or defend their systematic implementation, particularly evidence on how to measure them appropriately, Dr. Arbelo said.

“Hopefully, following the [class I] recommendation by the 2020 ESC guidelines to routinely collect patient-reported outcomes will allow us to collect further evidence and in the future have sufficient evidence to include these as a main outcome,” she said.

The QI work was driven in parallel with the guidelines and had a huge impact on its development, including inclusion of clear recommendations on how to measure quality, Dr. Hindricks said. “I believe that the whole issue of quality management in the treatment of patients with a focus on patient values cannot be overestimated.”

Disclosure information for all writing committee members is in the report. Dr. Mandrola is a writer and podcaster for Medscape.
 

A version of this article originally appeared on Medscape.com.

New atrial fibrillation (AFib) management guidelines from the European Society of Cardiology (ESC) call for diagnostic confirmation and structured characterization of AFib and the need to streamline integrated care with the Atrial fibrillation Better Care (ABC) pathway.

“It’s as simple as CC to ABC,” quipped one task force member during the virtual unveiling of the guidelines at the ESC Congress 2020.

The guidelines were developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS) and published simultaneously August 29 in the European Heart Journal.

Acknowledging the slew of novel screening tools now available and their reported sensitivity and specificity rates, the document supports opportunistic screening for AFib by pulse taking or electrocardiogram (ECG) rhythm strip in patients at least 65 years of age, with a class 1 recommendation, evidence level B.

Systematic ECG screening should also be considered to detect AFib in individuals at least 75 years of age or in those at high risk for stroke (class IIa, level B).

Other new class I screening recommendations are to inform individuals undergoing screening about the significance and treatment implications of detecting AFib and to have a structured referral platform in place for further physician-led evaluation.

A definite diagnosis of clinical AFib is established only after confirmation by a conventional 12-lead ECG or single-lead ECG strip with at least 30 seconds of AFib.

In line with ESC’s 2016 AFib guidelines, the new iteration classifies AFib as first diagnosed, paroxysmal, persistent, long-standing persistent, and permanent. But it’s also important to classify the clinical profile of AFib, task force member Giuseppe Boriani, MD, PhD, University of Modena, Italy, said in the first of five presentations.

“So the novelty of the 2020 guidelines is related to the proposal of the 4S-AF scheme for a structured characterization of atrial fibrillation that takes into account Stroke risk, severity of Symptoms, Severity of atrial fibrillation burden, and Substrate severity,” he said.

This represents a paradigm shift from a single-domain conventional classification of AFib toward a structured characterization that streamlines assessment, informs treatment decision-making, and facilitates communication among physicians of various specialties, said Tatjana Potpara, MD, PhD, guideline co-chair and head of the Department for Intensive Arrhythmia Care, Clinical Centre of Serbia, Belgrade.

“The beauty of this approach is that, at present, the assessment of the ‘S’ components are performed using available tools, but in the future, the 4S-AF has a great potential to incorporate whatever becomes available for a more precision assessment of substrate or symptoms or arrhythmia burden and so forth,” she said.


 

ABC pathway

The guidelines advocate the previously described ABC pathway for integrated care management, which includes ‘A’ for Anticoagulation/Avoid stroke, ‘B’ for Better symptom control, and ‘C’ for Comorbidity/Cardiovascular risk factor optimization.

The document strengthens support for formal risk score–based assessment of bleeding risk in all patients, including use of the HAS-BLED score to help address modifiable bleeding risk factors and to identify patients at high bleeding risk (HAS-BLED score ≥3) for early and more frequent follow-up.

These assessments should be done regularly, given that both stroke and bleeding risk are dynamic and change over time with aging and comorbidities, Dr. Potpara stressed. In patients with AFib initially at low risk for stroke, the next assessment should be optimally performed at 4-6 months.

The guideline also targets weight loss in patients who are obese and have AFib, particularly those being evaluated for ablation, and good blood pressure control in patients with AFib and hypertension to reduce AFib recurrences and risk for stroke and bleeding (both class I, up from IIa). 

It’s particularly important that these risk factors are addressed, and that modifiable risk factors that go along with increased AFib occurrence and persistence are addressed and communicated to patients, said Gerhard Hindricks, MD, PhD, guideline cochair and medical director of the Rhythmology Department, Heart Centre Leipzig (Germany).

“I have to confess, as an interventional electrophysiologist, there has been a time where I have not appreciated these risk factors intensely enough,” he said. “But we have learned, also in the field of catheter ablation, that weight loss is an essential basis for a good procedure. If we can motivate patients to lose weight and then come to the intervention with better outcome, it’s a true benefit for the patient and addresses patient values. So I’m particularly happy we have introduced that with such intensity in the guidelines.”
 

Rate and rhythm control

The guidelines make no recommendation of one novel oral anticoagulant (NOAC) over another. However, in patients already receiving vitamin K antagonists with low time in the therapeutic range, they recommend switching to a different NOAC but ensuring good adherence and persistence with therapy (class I recommendation) or efforts to improve time in therapeutic range (class IIa).

Catheter ablation takes on a more prominent role for rhythm control and is now recommended after one antiarrhythmic drug therapy fails to improve symptoms of AF recurrence in patients with paroxysmal AFib, or persistent AFib with or without major risk factors for recurrence. The class I recommendation is based on results from the CAPTAF and CABANA trials, said task force member Carina Blomström-Lundqvist, MD, PhD, Uppsala University, Sweden.

Catheter ablation is also now a first-line therapy for patients with AFib who have a high likelihood of tachycardia-induced cardiomyopathy, independent of symptom status. “In this subset of patients, catheter ablation may offer a lot with respect to restoration of left ventricular function,” observed Dr. Hindricks.

Complete electrical isolation of the pulmonary veins is recommended during all AFib catheter ablation procedures (class I).

“Even as a medical conservative, I think it is totally reasonable to move to catheter ablation after a failed drug trial,” commented John Mandrola, MD, Baptist Health, Louisville, Ky., who was not a part of the guideline development. 

Although the chance of a second drug working after one failure is low, he noted that operators in the United States have dofetilide, which is not used much in Europe, and sometimes works surprisingly well.

“That said, the caveat is that moving to catheter ablation after drug failure is only appropriate if we have addressed all the pertinent risk factors: sleep apnea, weight loss, lack of fitness, blood pressure control, and alcohol excess,” he said. 

As for tachycardia-mediated cardiomyopathy, this too can be reasonable, Dr. Mandrola said. “I often get people ‘out of a hole’ with amiodarone plus cardioversion for a few months and then proceed to ablation.”

Notably, the 2020 iteration sharpens its recommendation that amiodarone not be used first-line for long-term rhythm control in all patients with AFib, including those with heart failure with reduced ejection fraction, given its extracardiac toxicity (class I, up from IIa).
 

Quality counts

In response to growing evidence that guideline-adherence is associated with significantly better outcomes in AFib, the 2020 ESC/EACTS guidelines explicitly included a recommendation on the need to measure quality of care to identify opportunities for improvement.

With this framework in mind, a task force with 23 people – including members from ESC and heart rhythm societies in the United States, Asia Pacific, and Latin America, along with patient representatives – was created to develop a list of quality indicators (QIs), ultimately settling on 17 main QIs and 17 secondary ones, said Elena Arbelo, MD, PhD, MSc, University of Barcelona.

The QIs are classified into six domains: patient assessment, anticoagulation, rate control, rhythm control, risk factor modification, and, importantly, outcome measures. A full list is accessible in a paper, simultaneously published in EP EuroPace.

Five patient-reported outcomes fall under the outcomes domain but only one – health-related quality of life – is a main quality indicator. The remaining outcomes are still important but are listed as secondary because of the lack of evidence to sustain or defend their systematic implementation, particularly evidence on how to measure them appropriately, Dr. Arbelo said.

“Hopefully, following the [class I] recommendation by the 2020 ESC guidelines to routinely collect patient-reported outcomes will allow us to collect further evidence and in the future have sufficient evidence to include these as a main outcome,” she said.

The QI work was driven in parallel with the guidelines and had a huge impact on its development, including inclusion of clear recommendations on how to measure quality, Dr. Hindricks said. “I believe that the whole issue of quality management in the treatment of patients with a focus on patient values cannot be overestimated.”

Disclosure information for all writing committee members is in the report. Dr. Mandrola is a writer and podcaster for Medscape.
 

A version of this article originally appeared on Medscape.com.

New atrial fibrillation (AFib) management guidelines from the European Society of Cardiology (ESC) call for diagnostic confirmation and structured characterization of AFib and the need to streamline integrated care with the Atrial fibrillation Better Care (ABC) pathway.

“It’s as simple as CC to ABC,” quipped one task force member during the virtual unveiling of the guidelines at the ESC Congress 2020.

The guidelines were developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS) and published simultaneously August 29 in the European Heart Journal.

Acknowledging the slew of novel screening tools now available and their reported sensitivity and specificity rates, the document supports opportunistic screening for AFib by pulse taking or electrocardiogram (ECG) rhythm strip in patients at least 65 years of age, with a class 1 recommendation, evidence level B.

Systematic ECG screening should also be considered to detect AFib in individuals at least 75 years of age or in those at high risk for stroke (class IIa, level B).

Other new class I screening recommendations are to inform individuals undergoing screening about the significance and treatment implications of detecting AFib and to have a structured referral platform in place for further physician-led evaluation.

A definite diagnosis of clinical AFib is established only after confirmation by a conventional 12-lead ECG or single-lead ECG strip with at least 30 seconds of AFib.

In line with ESC’s 2016 AFib guidelines, the new iteration classifies AFib as first diagnosed, paroxysmal, persistent, long-standing persistent, and permanent. But it’s also important to classify the clinical profile of AFib, task force member Giuseppe Boriani, MD, PhD, University of Modena, Italy, said in the first of five presentations.

“So the novelty of the 2020 guidelines is related to the proposal of the 4S-AF scheme for a structured characterization of atrial fibrillation that takes into account Stroke risk, severity of Symptoms, Severity of atrial fibrillation burden, and Substrate severity,” he said.

This represents a paradigm shift from a single-domain conventional classification of AFib toward a structured characterization that streamlines assessment, informs treatment decision-making, and facilitates communication among physicians of various specialties, said Tatjana Potpara, MD, PhD, guideline co-chair and head of the Department for Intensive Arrhythmia Care, Clinical Centre of Serbia, Belgrade.

“The beauty of this approach is that, at present, the assessment of the ‘S’ components are performed using available tools, but in the future, the 4S-AF has a great potential to incorporate whatever becomes available for a more precision assessment of substrate or symptoms or arrhythmia burden and so forth,” she said.


 

ABC pathway

The guidelines advocate the previously described ABC pathway for integrated care management, which includes ‘A’ for Anticoagulation/Avoid stroke, ‘B’ for Better symptom control, and ‘C’ for Comorbidity/Cardiovascular risk factor optimization.

The document strengthens support for formal risk score–based assessment of bleeding risk in all patients, including use of the HAS-BLED score to help address modifiable bleeding risk factors and to identify patients at high bleeding risk (HAS-BLED score ≥3) for early and more frequent follow-up.

These assessments should be done regularly, given that both stroke and bleeding risk are dynamic and change over time with aging and comorbidities, Dr. Potpara stressed. In patients with AFib initially at low risk for stroke, the next assessment should be optimally performed at 4-6 months.

The guideline also targets weight loss in patients who are obese and have AFib, particularly those being evaluated for ablation, and good blood pressure control in patients with AFib and hypertension to reduce AFib recurrences and risk for stroke and bleeding (both class I, up from IIa). 

It’s particularly important that these risk factors are addressed, and that modifiable risk factors that go along with increased AFib occurrence and persistence are addressed and communicated to patients, said Gerhard Hindricks, MD, PhD, guideline cochair and medical director of the Rhythmology Department, Heart Centre Leipzig (Germany).

“I have to confess, as an interventional electrophysiologist, there has been a time where I have not appreciated these risk factors intensely enough,” he said. “But we have learned, also in the field of catheter ablation, that weight loss is an essential basis for a good procedure. If we can motivate patients to lose weight and then come to the intervention with better outcome, it’s a true benefit for the patient and addresses patient values. So I’m particularly happy we have introduced that with such intensity in the guidelines.”
 

Rate and rhythm control

The guidelines make no recommendation of one novel oral anticoagulant (NOAC) over another. However, in patients already receiving vitamin K antagonists with low time in the therapeutic range, they recommend switching to a different NOAC but ensuring good adherence and persistence with therapy (class I recommendation) or efforts to improve time in therapeutic range (class IIa).

Catheter ablation takes on a more prominent role for rhythm control and is now recommended after one antiarrhythmic drug therapy fails to improve symptoms of AF recurrence in patients with paroxysmal AFib, or persistent AFib with or without major risk factors for recurrence. The class I recommendation is based on results from the CAPTAF and CABANA trials, said task force member Carina Blomström-Lundqvist, MD, PhD, Uppsala University, Sweden.

Catheter ablation is also now a first-line therapy for patients with AFib who have a high likelihood of tachycardia-induced cardiomyopathy, independent of symptom status. “In this subset of patients, catheter ablation may offer a lot with respect to restoration of left ventricular function,” observed Dr. Hindricks.

Complete electrical isolation of the pulmonary veins is recommended during all AFib catheter ablation procedures (class I).

“Even as a medical conservative, I think it is totally reasonable to move to catheter ablation after a failed drug trial,” commented John Mandrola, MD, Baptist Health, Louisville, Ky., who was not a part of the guideline development. 

Although the chance of a second drug working after one failure is low, he noted that operators in the United States have dofetilide, which is not used much in Europe, and sometimes works surprisingly well.

“That said, the caveat is that moving to catheter ablation after drug failure is only appropriate if we have addressed all the pertinent risk factors: sleep apnea, weight loss, lack of fitness, blood pressure control, and alcohol excess,” he said. 

As for tachycardia-mediated cardiomyopathy, this too can be reasonable, Dr. Mandrola said. “I often get people ‘out of a hole’ with amiodarone plus cardioversion for a few months and then proceed to ablation.”

Notably, the 2020 iteration sharpens its recommendation that amiodarone not be used first-line for long-term rhythm control in all patients with AFib, including those with heart failure with reduced ejection fraction, given its extracardiac toxicity (class I, up from IIa).
 

Quality counts

In response to growing evidence that guideline-adherence is associated with significantly better outcomes in AFib, the 2020 ESC/EACTS guidelines explicitly included a recommendation on the need to measure quality of care to identify opportunities for improvement.

With this framework in mind, a task force with 23 people – including members from ESC and heart rhythm societies in the United States, Asia Pacific, and Latin America, along with patient representatives – was created to develop a list of quality indicators (QIs), ultimately settling on 17 main QIs and 17 secondary ones, said Elena Arbelo, MD, PhD, MSc, University of Barcelona.

The QIs are classified into six domains: patient assessment, anticoagulation, rate control, rhythm control, risk factor modification, and, importantly, outcome measures. A full list is accessible in a paper, simultaneously published in EP EuroPace.

Five patient-reported outcomes fall under the outcomes domain but only one – health-related quality of life – is a main quality indicator. The remaining outcomes are still important but are listed as secondary because of the lack of evidence to sustain or defend their systematic implementation, particularly evidence on how to measure them appropriately, Dr. Arbelo said.

“Hopefully, following the [class I] recommendation by the 2020 ESC guidelines to routinely collect patient-reported outcomes will allow us to collect further evidence and in the future have sufficient evidence to include these as a main outcome,” she said.

The QI work was driven in parallel with the guidelines and had a huge impact on its development, including inclusion of clear recommendations on how to measure quality, Dr. Hindricks said. “I believe that the whole issue of quality management in the treatment of patients with a focus on patient values cannot be overestimated.”

Disclosure information for all writing committee members is in the report. Dr. Mandrola is a writer and podcaster for Medscape.
 

A version of this article originally appeared on Medscape.com.

An investigational drug that targets part of the molecular machinery underlying obstructive hypertrophic cardiomyopathy (HCM) can improve both symptoms and functional status in patients with the genetic disorder, suggests a placebo-controlled phase 3 trial.

Treatment with mavacamten (MyoKardia) worked partly by alleviating high-pressure gradients in the left ventricular outflow tract (LVOT), a key characteristic of obstructive HCM. Its effects appeared consistent across a wide range of objective and patient-assessed endpoints.

Mavacamten is “the first potential medical therapy addressing the underlying biology of symptoms in hypertrophic obstructive cardiomyopathy,” observed Iacopo Olivotto, MD, Careggi University Hospital, Florence, Italy.

Patients in the EXPLORER-HCM trial who took the new drug showed improvements in “every aspect of objective performance and subjective well-being,” Dr. Olivotto said at a preview for journalists before his formal online presentation of the results during the virtual European Society of Cardiology Congress 2020, staged in lieu of the traditional annual meeting because of the COVID-19 pandemic.

Dr. Olivotto, also lead author on the study’s same-day publication in The Lancet, was exuberant about the findings. “It is really hard to convey what this actually means for a scientific and clinical community that has spent over 60 years trying to understand and cure hypertrophic cardiomyopathy.”

MyoKardia released abbreviated top-line results of EXPLORER-HCM in May, which were reported by theheart.org | Medscape Cardiology at the time.

“I think it’s pretty exciting. We certainly need more and better drugs for this patient population,” Arnon Adler, MD, who is not associated with the trial but follows HCM at the Peter Munk Cardiac Centre, Toronto General Hospital, said in an interview.

The trial compared the new drug to placebo rather than full contemporary drug therapy for obstructive HCM, Adler cautioned, and had a fairly short follow-up time. But he was impressed that mavacamten’s apparent benefits seemed consistent not only for endpoints like change in New York Heart Association (NYHA) functional class and quality of life but also for more objective measures like peak VO₂ and LVOT gradients.

“I think the results were promising across the board,” he told.
 

Unique mechanism of action

Mavacamten is described as a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin adenosine triphosphatase that addresses the underlying pathophysiology of HCM by reducing actin–myosin cross-bridge formation. It thereby inhibits the excessive myocyte contractility that is a key mechanism of the disorder’s tell-tale hypertrophy, something the available HCM drug therapies don’t do.

Almost three-fourths of patients in the trial were initially in NYHA class 2. Such patients in practice tend to be treated pharmacologically, with more invasive but generally effective surgical myectomy and alcohol septal ablation performed more often for patients in NYHA class 3.

“In the EXPLORER-HCM trial, patients enrolled did not have any immediate indication for surgery,” although many of them in NYHA class 2 would likely progress to NYHA 3, Dr. Olivotto said in an interview.

Based on the trial, he said, it’s possible that mavacamten could lead to “earlier and broader treatment of obstruction symptoms in patients who would never have qualified for surgery in the first place because their symptoms may not be severe enough, but they are still limited.”

Notably, the published report notes, 27% of patients taking mavacamten achieved what was defined as a complete response – that is, a reduction of all LVOT gradients to less than 30 mm Hg in the total absence of symptoms.

Only 1% of patients in the placebo-treated control group met that goal, “showing that mavacamten might be capable of achieving marked relief of symptoms and LVOT obstruction,” the report states.

In the trial, “treatment with mavacamten led to clinically meaningful improvements in hemodynamic status, functional capacity, and subjective well-being in patients with obstructive hypertrophic cardiomyopathy,” agrees an editorial accompanying the EXPLORER-HCM publication.

Mavacamten might even compare favorably to surgery and ablative therapy, speculated the editorialists, Michael Papadakis, MBBS, MD, and colleagues of St. George’s University Hospitals NHS Foundation Trust, London. The drug appeared to reduce the peak LVOT gradient “to less than the guideline-based threshold for septal reduction therapy, 50 mm Hg, in 74% of patients, compared with 21% in the placebo group, indicating that mavacamten could represent a valid alternative to highly specialized invasive therapy,” they wrote.
 

Standard drug therapy

“There are approved drugs for obstructive hypertrophic cardiomyopathy, but they are ancient and were developed for other diseases,” observed Dr. Olivotto at the media briefing. Those drug options – primarily beta-blockers, nondihydropyridine calcium-channel blockers, and the sodium-channel blocker disopyramide – are often ineffective or cause onerous side effects, he said.

Notably in EXPLORER-HCM, patients in both the mavacamten and placebo groups could also be receiving beta-blockers and calcium-channel blockers, but no one in the trial could be receiving disopyramide, which can prolong the QT interval.

“By design,” mavacamten wasn’t compared to disopyramide, “a much more potent drug for lowering gradient and improving symptoms than beta-blockers or calcium-channel blockers,” said Martin S. Maron, MD, medical director at the Hypertrophic Cardiomyopathy Center and Research Institute, Tufts Medical Center, Boston.

Therefore, the trial’s results can’t be extrapolated to conclude that the new drug is superior to disopyramide “or the gold standard, surgical myectomy,” he said in an interview.

Dr. Adler agreed that observational studies suggest a benefit from disopyramide that may rival the apparent effect of mavacamten. “But of course, you can’t make direct comparisons because we never had a study like this for disopyramide.” Because it has many side effects and limitations, “it’s not a drug that I like using, but it is beneficial for some patients and I do use it quite a bit.”

What EXPLORER-HCM does seem to show, Dr. Maron said, “is that the mechanism of action of the drug does seem to play out. It lowers gradients in a pretty reliable and powerful way, and that translates into clinical improvement in many patients. So it starts to support the idea that this drug and the class of drugs, myosin inhibitors, may represent another medical therapy option for symptomatic obstructive HCM.”

And, he pointed out, about one-fifth of patients with obstructive HCM don’t respond to disopyramide with fewer symptoms, and in others the drug “starts to lose efficacy over time.” So disopyramide has limitations, and EXPLORER-HCM “provides the possibility of an additional drug option.”

EXPLORER-HCM randomly assigned 251 adults with obstructive HCM in 13 countries to receive mavacamten, titrated from a starting dosage of 5 mg/day to a possible 15 mg/day or to placebo for 30 weeks.

The patients were required to have a peak LVOT gradient at least 50 mm Hg, a left ventricular ejection fraction (LVEF) of at least 55%, and symptoms indicating NYHA class 2 or 3; ultimately, 73% started the trial in NYHA class 2.

In the intention-to-treat analysis, 36.6% of patients receiving mavacamten and 17.2% of control patients met the composite primary endpoint (P = .0005), which consisted of either a 1.5–mL/kg per minute or greater improvement in peak oxygen consumption (pVO₂) and at least a one-step reduction in NYHA functional class or at least a 3.0–mL/kg per minute pVO₂ increase without deterioration in NYHA class, by week 30.

Medscape.com

A version of this article originally appeared on Medscape.com.

An investigational drug that targets part of the molecular machinery underlying obstructive hypertrophic cardiomyopathy (HCM) can improve both symptoms and functional status in patients with the genetic disorder, suggests a placebo-controlled phase 3 trial.

Treatment with mavacamten (MyoKardia) worked partly by alleviating high-pressure gradients in the left ventricular outflow tract (LVOT), a key characteristic of obstructive HCM. Its effects appeared consistent across a wide range of objective and patient-assessed endpoints.

Mavacamten is “the first potential medical therapy addressing the underlying biology of symptoms in hypertrophic obstructive cardiomyopathy,” observed Iacopo Olivotto, MD, Careggi University Hospital, Florence, Italy.

Patients in the EXPLORER-HCM trial who took the new drug showed improvements in “every aspect of objective performance and subjective well-being,” Dr. Olivotto said at a preview for journalists before his formal online presentation of the results during the virtual European Society of Cardiology Congress 2020, staged in lieu of the traditional annual meeting because of the COVID-19 pandemic.

Dr. Olivotto, also lead author on the study’s same-day publication in The Lancet, was exuberant about the findings. “It is really hard to convey what this actually means for a scientific and clinical community that has spent over 60 years trying to understand and cure hypertrophic cardiomyopathy.”

MyoKardia released abbreviated top-line results of EXPLORER-HCM in May, which were reported by theheart.org | Medscape Cardiology at the time.

“I think it’s pretty exciting. We certainly need more and better drugs for this patient population,” Arnon Adler, MD, who is not associated with the trial but follows HCM at the Peter Munk Cardiac Centre, Toronto General Hospital, said in an interview.

The trial compared the new drug to placebo rather than full contemporary drug therapy for obstructive HCM, Adler cautioned, and had a fairly short follow-up time. But he was impressed that mavacamten’s apparent benefits seemed consistent not only for endpoints like change in New York Heart Association (NYHA) functional class and quality of life but also for more objective measures like peak VO₂ and LVOT gradients.

“I think the results were promising across the board,” he told.
 

Unique mechanism of action

Mavacamten is described as a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin adenosine triphosphatase that addresses the underlying pathophysiology of HCM by reducing actin–myosin cross-bridge formation. It thereby inhibits the excessive myocyte contractility that is a key mechanism of the disorder’s tell-tale hypertrophy, something the available HCM drug therapies don’t do.

Almost three-fourths of patients in the trial were initially in NYHA class 2. Such patients in practice tend to be treated pharmacologically, with more invasive but generally effective surgical myectomy and alcohol septal ablation performed more often for patients in NYHA class 3.

“In the EXPLORER-HCM trial, patients enrolled did not have any immediate indication for surgery,” although many of them in NYHA class 2 would likely progress to NYHA 3, Dr. Olivotto said in an interview.

Based on the trial, he said, it’s possible that mavacamten could lead to “earlier and broader treatment of obstruction symptoms in patients who would never have qualified for surgery in the first place because their symptoms may not be severe enough, but they are still limited.”

Notably, the published report notes, 27% of patients taking mavacamten achieved what was defined as a complete response – that is, a reduction of all LVOT gradients to less than 30 mm Hg in the total absence of symptoms.

Only 1% of patients in the placebo-treated control group met that goal, “showing that mavacamten might be capable of achieving marked relief of symptoms and LVOT obstruction,” the report states.

In the trial, “treatment with mavacamten led to clinically meaningful improvements in hemodynamic status, functional capacity, and subjective well-being in patients with obstructive hypertrophic cardiomyopathy,” agrees an editorial accompanying the EXPLORER-HCM publication.

Mavacamten might even compare favorably to surgery and ablative therapy, speculated the editorialists, Michael Papadakis, MBBS, MD, and colleagues of St. George’s University Hospitals NHS Foundation Trust, London. The drug appeared to reduce the peak LVOT gradient “to less than the guideline-based threshold for septal reduction therapy, 50 mm Hg, in 74% of patients, compared with 21% in the placebo group, indicating that mavacamten could represent a valid alternative to highly specialized invasive therapy,” they wrote.
 

Standard drug therapy

“There are approved drugs for obstructive hypertrophic cardiomyopathy, but they are ancient and were developed for other diseases,” observed Dr. Olivotto at the media briefing. Those drug options – primarily beta-blockers, nondihydropyridine calcium-channel blockers, and the sodium-channel blocker disopyramide – are often ineffective or cause onerous side effects, he said.

Notably in EXPLORER-HCM, patients in both the mavacamten and placebo groups could also be receiving beta-blockers and calcium-channel blockers, but no one in the trial could be receiving disopyramide, which can prolong the QT interval.

“By design,” mavacamten wasn’t compared to disopyramide, “a much more potent drug for lowering gradient and improving symptoms than beta-blockers or calcium-channel blockers,” said Martin S. Maron, MD, medical director at the Hypertrophic Cardiomyopathy Center and Research Institute, Tufts Medical Center, Boston.

Therefore, the trial’s results can’t be extrapolated to conclude that the new drug is superior to disopyramide “or the gold standard, surgical myectomy,” he said in an interview.

Dr. Adler agreed that observational studies suggest a benefit from disopyramide that may rival the apparent effect of mavacamten. “But of course, you can’t make direct comparisons because we never had a study like this for disopyramide.” Because it has many side effects and limitations, “it’s not a drug that I like using, but it is beneficial for some patients and I do use it quite a bit.”

What EXPLORER-HCM does seem to show, Dr. Maron said, “is that the mechanism of action of the drug does seem to play out. It lowers gradients in a pretty reliable and powerful way, and that translates into clinical improvement in many patients. So it starts to support the idea that this drug and the class of drugs, myosin inhibitors, may represent another medical therapy option for symptomatic obstructive HCM.”

And, he pointed out, about one-fifth of patients with obstructive HCM don’t respond to disopyramide with fewer symptoms, and in others the drug “starts to lose efficacy over time.” So disopyramide has limitations, and EXPLORER-HCM “provides the possibility of an additional drug option.”

EXPLORER-HCM randomly assigned 251 adults with obstructive HCM in 13 countries to receive mavacamten, titrated from a starting dosage of 5 mg/day to a possible 15 mg/day or to placebo for 30 weeks.

The patients were required to have a peak LVOT gradient at least 50 mm Hg, a left ventricular ejection fraction (LVEF) of at least 55%, and symptoms indicating NYHA class 2 or 3; ultimately, 73% started the trial in NYHA class 2.

In the intention-to-treat analysis, 36.6% of patients receiving mavacamten and 17.2% of control patients met the composite primary endpoint (P = .0005), which consisted of either a 1.5–mL/kg per minute or greater improvement in peak oxygen consumption (pVO₂) and at least a one-step reduction in NYHA functional class or at least a 3.0–mL/kg per minute pVO₂ increase without deterioration in NYHA class, by week 30.

Medscape.com

A version of this article originally appeared on Medscape.com.

An investigational drug that targets part of the molecular machinery underlying obstructive hypertrophic cardiomyopathy (HCM) can improve both symptoms and functional status in patients with the genetic disorder, suggests a placebo-controlled phase 3 trial.

Treatment with mavacamten (MyoKardia) worked partly by alleviating high-pressure gradients in the left ventricular outflow tract (LVOT), a key characteristic of obstructive HCM. Its effects appeared consistent across a wide range of objective and patient-assessed endpoints.

Mavacamten is “the first potential medical therapy addressing the underlying biology of symptoms in hypertrophic obstructive cardiomyopathy,” observed Iacopo Olivotto, MD, Careggi University Hospital, Florence, Italy.

Patients in the EXPLORER-HCM trial who took the new drug showed improvements in “every aspect of objective performance and subjective well-being,” Dr. Olivotto said at a preview for journalists before his formal online presentation of the results during the virtual European Society of Cardiology Congress 2020, staged in lieu of the traditional annual meeting because of the COVID-19 pandemic.

Dr. Olivotto, also lead author on the study’s same-day publication in The Lancet, was exuberant about the findings. “It is really hard to convey what this actually means for a scientific and clinical community that has spent over 60 years trying to understand and cure hypertrophic cardiomyopathy.”

MyoKardia released abbreviated top-line results of EXPLORER-HCM in May, which were reported by theheart.org | Medscape Cardiology at the time.

“I think it’s pretty exciting. We certainly need more and better drugs for this patient population,” Arnon Adler, MD, who is not associated with the trial but follows HCM at the Peter Munk Cardiac Centre, Toronto General Hospital, said in an interview.

The trial compared the new drug to placebo rather than full contemporary drug therapy for obstructive HCM, Adler cautioned, and had a fairly short follow-up time. But he was impressed that mavacamten’s apparent benefits seemed consistent not only for endpoints like change in New York Heart Association (NYHA) functional class and quality of life but also for more objective measures like peak VO₂ and LVOT gradients.

“I think the results were promising across the board,” he told.
 

Unique mechanism of action

Mavacamten is described as a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin adenosine triphosphatase that addresses the underlying pathophysiology of HCM by reducing actin–myosin cross-bridge formation. It thereby inhibits the excessive myocyte contractility that is a key mechanism of the disorder’s tell-tale hypertrophy, something the available HCM drug therapies don’t do.

Almost three-fourths of patients in the trial were initially in NYHA class 2. Such patients in practice tend to be treated pharmacologically, with more invasive but generally effective surgical myectomy and alcohol septal ablation performed more often for patients in NYHA class 3.

“In the EXPLORER-HCM trial, patients enrolled did not have any immediate indication for surgery,” although many of them in NYHA class 2 would likely progress to NYHA 3, Dr. Olivotto said in an interview.

Based on the trial, he said, it’s possible that mavacamten could lead to “earlier and broader treatment of obstruction symptoms in patients who would never have qualified for surgery in the first place because their symptoms may not be severe enough, but they are still limited.”

Notably, the published report notes, 27% of patients taking mavacamten achieved what was defined as a complete response – that is, a reduction of all LVOT gradients to less than 30 mm Hg in the total absence of symptoms.

Only 1% of patients in the placebo-treated control group met that goal, “showing that mavacamten might be capable of achieving marked relief of symptoms and LVOT obstruction,” the report states.

In the trial, “treatment with mavacamten led to clinically meaningful improvements in hemodynamic status, functional capacity, and subjective well-being in patients with obstructive hypertrophic cardiomyopathy,” agrees an editorial accompanying the EXPLORER-HCM publication.

Mavacamten might even compare favorably to surgery and ablative therapy, speculated the editorialists, Michael Papadakis, MBBS, MD, and colleagues of St. George’s University Hospitals NHS Foundation Trust, London. The drug appeared to reduce the peak LVOT gradient “to less than the guideline-based threshold for septal reduction therapy, 50 mm Hg, in 74% of patients, compared with 21% in the placebo group, indicating that mavacamten could represent a valid alternative to highly specialized invasive therapy,” they wrote.
 

Standard drug therapy

“There are approved drugs for obstructive hypertrophic cardiomyopathy, but they are ancient and were developed for other diseases,” observed Dr. Olivotto at the media briefing. Those drug options – primarily beta-blockers, nondihydropyridine calcium-channel blockers, and the sodium-channel blocker disopyramide – are often ineffective or cause onerous side effects, he said.

Notably in EXPLORER-HCM, patients in both the mavacamten and placebo groups could also be receiving beta-blockers and calcium-channel blockers, but no one in the trial could be receiving disopyramide, which can prolong the QT interval.

“By design,” mavacamten wasn’t compared to disopyramide, “a much more potent drug for lowering gradient and improving symptoms than beta-blockers or calcium-channel blockers,” said Martin S. Maron, MD, medical director at the Hypertrophic Cardiomyopathy Center and Research Institute, Tufts Medical Center, Boston.

Therefore, the trial’s results can’t be extrapolated to conclude that the new drug is superior to disopyramide “or the gold standard, surgical myectomy,” he said in an interview.

Dr. Adler agreed that observational studies suggest a benefit from disopyramide that may rival the apparent effect of mavacamten. “But of course, you can’t make direct comparisons because we never had a study like this for disopyramide.” Because it has many side effects and limitations, “it’s not a drug that I like using, but it is beneficial for some patients and I do use it quite a bit.”

What EXPLORER-HCM does seem to show, Dr. Maron said, “is that the mechanism of action of the drug does seem to play out. It lowers gradients in a pretty reliable and powerful way, and that translates into clinical improvement in many patients. So it starts to support the idea that this drug and the class of drugs, myosin inhibitors, may represent another medical therapy option for symptomatic obstructive HCM.”

And, he pointed out, about one-fifth of patients with obstructive HCM don’t respond to disopyramide with fewer symptoms, and in others the drug “starts to lose efficacy over time.” So disopyramide has limitations, and EXPLORER-HCM “provides the possibility of an additional drug option.”

EXPLORER-HCM randomly assigned 251 adults with obstructive HCM in 13 countries to receive mavacamten, titrated from a starting dosage of 5 mg/day to a possible 15 mg/day or to placebo for 30 weeks.

The patients were required to have a peak LVOT gradient at least 50 mm Hg, a left ventricular ejection fraction (LVEF) of at least 55%, and symptoms indicating NYHA class 2 or 3; ultimately, 73% started the trial in NYHA class 2.

In the intention-to-treat analysis, 36.6% of patients receiving mavacamten and 17.2% of control patients met the composite primary endpoint (P = .0005), which consisted of either a 1.5–mL/kg per minute or greater improvement in peak oxygen consumption (pVO₂) and at least a one-step reduction in NYHA functional class or at least a 3.0–mL/kg per minute pVO₂ increase without deterioration in NYHA class, by week 30.

Medscape.com

A version of this article originally appeared on Medscape.com.

The SGLT2 inhibitor drug class solidified its role as a major, new treatment for patients with heart failure with reduced ejection fraction and no diabetes, with results from a second large, controlled trial showing clear efficacy and safety in this population.

Patients with heart failure with reduced ejection fraction (HFrEF) treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) had a statistically significant 25% relative cut in their incidence of cardiovascular death or first heart failure hospitalization, compared with placebo-treated controls when added on top of standard HFrEF treatment, and this benefit was consistent regardless of whether the treated patients also had type 2 diabetes, Milton Packer, MD, reported at the virtual annual congress of the European Society of Cardiology.

This 25% drop in the primary endpoint with empagliflozin treatment in the EMPEROR-Reduced trial exactly matched the cut in incidence of cardiovascular death or heart failure hospitalization produced by treatment with a another SGLT2 inhibitor, dapagliflozin (Farxiga), in the DAPA-HF trial (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

The performance of these two SGLT2 inhibitors was “incredibly consistent” across the their respective trials run in HFrEF patients with and without type 2 diabetes, and the combined evidence base of the two trials makes for “really compelling evidence” of both safety and efficacy that should prompt a change to U.S. practice, with both of these drugs forming a new cornerstone of HFrEF treatment, Dr. Packer said.
 

Results plant drug class firmly as HFrEF treatment

Dr. Packer stressed in his presentation that optimal treatment of patients with HFrEF now demands use of one of these two SGLT2 inhibitors, as well as sacubitril plus valsartan (Entresto), a beta-blocker, and a mineralocorticoid receptor antagonist, plus a diuretic as a fifth drug class for the many HFrEF patients who also need treatment for fluid overload. He further advocated for rapid introduction of these four cornerstone agents with proven survival benefits once a patient receives a HFrEF diagnosis, suggesting that sacubitril plus valsartan, an SGLT2 inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist could all be initiated within 6 weeks or less while acknowledging that optimal up-titration of the beta-blocker would likely take longer.

The order in which a patient starts these drugs shouldn’t matter, and there currently seems to be no evidence that clearly points toward using either dapagliflozin or empagliflozin over the other, Dr. Packer added.

In recognition of the importance of sending a message to heart failure clinicians about the newly proven efficacy of SGLT2 inhibitors in HFrEF patients, the American College of Cardiology and American Heart Association are now drafting an “expert decision pathway” to help clinicians as they enter this new prescribing space. This interim guidance should come out before the end of 2020, prior to release of fully revised HFrEF management guidelines in 2021, said Athena Poppas, MD, president of the ACC, in an interview.

“There is clearly need for education” that can help guide physicians who care for HFrEF patients on how to introduce an SGLT2 inhibitor along with the additional, lengthy list of drug classes proven to benefit these patients, noted Dr. Poppas, who is also a professor and chief of cardiology at the Brown University in Providence, R.I. Physicians may find that they need extra backup for successfully starting both sacubitril plus valsartan and an SGLT2 inhibitor in HFrEF patients because recent history has shown substantial pushback from third-party payers in reimbursing for these relatively expensive drugs, Dr. Poppas noted. She added that this is a problem that may be compounded when patients should ideally get both drug classes.

Physicians who care for heart failure patients have their own history of dragging their feet when adding new drugs to the regimens HFrEF patients receive. The angiotensin converting enzyme inhibitors and beta-blockers took about 17 years each to start reaching a majority of U.S. HFrEF patients, and sacubitril plus valsartan is now used on perhaps a quarter to a third of HFrEF patients despite receiving Food and Drug Administration approval for these patients in mid 2015, noted Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart and Vascular Institute in Fairfax, Va.

Despite dapagliflozin receiving FDA approval in May 2020 for treating HFrEF in patients without diabetes, early uptake in U.S. practice has been very slow, with findings from large U.S. patient registries suggesting that perhaps 1% of suitable HFrEF patients currently get the drug, estimated Dr. O’Connor in an interview.

Given how strong the evidence now is for benefit and safety from dapagliflozin and empagliflozin, it may take as little as 5 years to reach greater than 50% penetration of one of these drugs into U.S. HFrEF patient populations, suggested Dr. Packer, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
 

EMPEROR-Reduced outcomes

The road to routine use of these SGLT2 inhibitor drugs should be hastened by empagliflozin’s impressive performance in EMPEROR-Reduced, in which the drug scored highly significant benefits over placebo for the prespecified primary and two major secondary endpoints, one of which was a measure of preserved renal function.

The trial randomized 3,730 patients at 520 sites in 20 countries during 2017-2019 and followed them on treatment for a median of 16 months. All patients had a left ventricular ejection fraction of 40% or less, and roughly three-quarters had New York Heart Association (NYHA) class II function, nearly one-quarter had class III function, and fewer than 1% of patients fell into the class IV category.

The primary endpoint occurred in 19% of the empagliflozin-treated patients and in 25% of those who received placebo. Among the half of patients with diabetes in the trial, the relative risk reduction by empagliflozin compared with placebo was a statistically significant 28%; among those without diabetes, it was a statistically significant 22%. Concurrently with Dr. Packer’s report, the results appeared in an article posted online (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

The study also had two main prespecified secondary endpoints: the incidence of total hospitalizations for heart failure, both first and recurrent, which fell by 30% in the empagliflozin-treated patients, compared with placebo, and the rate of declining renal function during the 16 months of the study as measured by estimated glomerular filtration rate, which dropped by roughly 1 mL/min per 1.73 m² among the empagliflozin recipients and by about 4 mL/min/ per 1.73 m² in the placebo patients.

Treatment with empagliflozin also achieved a notable, statistically significant 50% drop in major adverse renal events, consistent with the performance of other drugs in the class.

“Renal protection is a big plus” of empagliflozin in this trial and from the other SGLT2 inhibitors in prior studies, noted Dr. O’Connor.

The EMPEROR-Reduced results also showed an important benefit for HFrEF patients from empagliflozin not previously seen as quickly with any other drug class, noted Dr. Packer. The SGLT2 inhibitor led to statistically a significant slowing in the progression of patients from NYHA class II function to class III, compared with placebo, and it also significantly promoted the recovery of patients from NYHA class III to class II, an effect that became apparent within the first month on treatment and a benefit that is a “big deal” for patients because it represents a “significant change in functional capacity.” This additional dimension of empagliflozin’s benefit “really impressed me,” Dr. Packer said.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Poppas and Dr. O’Connor had no relevant disclosures.
 

[email protected]

SOURCE: Packer M. ESC 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.

The SGLT2 inhibitor drug class solidified its role as a major, new treatment for patients with heart failure with reduced ejection fraction and no diabetes, with results from a second large, controlled trial showing clear efficacy and safety in this population.

Patients with heart failure with reduced ejection fraction (HFrEF) treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) had a statistically significant 25% relative cut in their incidence of cardiovascular death or first heart failure hospitalization, compared with placebo-treated controls when added on top of standard HFrEF treatment, and this benefit was consistent regardless of whether the treated patients also had type 2 diabetes, Milton Packer, MD, reported at the virtual annual congress of the European Society of Cardiology.

This 25% drop in the primary endpoint with empagliflozin treatment in the EMPEROR-Reduced trial exactly matched the cut in incidence of cardiovascular death or heart failure hospitalization produced by treatment with a another SGLT2 inhibitor, dapagliflozin (Farxiga), in the DAPA-HF trial (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

The performance of these two SGLT2 inhibitors was “incredibly consistent” across the their respective trials run in HFrEF patients with and without type 2 diabetes, and the combined evidence base of the two trials makes for “really compelling evidence” of both safety and efficacy that should prompt a change to U.S. practice, with both of these drugs forming a new cornerstone of HFrEF treatment, Dr. Packer said.
 

Results plant drug class firmly as HFrEF treatment

Dr. Packer stressed in his presentation that optimal treatment of patients with HFrEF now demands use of one of these two SGLT2 inhibitors, as well as sacubitril plus valsartan (Entresto), a beta-blocker, and a mineralocorticoid receptor antagonist, plus a diuretic as a fifth drug class for the many HFrEF patients who also need treatment for fluid overload. He further advocated for rapid introduction of these four cornerstone agents with proven survival benefits once a patient receives a HFrEF diagnosis, suggesting that sacubitril plus valsartan, an SGLT2 inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist could all be initiated within 6 weeks or less while acknowledging that optimal up-titration of the beta-blocker would likely take longer.

The order in which a patient starts these drugs shouldn’t matter, and there currently seems to be no evidence that clearly points toward using either dapagliflozin or empagliflozin over the other, Dr. Packer added.

In recognition of the importance of sending a message to heart failure clinicians about the newly proven efficacy of SGLT2 inhibitors in HFrEF patients, the American College of Cardiology and American Heart Association are now drafting an “expert decision pathway” to help clinicians as they enter this new prescribing space. This interim guidance should come out before the end of 2020, prior to release of fully revised HFrEF management guidelines in 2021, said Athena Poppas, MD, president of the ACC, in an interview.

“There is clearly need for education” that can help guide physicians who care for HFrEF patients on how to introduce an SGLT2 inhibitor along with the additional, lengthy list of drug classes proven to benefit these patients, noted Dr. Poppas, who is also a professor and chief of cardiology at the Brown University in Providence, R.I. Physicians may find that they need extra backup for successfully starting both sacubitril plus valsartan and an SGLT2 inhibitor in HFrEF patients because recent history has shown substantial pushback from third-party payers in reimbursing for these relatively expensive drugs, Dr. Poppas noted. She added that this is a problem that may be compounded when patients should ideally get both drug classes.

Physicians who care for heart failure patients have their own history of dragging their feet when adding new drugs to the regimens HFrEF patients receive. The angiotensin converting enzyme inhibitors and beta-blockers took about 17 years each to start reaching a majority of U.S. HFrEF patients, and sacubitril plus valsartan is now used on perhaps a quarter to a third of HFrEF patients despite receiving Food and Drug Administration approval for these patients in mid 2015, noted Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart and Vascular Institute in Fairfax, Va.

Despite dapagliflozin receiving FDA approval in May 2020 for treating HFrEF in patients without diabetes, early uptake in U.S. practice has been very slow, with findings from large U.S. patient registries suggesting that perhaps 1% of suitable HFrEF patients currently get the drug, estimated Dr. O’Connor in an interview.

Given how strong the evidence now is for benefit and safety from dapagliflozin and empagliflozin, it may take as little as 5 years to reach greater than 50% penetration of one of these drugs into U.S. HFrEF patient populations, suggested Dr. Packer, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
 

EMPEROR-Reduced outcomes

The road to routine use of these SGLT2 inhibitor drugs should be hastened by empagliflozin’s impressive performance in EMPEROR-Reduced, in which the drug scored highly significant benefits over placebo for the prespecified primary and two major secondary endpoints, one of which was a measure of preserved renal function.

The trial randomized 3,730 patients at 520 sites in 20 countries during 2017-2019 and followed them on treatment for a median of 16 months. All patients had a left ventricular ejection fraction of 40% or less, and roughly three-quarters had New York Heart Association (NYHA) class II function, nearly one-quarter had class III function, and fewer than 1% of patients fell into the class IV category.

The primary endpoint occurred in 19% of the empagliflozin-treated patients and in 25% of those who received placebo. Among the half of patients with diabetes in the trial, the relative risk reduction by empagliflozin compared with placebo was a statistically significant 28%; among those without diabetes, it was a statistically significant 22%. Concurrently with Dr. Packer’s report, the results appeared in an article posted online (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

The study also had two main prespecified secondary endpoints: the incidence of total hospitalizations for heart failure, both first and recurrent, which fell by 30% in the empagliflozin-treated patients, compared with placebo, and the rate of declining renal function during the 16 months of the study as measured by estimated glomerular filtration rate, which dropped by roughly 1 mL/min per 1.73 m² among the empagliflozin recipients and by about 4 mL/min/ per 1.73 m² in the placebo patients.

Treatment with empagliflozin also achieved a notable, statistically significant 50% drop in major adverse renal events, consistent with the performance of other drugs in the class.

“Renal protection is a big plus” of empagliflozin in this trial and from the other SGLT2 inhibitors in prior studies, noted Dr. O’Connor.

The EMPEROR-Reduced results also showed an important benefit for HFrEF patients from empagliflozin not previously seen as quickly with any other drug class, noted Dr. Packer. The SGLT2 inhibitor led to statistically a significant slowing in the progression of patients from NYHA class II function to class III, compared with placebo, and it also significantly promoted the recovery of patients from NYHA class III to class II, an effect that became apparent within the first month on treatment and a benefit that is a “big deal” for patients because it represents a “significant change in functional capacity.” This additional dimension of empagliflozin’s benefit “really impressed me,” Dr. Packer said.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Poppas and Dr. O’Connor had no relevant disclosures.
 

[email protected]

SOURCE: Packer M. ESC 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.

The SGLT2 inhibitor drug class solidified its role as a major, new treatment for patients with heart failure with reduced ejection fraction and no diabetes, with results from a second large, controlled trial showing clear efficacy and safety in this population.

Patients with heart failure with reduced ejection fraction (HFrEF) treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) had a statistically significant 25% relative cut in their incidence of cardiovascular death or first heart failure hospitalization, compared with placebo-treated controls when added on top of standard HFrEF treatment, and this benefit was consistent regardless of whether the treated patients also had type 2 diabetes, Milton Packer, MD, reported at the virtual annual congress of the European Society of Cardiology.

This 25% drop in the primary endpoint with empagliflozin treatment in the EMPEROR-Reduced trial exactly matched the cut in incidence of cardiovascular death or heart failure hospitalization produced by treatment with a another SGLT2 inhibitor, dapagliflozin (Farxiga), in the DAPA-HF trial (N Engl J Med. 2019 Nov 21;381[21]:1995-2008).

The performance of these two SGLT2 inhibitors was “incredibly consistent” across the their respective trials run in HFrEF patients with and without type 2 diabetes, and the combined evidence base of the two trials makes for “really compelling evidence” of both safety and efficacy that should prompt a change to U.S. practice, with both of these drugs forming a new cornerstone of HFrEF treatment, Dr. Packer said.
 

Results plant drug class firmly as HFrEF treatment

Dr. Packer stressed in his presentation that optimal treatment of patients with HFrEF now demands use of one of these two SGLT2 inhibitors, as well as sacubitril plus valsartan (Entresto), a beta-blocker, and a mineralocorticoid receptor antagonist, plus a diuretic as a fifth drug class for the many HFrEF patients who also need treatment for fluid overload. He further advocated for rapid introduction of these four cornerstone agents with proven survival benefits once a patient receives a HFrEF diagnosis, suggesting that sacubitril plus valsartan, an SGLT2 inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist could all be initiated within 6 weeks or less while acknowledging that optimal up-titration of the beta-blocker would likely take longer.

The order in which a patient starts these drugs shouldn’t matter, and there currently seems to be no evidence that clearly points toward using either dapagliflozin or empagliflozin over the other, Dr. Packer added.

In recognition of the importance of sending a message to heart failure clinicians about the newly proven efficacy of SGLT2 inhibitors in HFrEF patients, the American College of Cardiology and American Heart Association are now drafting an “expert decision pathway” to help clinicians as they enter this new prescribing space. This interim guidance should come out before the end of 2020, prior to release of fully revised HFrEF management guidelines in 2021, said Athena Poppas, MD, president of the ACC, in an interview.

“There is clearly need for education” that can help guide physicians who care for HFrEF patients on how to introduce an SGLT2 inhibitor along with the additional, lengthy list of drug classes proven to benefit these patients, noted Dr. Poppas, who is also a professor and chief of cardiology at the Brown University in Providence, R.I. Physicians may find that they need extra backup for successfully starting both sacubitril plus valsartan and an SGLT2 inhibitor in HFrEF patients because recent history has shown substantial pushback from third-party payers in reimbursing for these relatively expensive drugs, Dr. Poppas noted. She added that this is a problem that may be compounded when patients should ideally get both drug classes.

Physicians who care for heart failure patients have their own history of dragging their feet when adding new drugs to the regimens HFrEF patients receive. The angiotensin converting enzyme inhibitors and beta-blockers took about 17 years each to start reaching a majority of U.S. HFrEF patients, and sacubitril plus valsartan is now used on perhaps a quarter to a third of HFrEF patients despite receiving Food and Drug Administration approval for these patients in mid 2015, noted Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart and Vascular Institute in Fairfax, Va.

Despite dapagliflozin receiving FDA approval in May 2020 for treating HFrEF in patients without diabetes, early uptake in U.S. practice has been very slow, with findings from large U.S. patient registries suggesting that perhaps 1% of suitable HFrEF patients currently get the drug, estimated Dr. O’Connor in an interview.

Given how strong the evidence now is for benefit and safety from dapagliflozin and empagliflozin, it may take as little as 5 years to reach greater than 50% penetration of one of these drugs into U.S. HFrEF patient populations, suggested Dr. Packer, a distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
 

EMPEROR-Reduced outcomes

The road to routine use of these SGLT2 inhibitor drugs should be hastened by empagliflozin’s impressive performance in EMPEROR-Reduced, in which the drug scored highly significant benefits over placebo for the prespecified primary and two major secondary endpoints, one of which was a measure of preserved renal function.

The trial randomized 3,730 patients at 520 sites in 20 countries during 2017-2019 and followed them on treatment for a median of 16 months. All patients had a left ventricular ejection fraction of 40% or less, and roughly three-quarters had New York Heart Association (NYHA) class II function, nearly one-quarter had class III function, and fewer than 1% of patients fell into the class IV category.

The primary endpoint occurred in 19% of the empagliflozin-treated patients and in 25% of those who received placebo. Among the half of patients with diabetes in the trial, the relative risk reduction by empagliflozin compared with placebo was a statistically significant 28%; among those without diabetes, it was a statistically significant 22%. Concurrently with Dr. Packer’s report, the results appeared in an article posted online (N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190).

The study also had two main prespecified secondary endpoints: the incidence of total hospitalizations for heart failure, both first and recurrent, which fell by 30% in the empagliflozin-treated patients, compared with placebo, and the rate of declining renal function during the 16 months of the study as measured by estimated glomerular filtration rate, which dropped by roughly 1 mL/min per 1.73 m² among the empagliflozin recipients and by about 4 mL/min/ per 1.73 m² in the placebo patients.

Treatment with empagliflozin also achieved a notable, statistically significant 50% drop in major adverse renal events, consistent with the performance of other drugs in the class.

“Renal protection is a big plus” of empagliflozin in this trial and from the other SGLT2 inhibitors in prior studies, noted Dr. O’Connor.

The EMPEROR-Reduced results also showed an important benefit for HFrEF patients from empagliflozin not previously seen as quickly with any other drug class, noted Dr. Packer. The SGLT2 inhibitor led to statistically a significant slowing in the progression of patients from NYHA class II function to class III, compared with placebo, and it also significantly promoted the recovery of patients from NYHA class III to class II, an effect that became apparent within the first month on treatment and a benefit that is a “big deal” for patients because it represents a “significant change in functional capacity.” This additional dimension of empagliflozin’s benefit “really impressed me,” Dr. Packer said.

EMPEROR-Reduced was funded by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin. Dr. Packer has received personal fees from Boehringer Ingelheim and Eli Lilly and from several other companies. Dr. Poppas and Dr. O’Connor had no relevant disclosures.
 

[email protected]

SOURCE: Packer M. ESC 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2022190.

Initiation of rhythm control with antiarrhythmic drugs and/or ablation in patients with early, recently diagnosed atrial fibrillation (AFib) led to a significantly lower risk of major adverse cardiovascular outcomes, compared with a rate-control strategy, during more than 5 years of follow-up in the large randomized EAST-AFNET 4 trial, Paulus Kirchhof, MD, said at the virtual annual congress of the European Society of Cardiology.

Previous trials of rate versus rhythm control in AFib, such as AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management), failed to show an advantage for rhythm over rate control in terms of clinical outcomes. Why was EAST-AFNET 4 different? Dr. Kirchhof offered two major reasons: The study incorporated AFib ablation as an option in the rhythm control strategy, and treatment started soon after diagnosis of the arrhythmia. Indeed, nearly 40% of patients had their first-ever AFib episode at the time of randomization, and the median time from diagnosis to randomization was just 36 days.

“Once you are in AFib for a few months, the atrium suffers severe damage, some of it irreversible, so it becomes more difficult to restore and maintain sinus rhythm when you wait longer,” explained Dr. Kirchhof, director of the department of cardiology at the University Heart and Vascular Center in Hamburg (Ger.) and professor of cardiovascular medicine at the University of Birmingham, England.

Also, epidemiologic studies show that the risk of cardiovascular complications is heightened in the first year following diagnosis of AFib. “So there’s a window of opportunity to prevent complications,” he added.

The impetus for conducting EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial ) was straightforward, according to the cardiologist: “The question of whether rhythm control is beneficial or not has been in the field for several decades. Most people, like me, always believed that maintaining sinus rhythm would help, but we didn’t have the data to show it.”
 

Early rhythm control shows sustained benefits

EAST-AFNET 4 was a prospective, open, blinded-outcome-assessement trial. It included 2,789 patients with early AFib and an average CHA₂DS₂-VASc score of 3.4 who were randomized at 135 sites in 11 European countries to early rhythm control or guideline-recommended rate control. At a median 5.1 years of follow-up, the primary outcome – a composite of cardiovascular death, stroke, acute coronary syndrome, or hospitalization for worsening heart failure – occurred at a pace of 3.9% per year in the rhythm control group and 5% per year with rate control. This translated to a statistically significant and clinically meaningful 21% relative risk reduction favoring early rhythm control.

The 28% reduction in cardiovascular death with rhythm control was statistically significant, as was the 35% reduction in stroke. However, the 19% reduction in heart failure hospitalizations and 17% decrease in hospitalizations for acute coronary syndrome were not.

The co–primary endpoint – the mean number of nights spent in the hospital per year, which served as a proxy for the cost of treatment to a health care system – didn’t differ between the two treatment arms, at roughly 5 nights per year.

The clinical benefit of early rhythm control was consistent across all 19 prespecified patient subgroups, including those who were asymptomatic and patients with or without heart failure.

Serious adverse events related to rhythm control therapy – most often drug-related bradycardia – occurred in 4.9% of patients over the course of 5.1 years, compared to a 1.4% serious event rate in patients assigned to rate control. Dr. Kirchhof called the roughly 1% per year serious event rate in the rhythm control group quite acceptable.

“To put that in perspective, the annualized rate of severe bleeds on oral anticoagulation – a very beneficial therapy used by more than 90% of participants at 2 years – is about 2%,” the cardiologist noted.

Only 8% of patients randomized to rhythm control received AFib ablation as initial therapy, consistent with current clinical practice. By 2 years, 19.4% of the rhythm control group had undergone AFib ablation. Also at that time, 15% of the rate control group was receiving rhythm control therapy to help manage AFib-related symptoms.

One of the big surprises in the study, he said, was that nearly three-quarters of patients in both groups were asymptomatic at 2 years.

“I think that shows how well we control symptoms, even without rhythm control,” he observed.
 

Results ‘move the field forward’

Dr. Kirchhof stressed that this was a trial of two different treatment strategies, and it’s not yet possible to single out any specific component of the rhythm control strategy as being responsible for the improved outcomes.

“I cannot tell you whether the outcome difference was due to AFib ablation or early treatment or the fact that we’re now better at using antiarrhythmic drugs than we were 20 years ago,” he said.

Asked if the EAST-AFNET 4 findings warrant more aggressive screening for AFib in order to detect and intervene early in the arrhythmia, Dr. Kirchhof replied with an unambiguous yes.

“My conclusion is that every patient with newly diagnosed AFib and a CHA₂DS₂-VASc score of 2 or more should not only receive anticoagulation and rate control, but should also be offered rhythm control therapy at the time of diagnosis, which also means that all of these people have to be seen by a cardiologist who has expertise in the domain of AFib management. It’s a big clinical challenge, but it leads to a 21% improvement in outcomes, and I think we have to do what’s best for our patients,” he said.

In an interview, Kalyanam Shivkumar, MD, PhD, called EAST-AFNET 4 “a very important study.”

“It moves the field forward, for sure. I think it will change clinical practice, and it should,” commented Dr. Shivkumar, who was not involved in the study.

“Now there are so many wearable technologies out there – the Apple Watch and others – which will enable rhythm abnormalities to be detected early on. This bodes well for the field,” said Dr. Shivkumar, who is editor-in-chief of JACC: Clinical Electrophysiology. He is also professor of medicine, radiology, and bioengineering at the University of California, Los Angeles, and director of the UCLA Cardiac Arrhythmia Center.

Dr. Kirchhof reported receiving research grants to conduct the EAST-AFNET 4 trial from the German Ministry of Education and Research, the German Center for Cardiovascular Research, the Atrial Fibrillation Network, the European Heart Rhythm Association, St. Jude Medical, Abbott, Sanofi, the German Heart Foundation, the European Union, the British Heart Foundation, and the Leducq Foundation.

Simultaneous with his presentation at ESC Congress 2020, the study results were published online at NEJM.org.
 

[email protected]

SOURCE: Kirchhof P. ESC Congress 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2019422.

Initiation of rhythm control with antiarrhythmic drugs and/or ablation in patients with early, recently diagnosed atrial fibrillation (AFib) led to a significantly lower risk of major adverse cardiovascular outcomes, compared with a rate-control strategy, during more than 5 years of follow-up in the large randomized EAST-AFNET 4 trial, Paulus Kirchhof, MD, said at the virtual annual congress of the European Society of Cardiology.

Previous trials of rate versus rhythm control in AFib, such as AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management), failed to show an advantage for rhythm over rate control in terms of clinical outcomes. Why was EAST-AFNET 4 different? Dr. Kirchhof offered two major reasons: The study incorporated AFib ablation as an option in the rhythm control strategy, and treatment started soon after diagnosis of the arrhythmia. Indeed, nearly 40% of patients had their first-ever AFib episode at the time of randomization, and the median time from diagnosis to randomization was just 36 days.

“Once you are in AFib for a few months, the atrium suffers severe damage, some of it irreversible, so it becomes more difficult to restore and maintain sinus rhythm when you wait longer,” explained Dr. Kirchhof, director of the department of cardiology at the University Heart and Vascular Center in Hamburg (Ger.) and professor of cardiovascular medicine at the University of Birmingham, England.

Also, epidemiologic studies show that the risk of cardiovascular complications is heightened in the first year following diagnosis of AFib. “So there’s a window of opportunity to prevent complications,” he added.

The impetus for conducting EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial ) was straightforward, according to the cardiologist: “The question of whether rhythm control is beneficial or not has been in the field for several decades. Most people, like me, always believed that maintaining sinus rhythm would help, but we didn’t have the data to show it.”
 

Early rhythm control shows sustained benefits

EAST-AFNET 4 was a prospective, open, blinded-outcome-assessement trial. It included 2,789 patients with early AFib and an average CHA₂DS₂-VASc score of 3.4 who were randomized at 135 sites in 11 European countries to early rhythm control or guideline-recommended rate control. At a median 5.1 years of follow-up, the primary outcome – a composite of cardiovascular death, stroke, acute coronary syndrome, or hospitalization for worsening heart failure – occurred at a pace of 3.9% per year in the rhythm control group and 5% per year with rate control. This translated to a statistically significant and clinically meaningful 21% relative risk reduction favoring early rhythm control.

The 28% reduction in cardiovascular death with rhythm control was statistically significant, as was the 35% reduction in stroke. However, the 19% reduction in heart failure hospitalizations and 17% decrease in hospitalizations for acute coronary syndrome were not.

The co–primary endpoint – the mean number of nights spent in the hospital per year, which served as a proxy for the cost of treatment to a health care system – didn’t differ between the two treatment arms, at roughly 5 nights per year.

The clinical benefit of early rhythm control was consistent across all 19 prespecified patient subgroups, including those who were asymptomatic and patients with or without heart failure.

Serious adverse events related to rhythm control therapy – most often drug-related bradycardia – occurred in 4.9% of patients over the course of 5.1 years, compared to a 1.4% serious event rate in patients assigned to rate control. Dr. Kirchhof called the roughly 1% per year serious event rate in the rhythm control group quite acceptable.

“To put that in perspective, the annualized rate of severe bleeds on oral anticoagulation – a very beneficial therapy used by more than 90% of participants at 2 years – is about 2%,” the cardiologist noted.

Only 8% of patients randomized to rhythm control received AFib ablation as initial therapy, consistent with current clinical practice. By 2 years, 19.4% of the rhythm control group had undergone AFib ablation. Also at that time, 15% of the rate control group was receiving rhythm control therapy to help manage AFib-related symptoms.

One of the big surprises in the study, he said, was that nearly three-quarters of patients in both groups were asymptomatic at 2 years.

“I think that shows how well we control symptoms, even without rhythm control,” he observed.
 

Results ‘move the field forward’

Dr. Kirchhof stressed that this was a trial of two different treatment strategies, and it’s not yet possible to single out any specific component of the rhythm control strategy as being responsible for the improved outcomes.

“I cannot tell you whether the outcome difference was due to AFib ablation or early treatment or the fact that we’re now better at using antiarrhythmic drugs than we were 20 years ago,” he said.

Asked if the EAST-AFNET 4 findings warrant more aggressive screening for AFib in order to detect and intervene early in the arrhythmia, Dr. Kirchhof replied with an unambiguous yes.

“My conclusion is that every patient with newly diagnosed AFib and a CHA₂DS₂-VASc score of 2 or more should not only receive anticoagulation and rate control, but should also be offered rhythm control therapy at the time of diagnosis, which also means that all of these people have to be seen by a cardiologist who has expertise in the domain of AFib management. It’s a big clinical challenge, but it leads to a 21% improvement in outcomes, and I think we have to do what’s best for our patients,” he said.

In an interview, Kalyanam Shivkumar, MD, PhD, called EAST-AFNET 4 “a very important study.”

“It moves the field forward, for sure. I think it will change clinical practice, and it should,” commented Dr. Shivkumar, who was not involved in the study.

“Now there are so many wearable technologies out there – the Apple Watch and others – which will enable rhythm abnormalities to be detected early on. This bodes well for the field,” said Dr. Shivkumar, who is editor-in-chief of JACC: Clinical Electrophysiology. He is also professor of medicine, radiology, and bioengineering at the University of California, Los Angeles, and director of the UCLA Cardiac Arrhythmia Center.

Dr. Kirchhof reported receiving research grants to conduct the EAST-AFNET 4 trial from the German Ministry of Education and Research, the German Center for Cardiovascular Research, the Atrial Fibrillation Network, the European Heart Rhythm Association, St. Jude Medical, Abbott, Sanofi, the German Heart Foundation, the European Union, the British Heart Foundation, and the Leducq Foundation.

Simultaneous with his presentation at ESC Congress 2020, the study results were published online at NEJM.org.
 

[email protected]

SOURCE: Kirchhof P. ESC Congress 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2019422.

Initiation of rhythm control with antiarrhythmic drugs and/or ablation in patients with early, recently diagnosed atrial fibrillation (AFib) led to a significantly lower risk of major adverse cardiovascular outcomes, compared with a rate-control strategy, during more than 5 years of follow-up in the large randomized EAST-AFNET 4 trial, Paulus Kirchhof, MD, said at the virtual annual congress of the European Society of Cardiology.

Previous trials of rate versus rhythm control in AFib, such as AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management), failed to show an advantage for rhythm over rate control in terms of clinical outcomes. Why was EAST-AFNET 4 different? Dr. Kirchhof offered two major reasons: The study incorporated AFib ablation as an option in the rhythm control strategy, and treatment started soon after diagnosis of the arrhythmia. Indeed, nearly 40% of patients had their first-ever AFib episode at the time of randomization, and the median time from diagnosis to randomization was just 36 days.

“Once you are in AFib for a few months, the atrium suffers severe damage, some of it irreversible, so it becomes more difficult to restore and maintain sinus rhythm when you wait longer,” explained Dr. Kirchhof, director of the department of cardiology at the University Heart and Vascular Center in Hamburg (Ger.) and professor of cardiovascular medicine at the University of Birmingham, England.

Also, epidemiologic studies show that the risk of cardiovascular complications is heightened in the first year following diagnosis of AFib. “So there’s a window of opportunity to prevent complications,” he added.

The impetus for conducting EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial ) was straightforward, according to the cardiologist: “The question of whether rhythm control is beneficial or not has been in the field for several decades. Most people, like me, always believed that maintaining sinus rhythm would help, but we didn’t have the data to show it.”
 

Early rhythm control shows sustained benefits

EAST-AFNET 4 was a prospective, open, blinded-outcome-assessement trial. It included 2,789 patients with early AFib and an average CHA₂DS₂-VASc score of 3.4 who were randomized at 135 sites in 11 European countries to early rhythm control or guideline-recommended rate control. At a median 5.1 years of follow-up, the primary outcome – a composite of cardiovascular death, stroke, acute coronary syndrome, or hospitalization for worsening heart failure – occurred at a pace of 3.9% per year in the rhythm control group and 5% per year with rate control. This translated to a statistically significant and clinically meaningful 21% relative risk reduction favoring early rhythm control.

The 28% reduction in cardiovascular death with rhythm control was statistically significant, as was the 35% reduction in stroke. However, the 19% reduction in heart failure hospitalizations and 17% decrease in hospitalizations for acute coronary syndrome were not.

The co–primary endpoint – the mean number of nights spent in the hospital per year, which served as a proxy for the cost of treatment to a health care system – didn’t differ between the two treatment arms, at roughly 5 nights per year.

The clinical benefit of early rhythm control was consistent across all 19 prespecified patient subgroups, including those who were asymptomatic and patients with or without heart failure.

Serious adverse events related to rhythm control therapy – most often drug-related bradycardia – occurred in 4.9% of patients over the course of 5.1 years, compared to a 1.4% serious event rate in patients assigned to rate control. Dr. Kirchhof called the roughly 1% per year serious event rate in the rhythm control group quite acceptable.

“To put that in perspective, the annualized rate of severe bleeds on oral anticoagulation – a very beneficial therapy used by more than 90% of participants at 2 years – is about 2%,” the cardiologist noted.

Only 8% of patients randomized to rhythm control received AFib ablation as initial therapy, consistent with current clinical practice. By 2 years, 19.4% of the rhythm control group had undergone AFib ablation. Also at that time, 15% of the rate control group was receiving rhythm control therapy to help manage AFib-related symptoms.

One of the big surprises in the study, he said, was that nearly three-quarters of patients in both groups were asymptomatic at 2 years.

“I think that shows how well we control symptoms, even without rhythm control,” he observed.
 

Results ‘move the field forward’

Dr. Kirchhof stressed that this was a trial of two different treatment strategies, and it’s not yet possible to single out any specific component of the rhythm control strategy as being responsible for the improved outcomes.

“I cannot tell you whether the outcome difference was due to AFib ablation or early treatment or the fact that we’re now better at using antiarrhythmic drugs than we were 20 years ago,” he said.

Asked if the EAST-AFNET 4 findings warrant more aggressive screening for AFib in order to detect and intervene early in the arrhythmia, Dr. Kirchhof replied with an unambiguous yes.

“My conclusion is that every patient with newly diagnosed AFib and a CHA₂DS₂-VASc score of 2 or more should not only receive anticoagulation and rate control, but should also be offered rhythm control therapy at the time of diagnosis, which also means that all of these people have to be seen by a cardiologist who has expertise in the domain of AFib management. It’s a big clinical challenge, but it leads to a 21% improvement in outcomes, and I think we have to do what’s best for our patients,” he said.

In an interview, Kalyanam Shivkumar, MD, PhD, called EAST-AFNET 4 “a very important study.”

“It moves the field forward, for sure. I think it will change clinical practice, and it should,” commented Dr. Shivkumar, who was not involved in the study.

“Now there are so many wearable technologies out there – the Apple Watch and others – which will enable rhythm abnormalities to be detected early on. This bodes well for the field,” said Dr. Shivkumar, who is editor-in-chief of JACC: Clinical Electrophysiology. He is also professor of medicine, radiology, and bioengineering at the University of California, Los Angeles, and director of the UCLA Cardiac Arrhythmia Center.

Dr. Kirchhof reported receiving research grants to conduct the EAST-AFNET 4 trial from the German Ministry of Education and Research, the German Center for Cardiovascular Research, the Atrial Fibrillation Network, the European Heart Rhythm Association, St. Jude Medical, Abbott, Sanofi, the German Heart Foundation, the European Union, the British Heart Foundation, and the Leducq Foundation.

Simultaneous with his presentation at ESC Congress 2020, the study results were published online at NEJM.org.
 

[email protected]

SOURCE: Kirchhof P. ESC Congress 2020. N Engl J Med. 2020 Aug 29. doi: 10.1056/NEJMoa2019422.

Breast milk is an unlikely source of transmission of SARS-CoV-2 from mothers to infants, according to data from case reports and breast milk samples from 18 women.

South_agency/Getty Images

“To date, SARS-CoV-2 has not been isolated from breast milk, and there are no documented cases of transmission of infectious virus to the infant through breast milk,” but the potential for transmission remains a concern among women who want to breastfeed, wrote Christina Chambers, PhD, of the University of California, San Diego, and colleagues.

In a research letter published in JAMA, the investigators identified 18 women with confirmed SARS-CoV-2 infections (all but 1 of the women had symptomatic COVID-19 disease) and infants aged 0-19 months between March 27 and May 6, 2020. The average age of the mothers was 34 years, and 78% were non-Hispanic White. The women provided 1-12 samples of breast milk for a total of 64 samples collected before and after positive COVID-19 tests.

One sample yielded detectable RNA from SARS-CoV-2 and was collected on the day of the woman’s symptom onset. However, one sample taken 2 days prior to symptom onset and two samples collected 12 and 41 days later tested negative for viral RNA, the researchers said. In addition, no replication-competent virus was identified in the positive sample or any of the other samples.

The researchers spiked two stored milk samples collected prior to the pandemic with replication-competent SARS-CoV-2. Virus was not detected by culture in the samples after Holder pasteurization, but was detected by culture in nonpasteurized aliquots of the same samples.

“These data suggest that SARS-CoV-2 RNA does not represent replication-competent virus and that breast milk may not be a source of infection for the infant,” Dr. Chambers and associates said.

The results were limited by several factors including the small sample size and potential for selection bias, as well as the use of self-reports of positive tests and self-collection of breast milk, the researchers noted. However, the findings are reassuring in light of the known benefits of breastfeeding and the use of milk banks.

“This research is important because the pandemic is ongoing and has far-reaching consequences: as the authors indicate, the potential for viral transmission through breast milk remains a critical question for women infected with SARS-CoV-2 who wish to breastfeed,” Janet R. Hardy, PhD, MPH, MSc, a consultant on global maternal-child health and pharmacoepidemiology, said in an interview.

“This virus has everyone on a rapid learning track, and all information that helps build evidence to support women’s decision-making in the care of their children is valuable,” she said. “These findings suggest that breast milk may not be a source of SARS-CoV-2 infection for the infant. They provide some reassurance given the recognized benefits of breastfeeding and human milk.”

However, “This study is very specific to breast milk,” she emphasized. “In advising women infected with SARS-CoV-2, clinicians may want to include a discussion of protection methods to prevent maternal transmission of the virus through respiratory droplets.”

Although the data are preliminary, “the investigators established and validated an RT-PCR [reverse transcription polymerase chain reaction] assay and developed tissue culture methods for replication-competent SARS-CoV-2 in breast milk, both valuable tools for further studies. Next steps will include controlled studies of greater sample size with independent verification of RT-PCR positivity,” said Dr. Hardy, a consultant to Biohaven Pharmaceuticals, New Haven, Conn.

The study was supported by the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health. Medela Corporation provided milk sample collection materials. The Family Larsson-Rosenquist Foundation provided an unrestricted COVID19 emergency gift fund. The Mothers’ Milk Bank at Austin paid for shipping costs.

SOURCE: Chambers C et al. JAMA. 2020 Aug 19. doi: 10.1001/jama.2020.15580.

Breast milk is an unlikely source of transmission of SARS-CoV-2 from mothers to infants, according to data from case reports and breast milk samples from 18 women.

South_agency/Getty Images

“To date, SARS-CoV-2 has not been isolated from breast milk, and there are no documented cases of transmission of infectious virus to the infant through breast milk,” but the potential for transmission remains a concern among women who want to breastfeed, wrote Christina Chambers, PhD, of the University of California, San Diego, and colleagues.

In a research letter published in JAMA, the investigators identified 18 women with confirmed SARS-CoV-2 infections (all but 1 of the women had symptomatic COVID-19 disease) and infants aged 0-19 months between March 27 and May 6, 2020. The average age of the mothers was 34 years, and 78% were non-Hispanic White. The women provided 1-12 samples of breast milk for a total of 64 samples collected before and after positive COVID-19 tests.

One sample yielded detectable RNA from SARS-CoV-2 and was collected on the day of the woman’s symptom onset. However, one sample taken 2 days prior to symptom onset and two samples collected 12 and 41 days later tested negative for viral RNA, the researchers said. In addition, no replication-competent virus was identified in the positive sample or any of the other samples.

The researchers spiked two stored milk samples collected prior to the pandemic with replication-competent SARS-CoV-2. Virus was not detected by culture in the samples after Holder pasteurization, but was detected by culture in nonpasteurized aliquots of the same samples.

“These data suggest that SARS-CoV-2 RNA does not represent replication-competent virus and that breast milk may not be a source of infection for the infant,” Dr. Chambers and associates said.

The results were limited by several factors including the small sample size and potential for selection bias, as well as the use of self-reports of positive tests and self-collection of breast milk, the researchers noted. However, the findings are reassuring in light of the known benefits of breastfeeding and the use of milk banks.

“This research is important because the pandemic is ongoing and has far-reaching consequences: as the authors indicate, the potential for viral transmission through breast milk remains a critical question for women infected with SARS-CoV-2 who wish to breastfeed,” Janet R. Hardy, PhD, MPH, MSc, a consultant on global maternal-child health and pharmacoepidemiology, said in an interview.

“This virus has everyone on a rapid learning track, and all information that helps build evidence to support women’s decision-making in the care of their children is valuable,” she said. “These findings suggest that breast milk may not be a source of SARS-CoV-2 infection for the infant. They provide some reassurance given the recognized benefits of breastfeeding and human milk.”

However, “This study is very specific to breast milk,” she emphasized. “In advising women infected with SARS-CoV-2, clinicians may want to include a discussion of protection methods to prevent maternal transmission of the virus through respiratory droplets.”

Although the data are preliminary, “the investigators established and validated an RT-PCR [reverse transcription polymerase chain reaction] assay and developed tissue culture methods for replication-competent SARS-CoV-2 in breast milk, both valuable tools for further studies. Next steps will include controlled studies of greater sample size with independent verification of RT-PCR positivity,” said Dr. Hardy, a consultant to Biohaven Pharmaceuticals, New Haven, Conn.

The study was supported by the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health. Medela Corporation provided milk sample collection materials. The Family Larsson-Rosenquist Foundation provided an unrestricted COVID19 emergency gift fund. The Mothers’ Milk Bank at Austin paid for shipping costs.

SOURCE: Chambers C et al. JAMA. 2020 Aug 19. doi: 10.1001/jama.2020.15580.

Breast milk is an unlikely source of transmission of SARS-CoV-2 from mothers to infants, according to data from case reports and breast milk samples from 18 women.

South_agency/Getty Images

“To date, SARS-CoV-2 has not been isolated from breast milk, and there are no documented cases of transmission of infectious virus to the infant through breast milk,” but the potential for transmission remains a concern among women who want to breastfeed, wrote Christina Chambers, PhD, of the University of California, San Diego, and colleagues.

In a research letter published in JAMA, the investigators identified 18 women with confirmed SARS-CoV-2 infections (all but 1 of the women had symptomatic COVID-19 disease) and infants aged 0-19 months between March 27 and May 6, 2020. The average age of the mothers was 34 years, and 78% were non-Hispanic White. The women provided 1-12 samples of breast milk for a total of 64 samples collected before and after positive COVID-19 tests.

One sample yielded detectable RNA from SARS-CoV-2 and was collected on the day of the woman’s symptom onset. However, one sample taken 2 days prior to symptom onset and two samples collected 12 and 41 days later tested negative for viral RNA, the researchers said. In addition, no replication-competent virus was identified in the positive sample or any of the other samples.

The researchers spiked two stored milk samples collected prior to the pandemic with replication-competent SARS-CoV-2. Virus was not detected by culture in the samples after Holder pasteurization, but was detected by culture in nonpasteurized aliquots of the same samples.

“These data suggest that SARS-CoV-2 RNA does not represent replication-competent virus and that breast milk may not be a source of infection for the infant,” Dr. Chambers and associates said.

The results were limited by several factors including the small sample size and potential for selection bias, as well as the use of self-reports of positive tests and self-collection of breast milk, the researchers noted. However, the findings are reassuring in light of the known benefits of breastfeeding and the use of milk banks.

“This research is important because the pandemic is ongoing and has far-reaching consequences: as the authors indicate, the potential for viral transmission through breast milk remains a critical question for women infected with SARS-CoV-2 who wish to breastfeed,” Janet R. Hardy, PhD, MPH, MSc, a consultant on global maternal-child health and pharmacoepidemiology, said in an interview.

“This virus has everyone on a rapid learning track, and all information that helps build evidence to support women’s decision-making in the care of their children is valuable,” she said. “These findings suggest that breast milk may not be a source of SARS-CoV-2 infection for the infant. They provide some reassurance given the recognized benefits of breastfeeding and human milk.”

However, “This study is very specific to breast milk,” she emphasized. “In advising women infected with SARS-CoV-2, clinicians may want to include a discussion of protection methods to prevent maternal transmission of the virus through respiratory droplets.”

Although the data are preliminary, “the investigators established and validated an RT-PCR [reverse transcription polymerase chain reaction] assay and developed tissue culture methods for replication-competent SARS-CoV-2 in breast milk, both valuable tools for further studies. Next steps will include controlled studies of greater sample size with independent verification of RT-PCR positivity,” said Dr. Hardy, a consultant to Biohaven Pharmaceuticals, New Haven, Conn.

The study was supported by the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health. Medela Corporation provided milk sample collection materials. The Family Larsson-Rosenquist Foundation provided an unrestricted COVID19 emergency gift fund. The Mothers’ Milk Bank at Austin paid for shipping costs.

SOURCE: Chambers C et al. JAMA. 2020 Aug 19. doi: 10.1001/jama.2020.15580.