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FDA revokes emergency use of hydroxychloroquine
The U.S. Food and Drug Administration revoked its decision from March 28 allowing use of hydroxychloroquine and chloroquine to treat people hospitalized with COVID-19 under an emergency use authorization (EUA).
“Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA,” the agency announced in a June 15 statement.
The FDA also warned today that the use of hydroxychloroquine or chloroquine may have a potential drug interaction with the investigational antiviral drug remdesivir that limits its effectiveness against COVID-19.
Remdesivir was granted emergency use authorization by the FDA on May 1.
“Based on a recently completed nonclinical laboratory study, the FDA is revising the fact sheet for healthcare providers that accompanies the drug to state that coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir. The agency is not aware of instances of this reduced activity occurring in the clinical setting but is continuing to evaluate all data related to remdesivir,” the FDA said in a news release.
Controversy over hydroxychloroquine
Even with such federal permission, since late March the use of these two agents has been mired in controversy.
President Donald J. Trump promoted the use of hydroxychloroquine and chloroquine to treat Americans with COVID-19, while scientific studies raised questions about their safety and effectiveness. Recent research, for example, pointed to elevated cardiovascular risks, as reported by Medscape Medical News.
The FDA acknowledged this recent evidence. “Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”
The full suspension of the EUA follows a warning the agency issued on April 24. The FDA’s Safety Communication cautioned against use of the two agents outside of a hospital setting, citing an increase in outpatient prescriptions and “reports of serious heart rhythm problems.”
“While additional clinical trials continue to evaluate the potential benefit of these drugs in treating or preventing COVID-19, we determined the emergency use authorization was no longer appropriate,” based on a rigorous assessment by scientists in our Center for Drug Evaluation and Research,” Patrizia Cavazzoni, MD, acting director of CDER, noted in the FDA statement.
This article first appeared on Medscape.com.
The U.S. Food and Drug Administration revoked its decision from March 28 allowing use of hydroxychloroquine and chloroquine to treat people hospitalized with COVID-19 under an emergency use authorization (EUA).
“Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA,” the agency announced in a June 15 statement.
The FDA also warned today that the use of hydroxychloroquine or chloroquine may have a potential drug interaction with the investigational antiviral drug remdesivir that limits its effectiveness against COVID-19.
Remdesivir was granted emergency use authorization by the FDA on May 1.
“Based on a recently completed nonclinical laboratory study, the FDA is revising the fact sheet for healthcare providers that accompanies the drug to state that coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir. The agency is not aware of instances of this reduced activity occurring in the clinical setting but is continuing to evaluate all data related to remdesivir,” the FDA said in a news release.
Controversy over hydroxychloroquine
Even with such federal permission, since late March the use of these two agents has been mired in controversy.
President Donald J. Trump promoted the use of hydroxychloroquine and chloroquine to treat Americans with COVID-19, while scientific studies raised questions about their safety and effectiveness. Recent research, for example, pointed to elevated cardiovascular risks, as reported by Medscape Medical News.
The FDA acknowledged this recent evidence. “Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”
The full suspension of the EUA follows a warning the agency issued on April 24. The FDA’s Safety Communication cautioned against use of the two agents outside of a hospital setting, citing an increase in outpatient prescriptions and “reports of serious heart rhythm problems.”
“While additional clinical trials continue to evaluate the potential benefit of these drugs in treating or preventing COVID-19, we determined the emergency use authorization was no longer appropriate,” based on a rigorous assessment by scientists in our Center for Drug Evaluation and Research,” Patrizia Cavazzoni, MD, acting director of CDER, noted in the FDA statement.
This article first appeared on Medscape.com.
The U.S. Food and Drug Administration revoked its decision from March 28 allowing use of hydroxychloroquine and chloroquine to treat people hospitalized with COVID-19 under an emergency use authorization (EUA).
“Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA,” the agency announced in a June 15 statement.
The FDA also warned today that the use of hydroxychloroquine or chloroquine may have a potential drug interaction with the investigational antiviral drug remdesivir that limits its effectiveness against COVID-19.
Remdesivir was granted emergency use authorization by the FDA on May 1.
“Based on a recently completed nonclinical laboratory study, the FDA is revising the fact sheet for healthcare providers that accompanies the drug to state that coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir. The agency is not aware of instances of this reduced activity occurring in the clinical setting but is continuing to evaluate all data related to remdesivir,” the FDA said in a news release.
Controversy over hydroxychloroquine
Even with such federal permission, since late March the use of these two agents has been mired in controversy.
President Donald J. Trump promoted the use of hydroxychloroquine and chloroquine to treat Americans with COVID-19, while scientific studies raised questions about their safety and effectiveness. Recent research, for example, pointed to elevated cardiovascular risks, as reported by Medscape Medical News.
The FDA acknowledged this recent evidence. “Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”
The full suspension of the EUA follows a warning the agency issued on April 24. The FDA’s Safety Communication cautioned against use of the two agents outside of a hospital setting, citing an increase in outpatient prescriptions and “reports of serious heart rhythm problems.”
“While additional clinical trials continue to evaluate the potential benefit of these drugs in treating or preventing COVID-19, we determined the emergency use authorization was no longer appropriate,” based on a rigorous assessment by scientists in our Center for Drug Evaluation and Research,” Patrizia Cavazzoni, MD, acting director of CDER, noted in the FDA statement.
This article first appeared on Medscape.com.
Perfect storm of SARS-CoV-2 during flu season
COVID-19 now. The urban phase of the U.S. pandemic is leveling somewhat, while the rural phase is accelerating – in part because of food processing and handling industries. The pediatric burden has been surprisingly small, with the multisystem inflammatory disease (MIS-c) in children noted in several hundred cases now being seen across the country.
Next wave? Given ongoing COVID-19 disease, controversy rages about when and how to re-open the country. Regardless how more reopening occurs over the next months, we should expect a next or ongoing COVID-19 wave, particularly given loss of social distancing during social justice protests. A sawtooth disease prevalence pattern is predicted by many experts: a drop in prevalence leading to reopening, leading to scattered prevalence increases and regional if not local restriction tightening, followed by another drop in prevalence. Then “rinse and repeat” until 70% of the population is immune either by disease experience or vaccine-induced immunity, likely sometime in 2021.
Influenza too. A COVID-19 up-cycle is likely during influenza season, although influenza season’s onset could be altered because of whatever social distancing rules are in place in November and December. That said, we need to consider the worst. We have seen what happens if we fail to prepare and then react only after a prevalent respiratory infection has surged into the overall population. Best estimates are that at most 20% of the U.S. population is currently immune to SARS-CoV-2. Given that at least some of that 20% of individuals currently immune to SARS-CoV-2 will lose their neutralizing antibody over the next 4-6 months, we can still expect 70%-80% of the U.S. population to be susceptible to SARS-CoV-2 infection in the fall of 2020.
Pediatric preparedness. As pediatric providers, we have struggled with lower patient loads and dramatic income losses/declines. Many clinics/offices’ attendance remain less than 50% of pre–COVID-19 levels, with necessary furloughs of personnel and spotty office hours. But influenza is coming, and SARS-CoV-2 will not be gone yet. How do we prepare for concurrent influenza and COVID-19?
The annual purchase/administration of influenza vaccine in summer/fall is expensive, time consuming, and logistically difficult even in the best times. Given the loss of income, likely reluctance of patients to come to clinics/offices if COVID-19 is still circulating, and likely need for some form of social distancing during late summer and early fall, how will providers, health departments, and hospitals implement influenza vaccine administration this year?
Minimize double whammy infections. It is easy to understand why we should maximize influenza protection in SARS-CoV-2 vulnerables (elderly or persons with existing comorbidities). But is it as critical for otherwise healthy children? My answer is yes.
Children are not currently known as SARS-CoV-2 vectors, but children are excellent influenza vectors, shedding higher titers for longer than other age groups. As with SARS-CoV-2, influenza exposure is cumulative, i.e., the more intense and more frequently a person is exposed, the more likely that infection/disease will result. So, the fewer who get and can transmit influenza during the COVID-19 pandemic, the fewer people are likely to get a double whammy of SARS-CoV-2 concurrent or in tandem with influenza. Double whammy infections likely would further increase the medical care burden and return us to March-April crisis mode.
One alarming new question is whether recent influenza could make children vulnerable to SARS-CoV-2 and trigger hospitalizations. A surge in pediatric plus adult COVID-19 disease plus a surge in all-ages influenza disease would likely break the medical care system, at least in some areas.
Staggering COVID-19 burden. As of June 8, we have had approximately 2 million SARS-CoV-2 cases with 500,000 hospitalizations and 120,000 deaths. Over the past 10 years, total annual U.S. influenza hospitalizations ranged from 180,000 (2011-2012) to 825,000 (2017-2018). The interquartile range for hospitalization length of stay for influenza is 4-6 days1 vs. 15-23 days2 for SARS-CoV-2. One COVID-19 hospitalization uses hospital resources roughly equal to four influenza hospitalizations. To date COVID-19 hospitalizations have used resources equal to an estimated 1.9 million influenza hospitalizations – over twice the worst influenza season in this century – and we are still on the rise. We are likely not even halfway to truly controlling the U.S. pandemic, so expect another 500,000 hospitalizations – equal to another 1.9 million influenza hospitalizations. Further, pneumonia deaths have skyrocketed this year when COVID-19 was superimposed on the last third of influenza season. One hope is that widespread use of antivirals (for example, new antivirals, convalescent plasma, or other interventions) can reduce length of stay by 30% for COVID-19 hospitalizations, yet even with that the numbers remain grim.
Less influenza disease can free up medical resources. Planning ahead could prevent a bad influenza season (for example, up to 850,000 hospitalizations just for influenza). Can we preemptively use vaccine to reduce influenza hospitalizations below 2011-2012 levels – less than 150,000 hospitalizations? Perhaps, if we start by reducing pediatric influenza.
1. Aim to exceed 75% influenza vaccine uptake in your patients.
a. It is ambitious, but if there was ever a year that needed influenza herd immunity, it is 2020-2021.
2. Review practice/group/institution plans for vaccine purchase and ensure adequate personnel to administer vaccine.
3. Plan safe and efficient processes to vaccinate large numbers in August through November.
a. Consider that routine and influenza vaccines can be given concurrently with the annual uptick in school and sports physical examinations.
b. What social distancing and masking rules will be needed?
i. Will patients need to bring their own masks, or will you supply them?
c. What extra supplies and efforts are needed, e.g. hand sanitizer, new signage, 6-foot interval markings on floors or sidewalks, families calling from parking lot to announce their arrivals, etc.?
d. Remember younger patients need two doses before Dec 1, 2020.
e. Be creative, for example, are parking-lot tents for influenza vaccination feasible?
f. Can we partner with other providers to implement influenza vaccine–specific mass clinics?
Ramping up to give seasonal influenza vaccine in 2020 is daunting. But if we do not prepare, it will be even more difficult. Let’s make this the mildest influenza season in memory by vaccinating more than any time in memory – and by doing so, we can hope to blunt medical care burdens despite ongoing COVID-19 disease.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Kansas City (Mo.). Children’s Mercy receives funding from GlaxoSmithKline, Merck, and Pfizer for vaccine research studies on which Dr. Harrison is an investigator. Email him at [email protected].
References
1.. HCUP Statistical Brief #253. 2019 Oct.
2. medrxiv. 2020 Apr 10. doi: 10.1101/2020.04.07.20057299.
COVID-19 now. The urban phase of the U.S. pandemic is leveling somewhat, while the rural phase is accelerating – in part because of food processing and handling industries. The pediatric burden has been surprisingly small, with the multisystem inflammatory disease (MIS-c) in children noted in several hundred cases now being seen across the country.
Next wave? Given ongoing COVID-19 disease, controversy rages about when and how to re-open the country. Regardless how more reopening occurs over the next months, we should expect a next or ongoing COVID-19 wave, particularly given loss of social distancing during social justice protests. A sawtooth disease prevalence pattern is predicted by many experts: a drop in prevalence leading to reopening, leading to scattered prevalence increases and regional if not local restriction tightening, followed by another drop in prevalence. Then “rinse and repeat” until 70% of the population is immune either by disease experience or vaccine-induced immunity, likely sometime in 2021.
Influenza too. A COVID-19 up-cycle is likely during influenza season, although influenza season’s onset could be altered because of whatever social distancing rules are in place in November and December. That said, we need to consider the worst. We have seen what happens if we fail to prepare and then react only after a prevalent respiratory infection has surged into the overall population. Best estimates are that at most 20% of the U.S. population is currently immune to SARS-CoV-2. Given that at least some of that 20% of individuals currently immune to SARS-CoV-2 will lose their neutralizing antibody over the next 4-6 months, we can still expect 70%-80% of the U.S. population to be susceptible to SARS-CoV-2 infection in the fall of 2020.
Pediatric preparedness. As pediatric providers, we have struggled with lower patient loads and dramatic income losses/declines. Many clinics/offices’ attendance remain less than 50% of pre–COVID-19 levels, with necessary furloughs of personnel and spotty office hours. But influenza is coming, and SARS-CoV-2 will not be gone yet. How do we prepare for concurrent influenza and COVID-19?
The annual purchase/administration of influenza vaccine in summer/fall is expensive, time consuming, and logistically difficult even in the best times. Given the loss of income, likely reluctance of patients to come to clinics/offices if COVID-19 is still circulating, and likely need for some form of social distancing during late summer and early fall, how will providers, health departments, and hospitals implement influenza vaccine administration this year?
Minimize double whammy infections. It is easy to understand why we should maximize influenza protection in SARS-CoV-2 vulnerables (elderly or persons with existing comorbidities). But is it as critical for otherwise healthy children? My answer is yes.
Children are not currently known as SARS-CoV-2 vectors, but children are excellent influenza vectors, shedding higher titers for longer than other age groups. As with SARS-CoV-2, influenza exposure is cumulative, i.e., the more intense and more frequently a person is exposed, the more likely that infection/disease will result. So, the fewer who get and can transmit influenza during the COVID-19 pandemic, the fewer people are likely to get a double whammy of SARS-CoV-2 concurrent or in tandem with influenza. Double whammy infections likely would further increase the medical care burden and return us to March-April crisis mode.
One alarming new question is whether recent influenza could make children vulnerable to SARS-CoV-2 and trigger hospitalizations. A surge in pediatric plus adult COVID-19 disease plus a surge in all-ages influenza disease would likely break the medical care system, at least in some areas.
Staggering COVID-19 burden. As of June 8, we have had approximately 2 million SARS-CoV-2 cases with 500,000 hospitalizations and 120,000 deaths. Over the past 10 years, total annual U.S. influenza hospitalizations ranged from 180,000 (2011-2012) to 825,000 (2017-2018). The interquartile range for hospitalization length of stay for influenza is 4-6 days1 vs. 15-23 days2 for SARS-CoV-2. One COVID-19 hospitalization uses hospital resources roughly equal to four influenza hospitalizations. To date COVID-19 hospitalizations have used resources equal to an estimated 1.9 million influenza hospitalizations – over twice the worst influenza season in this century – and we are still on the rise. We are likely not even halfway to truly controlling the U.S. pandemic, so expect another 500,000 hospitalizations – equal to another 1.9 million influenza hospitalizations. Further, pneumonia deaths have skyrocketed this year when COVID-19 was superimposed on the last third of influenza season. One hope is that widespread use of antivirals (for example, new antivirals, convalescent plasma, or other interventions) can reduce length of stay by 30% for COVID-19 hospitalizations, yet even with that the numbers remain grim.
Less influenza disease can free up medical resources. Planning ahead could prevent a bad influenza season (for example, up to 850,000 hospitalizations just for influenza). Can we preemptively use vaccine to reduce influenza hospitalizations below 2011-2012 levels – less than 150,000 hospitalizations? Perhaps, if we start by reducing pediatric influenza.
1. Aim to exceed 75% influenza vaccine uptake in your patients.
a. It is ambitious, but if there was ever a year that needed influenza herd immunity, it is 2020-2021.
2. Review practice/group/institution plans for vaccine purchase and ensure adequate personnel to administer vaccine.
3. Plan safe and efficient processes to vaccinate large numbers in August through November.
a. Consider that routine and influenza vaccines can be given concurrently with the annual uptick in school and sports physical examinations.
b. What social distancing and masking rules will be needed?
i. Will patients need to bring their own masks, or will you supply them?
c. What extra supplies and efforts are needed, e.g. hand sanitizer, new signage, 6-foot interval markings on floors or sidewalks, families calling from parking lot to announce their arrivals, etc.?
d. Remember younger patients need two doses before Dec 1, 2020.
e. Be creative, for example, are parking-lot tents for influenza vaccination feasible?
f. Can we partner with other providers to implement influenza vaccine–specific mass clinics?
Ramping up to give seasonal influenza vaccine in 2020 is daunting. But if we do not prepare, it will be even more difficult. Let’s make this the mildest influenza season in memory by vaccinating more than any time in memory – and by doing so, we can hope to blunt medical care burdens despite ongoing COVID-19 disease.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Kansas City (Mo.). Children’s Mercy receives funding from GlaxoSmithKline, Merck, and Pfizer for vaccine research studies on which Dr. Harrison is an investigator. Email him at [email protected].
References
1.. HCUP Statistical Brief #253. 2019 Oct.
2. medrxiv. 2020 Apr 10. doi: 10.1101/2020.04.07.20057299.
COVID-19 now. The urban phase of the U.S. pandemic is leveling somewhat, while the rural phase is accelerating – in part because of food processing and handling industries. The pediatric burden has been surprisingly small, with the multisystem inflammatory disease (MIS-c) in children noted in several hundred cases now being seen across the country.
Next wave? Given ongoing COVID-19 disease, controversy rages about when and how to re-open the country. Regardless how more reopening occurs over the next months, we should expect a next or ongoing COVID-19 wave, particularly given loss of social distancing during social justice protests. A sawtooth disease prevalence pattern is predicted by many experts: a drop in prevalence leading to reopening, leading to scattered prevalence increases and regional if not local restriction tightening, followed by another drop in prevalence. Then “rinse and repeat” until 70% of the population is immune either by disease experience or vaccine-induced immunity, likely sometime in 2021.
Influenza too. A COVID-19 up-cycle is likely during influenza season, although influenza season’s onset could be altered because of whatever social distancing rules are in place in November and December. That said, we need to consider the worst. We have seen what happens if we fail to prepare and then react only after a prevalent respiratory infection has surged into the overall population. Best estimates are that at most 20% of the U.S. population is currently immune to SARS-CoV-2. Given that at least some of that 20% of individuals currently immune to SARS-CoV-2 will lose their neutralizing antibody over the next 4-6 months, we can still expect 70%-80% of the U.S. population to be susceptible to SARS-CoV-2 infection in the fall of 2020.
Pediatric preparedness. As pediatric providers, we have struggled with lower patient loads and dramatic income losses/declines. Many clinics/offices’ attendance remain less than 50% of pre–COVID-19 levels, with necessary furloughs of personnel and spotty office hours. But influenza is coming, and SARS-CoV-2 will not be gone yet. How do we prepare for concurrent influenza and COVID-19?
The annual purchase/administration of influenza vaccine in summer/fall is expensive, time consuming, and logistically difficult even in the best times. Given the loss of income, likely reluctance of patients to come to clinics/offices if COVID-19 is still circulating, and likely need for some form of social distancing during late summer and early fall, how will providers, health departments, and hospitals implement influenza vaccine administration this year?
Minimize double whammy infections. It is easy to understand why we should maximize influenza protection in SARS-CoV-2 vulnerables (elderly or persons with existing comorbidities). But is it as critical for otherwise healthy children? My answer is yes.
Children are not currently known as SARS-CoV-2 vectors, but children are excellent influenza vectors, shedding higher titers for longer than other age groups. As with SARS-CoV-2, influenza exposure is cumulative, i.e., the more intense and more frequently a person is exposed, the more likely that infection/disease will result. So, the fewer who get and can transmit influenza during the COVID-19 pandemic, the fewer people are likely to get a double whammy of SARS-CoV-2 concurrent or in tandem with influenza. Double whammy infections likely would further increase the medical care burden and return us to March-April crisis mode.
One alarming new question is whether recent influenza could make children vulnerable to SARS-CoV-2 and trigger hospitalizations. A surge in pediatric plus adult COVID-19 disease plus a surge in all-ages influenza disease would likely break the medical care system, at least in some areas.
Staggering COVID-19 burden. As of June 8, we have had approximately 2 million SARS-CoV-2 cases with 500,000 hospitalizations and 120,000 deaths. Over the past 10 years, total annual U.S. influenza hospitalizations ranged from 180,000 (2011-2012) to 825,000 (2017-2018). The interquartile range for hospitalization length of stay for influenza is 4-6 days1 vs. 15-23 days2 for SARS-CoV-2. One COVID-19 hospitalization uses hospital resources roughly equal to four influenza hospitalizations. To date COVID-19 hospitalizations have used resources equal to an estimated 1.9 million influenza hospitalizations – over twice the worst influenza season in this century – and we are still on the rise. We are likely not even halfway to truly controlling the U.S. pandemic, so expect another 500,000 hospitalizations – equal to another 1.9 million influenza hospitalizations. Further, pneumonia deaths have skyrocketed this year when COVID-19 was superimposed on the last third of influenza season. One hope is that widespread use of antivirals (for example, new antivirals, convalescent plasma, or other interventions) can reduce length of stay by 30% for COVID-19 hospitalizations, yet even with that the numbers remain grim.
Less influenza disease can free up medical resources. Planning ahead could prevent a bad influenza season (for example, up to 850,000 hospitalizations just for influenza). Can we preemptively use vaccine to reduce influenza hospitalizations below 2011-2012 levels – less than 150,000 hospitalizations? Perhaps, if we start by reducing pediatric influenza.
1. Aim to exceed 75% influenza vaccine uptake in your patients.
a. It is ambitious, but if there was ever a year that needed influenza herd immunity, it is 2020-2021.
2. Review practice/group/institution plans for vaccine purchase and ensure adequate personnel to administer vaccine.
3. Plan safe and efficient processes to vaccinate large numbers in August through November.
a. Consider that routine and influenza vaccines can be given concurrently with the annual uptick in school and sports physical examinations.
b. What social distancing and masking rules will be needed?
i. Will patients need to bring their own masks, or will you supply them?
c. What extra supplies and efforts are needed, e.g. hand sanitizer, new signage, 6-foot interval markings on floors or sidewalks, families calling from parking lot to announce their arrivals, etc.?
d. Remember younger patients need two doses before Dec 1, 2020.
e. Be creative, for example, are parking-lot tents for influenza vaccination feasible?
f. Can we partner with other providers to implement influenza vaccine–specific mass clinics?
Ramping up to give seasonal influenza vaccine in 2020 is daunting. But if we do not prepare, it will be even more difficult. Let’s make this the mildest influenza season in memory by vaccinating more than any time in memory – and by doing so, we can hope to blunt medical care burdens despite ongoing COVID-19 disease.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Kansas City (Mo.). Children’s Mercy receives funding from GlaxoSmithKline, Merck, and Pfizer for vaccine research studies on which Dr. Harrison is an investigator. Email him at [email protected].
References
1.. HCUP Statistical Brief #253. 2019 Oct.
2. medrxiv. 2020 Apr 10. doi: 10.1101/2020.04.07.20057299.
Learning the ICU
Although deployment of hospitalists into ICUs during the COVID-19 crisis varies widely, in that sense it reflects the pre-COVID hospital landscape of variable involvement, in which many hospitalists pressed into this role expressed discomfort practicing critical care beyond their scope of training, according to a survey published in the Journal of Hospital Medicine in 2018.1 “Hospitalists frequently deliver critical care services without adequate training or support, most prevalently in rural hospitals,” the authors concluded.
A Critical Care for the Hospitalist Series of resources and lectures developed by Eric Siegal, MD, a pulmonologist in Milwaukee, Wisc., and David Aymond, MD, a hospitalist in Alexandria, La., is available on the SHM website. They recommend that hospitalists trying to get oriented to working in the ICU start with the online courses on fluid resuscitation, mechanical ventilation, and noninvasive ventilation.
“Ninety-five percent of management of COVID-19 patients is nothing other than practicing sound critical care medicine,” Dr. Siegal said. “If you want to take effective care of sick COVID patients, you need to develop good foundational critical care skills and knowledge. Without them, you’re doing stuff without understand it.”
Dr. Aymond also encourages hospitalists to develop a stronger understanding of key physiological concepts by reviewing the critical care clinical topics compiled at SHM’s website.
References
1. Sweigart JR et al. Characterizing hospitalist practice and perceptions of critical care delivery. J Hosp Med. 2018 Jan;13(1):6-12.
Although deployment of hospitalists into ICUs during the COVID-19 crisis varies widely, in that sense it reflects the pre-COVID hospital landscape of variable involvement, in which many hospitalists pressed into this role expressed discomfort practicing critical care beyond their scope of training, according to a survey published in the Journal of Hospital Medicine in 2018.1 “Hospitalists frequently deliver critical care services without adequate training or support, most prevalently in rural hospitals,” the authors concluded.
A Critical Care for the Hospitalist Series of resources and lectures developed by Eric Siegal, MD, a pulmonologist in Milwaukee, Wisc., and David Aymond, MD, a hospitalist in Alexandria, La., is available on the SHM website. They recommend that hospitalists trying to get oriented to working in the ICU start with the online courses on fluid resuscitation, mechanical ventilation, and noninvasive ventilation.
“Ninety-five percent of management of COVID-19 patients is nothing other than practicing sound critical care medicine,” Dr. Siegal said. “If you want to take effective care of sick COVID patients, you need to develop good foundational critical care skills and knowledge. Without them, you’re doing stuff without understand it.”
Dr. Aymond also encourages hospitalists to develop a stronger understanding of key physiological concepts by reviewing the critical care clinical topics compiled at SHM’s website.
References
1. Sweigart JR et al. Characterizing hospitalist practice and perceptions of critical care delivery. J Hosp Med. 2018 Jan;13(1):6-12.
Although deployment of hospitalists into ICUs during the COVID-19 crisis varies widely, in that sense it reflects the pre-COVID hospital landscape of variable involvement, in which many hospitalists pressed into this role expressed discomfort practicing critical care beyond their scope of training, according to a survey published in the Journal of Hospital Medicine in 2018.1 “Hospitalists frequently deliver critical care services without adequate training or support, most prevalently in rural hospitals,” the authors concluded.
A Critical Care for the Hospitalist Series of resources and lectures developed by Eric Siegal, MD, a pulmonologist in Milwaukee, Wisc., and David Aymond, MD, a hospitalist in Alexandria, La., is available on the SHM website. They recommend that hospitalists trying to get oriented to working in the ICU start with the online courses on fluid resuscitation, mechanical ventilation, and noninvasive ventilation.
“Ninety-five percent of management of COVID-19 patients is nothing other than practicing sound critical care medicine,” Dr. Siegal said. “If you want to take effective care of sick COVID patients, you need to develop good foundational critical care skills and knowledge. Without them, you’re doing stuff without understand it.”
Dr. Aymond also encourages hospitalists to develop a stronger understanding of key physiological concepts by reviewing the critical care clinical topics compiled at SHM’s website.
References
1. Sweigart JR et al. Characterizing hospitalist practice and perceptions of critical care delivery. J Hosp Med. 2018 Jan;13(1):6-12.
It’s official: COVID-19 was bad for the health care business
COVID-19 took a huge cut of clinicians’ business in March and April
In the first 2 months of the COVID-19 pandemic, health care professionals experienced sharp drops in both utilization and revenue, according to an analysis of the nation’s largest collection of private health care claims data.
For the months of March and April 2020, use of medical professional services dropped by 65% and 68%, respectively, compared with last year, and estimated revenue fell by 45% and 48%, FAIR Health, a nonprofit organization that manages a database of 31 billion claim records, said in a new report.
For the Northeast states – the epicenter of the pandemic in March and April – patient volume was down by 60% in March and 80% in April, while revenue fell by 55% in March and 79% in April, the organization said.
For this analysis, “a professional service was defined as any service provided by an individual (e.g., physician, nurse, nurse practitioner, physician assistant) instead of being billed by a facility,” FAIR Health noted. Figures for 2019 were adjusted using the Consumer Price Index.
The size of the pandemic-related decreases in utilization and income varied by specialty. Of the seven specialties included in the study, oral surgery was hit the hardest, followed by gastroenterology, cardiology, orthopedics, dermatology, adult primary care, and pediatric primary care, FAIR Health said.
After experiencing a 2% drop in utilization this January and an increase of 4% in February, compared with 2019, gastroenterology saw corresponding drops of 73% in March and 77% in April. Estimated revenue for the specialty was flat in January and rose by 10% in February, but plummeted by 75% in March and 80% in April, the FAIR Health data show.
In cardiology, patient volume from 2019 to 2020 looked like this: Down by 4% in January, up 5% in February, down by 62% in March, and down by 71% in April. The earnings numbers tell a similar story: Down by 2% in January, up by 15% in February, down by 57% in March, and down by 73% in April, the organization reported.
Dermatology did the best among the non–primary care specialties, but that was just a relative success. Utilization still dropped by 62% and 68% in March and April of 2020, compared with last year, and revenue declined by 50% in March and 59% in April, FAIR Health said.
For adult primary care, the utilization numbers were similar, but revenue took a somewhat smaller hit. Patient volume from 2019 to 2020 was fairly steady in January and February, then nosedived in March (down 60%) and April (down 68%). Earnings were up initially, rising 1% in January and 2% in February, but fell 47% in March and 54% in April, FAIR Health said.
Pediatric primary care, it appears, may have been buoyed somewhat by its younger patients. The specialty as a whole saw utilization tumble by 52% in March and 58% in April, but revenue dropped by just 32% and 35%, respectively, according to the report.
A little extra data diving showed that the figures for preventive care visits for patients aged 0-4 years in March and April were –2% and 0% for volume and –2% and 1% for revenue. Meanwhile, the volume of immunizations only dropped by 14% and 10% and vaccine-related revenue slipped by just 7% and 2%, FAIR Health noted.
“Across many specialties from January to April 2020, office or other outpatient [evaluation and management] visits became more common relative to other procedures. ... This may have been due in part to the fact that many of these E&M services could be rendered via telehealth,” FAIR Health said.
Telehealth, however, was no panacea, the report explained: “Even when medical practices have continued to function via telehealth, many have experienced lower reimbursements for telehealth visits than for in-person visits and more time educating patients on how to use the technology.”
COVID-19 took a huge cut of clinicians’ business in March and April
COVID-19 took a huge cut of clinicians’ business in March and April
In the first 2 months of the COVID-19 pandemic, health care professionals experienced sharp drops in both utilization and revenue, according to an analysis of the nation’s largest collection of private health care claims data.
For the months of March and April 2020, use of medical professional services dropped by 65% and 68%, respectively, compared with last year, and estimated revenue fell by 45% and 48%, FAIR Health, a nonprofit organization that manages a database of 31 billion claim records, said in a new report.
For the Northeast states – the epicenter of the pandemic in March and April – patient volume was down by 60% in March and 80% in April, while revenue fell by 55% in March and 79% in April, the organization said.
For this analysis, “a professional service was defined as any service provided by an individual (e.g., physician, nurse, nurse practitioner, physician assistant) instead of being billed by a facility,” FAIR Health noted. Figures for 2019 were adjusted using the Consumer Price Index.
The size of the pandemic-related decreases in utilization and income varied by specialty. Of the seven specialties included in the study, oral surgery was hit the hardest, followed by gastroenterology, cardiology, orthopedics, dermatology, adult primary care, and pediatric primary care, FAIR Health said.
After experiencing a 2% drop in utilization this January and an increase of 4% in February, compared with 2019, gastroenterology saw corresponding drops of 73% in March and 77% in April. Estimated revenue for the specialty was flat in January and rose by 10% in February, but plummeted by 75% in March and 80% in April, the FAIR Health data show.
In cardiology, patient volume from 2019 to 2020 looked like this: Down by 4% in January, up 5% in February, down by 62% in March, and down by 71% in April. The earnings numbers tell a similar story: Down by 2% in January, up by 15% in February, down by 57% in March, and down by 73% in April, the organization reported.
Dermatology did the best among the non–primary care specialties, but that was just a relative success. Utilization still dropped by 62% and 68% in March and April of 2020, compared with last year, and revenue declined by 50% in March and 59% in April, FAIR Health said.
For adult primary care, the utilization numbers were similar, but revenue took a somewhat smaller hit. Patient volume from 2019 to 2020 was fairly steady in January and February, then nosedived in March (down 60%) and April (down 68%). Earnings were up initially, rising 1% in January and 2% in February, but fell 47% in March and 54% in April, FAIR Health said.
Pediatric primary care, it appears, may have been buoyed somewhat by its younger patients. The specialty as a whole saw utilization tumble by 52% in March and 58% in April, but revenue dropped by just 32% and 35%, respectively, according to the report.
A little extra data diving showed that the figures for preventive care visits for patients aged 0-4 years in March and April were –2% and 0% for volume and –2% and 1% for revenue. Meanwhile, the volume of immunizations only dropped by 14% and 10% and vaccine-related revenue slipped by just 7% and 2%, FAIR Health noted.
“Across many specialties from January to April 2020, office or other outpatient [evaluation and management] visits became more common relative to other procedures. ... This may have been due in part to the fact that many of these E&M services could be rendered via telehealth,” FAIR Health said.
Telehealth, however, was no panacea, the report explained: “Even when medical practices have continued to function via telehealth, many have experienced lower reimbursements for telehealth visits than for in-person visits and more time educating patients on how to use the technology.”
In the first 2 months of the COVID-19 pandemic, health care professionals experienced sharp drops in both utilization and revenue, according to an analysis of the nation’s largest collection of private health care claims data.
For the months of March and April 2020, use of medical professional services dropped by 65% and 68%, respectively, compared with last year, and estimated revenue fell by 45% and 48%, FAIR Health, a nonprofit organization that manages a database of 31 billion claim records, said in a new report.
For the Northeast states – the epicenter of the pandemic in March and April – patient volume was down by 60% in March and 80% in April, while revenue fell by 55% in March and 79% in April, the organization said.
For this analysis, “a professional service was defined as any service provided by an individual (e.g., physician, nurse, nurse practitioner, physician assistant) instead of being billed by a facility,” FAIR Health noted. Figures for 2019 were adjusted using the Consumer Price Index.
The size of the pandemic-related decreases in utilization and income varied by specialty. Of the seven specialties included in the study, oral surgery was hit the hardest, followed by gastroenterology, cardiology, orthopedics, dermatology, adult primary care, and pediatric primary care, FAIR Health said.
After experiencing a 2% drop in utilization this January and an increase of 4% in February, compared with 2019, gastroenterology saw corresponding drops of 73% in March and 77% in April. Estimated revenue for the specialty was flat in January and rose by 10% in February, but plummeted by 75% in March and 80% in April, the FAIR Health data show.
In cardiology, patient volume from 2019 to 2020 looked like this: Down by 4% in January, up 5% in February, down by 62% in March, and down by 71% in April. The earnings numbers tell a similar story: Down by 2% in January, up by 15% in February, down by 57% in March, and down by 73% in April, the organization reported.
Dermatology did the best among the non–primary care specialties, but that was just a relative success. Utilization still dropped by 62% and 68% in March and April of 2020, compared with last year, and revenue declined by 50% in March and 59% in April, FAIR Health said.
For adult primary care, the utilization numbers were similar, but revenue took a somewhat smaller hit. Patient volume from 2019 to 2020 was fairly steady in January and February, then nosedived in March (down 60%) and April (down 68%). Earnings were up initially, rising 1% in January and 2% in February, but fell 47% in March and 54% in April, FAIR Health said.
Pediatric primary care, it appears, may have been buoyed somewhat by its younger patients. The specialty as a whole saw utilization tumble by 52% in March and 58% in April, but revenue dropped by just 32% and 35%, respectively, according to the report.
A little extra data diving showed that the figures for preventive care visits for patients aged 0-4 years in March and April were –2% and 0% for volume and –2% and 1% for revenue. Meanwhile, the volume of immunizations only dropped by 14% and 10% and vaccine-related revenue slipped by just 7% and 2%, FAIR Health noted.
“Across many specialties from January to April 2020, office or other outpatient [evaluation and management] visits became more common relative to other procedures. ... This may have been due in part to the fact that many of these E&M services could be rendered via telehealth,” FAIR Health said.
Telehealth, however, was no panacea, the report explained: “Even when medical practices have continued to function via telehealth, many have experienced lower reimbursements for telehealth visits than for in-person visits and more time educating patients on how to use the technology.”
Smart phones boosted compliance for cardiac device data transmission
A phone, an app, and the next generation of implanted cardiac device data signaling produced an unprecedented level of data transmission compliance in a single-arm, multicenter, pilot study with 245 patients, adding momentum to the expanding penetration of personal smart devices into cardiac electrophysiology.
During 12-month follow-up, the 245 patients who received either a medically indicated pacemaker or cardiac resynchronization therapy (CRT)–pacemaker equipped with Bluetooth remote transmission capability had successful data transfer to their clinicians for 95% of their scheduled data uploads while using a personal phone or tablet as the link between their heart implant and the Internet. This rate significantly surpassed the transmission-success rates tallied by traditional, bedside transmitters in historical control groups, Khaldoun G. Tarakji, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.
A related analysis by Dr. Tarakji and colleagues of 811 patients from real-world practice who received similar implanted cardiac devices with the same remote-transmission capability showed a 93% rate of successful data transfers via smart devices.
In contrast, historical performance showed a 77% success rate in matched patients drawn from a pool of more than 69,000 people in routine care who had received a pacemaker or CRT-pacemaker that automatically transmitted to a bedside monitor. Historical transmission success among matched patients from a pool of more than 128,000 routine-care patients with similar implants who used a wand to interrogate their implants before the attached monitor transmitted their data had a 56% rate of successful transmissions.
Cardiac device signals that flow directly into a patient’s phone or pad and then relay automatically via an app to the clinic “are clearly much easier,” than the methods now used, observed Dr. Tarakji, a cardiac electrophysiologist at the Cleveland Clinic. “It is truly as seamless as possible. Patients don’t really need to do anything,” he said during a press briefing. The key is that most patients tend to keep their smart devices, especially their phones, near them all the time, which minimizes the chance that the implanted cardiac device might try to file a report when the patient is not positioned near the device that’s facilitating transmission. When patients use conventional, bedside transmitters they can forget to bring them on trips, while many fewer fail to take their phone. Another advantage is that the link between a phone and a cardiac implant can be started in the clinic once the patient downloads an app. Bedside units need home setup, and “some patients never even get theirs out of the box,” Dr. Tarakji lamented.
Another feature of handheld device transmissions that run off an app is that the app can display clinical metrics, activity, device performance, and transmission history, as well as educational information. All of these features can enhance patient engagement with their implanted device, their arrhythmia, and their health status. Bedside units often give patients little feedback, and they don’t display clinical data. “The real challenge for clinicians is what data you let patients see. That’s complicated,” Dr. Tarakji said.
“This study was designed to see whether the technology works. The next step is to study how it affects risk-factor modification” or other outcomes. “There are many opportunities” to explore with this new data transmission and processing capability, he concluded.
The BlueSync Field Evaluation study enrolled patients at 20 centers in the United States, France, Italy, and the United Kingdom during 2018, and the 245 patients who received a BlueSync device and were included in the analysis sent at least one of their scheduled data transmissions during their 12 months of follow-up. Participants were eligible if they were willing to use their own smart phone or pad that could interact with their cardiac implant, and included both first-time implant recipients as well as some patients who received replacement units.
Personal device–based data transmission from cardiac implants “will no doubt change the way we manage patients,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University in New Orleans, and a designated discussant for the report. “Every implanted cardiac device should be able to connect with a phone, which can improve adoption and adherence,” he said.
But the study has several limitations for interpreting the implications of the findings, starting with its limited size and single-arm design, noted a second discussant, Roderick Tung, MD, director of cardiac electrophysiology at the University of Chicago. Another issue is the generalizability of the findings, which are likely biased by involving only patients who own a smart phone or tablet and may be more likely to transmit their data regardless of the means. And comparing transmission success in a prospective study with rates that occurred during real-world, routine practice could have a Hawthorne effect bias, where people under study behave differently than they do in everyday life. But that effect may be mitigated by confirmatory findings from a real-world group that also used smart-device transmission included in the report. Despite these caveats, it’s valuable to develop new ways of improving data collection from cardiac devices, Dr. Tung said.
The BlueSync Field Evaluation study was sponsored by Medtronic, the company that markets Bluetooth-enabled cardiac devices. Dr. Tarakji has been a consultant to Medtronic, and also to AliveCor, Boston Scientific, and Johnson & Johnson. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and he has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster.
SOURCE: Tarakji KG. Heart Rhythm 2020, Abstract D-LBCT04-01.
A phone, an app, and the next generation of implanted cardiac device data signaling produced an unprecedented level of data transmission compliance in a single-arm, multicenter, pilot study with 245 patients, adding momentum to the expanding penetration of personal smart devices into cardiac electrophysiology.
During 12-month follow-up, the 245 patients who received either a medically indicated pacemaker or cardiac resynchronization therapy (CRT)–pacemaker equipped with Bluetooth remote transmission capability had successful data transfer to their clinicians for 95% of their scheduled data uploads while using a personal phone or tablet as the link between their heart implant and the Internet. This rate significantly surpassed the transmission-success rates tallied by traditional, bedside transmitters in historical control groups, Khaldoun G. Tarakji, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.
A related analysis by Dr. Tarakji and colleagues of 811 patients from real-world practice who received similar implanted cardiac devices with the same remote-transmission capability showed a 93% rate of successful data transfers via smart devices.
In contrast, historical performance showed a 77% success rate in matched patients drawn from a pool of more than 69,000 people in routine care who had received a pacemaker or CRT-pacemaker that automatically transmitted to a bedside monitor. Historical transmission success among matched patients from a pool of more than 128,000 routine-care patients with similar implants who used a wand to interrogate their implants before the attached monitor transmitted their data had a 56% rate of successful transmissions.
Cardiac device signals that flow directly into a patient’s phone or pad and then relay automatically via an app to the clinic “are clearly much easier,” than the methods now used, observed Dr. Tarakji, a cardiac electrophysiologist at the Cleveland Clinic. “It is truly as seamless as possible. Patients don’t really need to do anything,” he said during a press briefing. The key is that most patients tend to keep their smart devices, especially their phones, near them all the time, which minimizes the chance that the implanted cardiac device might try to file a report when the patient is not positioned near the device that’s facilitating transmission. When patients use conventional, bedside transmitters they can forget to bring them on trips, while many fewer fail to take their phone. Another advantage is that the link between a phone and a cardiac implant can be started in the clinic once the patient downloads an app. Bedside units need home setup, and “some patients never even get theirs out of the box,” Dr. Tarakji lamented.
Another feature of handheld device transmissions that run off an app is that the app can display clinical metrics, activity, device performance, and transmission history, as well as educational information. All of these features can enhance patient engagement with their implanted device, their arrhythmia, and their health status. Bedside units often give patients little feedback, and they don’t display clinical data. “The real challenge for clinicians is what data you let patients see. That’s complicated,” Dr. Tarakji said.
“This study was designed to see whether the technology works. The next step is to study how it affects risk-factor modification” or other outcomes. “There are many opportunities” to explore with this new data transmission and processing capability, he concluded.
The BlueSync Field Evaluation study enrolled patients at 20 centers in the United States, France, Italy, and the United Kingdom during 2018, and the 245 patients who received a BlueSync device and were included in the analysis sent at least one of their scheduled data transmissions during their 12 months of follow-up. Participants were eligible if they were willing to use their own smart phone or pad that could interact with their cardiac implant, and included both first-time implant recipients as well as some patients who received replacement units.
Personal device–based data transmission from cardiac implants “will no doubt change the way we manage patients,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University in New Orleans, and a designated discussant for the report. “Every implanted cardiac device should be able to connect with a phone, which can improve adoption and adherence,” he said.
But the study has several limitations for interpreting the implications of the findings, starting with its limited size and single-arm design, noted a second discussant, Roderick Tung, MD, director of cardiac electrophysiology at the University of Chicago. Another issue is the generalizability of the findings, which are likely biased by involving only patients who own a smart phone or tablet and may be more likely to transmit their data regardless of the means. And comparing transmission success in a prospective study with rates that occurred during real-world, routine practice could have a Hawthorne effect bias, where people under study behave differently than they do in everyday life. But that effect may be mitigated by confirmatory findings from a real-world group that also used smart-device transmission included in the report. Despite these caveats, it’s valuable to develop new ways of improving data collection from cardiac devices, Dr. Tung said.
The BlueSync Field Evaluation study was sponsored by Medtronic, the company that markets Bluetooth-enabled cardiac devices. Dr. Tarakji has been a consultant to Medtronic, and also to AliveCor, Boston Scientific, and Johnson & Johnson. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and he has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster.
SOURCE: Tarakji KG. Heart Rhythm 2020, Abstract D-LBCT04-01.
A phone, an app, and the next generation of implanted cardiac device data signaling produced an unprecedented level of data transmission compliance in a single-arm, multicenter, pilot study with 245 patients, adding momentum to the expanding penetration of personal smart devices into cardiac electrophysiology.
During 12-month follow-up, the 245 patients who received either a medically indicated pacemaker or cardiac resynchronization therapy (CRT)–pacemaker equipped with Bluetooth remote transmission capability had successful data transfer to their clinicians for 95% of their scheduled data uploads while using a personal phone or tablet as the link between their heart implant and the Internet. This rate significantly surpassed the transmission-success rates tallied by traditional, bedside transmitters in historical control groups, Khaldoun G. Tarakji, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.
A related analysis by Dr. Tarakji and colleagues of 811 patients from real-world practice who received similar implanted cardiac devices with the same remote-transmission capability showed a 93% rate of successful data transfers via smart devices.
In contrast, historical performance showed a 77% success rate in matched patients drawn from a pool of more than 69,000 people in routine care who had received a pacemaker or CRT-pacemaker that automatically transmitted to a bedside monitor. Historical transmission success among matched patients from a pool of more than 128,000 routine-care patients with similar implants who used a wand to interrogate their implants before the attached monitor transmitted their data had a 56% rate of successful transmissions.
Cardiac device signals that flow directly into a patient’s phone or pad and then relay automatically via an app to the clinic “are clearly much easier,” than the methods now used, observed Dr. Tarakji, a cardiac electrophysiologist at the Cleveland Clinic. “It is truly as seamless as possible. Patients don’t really need to do anything,” he said during a press briefing. The key is that most patients tend to keep their smart devices, especially their phones, near them all the time, which minimizes the chance that the implanted cardiac device might try to file a report when the patient is not positioned near the device that’s facilitating transmission. When patients use conventional, bedside transmitters they can forget to bring them on trips, while many fewer fail to take their phone. Another advantage is that the link between a phone and a cardiac implant can be started in the clinic once the patient downloads an app. Bedside units need home setup, and “some patients never even get theirs out of the box,” Dr. Tarakji lamented.
Another feature of handheld device transmissions that run off an app is that the app can display clinical metrics, activity, device performance, and transmission history, as well as educational information. All of these features can enhance patient engagement with their implanted device, their arrhythmia, and their health status. Bedside units often give patients little feedback, and they don’t display clinical data. “The real challenge for clinicians is what data you let patients see. That’s complicated,” Dr. Tarakji said.
“This study was designed to see whether the technology works. The next step is to study how it affects risk-factor modification” or other outcomes. “There are many opportunities” to explore with this new data transmission and processing capability, he concluded.
The BlueSync Field Evaluation study enrolled patients at 20 centers in the United States, France, Italy, and the United Kingdom during 2018, and the 245 patients who received a BlueSync device and were included in the analysis sent at least one of their scheduled data transmissions during their 12 months of follow-up. Participants were eligible if they were willing to use their own smart phone or pad that could interact with their cardiac implant, and included both first-time implant recipients as well as some patients who received replacement units.
Personal device–based data transmission from cardiac implants “will no doubt change the way we manage patients,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University in New Orleans, and a designated discussant for the report. “Every implanted cardiac device should be able to connect with a phone, which can improve adoption and adherence,” he said.
But the study has several limitations for interpreting the implications of the findings, starting with its limited size and single-arm design, noted a second discussant, Roderick Tung, MD, director of cardiac electrophysiology at the University of Chicago. Another issue is the generalizability of the findings, which are likely biased by involving only patients who own a smart phone or tablet and may be more likely to transmit their data regardless of the means. And comparing transmission success in a prospective study with rates that occurred during real-world, routine practice could have a Hawthorne effect bias, where people under study behave differently than they do in everyday life. But that effect may be mitigated by confirmatory findings from a real-world group that also used smart-device transmission included in the report. Despite these caveats, it’s valuable to develop new ways of improving data collection from cardiac devices, Dr. Tung said.
The BlueSync Field Evaluation study was sponsored by Medtronic, the company that markets Bluetooth-enabled cardiac devices. Dr. Tarakji has been a consultant to Medtronic, and also to AliveCor, Boston Scientific, and Johnson & Johnson. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and he has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster.
SOURCE: Tarakji KG. Heart Rhythm 2020, Abstract D-LBCT04-01.
FROM HEART RHYTHM 2020
Renal denervation response similar regardless of CV risks, comorbidities
In a new analysis of international registry data, renal denervation resulted in similar reduced blood pressure levels in patients with varying high-risk comorbidities and across a range of cardiovascular risk scores.
At 3 years, 24-hour systolic BP was reduced by an average of –8.9 mm Hg overall, with slightly higher or lower readings seen in those with higher cardiovascular risk scores (–10.4 mm Hg) and 65 years or older (–10.2 mm Hg). Similar reductions were seen in those with resistant hypertension (–8.7 mm Hg), diabetes (–8.6 mm Hg), isolated systolic hypertension (–10.1 mm Hg), chronic kidney disease (–10.1 mm Hg), or atrial fibrillation (–10.0 mm Hg).
“In the largest international registry of its kind, the efficacy of renal denervation was similar in patients with and without baseline conditions associated with increased sympathetic activity and irrespective of ASCVD [atherosclerotic cardiovascular disease] risk,” first author Felix Mahfoud, MD, said in an interview.
Dr. Mahfoud, from University Hospital of Saarland, Homburg, Germany, and colleagues published their analysis in the Journal of the American College of Cardiology.
The article reported a post hoc analysis of data from the Global SYMPLICITY Registry (GSR), an international, Medtronic-funded effort that includes 2,652 patients with uncontrolled hypertension treated with a Symplicity denervation system. Data were obtained from 196 centers in 45 countries.
“Blood pressure reductions were durable and sustained to 3 years and the rates of new-onset, end-stage renal disease and elevation in serum creatinine levels were very low in patients at high and low [cardiovascular] risk,” reported Dr. Mahfoud.
As expected, adverse event rates were higher for patients with higher baseline cardiovascular risk. “Elevated rates were also seen in patients with [atrial fibrillation] and diabetes, identifying these subgroups who might derive even greater clinical benefit from improved BP control using renal denervation,” said Dr. Mahfoud.
Asked which patients might be optimal candidates for renal denervation, Dr. Mahfoud recommended the technology for “patients with uncontrolled hypertension on medication, patients with nonadherence, unwillingness, or intolerability to medication, and patients with combined systolic and diastolic hypertension.”
Analyses limited by incomplete data
Stephen C. Textor, MD, has concerns over the amount of missing data in the GSR database and its continued use as a repository of information on renal denervation.
“I am a bit lukewarm on this paper in part because of the nature of the registry data they’re using,” he added in an interview. “The problem I see is that the registry is not terribly uniform as to what information they collect on each patient, not terribly uniform in terms of how the procedure is performed, and not terribly uniform on how they follow up patients.”
Indeed, the post hoc subgroup analyses represent only a limited subset because of incomplete data, added Dr. Textor, a nephrologist at the Cleveland Clinic in Rochester, Minn.
“Remarkably, only 504 [patients] had “matched” data for office [systolic BP] levels at the time points defined in the report,” he wrote in an editorial comment accompanying the registry report (J Am Coll Cardiol. 2020 Jun 16;75[23]:2889-91).
Similarly, the researchers were able to calculate baseline atherosclerotic cardiovascular risk scores in only 1,485 patients (56% of total), primarily because of missing cholesterol measurements.
“They simply did these paired comparison that may have included a couple hundred cases, and on average, there were no differences in response, but what I would have liked to see is a multivariate analysis, where you have all the data on everybody and look at what are the factors that impact response?” Dr. Textor said in the interview.
“They really couldn’t do that because they just, they’re just too many holes in the data,” he added.
On the bright side, Dr. Textor noted that, while the impact overall on systolic BP was “modest,” the standard deviations in some cases were large, indicating that some people had large reductions of systolic BP of more than 30-40 mm Hg.
“There is a belief out there that there are some people that really benefit from this, but how to identify them has been the question,” Dr. Textor said.
Enthusiasm for renal denervation plummeted after results from the SYMPLICITY HTN-3 showed the procedure failing to meet its efficacy endpoint in resistant hypertension. The procedure was associated with a 14–mm Hg fall in systolic BP, compared with an 11–mm Hg drop in the “sham” control group (N Engl J Med. 2014 Apr 10;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution.
No renal denervation device is approved in the United States. The Symplicity device used in this registry is approved in the European Union.
In early 2020, the Food and Drug Administration promised a rigorous review of new renal denervation trials. Subsequently, primary results from the SPYRAL HTN-OFF MED pivotal trial were presented at the annual meeting of the American College of Cardiology in March and showed promising efficacy.
SPYRAL HTN OFF-MED was designed in collaboration with the FDA to obtain meaningful evidence of whether renal denervation performed with the Symplicity Spyral multielectrode catheter (Medtronic Vascular) could reduce BP in patients not taking antihypertensive medication.
Dr. Mahfoud reported he has received speaking honoraria from Medtronic and ReCor. Two other authors are employees of Medtronic. Dr. Textor reported no relationships relevant to the contents of this paper. The Global SYMPLICITY Registry is funded by Medtronic Vascular.
SOURCE: Mahfoud F et al. J Am Coll Cardiol. 2020 June 16;75:2879-88.
This article was updated 6/16/20.
In a new analysis of international registry data, renal denervation resulted in similar reduced blood pressure levels in patients with varying high-risk comorbidities and across a range of cardiovascular risk scores.
At 3 years, 24-hour systolic BP was reduced by an average of –8.9 mm Hg overall, with slightly higher or lower readings seen in those with higher cardiovascular risk scores (–10.4 mm Hg) and 65 years or older (–10.2 mm Hg). Similar reductions were seen in those with resistant hypertension (–8.7 mm Hg), diabetes (–8.6 mm Hg), isolated systolic hypertension (–10.1 mm Hg), chronic kidney disease (–10.1 mm Hg), or atrial fibrillation (–10.0 mm Hg).
“In the largest international registry of its kind, the efficacy of renal denervation was similar in patients with and without baseline conditions associated with increased sympathetic activity and irrespective of ASCVD [atherosclerotic cardiovascular disease] risk,” first author Felix Mahfoud, MD, said in an interview.
Dr. Mahfoud, from University Hospital of Saarland, Homburg, Germany, and colleagues published their analysis in the Journal of the American College of Cardiology.
The article reported a post hoc analysis of data from the Global SYMPLICITY Registry (GSR), an international, Medtronic-funded effort that includes 2,652 patients with uncontrolled hypertension treated with a Symplicity denervation system. Data were obtained from 196 centers in 45 countries.
“Blood pressure reductions were durable and sustained to 3 years and the rates of new-onset, end-stage renal disease and elevation in serum creatinine levels were very low in patients at high and low [cardiovascular] risk,” reported Dr. Mahfoud.
As expected, adverse event rates were higher for patients with higher baseline cardiovascular risk. “Elevated rates were also seen in patients with [atrial fibrillation] and diabetes, identifying these subgroups who might derive even greater clinical benefit from improved BP control using renal denervation,” said Dr. Mahfoud.
Asked which patients might be optimal candidates for renal denervation, Dr. Mahfoud recommended the technology for “patients with uncontrolled hypertension on medication, patients with nonadherence, unwillingness, or intolerability to medication, and patients with combined systolic and diastolic hypertension.”
Analyses limited by incomplete data
Stephen C. Textor, MD, has concerns over the amount of missing data in the GSR database and its continued use as a repository of information on renal denervation.
“I am a bit lukewarm on this paper in part because of the nature of the registry data they’re using,” he added in an interview. “The problem I see is that the registry is not terribly uniform as to what information they collect on each patient, not terribly uniform in terms of how the procedure is performed, and not terribly uniform on how they follow up patients.”
Indeed, the post hoc subgroup analyses represent only a limited subset because of incomplete data, added Dr. Textor, a nephrologist at the Cleveland Clinic in Rochester, Minn.
“Remarkably, only 504 [patients] had “matched” data for office [systolic BP] levels at the time points defined in the report,” he wrote in an editorial comment accompanying the registry report (J Am Coll Cardiol. 2020 Jun 16;75[23]:2889-91).
Similarly, the researchers were able to calculate baseline atherosclerotic cardiovascular risk scores in only 1,485 patients (56% of total), primarily because of missing cholesterol measurements.
“They simply did these paired comparison that may have included a couple hundred cases, and on average, there were no differences in response, but what I would have liked to see is a multivariate analysis, where you have all the data on everybody and look at what are the factors that impact response?” Dr. Textor said in the interview.
“They really couldn’t do that because they just, they’re just too many holes in the data,” he added.
On the bright side, Dr. Textor noted that, while the impact overall on systolic BP was “modest,” the standard deviations in some cases were large, indicating that some people had large reductions of systolic BP of more than 30-40 mm Hg.
“There is a belief out there that there are some people that really benefit from this, but how to identify them has been the question,” Dr. Textor said.
Enthusiasm for renal denervation plummeted after results from the SYMPLICITY HTN-3 showed the procedure failing to meet its efficacy endpoint in resistant hypertension. The procedure was associated with a 14–mm Hg fall in systolic BP, compared with an 11–mm Hg drop in the “sham” control group (N Engl J Med. 2014 Apr 10;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution.
No renal denervation device is approved in the United States. The Symplicity device used in this registry is approved in the European Union.
In early 2020, the Food and Drug Administration promised a rigorous review of new renal denervation trials. Subsequently, primary results from the SPYRAL HTN-OFF MED pivotal trial were presented at the annual meeting of the American College of Cardiology in March and showed promising efficacy.
SPYRAL HTN OFF-MED was designed in collaboration with the FDA to obtain meaningful evidence of whether renal denervation performed with the Symplicity Spyral multielectrode catheter (Medtronic Vascular) could reduce BP in patients not taking antihypertensive medication.
Dr. Mahfoud reported he has received speaking honoraria from Medtronic and ReCor. Two other authors are employees of Medtronic. Dr. Textor reported no relationships relevant to the contents of this paper. The Global SYMPLICITY Registry is funded by Medtronic Vascular.
SOURCE: Mahfoud F et al. J Am Coll Cardiol. 2020 June 16;75:2879-88.
This article was updated 6/16/20.
In a new analysis of international registry data, renal denervation resulted in similar reduced blood pressure levels in patients with varying high-risk comorbidities and across a range of cardiovascular risk scores.
At 3 years, 24-hour systolic BP was reduced by an average of –8.9 mm Hg overall, with slightly higher or lower readings seen in those with higher cardiovascular risk scores (–10.4 mm Hg) and 65 years or older (–10.2 mm Hg). Similar reductions were seen in those with resistant hypertension (–8.7 mm Hg), diabetes (–8.6 mm Hg), isolated systolic hypertension (–10.1 mm Hg), chronic kidney disease (–10.1 mm Hg), or atrial fibrillation (–10.0 mm Hg).
“In the largest international registry of its kind, the efficacy of renal denervation was similar in patients with and without baseline conditions associated with increased sympathetic activity and irrespective of ASCVD [atherosclerotic cardiovascular disease] risk,” first author Felix Mahfoud, MD, said in an interview.
Dr. Mahfoud, from University Hospital of Saarland, Homburg, Germany, and colleagues published their analysis in the Journal of the American College of Cardiology.
The article reported a post hoc analysis of data from the Global SYMPLICITY Registry (GSR), an international, Medtronic-funded effort that includes 2,652 patients with uncontrolled hypertension treated with a Symplicity denervation system. Data were obtained from 196 centers in 45 countries.
“Blood pressure reductions were durable and sustained to 3 years and the rates of new-onset, end-stage renal disease and elevation in serum creatinine levels were very low in patients at high and low [cardiovascular] risk,” reported Dr. Mahfoud.
As expected, adverse event rates were higher for patients with higher baseline cardiovascular risk. “Elevated rates were also seen in patients with [atrial fibrillation] and diabetes, identifying these subgroups who might derive even greater clinical benefit from improved BP control using renal denervation,” said Dr. Mahfoud.
Asked which patients might be optimal candidates for renal denervation, Dr. Mahfoud recommended the technology for “patients with uncontrolled hypertension on medication, patients with nonadherence, unwillingness, or intolerability to medication, and patients with combined systolic and diastolic hypertension.”
Analyses limited by incomplete data
Stephen C. Textor, MD, has concerns over the amount of missing data in the GSR database and its continued use as a repository of information on renal denervation.
“I am a bit lukewarm on this paper in part because of the nature of the registry data they’re using,” he added in an interview. “The problem I see is that the registry is not terribly uniform as to what information they collect on each patient, not terribly uniform in terms of how the procedure is performed, and not terribly uniform on how they follow up patients.”
Indeed, the post hoc subgroup analyses represent only a limited subset because of incomplete data, added Dr. Textor, a nephrologist at the Cleveland Clinic in Rochester, Minn.
“Remarkably, only 504 [patients] had “matched” data for office [systolic BP] levels at the time points defined in the report,” he wrote in an editorial comment accompanying the registry report (J Am Coll Cardiol. 2020 Jun 16;75[23]:2889-91).
Similarly, the researchers were able to calculate baseline atherosclerotic cardiovascular risk scores in only 1,485 patients (56% of total), primarily because of missing cholesterol measurements.
“They simply did these paired comparison that may have included a couple hundred cases, and on average, there were no differences in response, but what I would have liked to see is a multivariate analysis, where you have all the data on everybody and look at what are the factors that impact response?” Dr. Textor said in the interview.
“They really couldn’t do that because they just, they’re just too many holes in the data,” he added.
On the bright side, Dr. Textor noted that, while the impact overall on systolic BP was “modest,” the standard deviations in some cases were large, indicating that some people had large reductions of systolic BP of more than 30-40 mm Hg.
“There is a belief out there that there are some people that really benefit from this, but how to identify them has been the question,” Dr. Textor said.
Enthusiasm for renal denervation plummeted after results from the SYMPLICITY HTN-3 showed the procedure failing to meet its efficacy endpoint in resistant hypertension. The procedure was associated with a 14–mm Hg fall in systolic BP, compared with an 11–mm Hg drop in the “sham” control group (N Engl J Med. 2014 Apr 10;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution.
No renal denervation device is approved in the United States. The Symplicity device used in this registry is approved in the European Union.
In early 2020, the Food and Drug Administration promised a rigorous review of new renal denervation trials. Subsequently, primary results from the SPYRAL HTN-OFF MED pivotal trial were presented at the annual meeting of the American College of Cardiology in March and showed promising efficacy.
SPYRAL HTN OFF-MED was designed in collaboration with the FDA to obtain meaningful evidence of whether renal denervation performed with the Symplicity Spyral multielectrode catheter (Medtronic Vascular) could reduce BP in patients not taking antihypertensive medication.
Dr. Mahfoud reported he has received speaking honoraria from Medtronic and ReCor. Two other authors are employees of Medtronic. Dr. Textor reported no relationships relevant to the contents of this paper. The Global SYMPLICITY Registry is funded by Medtronic Vascular.
SOURCE: Mahfoud F et al. J Am Coll Cardiol. 2020 June 16;75:2879-88.
This article was updated 6/16/20.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Cognitive-behavioral therapy a standout for better immune function
Psychosocial interventions, particularly cognitive-behavioral therapy (CBT), are associated with enhanced immune system function, new research suggests.
Results of a systematic review and meta-analysis that included 56 randomized controlled trials and more than 4,000 participants showed that over time, psychosocial interventions appeared to augment beneficial immune system function while concurrently decreasing harmful immune system function in comparison with control conditions.
“These associations were most reliable for cognitive-behavioral therapy and multiple or combined interventions and for studies that assessed proinflammatory cytokines or markers, which are key indicators of inflammation in the body,” study investigator George M. Slavich, PhD, said in an interview.
“The analysis helps address the question of which types of psychosocial interventions are most consistently associated with changes in immune system function, under what conditions, and for whom. This knowledge could, in turn, be used to inform research efforts and public policy aimed at using psychosocial interventions to improve immune-related health outcomes,” added Dr. Slavich, director of the Laboratory for Stress Assessment and Research, University of California, Los Angeles.
The study was published online June 3 in JAMA Psychiatry.
Link to serious physical, mental illnesses
There is substantial evidence that the immune system plays a role in a variety of mental and physical health problems. Such problems include anxiety disorders, depression, suicide, schizophrenia, cardiovascular disease, autoimmune disorders, and neurodegenerative diseases. It has been recently suggested that more than half of all deaths worldwide are attributable to inflammation-related conditions.
Although pharmacologic interventions can play a role in addressing inflammation, they are not without drawbacks, most notably, cost and adverse side effects.
The World Health Organization, the National Academy of Medicine, the National Institutes of Health, and other groups have emphasized the importance of addressing global disease burden through psychosocial interventions when possible.
Such recommendations are supported by scientific evidence. Previous research has shown that immune system processes are influenced by a variety of social, neurocognitive, and behavioral factors.
Given such findings, researchers have examined the effects of interventions that reduce stress or bolster psychological resources on immune system function.
However, such research has yielded conflicting findings. Some studies show that psychosocial interventions clearly enhance immunity, whereas others do not.
In addition, questions remain regarding which types of interventions reliably improve immune system function, under what conditions, and for whom.
“Research has shown that psychological factors – such as life stress, negative emotions, and social support – are associated with changes in immune system function,” Dr. Slavich noted.
“In addition, there is growing appreciation that immune system processes involved in inflammation may contribute to peoples’ risk for several major mental and physical health problems, including anxiety disorders, depression, heart disease, and autoimmune and neurodegenerative disorders.”
First study of its kind
To shed light on these potential links, the researchers conducted what they believe is the first systematic review and meta-analysis of randomized clinical trials of the effects of psychosocial interventions on immune system outcomes.
As part of the review, Dr. Slavich and colleagues estimated the associations between eight psychosocial interventions and seven markers of immune system function.
The eight psychosocial interventions were behavior therapy, cognitive therapy, CBT, CBT plus additive treatment or mode of delivery, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation.
The seven immune outcomes that might be influenced by these interventions are proinflammatory cytokines and markers, anti-inflammatory cytokines, antibodies, immune cell counts, natural killer cell activity, viral load, and other immune outcomes.
The researchers also examined nine potential factors that might moderate the associations between psychosocial interventions and immune system function.
They searched a variety of databases for all relevant randomized controlled trials published through Dec. 31, 2018. Studies were eligible for inclusion if they included a psychosocial intervention and immune outcome, as well as preintervention and postintervention immunologic assessments.
The researchers identified 4,621 studies. Of these studies, 62 were eligible for inclusion; 56, which included 4,060 patients, were included in the final meta-analysis.
Results showed that psychosocial interventions were associated with enhanced immune system function (P < .001). There was relatively low heterogeneity between studies in these effect sizes, which, the investigators said, indicates that the association was relatively consistent across studies and conditions.
The meta-analysis showed that individuals who were assigned to a psychosocial intervention condition demonstrated a 14.7% improvement (95% confidence interval [CI], 5.7%–23.8%) in beneficial immune system function compared with their counterparts who were assigned to a control condition.
Similarly, participants who received psychosocial interventions demonstrated an 18.0% decrease (95% CI, 7.2%–28.8%) in harmful immune system function over time.
A standout
Regarding the effect of the type of intervention on the association, only CBT (31 studies; P < .001) and multiple or combined interventions (seven studies; P = .01) were significantly associated with changes in immune system outcomes.
The analysis also found that interventions that included a group component were more consistently associated with enhanced immune function than were those that did not include a group component. Nevertheless, this difference did not reach statistical significance (P = .06).
Contrary to the researchers’ expectations, the analysis also revealed that intervention length did not moderate the association between psychosocial interventions and immune system function (P = .93).
With respect to the type of immune marker studied, the meta-analysis found that psychosocial interventions had significantly different associations with the various immune markers studied. Of the seven immune outcomes investigated, only proinflammatory cytokine or marker levels (33 studies; P < .001) and immune cell counts (27 studies; P < .001) were significantly associated with the psychosocial interventions examined.
and were robust across age, sex, and intervention duration.
These results suggest that psychosocial interventions – particularly CBT and multiple or combined psychotherapeutic modalities – may play an important role in improving immune-related health outcomes.
Such interventions may not only be effective, they may also prove to be affordable alternatives to current therapeutic options. The mean length of a CBT intervention in the meta-analysis was 10.4 weeks, which the investigators equated with a total cost of $1,560 per patient.
“By comparison, the cost of using infliximab to reduce inflammation in persons with an autoimmune disorder is approximately $25,000 per patient per year,” they wrote.
“The results suggest the possibility that psychotherapy may be helpful for reducing inflammation and improving immune-related health in certain circumstances,” Dr. Slavich concluded. “However, the studies that we examined differed in terms of their quality, and we did not examine health outcomes in the present investigation.
“Therefore, more research needs to be done to determine how the present findings might be translated into treatment options or public policy.”
A path to better health
In an accompanying editorial, Veronika Engert, PhD, Joshua A. Grant, PhD, and Bernhard Strauss, PhD, noted that although infectious disease was once the primary cause of death in society, it has been supplanted by other complex and chronic illnesses, which often do not follow simple cause-and-effect associations.
“Rather,” they wrote, “these illnesses develop from a complex milieu of biological, psychological, and social factors that may also influence the disease progress and its prognosis. Against this backdrop, the meta-analysis by Shields and colleagues is an important confirmation of the biopsychosocial model.”
The editorialists explained that recent psychophysiological, neurobiological, and epigenetic research offers a glimpse into the relationship between psychological and social factors in pathogenesis. Nevertheless, the authors noted that a comprehensive examination of the potential effects of psychosocial interventions on immune parameters in various physical health conditions has been lacking.
“The evidence provided by Shields et al. is exactly what is needed to more fully shift treatment from an illness-centered to a patient-centered approach,” they wrote. “To that end, this meta-analysis may serve as a guide for policy makers aiming to improve immune-associated health.”
The research was supported by a Society in Science–Branco Weiss Fellowship, Brain and Behavior Research, and the National Institutes of Health. Dr. Slavich, Dr. Engert, Dr. Grant, and Dr. Strauss have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Psychosocial interventions, particularly cognitive-behavioral therapy (CBT), are associated with enhanced immune system function, new research suggests.
Results of a systematic review and meta-analysis that included 56 randomized controlled trials and more than 4,000 participants showed that over time, psychosocial interventions appeared to augment beneficial immune system function while concurrently decreasing harmful immune system function in comparison with control conditions.
“These associations were most reliable for cognitive-behavioral therapy and multiple or combined interventions and for studies that assessed proinflammatory cytokines or markers, which are key indicators of inflammation in the body,” study investigator George M. Slavich, PhD, said in an interview.
“The analysis helps address the question of which types of psychosocial interventions are most consistently associated with changes in immune system function, under what conditions, and for whom. This knowledge could, in turn, be used to inform research efforts and public policy aimed at using psychosocial interventions to improve immune-related health outcomes,” added Dr. Slavich, director of the Laboratory for Stress Assessment and Research, University of California, Los Angeles.
The study was published online June 3 in JAMA Psychiatry.
Link to serious physical, mental illnesses
There is substantial evidence that the immune system plays a role in a variety of mental and physical health problems. Such problems include anxiety disorders, depression, suicide, schizophrenia, cardiovascular disease, autoimmune disorders, and neurodegenerative diseases. It has been recently suggested that more than half of all deaths worldwide are attributable to inflammation-related conditions.
Although pharmacologic interventions can play a role in addressing inflammation, they are not without drawbacks, most notably, cost and adverse side effects.
The World Health Organization, the National Academy of Medicine, the National Institutes of Health, and other groups have emphasized the importance of addressing global disease burden through psychosocial interventions when possible.
Such recommendations are supported by scientific evidence. Previous research has shown that immune system processes are influenced by a variety of social, neurocognitive, and behavioral factors.
Given such findings, researchers have examined the effects of interventions that reduce stress or bolster psychological resources on immune system function.
However, such research has yielded conflicting findings. Some studies show that psychosocial interventions clearly enhance immunity, whereas others do not.
In addition, questions remain regarding which types of interventions reliably improve immune system function, under what conditions, and for whom.
“Research has shown that psychological factors – such as life stress, negative emotions, and social support – are associated with changes in immune system function,” Dr. Slavich noted.
“In addition, there is growing appreciation that immune system processes involved in inflammation may contribute to peoples’ risk for several major mental and physical health problems, including anxiety disorders, depression, heart disease, and autoimmune and neurodegenerative disorders.”
First study of its kind
To shed light on these potential links, the researchers conducted what they believe is the first systematic review and meta-analysis of randomized clinical trials of the effects of psychosocial interventions on immune system outcomes.
As part of the review, Dr. Slavich and colleagues estimated the associations between eight psychosocial interventions and seven markers of immune system function.
The eight psychosocial interventions were behavior therapy, cognitive therapy, CBT, CBT plus additive treatment or mode of delivery, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation.
The seven immune outcomes that might be influenced by these interventions are proinflammatory cytokines and markers, anti-inflammatory cytokines, antibodies, immune cell counts, natural killer cell activity, viral load, and other immune outcomes.
The researchers also examined nine potential factors that might moderate the associations between psychosocial interventions and immune system function.
They searched a variety of databases for all relevant randomized controlled trials published through Dec. 31, 2018. Studies were eligible for inclusion if they included a psychosocial intervention and immune outcome, as well as preintervention and postintervention immunologic assessments.
The researchers identified 4,621 studies. Of these studies, 62 were eligible for inclusion; 56, which included 4,060 patients, were included in the final meta-analysis.
Results showed that psychosocial interventions were associated with enhanced immune system function (P < .001). There was relatively low heterogeneity between studies in these effect sizes, which, the investigators said, indicates that the association was relatively consistent across studies and conditions.
The meta-analysis showed that individuals who were assigned to a psychosocial intervention condition demonstrated a 14.7% improvement (95% confidence interval [CI], 5.7%–23.8%) in beneficial immune system function compared with their counterparts who were assigned to a control condition.
Similarly, participants who received psychosocial interventions demonstrated an 18.0% decrease (95% CI, 7.2%–28.8%) in harmful immune system function over time.
A standout
Regarding the effect of the type of intervention on the association, only CBT (31 studies; P < .001) and multiple or combined interventions (seven studies; P = .01) were significantly associated with changes in immune system outcomes.
The analysis also found that interventions that included a group component were more consistently associated with enhanced immune function than were those that did not include a group component. Nevertheless, this difference did not reach statistical significance (P = .06).
Contrary to the researchers’ expectations, the analysis also revealed that intervention length did not moderate the association between psychosocial interventions and immune system function (P = .93).
With respect to the type of immune marker studied, the meta-analysis found that psychosocial interventions had significantly different associations with the various immune markers studied. Of the seven immune outcomes investigated, only proinflammatory cytokine or marker levels (33 studies; P < .001) and immune cell counts (27 studies; P < .001) were significantly associated with the psychosocial interventions examined.
and were robust across age, sex, and intervention duration.
These results suggest that psychosocial interventions – particularly CBT and multiple or combined psychotherapeutic modalities – may play an important role in improving immune-related health outcomes.
Such interventions may not only be effective, they may also prove to be affordable alternatives to current therapeutic options. The mean length of a CBT intervention in the meta-analysis was 10.4 weeks, which the investigators equated with a total cost of $1,560 per patient.
“By comparison, the cost of using infliximab to reduce inflammation in persons with an autoimmune disorder is approximately $25,000 per patient per year,” they wrote.
“The results suggest the possibility that psychotherapy may be helpful for reducing inflammation and improving immune-related health in certain circumstances,” Dr. Slavich concluded. “However, the studies that we examined differed in terms of their quality, and we did not examine health outcomes in the present investigation.
“Therefore, more research needs to be done to determine how the present findings might be translated into treatment options or public policy.”
A path to better health
In an accompanying editorial, Veronika Engert, PhD, Joshua A. Grant, PhD, and Bernhard Strauss, PhD, noted that although infectious disease was once the primary cause of death in society, it has been supplanted by other complex and chronic illnesses, which often do not follow simple cause-and-effect associations.
“Rather,” they wrote, “these illnesses develop from a complex milieu of biological, psychological, and social factors that may also influence the disease progress and its prognosis. Against this backdrop, the meta-analysis by Shields and colleagues is an important confirmation of the biopsychosocial model.”
The editorialists explained that recent psychophysiological, neurobiological, and epigenetic research offers a glimpse into the relationship between psychological and social factors in pathogenesis. Nevertheless, the authors noted that a comprehensive examination of the potential effects of psychosocial interventions on immune parameters in various physical health conditions has been lacking.
“The evidence provided by Shields et al. is exactly what is needed to more fully shift treatment from an illness-centered to a patient-centered approach,” they wrote. “To that end, this meta-analysis may serve as a guide for policy makers aiming to improve immune-associated health.”
The research was supported by a Society in Science–Branco Weiss Fellowship, Brain and Behavior Research, and the National Institutes of Health. Dr. Slavich, Dr. Engert, Dr. Grant, and Dr. Strauss have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Psychosocial interventions, particularly cognitive-behavioral therapy (CBT), are associated with enhanced immune system function, new research suggests.
Results of a systematic review and meta-analysis that included 56 randomized controlled trials and more than 4,000 participants showed that over time, psychosocial interventions appeared to augment beneficial immune system function while concurrently decreasing harmful immune system function in comparison with control conditions.
“These associations were most reliable for cognitive-behavioral therapy and multiple or combined interventions and for studies that assessed proinflammatory cytokines or markers, which are key indicators of inflammation in the body,” study investigator George M. Slavich, PhD, said in an interview.
“The analysis helps address the question of which types of psychosocial interventions are most consistently associated with changes in immune system function, under what conditions, and for whom. This knowledge could, in turn, be used to inform research efforts and public policy aimed at using psychosocial interventions to improve immune-related health outcomes,” added Dr. Slavich, director of the Laboratory for Stress Assessment and Research, University of California, Los Angeles.
The study was published online June 3 in JAMA Psychiatry.
Link to serious physical, mental illnesses
There is substantial evidence that the immune system plays a role in a variety of mental and physical health problems. Such problems include anxiety disorders, depression, suicide, schizophrenia, cardiovascular disease, autoimmune disorders, and neurodegenerative diseases. It has been recently suggested that more than half of all deaths worldwide are attributable to inflammation-related conditions.
Although pharmacologic interventions can play a role in addressing inflammation, they are not without drawbacks, most notably, cost and adverse side effects.
The World Health Organization, the National Academy of Medicine, the National Institutes of Health, and other groups have emphasized the importance of addressing global disease burden through psychosocial interventions when possible.
Such recommendations are supported by scientific evidence. Previous research has shown that immune system processes are influenced by a variety of social, neurocognitive, and behavioral factors.
Given such findings, researchers have examined the effects of interventions that reduce stress or bolster psychological resources on immune system function.
However, such research has yielded conflicting findings. Some studies show that psychosocial interventions clearly enhance immunity, whereas others do not.
In addition, questions remain regarding which types of interventions reliably improve immune system function, under what conditions, and for whom.
“Research has shown that psychological factors – such as life stress, negative emotions, and social support – are associated with changes in immune system function,” Dr. Slavich noted.
“In addition, there is growing appreciation that immune system processes involved in inflammation may contribute to peoples’ risk for several major mental and physical health problems, including anxiety disorders, depression, heart disease, and autoimmune and neurodegenerative disorders.”
First study of its kind
To shed light on these potential links, the researchers conducted what they believe is the first systematic review and meta-analysis of randomized clinical trials of the effects of psychosocial interventions on immune system outcomes.
As part of the review, Dr. Slavich and colleagues estimated the associations between eight psychosocial interventions and seven markers of immune system function.
The eight psychosocial interventions were behavior therapy, cognitive therapy, CBT, CBT plus additive treatment or mode of delivery, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation.
The seven immune outcomes that might be influenced by these interventions are proinflammatory cytokines and markers, anti-inflammatory cytokines, antibodies, immune cell counts, natural killer cell activity, viral load, and other immune outcomes.
The researchers also examined nine potential factors that might moderate the associations between psychosocial interventions and immune system function.
They searched a variety of databases for all relevant randomized controlled trials published through Dec. 31, 2018. Studies were eligible for inclusion if they included a psychosocial intervention and immune outcome, as well as preintervention and postintervention immunologic assessments.
The researchers identified 4,621 studies. Of these studies, 62 were eligible for inclusion; 56, which included 4,060 patients, were included in the final meta-analysis.
Results showed that psychosocial interventions were associated with enhanced immune system function (P < .001). There was relatively low heterogeneity between studies in these effect sizes, which, the investigators said, indicates that the association was relatively consistent across studies and conditions.
The meta-analysis showed that individuals who were assigned to a psychosocial intervention condition demonstrated a 14.7% improvement (95% confidence interval [CI], 5.7%–23.8%) in beneficial immune system function compared with their counterparts who were assigned to a control condition.
Similarly, participants who received psychosocial interventions demonstrated an 18.0% decrease (95% CI, 7.2%–28.8%) in harmful immune system function over time.
A standout
Regarding the effect of the type of intervention on the association, only CBT (31 studies; P < .001) and multiple or combined interventions (seven studies; P = .01) were significantly associated with changes in immune system outcomes.
The analysis also found that interventions that included a group component were more consistently associated with enhanced immune function than were those that did not include a group component. Nevertheless, this difference did not reach statistical significance (P = .06).
Contrary to the researchers’ expectations, the analysis also revealed that intervention length did not moderate the association between psychosocial interventions and immune system function (P = .93).
With respect to the type of immune marker studied, the meta-analysis found that psychosocial interventions had significantly different associations with the various immune markers studied. Of the seven immune outcomes investigated, only proinflammatory cytokine or marker levels (33 studies; P < .001) and immune cell counts (27 studies; P < .001) were significantly associated with the psychosocial interventions examined.
and were robust across age, sex, and intervention duration.
These results suggest that psychosocial interventions – particularly CBT and multiple or combined psychotherapeutic modalities – may play an important role in improving immune-related health outcomes.
Such interventions may not only be effective, they may also prove to be affordable alternatives to current therapeutic options. The mean length of a CBT intervention in the meta-analysis was 10.4 weeks, which the investigators equated with a total cost of $1,560 per patient.
“By comparison, the cost of using infliximab to reduce inflammation in persons with an autoimmune disorder is approximately $25,000 per patient per year,” they wrote.
“The results suggest the possibility that psychotherapy may be helpful for reducing inflammation and improving immune-related health in certain circumstances,” Dr. Slavich concluded. “However, the studies that we examined differed in terms of their quality, and we did not examine health outcomes in the present investigation.
“Therefore, more research needs to be done to determine how the present findings might be translated into treatment options or public policy.”
A path to better health
In an accompanying editorial, Veronika Engert, PhD, Joshua A. Grant, PhD, and Bernhard Strauss, PhD, noted that although infectious disease was once the primary cause of death in society, it has been supplanted by other complex and chronic illnesses, which often do not follow simple cause-and-effect associations.
“Rather,” they wrote, “these illnesses develop from a complex milieu of biological, psychological, and social factors that may also influence the disease progress and its prognosis. Against this backdrop, the meta-analysis by Shields and colleagues is an important confirmation of the biopsychosocial model.”
The editorialists explained that recent psychophysiological, neurobiological, and epigenetic research offers a glimpse into the relationship between psychological and social factors in pathogenesis. Nevertheless, the authors noted that a comprehensive examination of the potential effects of psychosocial interventions on immune parameters in various physical health conditions has been lacking.
“The evidence provided by Shields et al. is exactly what is needed to more fully shift treatment from an illness-centered to a patient-centered approach,” they wrote. “To that end, this meta-analysis may serve as a guide for policy makers aiming to improve immune-associated health.”
The research was supported by a Society in Science–Branco Weiss Fellowship, Brain and Behavior Research, and the National Institutes of Health. Dr. Slavich, Dr. Engert, Dr. Grant, and Dr. Strauss have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
For COVID-19 plus diabetes, glycemic control tops treatment list
Optimizing glycemic control “is the key to overall treatment in people with diabetes and COVID-19,” said Antonio Ceriello, MD, during a June 5 webinar sponsored by Harvard Medical School, Boston.
Dr. Ceriello, a research consultant with the Italian Ministry of Health, IRCCS Multi-Medica, Milan, highlighted a recent study that examined the association of blood glucose control and outcomes in COVID-19 patients with preexisting type 2 diabetes.
Among 7,000 cases of COVID-19, type 2 diabetes correlated with a higher death rate. However, those with well-controlled blood glucose (upper limit ≤10 mmol/L) had a survival rate of 98.9%, compared with just 11% among those with poorly controlled blood glucose (upper limit >10 mmol/L), a reduction in risk of 86% (adjusted hazard ratio, 0.14; Cell Metab. 2020 May 1. doi: 10.1016/j.cmet.2020.04.021).
Clinicians should also consider the possible side effects of hypoglycemic agents in the evolution of this disease. This is true of all patients, not just diabetes patients, Dr. Ceriello said. “We have data showing that ... hyperglycemia contributes directly to worsening the prognosis of COVID-19 independent of the presence of diabetes.”
One study found that the glycosylation of ACE-2 played an important role in allowing cellular entry of the virus (Am J Physiol Endocrinol Metab. 2020 Mar 31;318:E736-41). “This is something that could be related to hyperglycemia,” he added.
Another risk factor is thrombosis, a clear contributor to death rates in COVID-19. Research on thrombosis incidence in COVID-19 patients with diabetes reported higher levels of D-dimer levels in people with diabetes, especially among those who couldn’t manage their disease.
Tying all of these factors together, Dr. Ceriello discussed how ACE-2 glycosylation, in combination with other factors in SARS-CoV-2 infection, could lead to hyperglycemia, thrombosis, and subsequently multiorgan damage in diabetes patients.
Other research has associated higher HbA1c levels (mean HbA1c, 7.5%) with higher mortality risk in COVID-19 patients, said another speaker, Linong Ji, MD, director for endocrinology and metabolism at Peking University People’s Hospital, Beijing, and director of Peking University’s Diabetes Center. Proper guidance is key to ensuring early detection of hyperglycemic crisis in people with diabetes, advised Dr. Ji.
Global management of diabetes in SARS-CoV-2 patients is “quite challenging,” given that most patients don’t have their diabetes under control, said host and moderator A. Enrique Caballero, MD, an endocrinologist/investigator in the division of endocrinology, diabetes, and hypertension and division of global health equity at Brigham and Women’s Hospital, Boston. “They are not meeting treatment targets for cholesterol or glucose control. So we’re not managing optimal care. And now on top of this, we have COVID-19.”
Optimizing glycemic control “is the key to overall treatment in people with diabetes and COVID-19,” said Antonio Ceriello, MD, during a June 5 webinar sponsored by Harvard Medical School, Boston.
Dr. Ceriello, a research consultant with the Italian Ministry of Health, IRCCS Multi-Medica, Milan, highlighted a recent study that examined the association of blood glucose control and outcomes in COVID-19 patients with preexisting type 2 diabetes.
Among 7,000 cases of COVID-19, type 2 diabetes correlated with a higher death rate. However, those with well-controlled blood glucose (upper limit ≤10 mmol/L) had a survival rate of 98.9%, compared with just 11% among those with poorly controlled blood glucose (upper limit >10 mmol/L), a reduction in risk of 86% (adjusted hazard ratio, 0.14; Cell Metab. 2020 May 1. doi: 10.1016/j.cmet.2020.04.021).
Clinicians should also consider the possible side effects of hypoglycemic agents in the evolution of this disease. This is true of all patients, not just diabetes patients, Dr. Ceriello said. “We have data showing that ... hyperglycemia contributes directly to worsening the prognosis of COVID-19 independent of the presence of diabetes.”
One study found that the glycosylation of ACE-2 played an important role in allowing cellular entry of the virus (Am J Physiol Endocrinol Metab. 2020 Mar 31;318:E736-41). “This is something that could be related to hyperglycemia,” he added.
Another risk factor is thrombosis, a clear contributor to death rates in COVID-19. Research on thrombosis incidence in COVID-19 patients with diabetes reported higher levels of D-dimer levels in people with diabetes, especially among those who couldn’t manage their disease.
Tying all of these factors together, Dr. Ceriello discussed how ACE-2 glycosylation, in combination with other factors in SARS-CoV-2 infection, could lead to hyperglycemia, thrombosis, and subsequently multiorgan damage in diabetes patients.
Other research has associated higher HbA1c levels (mean HbA1c, 7.5%) with higher mortality risk in COVID-19 patients, said another speaker, Linong Ji, MD, director for endocrinology and metabolism at Peking University People’s Hospital, Beijing, and director of Peking University’s Diabetes Center. Proper guidance is key to ensuring early detection of hyperglycemic crisis in people with diabetes, advised Dr. Ji.
Global management of diabetes in SARS-CoV-2 patients is “quite challenging,” given that most patients don’t have their diabetes under control, said host and moderator A. Enrique Caballero, MD, an endocrinologist/investigator in the division of endocrinology, diabetes, and hypertension and division of global health equity at Brigham and Women’s Hospital, Boston. “They are not meeting treatment targets for cholesterol or glucose control. So we’re not managing optimal care. And now on top of this, we have COVID-19.”
Optimizing glycemic control “is the key to overall treatment in people with diabetes and COVID-19,” said Antonio Ceriello, MD, during a June 5 webinar sponsored by Harvard Medical School, Boston.
Dr. Ceriello, a research consultant with the Italian Ministry of Health, IRCCS Multi-Medica, Milan, highlighted a recent study that examined the association of blood glucose control and outcomes in COVID-19 patients with preexisting type 2 diabetes.
Among 7,000 cases of COVID-19, type 2 diabetes correlated with a higher death rate. However, those with well-controlled blood glucose (upper limit ≤10 mmol/L) had a survival rate of 98.9%, compared with just 11% among those with poorly controlled blood glucose (upper limit >10 mmol/L), a reduction in risk of 86% (adjusted hazard ratio, 0.14; Cell Metab. 2020 May 1. doi: 10.1016/j.cmet.2020.04.021).
Clinicians should also consider the possible side effects of hypoglycemic agents in the evolution of this disease. This is true of all patients, not just diabetes patients, Dr. Ceriello said. “We have data showing that ... hyperglycemia contributes directly to worsening the prognosis of COVID-19 independent of the presence of diabetes.”
One study found that the glycosylation of ACE-2 played an important role in allowing cellular entry of the virus (Am J Physiol Endocrinol Metab. 2020 Mar 31;318:E736-41). “This is something that could be related to hyperglycemia,” he added.
Another risk factor is thrombosis, a clear contributor to death rates in COVID-19. Research on thrombosis incidence in COVID-19 patients with diabetes reported higher levels of D-dimer levels in people with diabetes, especially among those who couldn’t manage their disease.
Tying all of these factors together, Dr. Ceriello discussed how ACE-2 glycosylation, in combination with other factors in SARS-CoV-2 infection, could lead to hyperglycemia, thrombosis, and subsequently multiorgan damage in diabetes patients.
Other research has associated higher HbA1c levels (mean HbA1c, 7.5%) with higher mortality risk in COVID-19 patients, said another speaker, Linong Ji, MD, director for endocrinology and metabolism at Peking University People’s Hospital, Beijing, and director of Peking University’s Diabetes Center. Proper guidance is key to ensuring early detection of hyperglycemic crisis in people with diabetes, advised Dr. Ji.
Global management of diabetes in SARS-CoV-2 patients is “quite challenging,” given that most patients don’t have their diabetes under control, said host and moderator A. Enrique Caballero, MD, an endocrinologist/investigator in the division of endocrinology, diabetes, and hypertension and division of global health equity at Brigham and Women’s Hospital, Boston. “They are not meeting treatment targets for cholesterol or glucose control. So we’re not managing optimal care. And now on top of this, we have COVID-19.”
Secondary infections common in COVID-19, implications unclear
but at this point, most pulmonologists aren’t sure what to make of this understudied phenomenon.
“We really do not understand the implications of secondary infections on outcomes in COVID-19 patients,” David L. Bowton, MD, FCCP, said in an interview. “In most early reports the incidence of secondary infections was much higher in patients dying from COVID-19, compared to survivors, but it isn’t clear whether this indicates that the secondary infection itself led to excess mortality or was more a marker of the severity of the COVID-19 infection.
“Further, details of the diagnostic criteria used, the microbiology, and the appropriateness of treatment of these secondary infections has not generally been included in these reports,” added Dr. Bowton, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C.
One such early retrospective cohort study included 191 COVID-19 patients in Wuhan, China. Of the 54 who died in hospital, half had secondary bacterial lung infections (Lancet. 2020 Mar 28;395[10229]:1054-62). That comes as no surprise to U.S. pulmonologists, who learned back in their training that many deaths during the so-called Spanish influenza epidemic of 1918-1920 were actually caused by secondary pneumonia involving Staphylococcus aureus, commented Daniel L. Ouellette, MD, FCCP, associate director of medical critical care at Henry Ford Hospital, Detroit.
“Critically ill patients are highly susceptible to secondary infections regardless of the cause of the patient’s critical illness,” he noted in an interview. “Recent reports of secondary infections in patients critically ill from COVID-19 are interesting but should be considered in this context. To confirm that COVID-19 patients have a different, or increased, risk of infection at specific sites or from specific agents will require careful study.”
That will be no easy matter given the challenges of obtaining bronchoalveolar lavage samples in mechanically ventilated patients with COVID-19, according to Eric J. Gartman, MD, FCCP, a pulmonologist at Brown University, Providence, R.I., and director of the pulmonary function laboratory at the Providence Veterans Affairs Medical Center.
“Unfortunately, many of the invasive modalities that are typically employed to help diagnose secondary infections in critically ill patients are being severely limited or even prohibited in COVID-19 patients due to infection control measures,” he said. As a result, Dr. Gartman noted, intensivists are often resorting to empiric broad-spectrum antimicrobial therapy in patients with severe COVID-19 and are without ready access to the bacterial cultures which might otherwise permit later treatment de-escalation or retargeting.
Among the myriad areas of uncertainty regarding COVID-19 is the proportion of bacterial coinfections that are hospital acquired. Given the lengthy duration of invasive mechanical ventilation in patients with severe COVID-19 – a mean of 9.1 days in the United Kingdom – the chances of hospital-acquired infection are likely substantial. Moreover, a recent single-center U.K. study involving microbiologic testing in 195 consecutive patients newly hospitalized for COVID-19 reported that community-acquired bacterial infection was uncommon: Just 4% of patients had pneumococcal coinfection at hospital admission, and S. aureus wasn’t detected in anyone (Lancet. 2020;1:362. doi:10.1016/S2666-5247[20]30036-7). French investigators have reported detecting putative invasive pulmonary aspergillosis in nearly one-third of a small series of 27 consecutive mechanically ventilated COVID-19 patients (Lancet Resp Med. 2020; 8[6]:e48-9). Dr. Gartman said the diagnostic testing methods utilized in this and similar reports haven’t been prospectively validated in COVID-19. The testing methods may not indicate invasive Aspergillus infection in this population with a high degree of certainty, since they have previously been performed mainly in patients with hematologic malignancies.
“Although there is nothing definitive regarding this research, as a practicing critical care doctor one should respect these findings and consider this secondary diagnosis if the supporting clinical data is positive, especially given that the mortality risk in this population is high,” he advised.
Dr. Bowton said that he and his fellow intensivists at Wake Forest Baptist Health don’t routinely screen COVID-19 patients for secondary bacterial or fungal infections. And in talking with colleagues around the country, it’s his impression that most have similarly elected not to do so.
“However, our clinical index of suspicion for secondary infections is heightened and, if triggered, will initiate a search for and treatment of these secondary infections,” Dr. Bowton said.
but at this point, most pulmonologists aren’t sure what to make of this understudied phenomenon.
“We really do not understand the implications of secondary infections on outcomes in COVID-19 patients,” David L. Bowton, MD, FCCP, said in an interview. “In most early reports the incidence of secondary infections was much higher in patients dying from COVID-19, compared to survivors, but it isn’t clear whether this indicates that the secondary infection itself led to excess mortality or was more a marker of the severity of the COVID-19 infection.
“Further, details of the diagnostic criteria used, the microbiology, and the appropriateness of treatment of these secondary infections has not generally been included in these reports,” added Dr. Bowton, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C.
One such early retrospective cohort study included 191 COVID-19 patients in Wuhan, China. Of the 54 who died in hospital, half had secondary bacterial lung infections (Lancet. 2020 Mar 28;395[10229]:1054-62). That comes as no surprise to U.S. pulmonologists, who learned back in their training that many deaths during the so-called Spanish influenza epidemic of 1918-1920 were actually caused by secondary pneumonia involving Staphylococcus aureus, commented Daniel L. Ouellette, MD, FCCP, associate director of medical critical care at Henry Ford Hospital, Detroit.
“Critically ill patients are highly susceptible to secondary infections regardless of the cause of the patient’s critical illness,” he noted in an interview. “Recent reports of secondary infections in patients critically ill from COVID-19 are interesting but should be considered in this context. To confirm that COVID-19 patients have a different, or increased, risk of infection at specific sites or from specific agents will require careful study.”
That will be no easy matter given the challenges of obtaining bronchoalveolar lavage samples in mechanically ventilated patients with COVID-19, according to Eric J. Gartman, MD, FCCP, a pulmonologist at Brown University, Providence, R.I., and director of the pulmonary function laboratory at the Providence Veterans Affairs Medical Center.
“Unfortunately, many of the invasive modalities that are typically employed to help diagnose secondary infections in critically ill patients are being severely limited or even prohibited in COVID-19 patients due to infection control measures,” he said. As a result, Dr. Gartman noted, intensivists are often resorting to empiric broad-spectrum antimicrobial therapy in patients with severe COVID-19 and are without ready access to the bacterial cultures which might otherwise permit later treatment de-escalation or retargeting.
Among the myriad areas of uncertainty regarding COVID-19 is the proportion of bacterial coinfections that are hospital acquired. Given the lengthy duration of invasive mechanical ventilation in patients with severe COVID-19 – a mean of 9.1 days in the United Kingdom – the chances of hospital-acquired infection are likely substantial. Moreover, a recent single-center U.K. study involving microbiologic testing in 195 consecutive patients newly hospitalized for COVID-19 reported that community-acquired bacterial infection was uncommon: Just 4% of patients had pneumococcal coinfection at hospital admission, and S. aureus wasn’t detected in anyone (Lancet. 2020;1:362. doi:10.1016/S2666-5247[20]30036-7). French investigators have reported detecting putative invasive pulmonary aspergillosis in nearly one-third of a small series of 27 consecutive mechanically ventilated COVID-19 patients (Lancet Resp Med. 2020; 8[6]:e48-9). Dr. Gartman said the diagnostic testing methods utilized in this and similar reports haven’t been prospectively validated in COVID-19. The testing methods may not indicate invasive Aspergillus infection in this population with a high degree of certainty, since they have previously been performed mainly in patients with hematologic malignancies.
“Although there is nothing definitive regarding this research, as a practicing critical care doctor one should respect these findings and consider this secondary diagnosis if the supporting clinical data is positive, especially given that the mortality risk in this population is high,” he advised.
Dr. Bowton said that he and his fellow intensivists at Wake Forest Baptist Health don’t routinely screen COVID-19 patients for secondary bacterial or fungal infections. And in talking with colleagues around the country, it’s his impression that most have similarly elected not to do so.
“However, our clinical index of suspicion for secondary infections is heightened and, if triggered, will initiate a search for and treatment of these secondary infections,” Dr. Bowton said.
but at this point, most pulmonologists aren’t sure what to make of this understudied phenomenon.
“We really do not understand the implications of secondary infections on outcomes in COVID-19 patients,” David L. Bowton, MD, FCCP, said in an interview. “In most early reports the incidence of secondary infections was much higher in patients dying from COVID-19, compared to survivors, but it isn’t clear whether this indicates that the secondary infection itself led to excess mortality or was more a marker of the severity of the COVID-19 infection.
“Further, details of the diagnostic criteria used, the microbiology, and the appropriateness of treatment of these secondary infections has not generally been included in these reports,” added Dr. Bowton, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C.
One such early retrospective cohort study included 191 COVID-19 patients in Wuhan, China. Of the 54 who died in hospital, half had secondary bacterial lung infections (Lancet. 2020 Mar 28;395[10229]:1054-62). That comes as no surprise to U.S. pulmonologists, who learned back in their training that many deaths during the so-called Spanish influenza epidemic of 1918-1920 were actually caused by secondary pneumonia involving Staphylococcus aureus, commented Daniel L. Ouellette, MD, FCCP, associate director of medical critical care at Henry Ford Hospital, Detroit.
“Critically ill patients are highly susceptible to secondary infections regardless of the cause of the patient’s critical illness,” he noted in an interview. “Recent reports of secondary infections in patients critically ill from COVID-19 are interesting but should be considered in this context. To confirm that COVID-19 patients have a different, or increased, risk of infection at specific sites or from specific agents will require careful study.”
That will be no easy matter given the challenges of obtaining bronchoalveolar lavage samples in mechanically ventilated patients with COVID-19, according to Eric J. Gartman, MD, FCCP, a pulmonologist at Brown University, Providence, R.I., and director of the pulmonary function laboratory at the Providence Veterans Affairs Medical Center.
“Unfortunately, many of the invasive modalities that are typically employed to help diagnose secondary infections in critically ill patients are being severely limited or even prohibited in COVID-19 patients due to infection control measures,” he said. As a result, Dr. Gartman noted, intensivists are often resorting to empiric broad-spectrum antimicrobial therapy in patients with severe COVID-19 and are without ready access to the bacterial cultures which might otherwise permit later treatment de-escalation or retargeting.
Among the myriad areas of uncertainty regarding COVID-19 is the proportion of bacterial coinfections that are hospital acquired. Given the lengthy duration of invasive mechanical ventilation in patients with severe COVID-19 – a mean of 9.1 days in the United Kingdom – the chances of hospital-acquired infection are likely substantial. Moreover, a recent single-center U.K. study involving microbiologic testing in 195 consecutive patients newly hospitalized for COVID-19 reported that community-acquired bacterial infection was uncommon: Just 4% of patients had pneumococcal coinfection at hospital admission, and S. aureus wasn’t detected in anyone (Lancet. 2020;1:362. doi:10.1016/S2666-5247[20]30036-7). French investigators have reported detecting putative invasive pulmonary aspergillosis in nearly one-third of a small series of 27 consecutive mechanically ventilated COVID-19 patients (Lancet Resp Med. 2020; 8[6]:e48-9). Dr. Gartman said the diagnostic testing methods utilized in this and similar reports haven’t been prospectively validated in COVID-19. The testing methods may not indicate invasive Aspergillus infection in this population with a high degree of certainty, since they have previously been performed mainly in patients with hematologic malignancies.
“Although there is nothing definitive regarding this research, as a practicing critical care doctor one should respect these findings and consider this secondary diagnosis if the supporting clinical data is positive, especially given that the mortality risk in this population is high,” he advised.
Dr. Bowton said that he and his fellow intensivists at Wake Forest Baptist Health don’t routinely screen COVID-19 patients for secondary bacterial or fungal infections. And in talking with colleagues around the country, it’s his impression that most have similarly elected not to do so.
“However, our clinical index of suspicion for secondary infections is heightened and, if triggered, will initiate a search for and treatment of these secondary infections,” Dr. Bowton said.
CV outcomes of SGLT2 inhibitors and GLP-1 agonists compared in real-world study
Drug adherence, healthcare use, medical costs, and heart failure rates were better among patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor than a glucagon-like peptide 1 (GLP-1) receptor agonist in a real-world, observational study.
Composite cardiovascular (CV) outcomes were similar between the two drug classes.
Insiya Poonawalla, PhD, a researcher at Humana Healthcare Research, Flower Mound, Texas, reported the study results in an oral presentation on June 12 at the virtual American Diabetes Association (ADA) 80th Scientific Sessions.
The investigators matched more than 10,000 patients with type 2 diabetes — half initiated on an SGLT2 inhibitor and half initiated on a GLP-1 agonist — from the Humana database of insurance claims data.
“These findings suggest potential benefits” of SGLT2 inhibitors, “particularly where risk related to heart failure is an important consideration,” Poonawalla said, but as always, any benefits need to be weighed against any risks.
And “while this study provides a pretty complete and current picture of claims until 2018,” it has limitations inherent to observational data (such as possible errors or omissions in the claims data), she conceded.
Mikhail Kosiborod, MD, invited to comment on the research, said this preliminary study was likely too short and small to definitively demonstrate differences in composite CV outcomes between the two drug classes, but he noted that the overall findings are not unexpected.
And often, the particular CV risk profile of an individual patient will point to one or the other of these drug classes as a best fit, he noted.
Too soon to alter clinical practice
Kosiborod, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said he nevertheless feels “it would be a bit premature to use these findings as a guide to change clinical practice.”
“The study is relatively small in scope and likely underpowered to examine CV outcomes,” he said in an email interview.
Larger population-based studies and ideally head-to-head randomized controlled trials of various type 2 diabetes agents could compare these two drug classes more definitively, he asserted.
In the meantime, safety profiles of both medication classes “have been well established — in tens of thousands of patients in clinical trials and millions of patients prescribed these therapies in clinical practice,” he noted.
In general, the drugs in both classes are well-tolerated and safe for most patients with type 2 diabetes when used appropriately.
“Certainly, patients with type 2 diabetes and established CV disease (or at high risk for CV complications) are ideal candidates for either an SGLT2 inhibitor or a GLP-1 receptor agonist,” Kosiborod said.
“Given the data we have from outcome trials, an SGLT2 inhibitor would be a better initial strategy in a patient with type 2 diabetes and heart failure (especially heart failure with reduced ejection fraction) and/or diabetic kidney disease,” he continued.
On the other hand, “a GLP-1 receptor agonist may be a better initial strategy in a type 2 diabetes patient with (or at very high risk for) atherosclerotic cardiovascular disease (ASCVD), especially if there is concomitant obesity contributing to the disease process.”
Limited comparisons of these two newer drug classes
“Real-world evidence comparing these two therapeutic classes based on CV outcomes is limited,” Poonawalla said at the start of her presentation, and relative treatment persistence, utilization, and cost data are even less well studied.
To investigate this, the researchers identified patients aged 19 to 89 years who were newly prescribed one of these two types of antidiabetic agents during January 1, 2015 through June 30, 2017.
Poonawalla and senior study author Phil Schwab, PhD, research lead, Humana Healthcare Research, Louisville, Kentucky, clarified the study design and findings in an email to this new organization.
The team matched 5507 patients initiated on a GLP-1 agonist with 5507 patients newly prescribed an SGLT2 inhibitor.
Patients were a mean age of 65 years and 53% were women.
More than a third (37%) had established ASCVD, including myocardial infarction (MI) (7.9%) and stroke (9.8%), and 11.5% had heart failure.
About two thirds were receiving metformin and about a third were receiving insulin.
In the GLP-1 agonist group, more than half of patients were prescribed liraglutide (57%), followed by dulaglutide (33%), exenatide, and lixisenatide (two patients).
In the SGLT2 inhibitor group, close to 70% received canagliflozin, about a quarter received empagliflozin, and the rest received dapagliflozin.
During up to 3.5 years of follow-up, a similar percentage of patients in each group had either an MI, stroke, or died (the primary composite CV outcome) (hazard ratio [HR], 0.98; 95% CI, 0.89 - 1.07).
However, more patients in the GLP-1 agonist group had heart failure or died (the secondary composite CV outcome), driven by a higher rate of heart failure in this group.
But after adjusting for time to events there was no significant between-group difference in the secondary composite CV outcome (HR, 1.09; 95% CI, 0.99 - 1.21).
During the 12-months after the initial prescription, patients who were started on a GLP-1 agonist versus an SGLT2 inhibitor had higher mean monthly medical costs, which included hospitalizations, emergency department (ED) visits, and outpatient visits ($904 vs $834; P < .001).
They also had higher pharmacy costs, which covered all drugs ($891 vs $783; P < .001).
And they were more likely to discontinue treatment (HR, 1.15; 95% CI, 1.10 - 1.21), be hospitalized (14.4% vs 11.9%; P < .001), or visit the ED (27.4% vs 23.5%; P < .001).
“Not too surprising” and “somewhat reassuring”
Overall, Kosiborod did not find the results surprising.
Given the sample size and follow-up time, event rates were probably quite low and insufficient to draw firm conclusions about the composite CV outcomes, he reiterated.
However, given the comparable effects of these two drug types on major adverse cardiac events (MACE) in similar patient populations with type 2 diabetes, it is not too surprising that there were no significant differences in these outcomes.
It was also “somewhat reassuring” to see that heart failure rates were lower with SGLT2 inhibitors, “as one would expect,” he said, because these agents “have been shown to significantly reduce the risk of hospitalization for heart failure in multiple outcome trials, whereas GLP-1 receptor agonists’ beneficial CV effects appear to be more limited to MACE reduction.”
The higher rates of discontinuation with GLP-1 receptor agonists “is also not a surprise, since patients experience more gastrointestinal tolerability issues with these agents (mainly nausea),” which can be mitigated in the majority of patients with appropriate education and close follow up — but is not done consistently.
Similarly, “the cost differences are also expected, since GLP-1 receptor agonists tend to be more expensive.”
On the other hand, the higher rates of hospitalizations with GLP-1 agonists compared to SGLT2 inhibitors “requires further exploration and confirmation,” Kosiborod said.
But he suspects this may be due to residual confounding, “since GLP-1 agonists are typically initiated later in the type 2 diabetes treatment algorithm,” so these patients could have lengthier, more difficult-to-manage type 2 diabetes with more comorbidities despite the propensity matching.
Poonawalla and Schwab are employed by Humana. Kosiborod has disclosed research support from AstraZeneca and Boehringer Ingelheim; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and consulting fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi Aventis .
This article first appeared on Medscape.com
Drug adherence, healthcare use, medical costs, and heart failure rates were better among patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor than a glucagon-like peptide 1 (GLP-1) receptor agonist in a real-world, observational study.
Composite cardiovascular (CV) outcomes were similar between the two drug classes.
Insiya Poonawalla, PhD, a researcher at Humana Healthcare Research, Flower Mound, Texas, reported the study results in an oral presentation on June 12 at the virtual American Diabetes Association (ADA) 80th Scientific Sessions.
The investigators matched more than 10,000 patients with type 2 diabetes — half initiated on an SGLT2 inhibitor and half initiated on a GLP-1 agonist — from the Humana database of insurance claims data.
“These findings suggest potential benefits” of SGLT2 inhibitors, “particularly where risk related to heart failure is an important consideration,” Poonawalla said, but as always, any benefits need to be weighed against any risks.
And “while this study provides a pretty complete and current picture of claims until 2018,” it has limitations inherent to observational data (such as possible errors or omissions in the claims data), she conceded.
Mikhail Kosiborod, MD, invited to comment on the research, said this preliminary study was likely too short and small to definitively demonstrate differences in composite CV outcomes between the two drug classes, but he noted that the overall findings are not unexpected.
And often, the particular CV risk profile of an individual patient will point to one or the other of these drug classes as a best fit, he noted.
Too soon to alter clinical practice
Kosiborod, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said he nevertheless feels “it would be a bit premature to use these findings as a guide to change clinical practice.”
“The study is relatively small in scope and likely underpowered to examine CV outcomes,” he said in an email interview.
Larger population-based studies and ideally head-to-head randomized controlled trials of various type 2 diabetes agents could compare these two drug classes more definitively, he asserted.
In the meantime, safety profiles of both medication classes “have been well established — in tens of thousands of patients in clinical trials and millions of patients prescribed these therapies in clinical practice,” he noted.
In general, the drugs in both classes are well-tolerated and safe for most patients with type 2 diabetes when used appropriately.
“Certainly, patients with type 2 diabetes and established CV disease (or at high risk for CV complications) are ideal candidates for either an SGLT2 inhibitor or a GLP-1 receptor agonist,” Kosiborod said.
“Given the data we have from outcome trials, an SGLT2 inhibitor would be a better initial strategy in a patient with type 2 diabetes and heart failure (especially heart failure with reduced ejection fraction) and/or diabetic kidney disease,” he continued.
On the other hand, “a GLP-1 receptor agonist may be a better initial strategy in a type 2 diabetes patient with (or at very high risk for) atherosclerotic cardiovascular disease (ASCVD), especially if there is concomitant obesity contributing to the disease process.”
Limited comparisons of these two newer drug classes
“Real-world evidence comparing these two therapeutic classes based on CV outcomes is limited,” Poonawalla said at the start of her presentation, and relative treatment persistence, utilization, and cost data are even less well studied.
To investigate this, the researchers identified patients aged 19 to 89 years who were newly prescribed one of these two types of antidiabetic agents during January 1, 2015 through June 30, 2017.
Poonawalla and senior study author Phil Schwab, PhD, research lead, Humana Healthcare Research, Louisville, Kentucky, clarified the study design and findings in an email to this new organization.
The team matched 5507 patients initiated on a GLP-1 agonist with 5507 patients newly prescribed an SGLT2 inhibitor.
Patients were a mean age of 65 years and 53% were women.
More than a third (37%) had established ASCVD, including myocardial infarction (MI) (7.9%) and stroke (9.8%), and 11.5% had heart failure.
About two thirds were receiving metformin and about a third were receiving insulin.
In the GLP-1 agonist group, more than half of patients were prescribed liraglutide (57%), followed by dulaglutide (33%), exenatide, and lixisenatide (two patients).
In the SGLT2 inhibitor group, close to 70% received canagliflozin, about a quarter received empagliflozin, and the rest received dapagliflozin.
During up to 3.5 years of follow-up, a similar percentage of patients in each group had either an MI, stroke, or died (the primary composite CV outcome) (hazard ratio [HR], 0.98; 95% CI, 0.89 - 1.07).
However, more patients in the GLP-1 agonist group had heart failure or died (the secondary composite CV outcome), driven by a higher rate of heart failure in this group.
But after adjusting for time to events there was no significant between-group difference in the secondary composite CV outcome (HR, 1.09; 95% CI, 0.99 - 1.21).
During the 12-months after the initial prescription, patients who were started on a GLP-1 agonist versus an SGLT2 inhibitor had higher mean monthly medical costs, which included hospitalizations, emergency department (ED) visits, and outpatient visits ($904 vs $834; P < .001).
They also had higher pharmacy costs, which covered all drugs ($891 vs $783; P < .001).
And they were more likely to discontinue treatment (HR, 1.15; 95% CI, 1.10 - 1.21), be hospitalized (14.4% vs 11.9%; P < .001), or visit the ED (27.4% vs 23.5%; P < .001).
“Not too surprising” and “somewhat reassuring”
Overall, Kosiborod did not find the results surprising.
Given the sample size and follow-up time, event rates were probably quite low and insufficient to draw firm conclusions about the composite CV outcomes, he reiterated.
However, given the comparable effects of these two drug types on major adverse cardiac events (MACE) in similar patient populations with type 2 diabetes, it is not too surprising that there were no significant differences in these outcomes.
It was also “somewhat reassuring” to see that heart failure rates were lower with SGLT2 inhibitors, “as one would expect,” he said, because these agents “have been shown to significantly reduce the risk of hospitalization for heart failure in multiple outcome trials, whereas GLP-1 receptor agonists’ beneficial CV effects appear to be more limited to MACE reduction.”
The higher rates of discontinuation with GLP-1 receptor agonists “is also not a surprise, since patients experience more gastrointestinal tolerability issues with these agents (mainly nausea),” which can be mitigated in the majority of patients with appropriate education and close follow up — but is not done consistently.
Similarly, “the cost differences are also expected, since GLP-1 receptor agonists tend to be more expensive.”
On the other hand, the higher rates of hospitalizations with GLP-1 agonists compared to SGLT2 inhibitors “requires further exploration and confirmation,” Kosiborod said.
But he suspects this may be due to residual confounding, “since GLP-1 agonists are typically initiated later in the type 2 diabetes treatment algorithm,” so these patients could have lengthier, more difficult-to-manage type 2 diabetes with more comorbidities despite the propensity matching.
Poonawalla and Schwab are employed by Humana. Kosiborod has disclosed research support from AstraZeneca and Boehringer Ingelheim; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and consulting fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi Aventis .
This article first appeared on Medscape.com
Drug adherence, healthcare use, medical costs, and heart failure rates were better among patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor than a glucagon-like peptide 1 (GLP-1) receptor agonist in a real-world, observational study.
Composite cardiovascular (CV) outcomes were similar between the two drug classes.
Insiya Poonawalla, PhD, a researcher at Humana Healthcare Research, Flower Mound, Texas, reported the study results in an oral presentation on June 12 at the virtual American Diabetes Association (ADA) 80th Scientific Sessions.
The investigators matched more than 10,000 patients with type 2 diabetes — half initiated on an SGLT2 inhibitor and half initiated on a GLP-1 agonist — from the Humana database of insurance claims data.
“These findings suggest potential benefits” of SGLT2 inhibitors, “particularly where risk related to heart failure is an important consideration,” Poonawalla said, but as always, any benefits need to be weighed against any risks.
And “while this study provides a pretty complete and current picture of claims until 2018,” it has limitations inherent to observational data (such as possible errors or omissions in the claims data), she conceded.
Mikhail Kosiborod, MD, invited to comment on the research, said this preliminary study was likely too short and small to definitively demonstrate differences in composite CV outcomes between the two drug classes, but he noted that the overall findings are not unexpected.
And often, the particular CV risk profile of an individual patient will point to one or the other of these drug classes as a best fit, he noted.
Too soon to alter clinical practice
Kosiborod, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said he nevertheless feels “it would be a bit premature to use these findings as a guide to change clinical practice.”
“The study is relatively small in scope and likely underpowered to examine CV outcomes,” he said in an email interview.
Larger population-based studies and ideally head-to-head randomized controlled trials of various type 2 diabetes agents could compare these two drug classes more definitively, he asserted.
In the meantime, safety profiles of both medication classes “have been well established — in tens of thousands of patients in clinical trials and millions of patients prescribed these therapies in clinical practice,” he noted.
In general, the drugs in both classes are well-tolerated and safe for most patients with type 2 diabetes when used appropriately.
“Certainly, patients with type 2 diabetes and established CV disease (or at high risk for CV complications) are ideal candidates for either an SGLT2 inhibitor or a GLP-1 receptor agonist,” Kosiborod said.
“Given the data we have from outcome trials, an SGLT2 inhibitor would be a better initial strategy in a patient with type 2 diabetes and heart failure (especially heart failure with reduced ejection fraction) and/or diabetic kidney disease,” he continued.
On the other hand, “a GLP-1 receptor agonist may be a better initial strategy in a type 2 diabetes patient with (or at very high risk for) atherosclerotic cardiovascular disease (ASCVD), especially if there is concomitant obesity contributing to the disease process.”
Limited comparisons of these two newer drug classes
“Real-world evidence comparing these two therapeutic classes based on CV outcomes is limited,” Poonawalla said at the start of her presentation, and relative treatment persistence, utilization, and cost data are even less well studied.
To investigate this, the researchers identified patients aged 19 to 89 years who were newly prescribed one of these two types of antidiabetic agents during January 1, 2015 through June 30, 2017.
Poonawalla and senior study author Phil Schwab, PhD, research lead, Humana Healthcare Research, Louisville, Kentucky, clarified the study design and findings in an email to this new organization.
The team matched 5507 patients initiated on a GLP-1 agonist with 5507 patients newly prescribed an SGLT2 inhibitor.
Patients were a mean age of 65 years and 53% were women.
More than a third (37%) had established ASCVD, including myocardial infarction (MI) (7.9%) and stroke (9.8%), and 11.5% had heart failure.
About two thirds were receiving metformin and about a third were receiving insulin.
In the GLP-1 agonist group, more than half of patients were prescribed liraglutide (57%), followed by dulaglutide (33%), exenatide, and lixisenatide (two patients).
In the SGLT2 inhibitor group, close to 70% received canagliflozin, about a quarter received empagliflozin, and the rest received dapagliflozin.
During up to 3.5 years of follow-up, a similar percentage of patients in each group had either an MI, stroke, or died (the primary composite CV outcome) (hazard ratio [HR], 0.98; 95% CI, 0.89 - 1.07).
However, more patients in the GLP-1 agonist group had heart failure or died (the secondary composite CV outcome), driven by a higher rate of heart failure in this group.
But after adjusting for time to events there was no significant between-group difference in the secondary composite CV outcome (HR, 1.09; 95% CI, 0.99 - 1.21).
During the 12-months after the initial prescription, patients who were started on a GLP-1 agonist versus an SGLT2 inhibitor had higher mean monthly medical costs, which included hospitalizations, emergency department (ED) visits, and outpatient visits ($904 vs $834; P < .001).
They also had higher pharmacy costs, which covered all drugs ($891 vs $783; P < .001).
And they were more likely to discontinue treatment (HR, 1.15; 95% CI, 1.10 - 1.21), be hospitalized (14.4% vs 11.9%; P < .001), or visit the ED (27.4% vs 23.5%; P < .001).
“Not too surprising” and “somewhat reassuring”
Overall, Kosiborod did not find the results surprising.
Given the sample size and follow-up time, event rates were probably quite low and insufficient to draw firm conclusions about the composite CV outcomes, he reiterated.
However, given the comparable effects of these two drug types on major adverse cardiac events (MACE) in similar patient populations with type 2 diabetes, it is not too surprising that there were no significant differences in these outcomes.
It was also “somewhat reassuring” to see that heart failure rates were lower with SGLT2 inhibitors, “as one would expect,” he said, because these agents “have been shown to significantly reduce the risk of hospitalization for heart failure in multiple outcome trials, whereas GLP-1 receptor agonists’ beneficial CV effects appear to be more limited to MACE reduction.”
The higher rates of discontinuation with GLP-1 receptor agonists “is also not a surprise, since patients experience more gastrointestinal tolerability issues with these agents (mainly nausea),” which can be mitigated in the majority of patients with appropriate education and close follow up — but is not done consistently.
Similarly, “the cost differences are also expected, since GLP-1 receptor agonists tend to be more expensive.”
On the other hand, the higher rates of hospitalizations with GLP-1 agonists compared to SGLT2 inhibitors “requires further exploration and confirmation,” Kosiborod said.
But he suspects this may be due to residual confounding, “since GLP-1 agonists are typically initiated later in the type 2 diabetes treatment algorithm,” so these patients could have lengthier, more difficult-to-manage type 2 diabetes with more comorbidities despite the propensity matching.
Poonawalla and Schwab are employed by Humana. Kosiborod has disclosed research support from AstraZeneca and Boehringer Ingelheim; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and consulting fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi Aventis .
This article first appeared on Medscape.com
FROM ADA 2020