Patrice Wendling

After more than 10 hours of intense debate, a Food and Drug Administration advisory panel gave its support to a premarket approval application (PMA) for the TransMedics Organ Care System (OCS) Heart system.

Courtesy Transmedics

The OCS Heart is a portable extracorporeal perfusion and monitoring system designed to keep a donor heart in a normothermic, beating state. The “heart in a box” technology allows donor hearts to be transported across longer distances than is possible with standard cold storage, which can safely preserve donor hearts for about 4 hours.

The Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 12 to 5, with 1 abstention, that the benefits of the OCS Heart System outweigh its risks.

The panel voted in favor of the OCS Heart being effective (10 yes, 6 no, and 2 abstaining) and safe (9 yes, 7 no, 2 abstaining) but not without mixed feelings.

James Blankenship, MD, a cardiologist at the University of New Mexico, Albuquerque, voted yes to all three questions but said: “If it had been compared to standard of care, I would have voted no to all three. But if it’s compared to getting an [left ventricular assist device] LVAD or not getting a heart at all, I would say the benefits outweigh the risks.”

Marc R. Katz, MD, chief of cardiothoracic surgery, Medical University of South Carolina, Charleston, also gave universal support, noting that the rate of heart transplantations has been flat for years. “This is a big step forward toward being able to expand that number. Now all that said, it obviously was a less-than-perfect study and I do think there needs to be some constraints put on the utilization.”

The panel reviewed data from the single-arm OCS Heart EXPAND trial and associated EXPAND Continued Access Protocol (CAP), as well the sponsor’s first OCS Heart trial, PROCEED II.

EXPAND met its effectiveness endpoint, with 88% of donor hearts successfully transplanted, an 8% incidence of severe primary graft dysfunction (PGD) 24 hours after transplantation, and 94.6% survival at 30 days.

Data from 41 patients with 30-day follow-up in the ongoing EXPAND CAP show 91% of donor hearts were utilized, a 2.4% incidence of severe PGD, and 100% 30-day survival.

The sponsor and the FDA clashed over changes made to the trial after the PMA was submitted, the appropriateness of the effectiveness outcome, and claims by the FDA that there was substantial overlap in demographic characteristics between the extended criteria donor hearts in the EXPAND trials and the standard criteria donor hearts in PROCEED II.

TransMedics previously submitted a PMA based on PROCEED II but it noted in submitted documents that it was withdrawn because of “fundamental disagreements with FDA” on the interpretation of a post hoc analysis with United Network for Organ Sharing registry data that identified increased all-cause mortality risk but comparable cardiac-related mortality in patients with OCS hearts.

During the marathon hearing, FDA officials presented several post hoc analyses, including one stratified by donor inclusion criteria, in which 30-day survival estimates were worse in recipients of single-criterion organs than for those receiving donor organs with multiple inclusion criteria (85% vs. 91.4%). In a second analysis, 2-year point estimates of survival also trended lower with donor organs having only one extended criterion.

Reported EXPAND CAP 6- and 12-month survival estimates were 100% and 93%, respectively, which was higher than EXPAND (93% and 84%), but there was substantial censoring (>50%) at 6 months and beyond, FDA officials said.

When EXPAND and CAP data were pooled, modeled survival curves shifted upward but there was a substantial site effect, with a single site contributing 46% of data, which may affect generalizability of the results, they noted.

“I voted yes for safety, no for efficacy, and no for approval and I’d just like to say I found this to be the most difficult vote in my experience on this panel,” John Hirshfeld, MD, University of Pennsylvania, Philadelphia, said. “I was very concerned that the PROCEED data suggests a possible harm, and in the absence of an interpretable comparator for the EXPAND trial, it’s really not possible to decide if there’s efficacy.”

Keith B. Allen, MD, director of surgical research at Saint Luke’s Hospital of Kansas City (Mo.), said, “I voted no on safety; I’m not going to give the company a pass. I think their animal data was sorely lacking and a lot of issues over the last 10 years could have been addressed with some key animal studies.

“For efficacy and risk/benefit, I voted yes for both,” he said. “Had this been standard of care and only PROCEED II, I would have voted no, but I do think there are a lot of hearts that go in the bucket and this is a challenging population.”

More than a dozen physicians and patients spoke at the open public hearing about the potential for the device to expand donor heart utilization, including a recipient whose own father died while waiting on the transplant list. Only about 3 out of every 10 donated hearts are used for transplant. To ensure fair access, particularly for patients in rural areas, federal changes in 2020 mandate that organs be allocated to the sickest patients first.

Data showed that the OCS Heart System was associated with shorter waiting list times, compared with U.S. averages but longer preservation times than cold static preservation.

In all, 13% of accepted donor organs were subsequently turned down after OCS heart preservation. Lactate levels were cited as the principal reason for turn-down but, FDA officials said, the validity of using lactate as a marker for transplantability is unclear.

Pathologic analysis of OCS Heart turned-down donor hearts with stable antemortem hemodynamics, normal or near-normal anatomy and normal ventricular function by echocardiography, and autopsy findings of acute diffuse or multifocal myocardial damage “suggest that in an important proportion of cases the OCS Heart system did not provide effective organ preservation or its use caused severe myocardial damage to what might have been an acceptable graft for transplant,” said Andrew Farb, MD, chief medical officer of the FDA’s Office of Cardiovascular Devices.
 

Proposed indication

In the present PMA, the OCS Heart System is indicated for donor hearts with one or more of the following characteristics: an expected cross-clamp or ischemic time of at least 4 hours because of donor or recipient characteristics; or an expected total cross-clamp time of at least 2 hours plus one of the following risk factors: donor age 55 or older, history of cardiac arrest and downtime of at least 20 minutes, history of alcoholism, history of diabetes, donor ejection fraction of 40%-50%,history of left ventricular hypertrophy, and donor angiogram with luminal irregularities but no significant coronary artery disease

Several members voiced concern about “indication creep” should the device be approved by the FDA, and highlighted the 2-hour cross-clamp time plus wide-ranging risk factors.

“I’m a surgeon and I voted no on all three counts,” said Murray H. Kwon, MD, Ronald Reagan University of California, Los Angeles Medical Center. “As far as risk/benefit, if it was just limited to one group – the 4-hour plus – I would say yes, but if you’re going to tell me that there’s a risk/benefit for the 2-hour with the alcoholic, I don’t know how that was proved in anything.”

Dr. Kwon was also troubled by lack of proper controls and by the one quarter of patients who ended up on mechanical circulatory support in the first 30 days after transplant. “I find that highly aberrant.”

Joaquin E. Cigarroa, MD, head of cardiovascular medicine, Oregon Health & Science University, Portland, said the unmet need for patients with refractory, end-stage heart failure is challenging and quite emotional, but also voted no across the board, citing concerns about a lack of comparator in the EXPAND trials and overall out-of-body ischemic time.

“As it relates to risk/benefit, I thought long and hard about voting yes despite all the unknowns because of this emotion, but ultimately I voted no because of the secondary 2-hours plus alcoholism, diabetes, or minor coronary disease, in which the ischemic burden and ongoing lactate production concern me,” he said.

Although the panel decision is nonbinding, there was strong support from the committee members for a randomized, postapproval trial and more complete animal studies.

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

After more than 10 hours of intense debate, a Food and Drug Administration advisory panel gave its support to a premarket approval application (PMA) for the TransMedics Organ Care System (OCS) Heart system.

Courtesy Transmedics

The OCS Heart is a portable extracorporeal perfusion and monitoring system designed to keep a donor heart in a normothermic, beating state. The “heart in a box” technology allows donor hearts to be transported across longer distances than is possible with standard cold storage, which can safely preserve donor hearts for about 4 hours.

The Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 12 to 5, with 1 abstention, that the benefits of the OCS Heart System outweigh its risks.

The panel voted in favor of the OCS Heart being effective (10 yes, 6 no, and 2 abstaining) and safe (9 yes, 7 no, 2 abstaining) but not without mixed feelings.

James Blankenship, MD, a cardiologist at the University of New Mexico, Albuquerque, voted yes to all three questions but said: “If it had been compared to standard of care, I would have voted no to all three. But if it’s compared to getting an [left ventricular assist device] LVAD or not getting a heart at all, I would say the benefits outweigh the risks.”

Marc R. Katz, MD, chief of cardiothoracic surgery, Medical University of South Carolina, Charleston, also gave universal support, noting that the rate of heart transplantations has been flat for years. “This is a big step forward toward being able to expand that number. Now all that said, it obviously was a less-than-perfect study and I do think there needs to be some constraints put on the utilization.”

The panel reviewed data from the single-arm OCS Heart EXPAND trial and associated EXPAND Continued Access Protocol (CAP), as well the sponsor’s first OCS Heart trial, PROCEED II.

EXPAND met its effectiveness endpoint, with 88% of donor hearts successfully transplanted, an 8% incidence of severe primary graft dysfunction (PGD) 24 hours after transplantation, and 94.6% survival at 30 days.

Data from 41 patients with 30-day follow-up in the ongoing EXPAND CAP show 91% of donor hearts were utilized, a 2.4% incidence of severe PGD, and 100% 30-day survival.

The sponsor and the FDA clashed over changes made to the trial after the PMA was submitted, the appropriateness of the effectiveness outcome, and claims by the FDA that there was substantial overlap in demographic characteristics between the extended criteria donor hearts in the EXPAND trials and the standard criteria donor hearts in PROCEED II.

TransMedics previously submitted a PMA based on PROCEED II but it noted in submitted documents that it was withdrawn because of “fundamental disagreements with FDA” on the interpretation of a post hoc analysis with United Network for Organ Sharing registry data that identified increased all-cause mortality risk but comparable cardiac-related mortality in patients with OCS hearts.

During the marathon hearing, FDA officials presented several post hoc analyses, including one stratified by donor inclusion criteria, in which 30-day survival estimates were worse in recipients of single-criterion organs than for those receiving donor organs with multiple inclusion criteria (85% vs. 91.4%). In a second analysis, 2-year point estimates of survival also trended lower with donor organs having only one extended criterion.

Reported EXPAND CAP 6- and 12-month survival estimates were 100% and 93%, respectively, which was higher than EXPAND (93% and 84%), but there was substantial censoring (>50%) at 6 months and beyond, FDA officials said.

When EXPAND and CAP data were pooled, modeled survival curves shifted upward but there was a substantial site effect, with a single site contributing 46% of data, which may affect generalizability of the results, they noted.

“I voted yes for safety, no for efficacy, and no for approval and I’d just like to say I found this to be the most difficult vote in my experience on this panel,” John Hirshfeld, MD, University of Pennsylvania, Philadelphia, said. “I was very concerned that the PROCEED data suggests a possible harm, and in the absence of an interpretable comparator for the EXPAND trial, it’s really not possible to decide if there’s efficacy.”

Keith B. Allen, MD, director of surgical research at Saint Luke’s Hospital of Kansas City (Mo.), said, “I voted no on safety; I’m not going to give the company a pass. I think their animal data was sorely lacking and a lot of issues over the last 10 years could have been addressed with some key animal studies.

“For efficacy and risk/benefit, I voted yes for both,” he said. “Had this been standard of care and only PROCEED II, I would have voted no, but I do think there are a lot of hearts that go in the bucket and this is a challenging population.”

More than a dozen physicians and patients spoke at the open public hearing about the potential for the device to expand donor heart utilization, including a recipient whose own father died while waiting on the transplant list. Only about 3 out of every 10 donated hearts are used for transplant. To ensure fair access, particularly for patients in rural areas, federal changes in 2020 mandate that organs be allocated to the sickest patients first.

Data showed that the OCS Heart System was associated with shorter waiting list times, compared with U.S. averages but longer preservation times than cold static preservation.

In all, 13% of accepted donor organs were subsequently turned down after OCS heart preservation. Lactate levels were cited as the principal reason for turn-down but, FDA officials said, the validity of using lactate as a marker for transplantability is unclear.

Pathologic analysis of OCS Heart turned-down donor hearts with stable antemortem hemodynamics, normal or near-normal anatomy and normal ventricular function by echocardiography, and autopsy findings of acute diffuse or multifocal myocardial damage “suggest that in an important proportion of cases the OCS Heart system did not provide effective organ preservation or its use caused severe myocardial damage to what might have been an acceptable graft for transplant,” said Andrew Farb, MD, chief medical officer of the FDA’s Office of Cardiovascular Devices.
 

Proposed indication

In the present PMA, the OCS Heart System is indicated for donor hearts with one or more of the following characteristics: an expected cross-clamp or ischemic time of at least 4 hours because of donor or recipient characteristics; or an expected total cross-clamp time of at least 2 hours plus one of the following risk factors: donor age 55 or older, history of cardiac arrest and downtime of at least 20 minutes, history of alcoholism, history of diabetes, donor ejection fraction of 40%-50%,history of left ventricular hypertrophy, and donor angiogram with luminal irregularities but no significant coronary artery disease

Several members voiced concern about “indication creep” should the device be approved by the FDA, and highlighted the 2-hour cross-clamp time plus wide-ranging risk factors.

“I’m a surgeon and I voted no on all three counts,” said Murray H. Kwon, MD, Ronald Reagan University of California, Los Angeles Medical Center. “As far as risk/benefit, if it was just limited to one group – the 4-hour plus – I would say yes, but if you’re going to tell me that there’s a risk/benefit for the 2-hour with the alcoholic, I don’t know how that was proved in anything.”

Dr. Kwon was also troubled by lack of proper controls and by the one quarter of patients who ended up on mechanical circulatory support in the first 30 days after transplant. “I find that highly aberrant.”

Joaquin E. Cigarroa, MD, head of cardiovascular medicine, Oregon Health & Science University, Portland, said the unmet need for patients with refractory, end-stage heart failure is challenging and quite emotional, but also voted no across the board, citing concerns about a lack of comparator in the EXPAND trials and overall out-of-body ischemic time.

“As it relates to risk/benefit, I thought long and hard about voting yes despite all the unknowns because of this emotion, but ultimately I voted no because of the secondary 2-hours plus alcoholism, diabetes, or minor coronary disease, in which the ischemic burden and ongoing lactate production concern me,” he said.

Although the panel decision is nonbinding, there was strong support from the committee members for a randomized, postapproval trial and more complete animal studies.

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

After more than 10 hours of intense debate, a Food and Drug Administration advisory panel gave its support to a premarket approval application (PMA) for the TransMedics Organ Care System (OCS) Heart system.

Courtesy Transmedics

The OCS Heart is a portable extracorporeal perfusion and monitoring system designed to keep a donor heart in a normothermic, beating state. The “heart in a box” technology allows donor hearts to be transported across longer distances than is possible with standard cold storage, which can safely preserve donor hearts for about 4 hours.

The Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 12 to 5, with 1 abstention, that the benefits of the OCS Heart System outweigh its risks.

The panel voted in favor of the OCS Heart being effective (10 yes, 6 no, and 2 abstaining) and safe (9 yes, 7 no, 2 abstaining) but not without mixed feelings.

James Blankenship, MD, a cardiologist at the University of New Mexico, Albuquerque, voted yes to all three questions but said: “If it had been compared to standard of care, I would have voted no to all three. But if it’s compared to getting an [left ventricular assist device] LVAD or not getting a heart at all, I would say the benefits outweigh the risks.”

Marc R. Katz, MD, chief of cardiothoracic surgery, Medical University of South Carolina, Charleston, also gave universal support, noting that the rate of heart transplantations has been flat for years. “This is a big step forward toward being able to expand that number. Now all that said, it obviously was a less-than-perfect study and I do think there needs to be some constraints put on the utilization.”

The panel reviewed data from the single-arm OCS Heart EXPAND trial and associated EXPAND Continued Access Protocol (CAP), as well the sponsor’s first OCS Heart trial, PROCEED II.

EXPAND met its effectiveness endpoint, with 88% of donor hearts successfully transplanted, an 8% incidence of severe primary graft dysfunction (PGD) 24 hours after transplantation, and 94.6% survival at 30 days.

Data from 41 patients with 30-day follow-up in the ongoing EXPAND CAP show 91% of donor hearts were utilized, a 2.4% incidence of severe PGD, and 100% 30-day survival.

The sponsor and the FDA clashed over changes made to the trial after the PMA was submitted, the appropriateness of the effectiveness outcome, and claims by the FDA that there was substantial overlap in demographic characteristics between the extended criteria donor hearts in the EXPAND trials and the standard criteria donor hearts in PROCEED II.

TransMedics previously submitted a PMA based on PROCEED II but it noted in submitted documents that it was withdrawn because of “fundamental disagreements with FDA” on the interpretation of a post hoc analysis with United Network for Organ Sharing registry data that identified increased all-cause mortality risk but comparable cardiac-related mortality in patients with OCS hearts.

During the marathon hearing, FDA officials presented several post hoc analyses, including one stratified by donor inclusion criteria, in which 30-day survival estimates were worse in recipients of single-criterion organs than for those receiving donor organs with multiple inclusion criteria (85% vs. 91.4%). In a second analysis, 2-year point estimates of survival also trended lower with donor organs having only one extended criterion.

Reported EXPAND CAP 6- and 12-month survival estimates were 100% and 93%, respectively, which was higher than EXPAND (93% and 84%), but there was substantial censoring (>50%) at 6 months and beyond, FDA officials said.

When EXPAND and CAP data were pooled, modeled survival curves shifted upward but there was a substantial site effect, with a single site contributing 46% of data, which may affect generalizability of the results, they noted.

“I voted yes for safety, no for efficacy, and no for approval and I’d just like to say I found this to be the most difficult vote in my experience on this panel,” John Hirshfeld, MD, University of Pennsylvania, Philadelphia, said. “I was very concerned that the PROCEED data suggests a possible harm, and in the absence of an interpretable comparator for the EXPAND trial, it’s really not possible to decide if there’s efficacy.”

Keith B. Allen, MD, director of surgical research at Saint Luke’s Hospital of Kansas City (Mo.), said, “I voted no on safety; I’m not going to give the company a pass. I think their animal data was sorely lacking and a lot of issues over the last 10 years could have been addressed with some key animal studies.

“For efficacy and risk/benefit, I voted yes for both,” he said. “Had this been standard of care and only PROCEED II, I would have voted no, but I do think there are a lot of hearts that go in the bucket and this is a challenging population.”

More than a dozen physicians and patients spoke at the open public hearing about the potential for the device to expand donor heart utilization, including a recipient whose own father died while waiting on the transplant list. Only about 3 out of every 10 donated hearts are used for transplant. To ensure fair access, particularly for patients in rural areas, federal changes in 2020 mandate that organs be allocated to the sickest patients first.

Data showed that the OCS Heart System was associated with shorter waiting list times, compared with U.S. averages but longer preservation times than cold static preservation.

In all, 13% of accepted donor organs were subsequently turned down after OCS heart preservation. Lactate levels were cited as the principal reason for turn-down but, FDA officials said, the validity of using lactate as a marker for transplantability is unclear.

Pathologic analysis of OCS Heart turned-down donor hearts with stable antemortem hemodynamics, normal or near-normal anatomy and normal ventricular function by echocardiography, and autopsy findings of acute diffuse or multifocal myocardial damage “suggest that in an important proportion of cases the OCS Heart system did not provide effective organ preservation or its use caused severe myocardial damage to what might have been an acceptable graft for transplant,” said Andrew Farb, MD, chief medical officer of the FDA’s Office of Cardiovascular Devices.
 

Proposed indication

In the present PMA, the OCS Heart System is indicated for donor hearts with one or more of the following characteristics: an expected cross-clamp or ischemic time of at least 4 hours because of donor or recipient characteristics; or an expected total cross-clamp time of at least 2 hours plus one of the following risk factors: donor age 55 or older, history of cardiac arrest and downtime of at least 20 minutes, history of alcoholism, history of diabetes, donor ejection fraction of 40%-50%,history of left ventricular hypertrophy, and donor angiogram with luminal irregularities but no significant coronary artery disease

Several members voiced concern about “indication creep” should the device be approved by the FDA, and highlighted the 2-hour cross-clamp time plus wide-ranging risk factors.

“I’m a surgeon and I voted no on all three counts,” said Murray H. Kwon, MD, Ronald Reagan University of California, Los Angeles Medical Center. “As far as risk/benefit, if it was just limited to one group – the 4-hour plus – I would say yes, but if you’re going to tell me that there’s a risk/benefit for the 2-hour with the alcoholic, I don’t know how that was proved in anything.”

Dr. Kwon was also troubled by lack of proper controls and by the one quarter of patients who ended up on mechanical circulatory support in the first 30 days after transplant. “I find that highly aberrant.”

Joaquin E. Cigarroa, MD, head of cardiovascular medicine, Oregon Health & Science University, Portland, said the unmet need for patients with refractory, end-stage heart failure is challenging and quite emotional, but also voted no across the board, citing concerns about a lack of comparator in the EXPAND trials and overall out-of-body ischemic time.

“As it relates to risk/benefit, I thought long and hard about voting yes despite all the unknowns because of this emotion, but ultimately I voted no because of the secondary 2-hours plus alcoholism, diabetes, or minor coronary disease, in which the ischemic burden and ongoing lactate production concern me,” he said.

Although the panel decision is nonbinding, there was strong support from the committee members for a randomized, postapproval trial and more complete animal studies.

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

Patients with rheumatic heart disease (RHD) appear to have comparable outcomes, whether undergoing transcatheter or surgical aortic valve replacement (TAVR/SAVR), and when compared with TAVR in patients with nonrheumatic aortic stenosis, a new Medicare study finds.

An analysis of data from 1,159 Medicare beneficiaries with rheumatic aortic stenosis revealed that, over a median follow-up of 19 months, there was no difference in all-cause mortality with TAVR vs. SAVR (11.2 vs. 7.0 per 100 person-years; adjusted hazard ratio, 1.53; P = .2).

Mortality was also similar after a median follow-up of 17 months between TAVR in patients with rheumatic aortic stenosis and 88,554 additional beneficiaries with nonrheumatic aortic stenosis (15.2 vs. 17.7 deaths per 100 person-years; aHR, 0.87; P = .2).

“We need collaboration between industry and society leaders in developed countries to initiate a randomized, controlled trial to address the feasibility of TAVR in rheumatic heart disease in younger populations who aren’t surgical candidates or if there’s a lack of surgical capabilities in countries, but this is an encouraging first sign,” lead author Amgad Mentias, MD, MSc, Cleveland Clinic Foundation, said in an interview.

Although the prevalence of rheumatic heart disease (RHD) has fallen to less than 5% or so in the United States and Europe, it remains a significant problem in developing and low-income countries, with more than 1 million deaths per year, he noted. RHD patients typically present at younger ages, often with concomitant aortic regurgitation and mitral valve disease, but have less calcification than degenerative calcific aortic stenosis.

Commenting on the results, published in the Journal of the American College of Cardiology, David F. Williams, PhD, said in an interview that “it is only now becoming possible to entertain the use of TAVR in such patients, and this paper demonstrates the feasibility of doing so.

“Although the study is based on geriatric patients of an industrialized country, it opens the door to the massive unmet clinical needs in poorer regions as well as emerging economies,” said Dr. Williams, a professor at the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., and coauthor of an accompanying editorial.

The study included Medicare beneficiaries treated from October 2015 to December 2017 for rheumatic aortic stenosis (TAVR, n = 605; SAVR, n = 55) or nonrheumatic aortic stenosis (n = 88,554).

Among those with rheumatic disease, SAVR patients were younger than TAVR patients (73.4 vs. 79.4 years), had a lower prevalence of most comorbidities, and were less frail (median frailty score, 5.3 vs. 11.3).

SAVR was associated with significantly higher weighted risk for in-hospital acute kidney injury (22.3% vs. 11.9%), blood transfusion (19.8% vs. 7.6%), cardiogenic shock (5.7% vs. 1.5%), new-onset atrial fibrillation (21.1% vs. 2.2%), and had longer hospital stays (median, 8 vs. 3 days), whereas new permanent pacemaker implantations trended higher with TAVR (12.5% vs 7.2%).

The TAVR and SAVR groups had comparable rates of adjusted in-hospital mortality (2.4% vs. 3.5%), 30-day mortality (3.6% vs. 3.2%), 30-day stroke (2.4% vs. 2.8%), and 1-year mortality (13.1% vs. 8.9%).

Among the two TAVR cohorts, patients with rheumatic disease were younger than those with nonrheumatic aortic stenosis (79.4 vs. 81.2 years); had a higher prevalence of heart failure, ischemic stroke, atrial fibrillation, and lung disease; and were more frail (median score, 11.3 vs. 6.9).

Still, there was no difference in weighted risk of in-hospital mortality (2.2% vs. 2.6%), 30-day mortality (3.6% vs. 3.7%), 30-day stroke (2.0% vs. 3.3%), or 1-year mortality (16.0% vs. 17.1%) between TAVR patients with and without rheumatic stenosis.

“We didn’t have specific information on echo[cardiography], so we don’t know how that affected our results, but one of the encouraging points is that after a median follow-up of almost 2 years, none of the patients who had TAVR in the rheumatic valve and who survived required redo aortic valve replacement,” Dr. Mentias said. “It’s still short term but it shows that for the short to mid term, the valve is durable.”

Data were not available on paravalvular regurgitation, an Achilles heel for TAVR, but Dr. Mentias said rates of this complication have come down significantly in the past 2 years with modifications to newer-generation TAVR valves.

Dr. Williams and colleagues say one main limitation of the study also highlights the major shortcoming of contemporary TAVRs when treating patients with RHD: “namely, their inadequate suitability for AR [aortic regurgitation], the predominant rheumatic lesion of the aortic valve” in low- to middle-income countries.

They pointed out that patients needing an aortic valve where RHD is rampant are at least 30 years younger than the 79-year-old TAVR recipients in the study.

In a comment, Dr. Williams said there are several unanswered questions about the full impact TAVR could have in the treatment of young RHD patients in underprivileged regions. “These mainly concern the durability of the valves in individuals who could expect greater longevity than the typical heart valve patient in the USA, and the adaptation of transcatheter techniques to provide cost-effective treatment in regions that lack the usual sophisticated clinical infrastructure.”

Dr. Mentias received support from a National Research Service Award institutional grant to the Abboud Cardiovascular Research Center. Dr. Williams and coauthors are directors of Strait Access Technologies.

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

Patients with rheumatic heart disease (RHD) appear to have comparable outcomes, whether undergoing transcatheter or surgical aortic valve replacement (TAVR/SAVR), and when compared with TAVR in patients with nonrheumatic aortic stenosis, a new Medicare study finds.

An analysis of data from 1,159 Medicare beneficiaries with rheumatic aortic stenosis revealed that, over a median follow-up of 19 months, there was no difference in all-cause mortality with TAVR vs. SAVR (11.2 vs. 7.0 per 100 person-years; adjusted hazard ratio, 1.53; P = .2).

Mortality was also similar after a median follow-up of 17 months between TAVR in patients with rheumatic aortic stenosis and 88,554 additional beneficiaries with nonrheumatic aortic stenosis (15.2 vs. 17.7 deaths per 100 person-years; aHR, 0.87; P = .2).

“We need collaboration between industry and society leaders in developed countries to initiate a randomized, controlled trial to address the feasibility of TAVR in rheumatic heart disease in younger populations who aren’t surgical candidates or if there’s a lack of surgical capabilities in countries, but this is an encouraging first sign,” lead author Amgad Mentias, MD, MSc, Cleveland Clinic Foundation, said in an interview.

Although the prevalence of rheumatic heart disease (RHD) has fallen to less than 5% or so in the United States and Europe, it remains a significant problem in developing and low-income countries, with more than 1 million deaths per year, he noted. RHD patients typically present at younger ages, often with concomitant aortic regurgitation and mitral valve disease, but have less calcification than degenerative calcific aortic stenosis.

Commenting on the results, published in the Journal of the American College of Cardiology, David F. Williams, PhD, said in an interview that “it is only now becoming possible to entertain the use of TAVR in such patients, and this paper demonstrates the feasibility of doing so.

“Although the study is based on geriatric patients of an industrialized country, it opens the door to the massive unmet clinical needs in poorer regions as well as emerging economies,” said Dr. Williams, a professor at the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., and coauthor of an accompanying editorial.

The study included Medicare beneficiaries treated from October 2015 to December 2017 for rheumatic aortic stenosis (TAVR, n = 605; SAVR, n = 55) or nonrheumatic aortic stenosis (n = 88,554).

Among those with rheumatic disease, SAVR patients were younger than TAVR patients (73.4 vs. 79.4 years), had a lower prevalence of most comorbidities, and were less frail (median frailty score, 5.3 vs. 11.3).

SAVR was associated with significantly higher weighted risk for in-hospital acute kidney injury (22.3% vs. 11.9%), blood transfusion (19.8% vs. 7.6%), cardiogenic shock (5.7% vs. 1.5%), new-onset atrial fibrillation (21.1% vs. 2.2%), and had longer hospital stays (median, 8 vs. 3 days), whereas new permanent pacemaker implantations trended higher with TAVR (12.5% vs 7.2%).

The TAVR and SAVR groups had comparable rates of adjusted in-hospital mortality (2.4% vs. 3.5%), 30-day mortality (3.6% vs. 3.2%), 30-day stroke (2.4% vs. 2.8%), and 1-year mortality (13.1% vs. 8.9%).

Among the two TAVR cohorts, patients with rheumatic disease were younger than those with nonrheumatic aortic stenosis (79.4 vs. 81.2 years); had a higher prevalence of heart failure, ischemic stroke, atrial fibrillation, and lung disease; and were more frail (median score, 11.3 vs. 6.9).

Still, there was no difference in weighted risk of in-hospital mortality (2.2% vs. 2.6%), 30-day mortality (3.6% vs. 3.7%), 30-day stroke (2.0% vs. 3.3%), or 1-year mortality (16.0% vs. 17.1%) between TAVR patients with and without rheumatic stenosis.

“We didn’t have specific information on echo[cardiography], so we don’t know how that affected our results, but one of the encouraging points is that after a median follow-up of almost 2 years, none of the patients who had TAVR in the rheumatic valve and who survived required redo aortic valve replacement,” Dr. Mentias said. “It’s still short term but it shows that for the short to mid term, the valve is durable.”

Data were not available on paravalvular regurgitation, an Achilles heel for TAVR, but Dr. Mentias said rates of this complication have come down significantly in the past 2 years with modifications to newer-generation TAVR valves.

Dr. Williams and colleagues say one main limitation of the study also highlights the major shortcoming of contemporary TAVRs when treating patients with RHD: “namely, their inadequate suitability for AR [aortic regurgitation], the predominant rheumatic lesion of the aortic valve” in low- to middle-income countries.

They pointed out that patients needing an aortic valve where RHD is rampant are at least 30 years younger than the 79-year-old TAVR recipients in the study.

In a comment, Dr. Williams said there are several unanswered questions about the full impact TAVR could have in the treatment of young RHD patients in underprivileged regions. “These mainly concern the durability of the valves in individuals who could expect greater longevity than the typical heart valve patient in the USA, and the adaptation of transcatheter techniques to provide cost-effective treatment in regions that lack the usual sophisticated clinical infrastructure.”

Dr. Mentias received support from a National Research Service Award institutional grant to the Abboud Cardiovascular Research Center. Dr. Williams and coauthors are directors of Strait Access Technologies.

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

Patients with rheumatic heart disease (RHD) appear to have comparable outcomes, whether undergoing transcatheter or surgical aortic valve replacement (TAVR/SAVR), and when compared with TAVR in patients with nonrheumatic aortic stenosis, a new Medicare study finds.

An analysis of data from 1,159 Medicare beneficiaries with rheumatic aortic stenosis revealed that, over a median follow-up of 19 months, there was no difference in all-cause mortality with TAVR vs. SAVR (11.2 vs. 7.0 per 100 person-years; adjusted hazard ratio, 1.53; P = .2).

Mortality was also similar after a median follow-up of 17 months between TAVR in patients with rheumatic aortic stenosis and 88,554 additional beneficiaries with nonrheumatic aortic stenosis (15.2 vs. 17.7 deaths per 100 person-years; aHR, 0.87; P = .2).

“We need collaboration between industry and society leaders in developed countries to initiate a randomized, controlled trial to address the feasibility of TAVR in rheumatic heart disease in younger populations who aren’t surgical candidates or if there’s a lack of surgical capabilities in countries, but this is an encouraging first sign,” lead author Amgad Mentias, MD, MSc, Cleveland Clinic Foundation, said in an interview.

Although the prevalence of rheumatic heart disease (RHD) has fallen to less than 5% or so in the United States and Europe, it remains a significant problem in developing and low-income countries, with more than 1 million deaths per year, he noted. RHD patients typically present at younger ages, often with concomitant aortic regurgitation and mitral valve disease, but have less calcification than degenerative calcific aortic stenosis.

Commenting on the results, published in the Journal of the American College of Cardiology, David F. Williams, PhD, said in an interview that “it is only now becoming possible to entertain the use of TAVR in such patients, and this paper demonstrates the feasibility of doing so.

“Although the study is based on geriatric patients of an industrialized country, it opens the door to the massive unmet clinical needs in poorer regions as well as emerging economies,” said Dr. Williams, a professor at the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., and coauthor of an accompanying editorial.

The study included Medicare beneficiaries treated from October 2015 to December 2017 for rheumatic aortic stenosis (TAVR, n = 605; SAVR, n = 55) or nonrheumatic aortic stenosis (n = 88,554).

Among those with rheumatic disease, SAVR patients were younger than TAVR patients (73.4 vs. 79.4 years), had a lower prevalence of most comorbidities, and were less frail (median frailty score, 5.3 vs. 11.3).

SAVR was associated with significantly higher weighted risk for in-hospital acute kidney injury (22.3% vs. 11.9%), blood transfusion (19.8% vs. 7.6%), cardiogenic shock (5.7% vs. 1.5%), new-onset atrial fibrillation (21.1% vs. 2.2%), and had longer hospital stays (median, 8 vs. 3 days), whereas new permanent pacemaker implantations trended higher with TAVR (12.5% vs 7.2%).

The TAVR and SAVR groups had comparable rates of adjusted in-hospital mortality (2.4% vs. 3.5%), 30-day mortality (3.6% vs. 3.2%), 30-day stroke (2.4% vs. 2.8%), and 1-year mortality (13.1% vs. 8.9%).

Among the two TAVR cohorts, patients with rheumatic disease were younger than those with nonrheumatic aortic stenosis (79.4 vs. 81.2 years); had a higher prevalence of heart failure, ischemic stroke, atrial fibrillation, and lung disease; and were more frail (median score, 11.3 vs. 6.9).

Still, there was no difference in weighted risk of in-hospital mortality (2.2% vs. 2.6%), 30-day mortality (3.6% vs. 3.7%), 30-day stroke (2.0% vs. 3.3%), or 1-year mortality (16.0% vs. 17.1%) between TAVR patients with and without rheumatic stenosis.

“We didn’t have specific information on echo[cardiography], so we don’t know how that affected our results, but one of the encouraging points is that after a median follow-up of almost 2 years, none of the patients who had TAVR in the rheumatic valve and who survived required redo aortic valve replacement,” Dr. Mentias said. “It’s still short term but it shows that for the short to mid term, the valve is durable.”

Data were not available on paravalvular regurgitation, an Achilles heel for TAVR, but Dr. Mentias said rates of this complication have come down significantly in the past 2 years with modifications to newer-generation TAVR valves.

Dr. Williams and colleagues say one main limitation of the study also highlights the major shortcoming of contemporary TAVRs when treating patients with RHD: “namely, their inadequate suitability for AR [aortic regurgitation], the predominant rheumatic lesion of the aortic valve” in low- to middle-income countries.

They pointed out that patients needing an aortic valve where RHD is rampant are at least 30 years younger than the 79-year-old TAVR recipients in the study.

In a comment, Dr. Williams said there are several unanswered questions about the full impact TAVR could have in the treatment of young RHD patients in underprivileged regions. “These mainly concern the durability of the valves in individuals who could expect greater longevity than the typical heart valve patient in the USA, and the adaptation of transcatheter techniques to provide cost-effective treatment in regions that lack the usual sophisticated clinical infrastructure.”

Dr. Mentias received support from a National Research Service Award institutional grant to the Abboud Cardiovascular Research Center. Dr. Williams and coauthors are directors of Strait Access Technologies.

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

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

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

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

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

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

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

Michigan cardiologist Dinesh M. Shah, MD, has paid the United States $2 million to resolve claims he violated the False Claims Act by knowingly billing federal health care programs for diagnostic tests that were unnecessary or not performed, the Department of Justice announced.

The settlement resolves allegations that, from 2006 to 2017, Dr. Shah and his practice, Michigan Physicians Group (MPG), of which he is sole owner, billed Medicare, Medicaid, and TRICARE for unnecessary diagnostic tests, including ankle brachial index and toe brachial index tests that were routinely performed on patients without first being ordered by a physician and without regard to medical necessity.

The prosecutors also alleged that Dr. Shah was routinely ordering, and MPG was providing, unnecessary nuclear stress tests to some patients.

“Subjecting patients to unnecessary testing in order to fill one’s pockets with taxpayer funds will not be tolerated. Such practices are particularly concerning because overuse of some tests can be harmful to patients,” acting U.S. Attorney Saima Mohsin said in the news release. “With these lawsuits and the accompanying resolution, Dr. Shah and Michigan Physicians Group are being held to account for these exploitative and improper past practices.”

In addition to the settlement, Dr. Shah and MPG entered into an Integrity Agreement with the Office of Inspector General for the Department of Health & Human Services, which will provide oversight of Dr. Shah and MPG’s billing practices for a 3-year period.

There was “no determination of liability” with the settlement, according to the Department of Justice. Dr. Shah’s case was sparked by two whistleblower lawsuits filed by Arlene Klinke and Khrystyna Malva, both former MPG employees.

The settlement comes after a years-long investigation by the HHS acting on behalf of TRICARE, a health care program for active and retired military members. Allegations that William Beaumont Hospital in Royal Oak, Mich., paid eight physicians excessive compensation to increase patient referrals led to an $84.5 million settlement in 2018.

Dr. Shah was one of three private practice cardiologists who denied involvement in the scheme but were named in the settlement, according to Crain’s Detroit Business.

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

Michigan cardiologist Dinesh M. Shah, MD, has paid the United States $2 million to resolve claims he violated the False Claims Act by knowingly billing federal health care programs for diagnostic tests that were unnecessary or not performed, the Department of Justice announced.

The settlement resolves allegations that, from 2006 to 2017, Dr. Shah and his practice, Michigan Physicians Group (MPG), of which he is sole owner, billed Medicare, Medicaid, and TRICARE for unnecessary diagnostic tests, including ankle brachial index and toe brachial index tests that were routinely performed on patients without first being ordered by a physician and without regard to medical necessity.

The prosecutors also alleged that Dr. Shah was routinely ordering, and MPG was providing, unnecessary nuclear stress tests to some patients.

“Subjecting patients to unnecessary testing in order to fill one’s pockets with taxpayer funds will not be tolerated. Such practices are particularly concerning because overuse of some tests can be harmful to patients,” acting U.S. Attorney Saima Mohsin said in the news release. “With these lawsuits and the accompanying resolution, Dr. Shah and Michigan Physicians Group are being held to account for these exploitative and improper past practices.”

In addition to the settlement, Dr. Shah and MPG entered into an Integrity Agreement with the Office of Inspector General for the Department of Health & Human Services, which will provide oversight of Dr. Shah and MPG’s billing practices for a 3-year period.

There was “no determination of liability” with the settlement, according to the Department of Justice. Dr. Shah’s case was sparked by two whistleblower lawsuits filed by Arlene Klinke and Khrystyna Malva, both former MPG employees.

The settlement comes after a years-long investigation by the HHS acting on behalf of TRICARE, a health care program for active and retired military members. Allegations that William Beaumont Hospital in Royal Oak, Mich., paid eight physicians excessive compensation to increase patient referrals led to an $84.5 million settlement in 2018.

Dr. Shah was one of three private practice cardiologists who denied involvement in the scheme but were named in the settlement, according to Crain’s Detroit Business.

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

Michigan cardiologist Dinesh M. Shah, MD, has paid the United States $2 million to resolve claims he violated the False Claims Act by knowingly billing federal health care programs for diagnostic tests that were unnecessary or not performed, the Department of Justice announced.

The settlement resolves allegations that, from 2006 to 2017, Dr. Shah and his practice, Michigan Physicians Group (MPG), of which he is sole owner, billed Medicare, Medicaid, and TRICARE for unnecessary diagnostic tests, including ankle brachial index and toe brachial index tests that were routinely performed on patients without first being ordered by a physician and without regard to medical necessity.

The prosecutors also alleged that Dr. Shah was routinely ordering, and MPG was providing, unnecessary nuclear stress tests to some patients.

“Subjecting patients to unnecessary testing in order to fill one’s pockets with taxpayer funds will not be tolerated. Such practices are particularly concerning because overuse of some tests can be harmful to patients,” acting U.S. Attorney Saima Mohsin said in the news release. “With these lawsuits and the accompanying resolution, Dr. Shah and Michigan Physicians Group are being held to account for these exploitative and improper past practices.”

In addition to the settlement, Dr. Shah and MPG entered into an Integrity Agreement with the Office of Inspector General for the Department of Health & Human Services, which will provide oversight of Dr. Shah and MPG’s billing practices for a 3-year period.

There was “no determination of liability” with the settlement, according to the Department of Justice. Dr. Shah’s case was sparked by two whistleblower lawsuits filed by Arlene Klinke and Khrystyna Malva, both former MPG employees.

The settlement comes after a years-long investigation by the HHS acting on behalf of TRICARE, a health care program for active and retired military members. Allegations that William Beaumont Hospital in Royal Oak, Mich., paid eight physicians excessive compensation to increase patient referrals led to an $84.5 million settlement in 2018.

Dr. Shah was one of three private practice cardiologists who denied involvement in the scheme but were named in the settlement, according to Crain’s Detroit Business.

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

The Food and Drug Administration has approved Medtronic’s Harmony Transcatheter Pulmonary Valve (TPV) System to treat severe pulmonary regurgitation in pediatric and adult patients who have a native or surgically repaired right ventricular outflow tract (RVOT).

The Harmony TPV is the first nonsurgical heart valve to treat severe pulmonary valve regurgitation, which is common in patients with congenital heart disease, the agency said in a news release. Its use can delay the time before a patient needs open-heart surgery and potentially reduce the number of these surgeries required over a lifetime.

“The Harmony TPV provides a new treatment option for adult and pediatric patients with certain types of congenital heart disease,” Bram Zuckerman, MD, director of the Office of Cardiovascular Devices in the FDA’s Center for Devices and Radiological Health, said in the statement.

“It offers a less-invasive treatment alternative to open-heart surgery to patients with a leaky native or surgically repaired RVOT and may help patients improve their quality of life and return to their normal activities more quickly, thus fulfilling an unmet clinical need of many patients with congenital heart disease,” he said.

The Harmony valve, which was granted breakthrough device designation, is a 22-mm or 25-mm porcine pericardium valve, sewn to a nitinol frame. It is implanted with a 25-French delivery system using a coil-loading catheter.

The FDA approval was based on the 70-patient prospective, nonrandomized, multicenter Harmony TPV Clinical study, in which 100% of patients achieved the primary safety endpoint of no procedure or device-related deaths 30 days after implantation.

Among 65 patients with evaluable echocardiographic data, 89.2% met the primary effectiveness endpoint of no additional surgical or interventional device-related procedures and acceptable heart blood flow at 6 months.

Adverse events included irregular or abnormal heart rhythms in 23.9% of patients, including 14.1% ventricular tachycardia; leakage around the valve in 8.5%, including 1.4% major leakage; minor bleeding in 7.0%, narrowing of the pulmonary valve in 4.2%, and movement of the implant in 4.2%.

Follow-up was scheduled annually through 5 years and has been extended to 10 years as part of the postapproval study, the FDA noted.

The Harmony TPV device is contraindicated for patients with an infection in the heart or elsewhere, for patients who cannot tolerate blood-thinning medicines, and for those with a sensitivity to nitinol (titanium or nickel).

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

The Food and Drug Administration has approved Medtronic’s Harmony Transcatheter Pulmonary Valve (TPV) System to treat severe pulmonary regurgitation in pediatric and adult patients who have a native or surgically repaired right ventricular outflow tract (RVOT).

The Harmony TPV is the first nonsurgical heart valve to treat severe pulmonary valve regurgitation, which is common in patients with congenital heart disease, the agency said in a news release. Its use can delay the time before a patient needs open-heart surgery and potentially reduce the number of these surgeries required over a lifetime.

“The Harmony TPV provides a new treatment option for adult and pediatric patients with certain types of congenital heart disease,” Bram Zuckerman, MD, director of the Office of Cardiovascular Devices in the FDA’s Center for Devices and Radiological Health, said in the statement.

“It offers a less-invasive treatment alternative to open-heart surgery to patients with a leaky native or surgically repaired RVOT and may help patients improve their quality of life and return to their normal activities more quickly, thus fulfilling an unmet clinical need of many patients with congenital heart disease,” he said.

The Harmony valve, which was granted breakthrough device designation, is a 22-mm or 25-mm porcine pericardium valve, sewn to a nitinol frame. It is implanted with a 25-French delivery system using a coil-loading catheter.

The FDA approval was based on the 70-patient prospective, nonrandomized, multicenter Harmony TPV Clinical study, in which 100% of patients achieved the primary safety endpoint of no procedure or device-related deaths 30 days after implantation.

Among 65 patients with evaluable echocardiographic data, 89.2% met the primary effectiveness endpoint of no additional surgical or interventional device-related procedures and acceptable heart blood flow at 6 months.

Adverse events included irregular or abnormal heart rhythms in 23.9% of patients, including 14.1% ventricular tachycardia; leakage around the valve in 8.5%, including 1.4% major leakage; minor bleeding in 7.0%, narrowing of the pulmonary valve in 4.2%, and movement of the implant in 4.2%.

Follow-up was scheduled annually through 5 years and has been extended to 10 years as part of the postapproval study, the FDA noted.

The Harmony TPV device is contraindicated for patients with an infection in the heart or elsewhere, for patients who cannot tolerate blood-thinning medicines, and for those with a sensitivity to nitinol (titanium or nickel).

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

The Food and Drug Administration has approved Medtronic’s Harmony Transcatheter Pulmonary Valve (TPV) System to treat severe pulmonary regurgitation in pediatric and adult patients who have a native or surgically repaired right ventricular outflow tract (RVOT).

The Harmony TPV is the first nonsurgical heart valve to treat severe pulmonary valve regurgitation, which is common in patients with congenital heart disease, the agency said in a news release. Its use can delay the time before a patient needs open-heart surgery and potentially reduce the number of these surgeries required over a lifetime.

“The Harmony TPV provides a new treatment option for adult and pediatric patients with certain types of congenital heart disease,” Bram Zuckerman, MD, director of the Office of Cardiovascular Devices in the FDA’s Center for Devices and Radiological Health, said in the statement.

“It offers a less-invasive treatment alternative to open-heart surgery to patients with a leaky native or surgically repaired RVOT and may help patients improve their quality of life and return to their normal activities more quickly, thus fulfilling an unmet clinical need of many patients with congenital heart disease,” he said.

The Harmony valve, which was granted breakthrough device designation, is a 22-mm or 25-mm porcine pericardium valve, sewn to a nitinol frame. It is implanted with a 25-French delivery system using a coil-loading catheter.

The FDA approval was based on the 70-patient prospective, nonrandomized, multicenter Harmony TPV Clinical study, in which 100% of patients achieved the primary safety endpoint of no procedure or device-related deaths 30 days after implantation.

Among 65 patients with evaluable echocardiographic data, 89.2% met the primary effectiveness endpoint of no additional surgical or interventional device-related procedures and acceptable heart blood flow at 6 months.

Adverse events included irregular or abnormal heart rhythms in 23.9% of patients, including 14.1% ventricular tachycardia; leakage around the valve in 8.5%, including 1.4% major leakage; minor bleeding in 7.0%, narrowing of the pulmonary valve in 4.2%, and movement of the implant in 4.2%.

Follow-up was scheduled annually through 5 years and has been extended to 10 years as part of the postapproval study, the FDA noted.

The Harmony TPV device is contraindicated for patients with an infection in the heart or elsewhere, for patients who cannot tolerate blood-thinning medicines, and for those with a sensitivity to nitinol (titanium or nickel).

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

The Food and Drug Administration has approved rilonacept (Arcalyst) to treat recurrent pericarditis and reduce the risk for recurrence in adults and children 12 years and older.

Approval of the weekly subcutaneous injection offers patients the first and only FDA-approved therapy for recurrent pericarditis, the agency said in a release.

Recurrent pericarditis is characterized by a remitting relapsing inflammation of the pericardium, and therapeutic options have been limited to NSAIDs, colchicine, and corticosteroids.

Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. It is already approved by the FDA to treat a group of rare inherited inflammatory diseases called cryopyrin-associated periodic syndromes.

The new indication is based on the pivotal phase 3 RHAPSODY trial in 86 patients with acute symptoms of recurrent pericarditis and systemic inflammation. After randomization, pericarditis recurred in 2 of 30 patients (7%) treated with rilonacept and in 23 of 31 patients (74%) treated with placebo, representing a 96% reduction in the relative risk for recurrence with rilonacept.

Patients who received rilonacept were also pain free or had minimal pain on 98% of trial days, whereas those who received placebo had minimal or no pain on 46% of trial days.

The most common adverse effects of rilonacept are injection-site reactions and upper-respiratory tract infections.

Serious, life-threatening infections have been reported in patients taking rilonacept, according to the FDA. Patients with active or chronic infections should not take the drug.

The FDA label also advises that patients should avoid live vaccines while taking rilonacept and that it should be discontinued if a hypersensitivity reaction occurs.

The commercial launch is expected in April, according to the company.

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

The Food and Drug Administration has approved rilonacept (Arcalyst) to treat recurrent pericarditis and reduce the risk for recurrence in adults and children 12 years and older.

Approval of the weekly subcutaneous injection offers patients the first and only FDA-approved therapy for recurrent pericarditis, the agency said in a release.

Recurrent pericarditis is characterized by a remitting relapsing inflammation of the pericardium, and therapeutic options have been limited to NSAIDs, colchicine, and corticosteroids.

Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. It is already approved by the FDA to treat a group of rare inherited inflammatory diseases called cryopyrin-associated periodic syndromes.

The new indication is based on the pivotal phase 3 RHAPSODY trial in 86 patients with acute symptoms of recurrent pericarditis and systemic inflammation. After randomization, pericarditis recurred in 2 of 30 patients (7%) treated with rilonacept and in 23 of 31 patients (74%) treated with placebo, representing a 96% reduction in the relative risk for recurrence with rilonacept.

Patients who received rilonacept were also pain free or had minimal pain on 98% of trial days, whereas those who received placebo had minimal or no pain on 46% of trial days.

The most common adverse effects of rilonacept are injection-site reactions and upper-respiratory tract infections.

Serious, life-threatening infections have been reported in patients taking rilonacept, according to the FDA. Patients with active or chronic infections should not take the drug.

The FDA label also advises that patients should avoid live vaccines while taking rilonacept and that it should be discontinued if a hypersensitivity reaction occurs.

The commercial launch is expected in April, according to the company.

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

The Food and Drug Administration has approved rilonacept (Arcalyst) to treat recurrent pericarditis and reduce the risk for recurrence in adults and children 12 years and older.

Approval of the weekly subcutaneous injection offers patients the first and only FDA-approved therapy for recurrent pericarditis, the agency said in a release.

Recurrent pericarditis is characterized by a remitting relapsing inflammation of the pericardium, and therapeutic options have been limited to NSAIDs, colchicine, and corticosteroids.

Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha and interleukin-1 beta signaling. It is already approved by the FDA to treat a group of rare inherited inflammatory diseases called cryopyrin-associated periodic syndromes.

The new indication is based on the pivotal phase 3 RHAPSODY trial in 86 patients with acute symptoms of recurrent pericarditis and systemic inflammation. After randomization, pericarditis recurred in 2 of 30 patients (7%) treated with rilonacept and in 23 of 31 patients (74%) treated with placebo, representing a 96% reduction in the relative risk for recurrence with rilonacept.

Patients who received rilonacept were also pain free or had minimal pain on 98% of trial days, whereas those who received placebo had minimal or no pain on 46% of trial days.

The most common adverse effects of rilonacept are injection-site reactions and upper-respiratory tract infections.

Serious, life-threatening infections have been reported in patients taking rilonacept, according to the FDA. Patients with active or chronic infections should not take the drug.

The FDA label also advises that patients should avoid live vaccines while taking rilonacept and that it should be discontinued if a hypersensitivity reaction occurs.

The commercial launch is expected in April, according to the company.

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

A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.

Bruce Jancin/Frontline Medical News

Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.

“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.

The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”

Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.

The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.

As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.

Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).

No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.

Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).

Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”

In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.

“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.

“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”

Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.

The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.

“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”

C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.

“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.

“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”

The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.

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

A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.

Bruce Jancin/Frontline Medical News

Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.

“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.

The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”

Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.

The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.

As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.

Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).

No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.

Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).

Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”

In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.

“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.

“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”

Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.

The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.

“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”

C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.

“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.

“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”

The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.

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

A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.

Bruce Jancin/Frontline Medical News

Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.

“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.

The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”

Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.

The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.

As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.

Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).

No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.

Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).

Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”

In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.

“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.

“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”

Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.

The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.

“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”

C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.

“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.

“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”

The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.

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

Being obese and pregnant raises the risk for cardiac complications in women with preexisting heart disease, new research suggests, highlighting the need for earlier interventions in this high-risk population.

The analysis of 790 pregnancies revealed that 23% of women with obesity, defined as body mass index greater than 30 kg/m2, had a cardiac event during pregnancy versus 14% of women with normal body weight (P = .006).

The difference was driven largely by an increase in heart failure (8% vs. 3%; P = .02), although arrhythmias also trended higher in obese women (14% vs. 10%; P = .19).

Nearly half of the women with obesity and a cardiac event presented in the postpartum period (47%).

In multivariate analysis, both obesity and Canadian Cardiac Disease in Pregnancy Study (CARPREG) II risk score were independent predictors of cardiac events (odds ratios for both, 1.7), the investigators, led by Birgit Pfaller, MD, University of Toronto, reported in the Journal of the American College of Cardiology.

Although obesity has been linked to worse pregnancy outcomes and higher cardiovascular risk after delivery in the general population, the authors noted that this is the first study to examine its effect on outcomes in women with heart disease.

“We wanted to look at this high-risk group of women that had preexisting heart disease, but in addition had obesity, to try and find out if there was a kind of double hit for these women – and that, in the end, is what we found. It’s not just simply having heart disease, not simply having obesity, but the combination that’s problematic,” senior author and cardiologist Candice Silversides, MD, University of Toronto, said in an interview.

The findings are concerning given the rising prevalence of obesity worldwide. National data from 2018 show that slightly more than half of women who gave birth in the United States were significantly overweight or obese before becoming pregnant.

Similarly, in the present analysis of 600 women in the CARPREG study who gave birth from 2004 to 2014, nearly 1 in 5 pregnancies (19%) occurred in women with obesity and 25% were in overweight women.

Obese women were significantly more likely than those without obesity to have coronary artery disease (6% vs. 2%), cardiomyopathies (19% vs. 8%) and left ventricular dysfunction (19% vs. 12%) and to be hypertensive or have a hypertensive disorder of pregnancy (13% vs. 3%).

Preeclampsia developed in 32 women during the index pregnancy and 69% of these women were obese or overweight. Cardiac event rates were similar in women with or without preeclampsia but trended higher in women with preeclampsia with versus without obesity (36% vs. 14%; P = .20).

The ill effects of obesity were also reflected in fetal and neonatal events. Overall, 43% of women with obesity and 33% of normal-weight women had at least one fetal event (P = .02), with higher rates of preterm birth (19% vs. 10%; P = .005) and respiratory distress syndrome (8% vs. 3%; P = .02) in women with obesity. Congenital cardiac malformations were present in 6% of women in both groups.

Taken together, the composite of cardiac events, preeclampsia, or fetal events was significantly more common in women with obesity than in normal-weight women (56% vs. 41%; P = .002).

“We’ve spent the last number of years trying to research and understand what the drivers of these adverse outcomes are in this high-risk pregnant cohort, but on a bigger picture the real issue is how do we start intervening in a meaningful way,” Dr. Silversides said.

Like many in the burgeoning field of cardio-obstetrics, the team proposed a multidisciplinary approach that stresses preconception counseling, educating pregnant women with heart disease and obesity about their risks, ensuring that dietary advice, weight-gain recommendations, and comorbidities are addressed as part of routine care, and providing postpartum surveillance.

Preconception screening “has been the recommendation for a long, long time; it’s just that it doesn’t always happen in reality,” she said. “Many pregnancies aren’t planned and not all women are filtered into preconception counseling. So sometimes you’ll do it at the first antenatal visit and try to ensure women are educated but optimally you want to do it well in advance of pregnancy.”

Part of that preconception counseling “should also include giving them appropriate advice for contraception, if what they want to do is avoid pregnancy,” added Dr. Silversides.

Garima Sharma, MD, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, and colleagues wrote in an accompanying editorial that the adverse events observed in this high-risk cohort have “important implications for cardio-obstetricians and should be incorporated in routine prepregnancy and antenatal counseling, monitoring, and risk stratification for women with existing cardiovascular disease.”

They pointed to a paucity of data incorporating maternal prepregnancy obesity and gestational weight gain in risk prediction and called for larger population-based studies on the additive impact of obesity severity on predicting adverse cardiac events in women with existing cardiovascular disease.

Randomized trials are also urgently needed to evaluate the effect of nutritional and behavioral interventions in pregnancy on short- and long-term outcomes in mother and child.

“As the obesity epidemic continues to grow and public health interventions promoting lifestyle changes for obesity management remain a major challenge, maternal obesity may prove to be the ‘Achilles’ heel’ of sustainable national efforts to reduce maternal mortality and improve health equity. This is a call to action,” Dr. Sharma and colleagues concluded.

The investigators noted that the study was conducted at a single center and used self-reported pregnancy weight collected at the first antenatal visit, which may have underestimated obesity rates. Other limitations are that weight changes over the course of pregnancy were not studied and there was a limited number of women with a body mass index of 40 or higher.

The study was supported by a grant from the Allan E. Tiffin Trust, Toronto General and Western Hospital Foundation, and by a donation from Mrs. Josephine Rogers, Toronto General Hospital. Dr. Silversides is supported by the Miles Nadal Chair in Pregnancy and Heart Disease. Dr. Sharma and colleagues disclosed no relevant financial relationships.

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

Being obese and pregnant raises the risk for cardiac complications in women with preexisting heart disease, new research suggests, highlighting the need for earlier interventions in this high-risk population.

The analysis of 790 pregnancies revealed that 23% of women with obesity, defined as body mass index greater than 30 kg/m2, had a cardiac event during pregnancy versus 14% of women with normal body weight (P = .006).

The difference was driven largely by an increase in heart failure (8% vs. 3%; P = .02), although arrhythmias also trended higher in obese women (14% vs. 10%; P = .19).

Nearly half of the women with obesity and a cardiac event presented in the postpartum period (47%).

In multivariate analysis, both obesity and Canadian Cardiac Disease in Pregnancy Study (CARPREG) II risk score were independent predictors of cardiac events (odds ratios for both, 1.7), the investigators, led by Birgit Pfaller, MD, University of Toronto, reported in the Journal of the American College of Cardiology.

Although obesity has been linked to worse pregnancy outcomes and higher cardiovascular risk after delivery in the general population, the authors noted that this is the first study to examine its effect on outcomes in women with heart disease.

“We wanted to look at this high-risk group of women that had preexisting heart disease, but in addition had obesity, to try and find out if there was a kind of double hit for these women – and that, in the end, is what we found. It’s not just simply having heart disease, not simply having obesity, but the combination that’s problematic,” senior author and cardiologist Candice Silversides, MD, University of Toronto, said in an interview.

The findings are concerning given the rising prevalence of obesity worldwide. National data from 2018 show that slightly more than half of women who gave birth in the United States were significantly overweight or obese before becoming pregnant.

Similarly, in the present analysis of 600 women in the CARPREG study who gave birth from 2004 to 2014, nearly 1 in 5 pregnancies (19%) occurred in women with obesity and 25% were in overweight women.

Obese women were significantly more likely than those without obesity to have coronary artery disease (6% vs. 2%), cardiomyopathies (19% vs. 8%) and left ventricular dysfunction (19% vs. 12%) and to be hypertensive or have a hypertensive disorder of pregnancy (13% vs. 3%).

Preeclampsia developed in 32 women during the index pregnancy and 69% of these women were obese or overweight. Cardiac event rates were similar in women with or without preeclampsia but trended higher in women with preeclampsia with versus without obesity (36% vs. 14%; P = .20).

The ill effects of obesity were also reflected in fetal and neonatal events. Overall, 43% of women with obesity and 33% of normal-weight women had at least one fetal event (P = .02), with higher rates of preterm birth (19% vs. 10%; P = .005) and respiratory distress syndrome (8% vs. 3%; P = .02) in women with obesity. Congenital cardiac malformations were present in 6% of women in both groups.

Taken together, the composite of cardiac events, preeclampsia, or fetal events was significantly more common in women with obesity than in normal-weight women (56% vs. 41%; P = .002).

“We’ve spent the last number of years trying to research and understand what the drivers of these adverse outcomes are in this high-risk pregnant cohort, but on a bigger picture the real issue is how do we start intervening in a meaningful way,” Dr. Silversides said.

Like many in the burgeoning field of cardio-obstetrics, the team proposed a multidisciplinary approach that stresses preconception counseling, educating pregnant women with heart disease and obesity about their risks, ensuring that dietary advice, weight-gain recommendations, and comorbidities are addressed as part of routine care, and providing postpartum surveillance.

Preconception screening “has been the recommendation for a long, long time; it’s just that it doesn’t always happen in reality,” she said. “Many pregnancies aren’t planned and not all women are filtered into preconception counseling. So sometimes you’ll do it at the first antenatal visit and try to ensure women are educated but optimally you want to do it well in advance of pregnancy.”

Part of that preconception counseling “should also include giving them appropriate advice for contraception, if what they want to do is avoid pregnancy,” added Dr. Silversides.

Garima Sharma, MD, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, and colleagues wrote in an accompanying editorial that the adverse events observed in this high-risk cohort have “important implications for cardio-obstetricians and should be incorporated in routine prepregnancy and antenatal counseling, monitoring, and risk stratification for women with existing cardiovascular disease.”

They pointed to a paucity of data incorporating maternal prepregnancy obesity and gestational weight gain in risk prediction and called for larger population-based studies on the additive impact of obesity severity on predicting adverse cardiac events in women with existing cardiovascular disease.

Randomized trials are also urgently needed to evaluate the effect of nutritional and behavioral interventions in pregnancy on short- and long-term outcomes in mother and child.

“As the obesity epidemic continues to grow and public health interventions promoting lifestyle changes for obesity management remain a major challenge, maternal obesity may prove to be the ‘Achilles’ heel’ of sustainable national efforts to reduce maternal mortality and improve health equity. This is a call to action,” Dr. Sharma and colleagues concluded.

The investigators noted that the study was conducted at a single center and used self-reported pregnancy weight collected at the first antenatal visit, which may have underestimated obesity rates. Other limitations are that weight changes over the course of pregnancy were not studied and there was a limited number of women with a body mass index of 40 or higher.

The study was supported by a grant from the Allan E. Tiffin Trust, Toronto General and Western Hospital Foundation, and by a donation from Mrs. Josephine Rogers, Toronto General Hospital. Dr. Silversides is supported by the Miles Nadal Chair in Pregnancy and Heart Disease. Dr. Sharma and colleagues disclosed no relevant financial relationships.

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

Being obese and pregnant raises the risk for cardiac complications in women with preexisting heart disease, new research suggests, highlighting the need for earlier interventions in this high-risk population.

The analysis of 790 pregnancies revealed that 23% of women with obesity, defined as body mass index greater than 30 kg/m2, had a cardiac event during pregnancy versus 14% of women with normal body weight (P = .006).

The difference was driven largely by an increase in heart failure (8% vs. 3%; P = .02), although arrhythmias also trended higher in obese women (14% vs. 10%; P = .19).

Nearly half of the women with obesity and a cardiac event presented in the postpartum period (47%).

In multivariate analysis, both obesity and Canadian Cardiac Disease in Pregnancy Study (CARPREG) II risk score were independent predictors of cardiac events (odds ratios for both, 1.7), the investigators, led by Birgit Pfaller, MD, University of Toronto, reported in the Journal of the American College of Cardiology.

Although obesity has been linked to worse pregnancy outcomes and higher cardiovascular risk after delivery in the general population, the authors noted that this is the first study to examine its effect on outcomes in women with heart disease.

“We wanted to look at this high-risk group of women that had preexisting heart disease, but in addition had obesity, to try and find out if there was a kind of double hit for these women – and that, in the end, is what we found. It’s not just simply having heart disease, not simply having obesity, but the combination that’s problematic,” senior author and cardiologist Candice Silversides, MD, University of Toronto, said in an interview.

The findings are concerning given the rising prevalence of obesity worldwide. National data from 2018 show that slightly more than half of women who gave birth in the United States were significantly overweight or obese before becoming pregnant.

Similarly, in the present analysis of 600 women in the CARPREG study who gave birth from 2004 to 2014, nearly 1 in 5 pregnancies (19%) occurred in women with obesity and 25% were in overweight women.

Obese women were significantly more likely than those without obesity to have coronary artery disease (6% vs. 2%), cardiomyopathies (19% vs. 8%) and left ventricular dysfunction (19% vs. 12%) and to be hypertensive or have a hypertensive disorder of pregnancy (13% vs. 3%).

Preeclampsia developed in 32 women during the index pregnancy and 69% of these women were obese or overweight. Cardiac event rates were similar in women with or without preeclampsia but trended higher in women with preeclampsia with versus without obesity (36% vs. 14%; P = .20).

The ill effects of obesity were also reflected in fetal and neonatal events. Overall, 43% of women with obesity and 33% of normal-weight women had at least one fetal event (P = .02), with higher rates of preterm birth (19% vs. 10%; P = .005) and respiratory distress syndrome (8% vs. 3%; P = .02) in women with obesity. Congenital cardiac malformations were present in 6% of women in both groups.

Taken together, the composite of cardiac events, preeclampsia, or fetal events was significantly more common in women with obesity than in normal-weight women (56% vs. 41%; P = .002).

“We’ve spent the last number of years trying to research and understand what the drivers of these adverse outcomes are in this high-risk pregnant cohort, but on a bigger picture the real issue is how do we start intervening in a meaningful way,” Dr. Silversides said.

Like many in the burgeoning field of cardio-obstetrics, the team proposed a multidisciplinary approach that stresses preconception counseling, educating pregnant women with heart disease and obesity about their risks, ensuring that dietary advice, weight-gain recommendations, and comorbidities are addressed as part of routine care, and providing postpartum surveillance.

Preconception screening “has been the recommendation for a long, long time; it’s just that it doesn’t always happen in reality,” she said. “Many pregnancies aren’t planned and not all women are filtered into preconception counseling. So sometimes you’ll do it at the first antenatal visit and try to ensure women are educated but optimally you want to do it well in advance of pregnancy.”

Part of that preconception counseling “should also include giving them appropriate advice for contraception, if what they want to do is avoid pregnancy,” added Dr. Silversides.

Garima Sharma, MD, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, and colleagues wrote in an accompanying editorial that the adverse events observed in this high-risk cohort have “important implications for cardio-obstetricians and should be incorporated in routine prepregnancy and antenatal counseling, monitoring, and risk stratification for women with existing cardiovascular disease.”

They pointed to a paucity of data incorporating maternal prepregnancy obesity and gestational weight gain in risk prediction and called for larger population-based studies on the additive impact of obesity severity on predicting adverse cardiac events in women with existing cardiovascular disease.

Randomized trials are also urgently needed to evaluate the effect of nutritional and behavioral interventions in pregnancy on short- and long-term outcomes in mother and child.

“As the obesity epidemic continues to grow and public health interventions promoting lifestyle changes for obesity management remain a major challenge, maternal obesity may prove to be the ‘Achilles’ heel’ of sustainable national efforts to reduce maternal mortality and improve health equity. This is a call to action,” Dr. Sharma and colleagues concluded.

The investigators noted that the study was conducted at a single center and used self-reported pregnancy weight collected at the first antenatal visit, which may have underestimated obesity rates. Other limitations are that weight changes over the course of pregnancy were not studied and there was a limited number of women with a body mass index of 40 or higher.

The study was supported by a grant from the Allan E. Tiffin Trust, Toronto General and Western Hospital Foundation, and by a donation from Mrs. Josephine Rogers, Toronto General Hospital. Dr. Silversides is supported by the Miles Nadal Chair in Pregnancy and Heart Disease. Dr. Sharma and colleagues disclosed no relevant financial relationships.

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

On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.

“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.

“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.

“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).

The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.

As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.

The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).

Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.

Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.

Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”

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

On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.

“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.

“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.

“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).

The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.

As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.

The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).

Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.

Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.

Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”

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

On the advice of its independent data monitoring committee (DMC), the RECOVERY trial has stopped recruitment to the colchicine arm for lack of efficacy in patients hospitalized with COVID-19.

“The DMC saw no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any prespecified subgroup,” the British investigators announced on March 5.

“The RECOVERY trial has already identified two anti-inflammatory drugs – dexamethasone and tocilizumab – that improve the chances of survival for patients with severe COVID-19. So, it is disappointing that colchicine, which is widely used to treat gout and other inflammatory conditions, has no effect in these patients,” cochief investigator Martin Landray, MBChB, PhD, said in a statement.

“We do large, randomized trials to establish whether a drug that seems promising in theory has real benefits for patients in practice. Unfortunately, colchicine is not one of those,” said Dr. Landry, University of Oxford (England).

The RECOVERY trial is evaluating a range of potential treatments for COVID-19 at 180 hospitals in the United Kingdom, Indonesia, and Nepal, and was designed with the expectation that drugs would be added or dropped as the evidence changes. Since November 2020, the trial has included an arm comparing colchicine with usual care alone.

As part of a routine meeting March 4, the DMC reviewed data from a preliminary analysis based on 2,178 deaths among 11,162 patients, 94% of whom were being treated with a corticosteroid such as dexamethasone.

The results showed no significant difference in the primary endpoint of 28-day mortality in patients randomized to colchicine versus usual care alone (20% vs. 19%; risk ratio, 1.02; 95% confidence interval, 0.94-1.11; P = .63).

Follow-up is ongoing and final results will be published as soon as possible, the investigators said. Thus far, there has been no convincing evidence of an effect of colchicine on clinical outcomes in hospitalized COVID-19 patients.

Recruitment will continue to all other treatment arms – aspirin, baricitinib, Regeneron’s antibody cocktail, and, in select hospitals, dimethyl fumarate – the investigators said.

Cochief investigator Peter Hornby, MD, PhD, also from the University of Oxford, noted that this has been the largest trial ever of colchicine. “Whilst we are disappointed that the overall result is negative, it is still important information for the future care of patients in the U.K. and worldwide.”

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

Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.

kali9/iStockphoto.com

“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”

To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.

The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.

High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.

Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.

As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.

Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.

In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).

There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.

Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.

“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”

Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.

“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”

Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”

The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.

William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.

“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”

The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.

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

Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.

kali9/iStockphoto.com

“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”

To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.

The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.

High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.

Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.

As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.

Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.

In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).

There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.

Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.

“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”

Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.

“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”

Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”

The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.

William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.

“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”

The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.

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

Exercise training – but not testosterone therapy – improved vascular health in aging men with widening midsections and low to normal testosterone, new research suggests.

kali9/iStockphoto.com

“Previous studies have suggested that men with higher levels of testosterone, who were more physically active, might have better health outcomes,” Bu Beng Yeap, MBBS, PhD, University of Western Australia, Perth, said in an interview. “We formulated the hypothesis that the combination of testosterone treatment and exercise training would improve the health of arteries more than either alone.”

To test this hypothesis, the investigators randomly assigned 80 men, aged 50-70 years, to 12 weeks of 5% testosterone cream 2 mL applied daily or placebo plus a supervised exercise program that included machine-based resistance and aerobic (cycling) exercises two to three times a week or no additional exercise.

The men (mean age, 59 years) had low-normal testosterone (6-14 nmol/L), a waist circumference of at least 95 cm (37.4 inches), and no known cardiovascular disease (CVD), type 1 diabetes, or other clinically significant illnesses. Current smokers and men on testosterone or medications that would alter testosterone levels were also excluded.

High-resolution ultrasound of the brachial artery was used to assess flow-mediated dilation (FMD) and sublingual glyceryl trinitrate (GTN) responses. FMD has been shown to be predictive of CVD risk, with a 1% increase in FMD associated with a 9%-13% decrease in future CVD events.

Based on participants’ daily dairies, testosterone adherence was 97.6%. Exercise adherence was 96.5% for twice-weekly attendance and 80.0% for thrice-weekly attendance, with no between-group differences.

As reported Feb. 22, 2021, in Hypertension, testosterone levels increased, on average, 3.0 nmol/L in both testosterone groups by week 12 (P = .003). In all, 62% of these men had levels of the hormone exceeding 14 nmol/L, compared with 29% of those receiving placebo.

Testosterone levels improved with exercise training plus placebo by 0.9 nmol/L, but fell with no exercise and placebo by 0.9 nmol/L.

In terms of vascular function, exercise training increased FMD when expressed as both the delta change (mm; P = .004) and relative rise from baseline diameter (%; P = .033).

There was no effect of exercise on GTN%, which is generally in line with exercise literature indicating that shear-mediated adaptations in response to episodic exercise occur largely in endothelial cells, the authors noted.

Testosterone did not affect any measures of FMD nor was there an effect on GTN response, despite previous evidence that lower testosterone doses might enhance smooth muscle function.

“Our main finding was that testosterone – at this dose over this duration of treatment – did not have a beneficial effect on artery health, nor did it enhance the effect of exercise,” said Dr. Yeap, who is also president of the Endocrine Society of Australia. “For middle-aged and older men wanting to improve the health of their arteries, exercise is better than testosterone!”

Shalender Bhasin, MBBS, director of research programs in men’s health, aging, and metabolism at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said the study is interesting from a mechanistic perspective and adds to the overall body of evidence on how testosterone affects performance, but was narrowly focused.

“They looked at very specific markers and what they’re showing is that this is not the mechanism by which testosterone improves performance,” he said. “That may be so, but it doesn’t negate the finding that testosterone improves endurance and has other vascular effects: it increases capillarity, increases blood flow to the tissues, and improves myocardial function.”

Although well done, the study doesn’t get at the larger question of whether testosterone increases cardiovascular risk, observed Dr. Bhasin. “None of the randomized studies have been large enough or long enough to determine the effect on cardiovascular events rates. There’s a lot of argument on both sides but we need some data to address that.”

The 6,000-patient TRAVERSE trial is specifically looking at long-term major cardiovascular events with topical testosterone, compared with placebo, in hypogonadal men aged 45-80 years age who have evidence of or are at increased risk for CVD. The study, which is set to be completed in April 2022, should also provide information on fracture risk in these men, said Dr. Bhasin, one of the trial’s principal investigators and lead author of the Endocrine Society’s 2018 clinical practice guideline on testosterone therapy for hypogonadism in men.

William Evans, MD, adjunct professor of human nutrition, University of California, Berkley, said in an interview that the positive effects of testosterone occur at much lower doses in men and women who are hypogonadal but, in this particular population, exercise is the key and the major recommendation.

“Testosterone has been overprescribed and overadvertised for essentially a lifetime of sedentary living, and it’s advertised as a way to get all that back without having to work for it,” he said. “Exercise has a profound and positive effect on control of blood pressure, function, and strength, and testosterone may only affect in people who are sick, people who have really low levels.”

The study was funded by the Heart Foundation of Australia. Lawley Pharmaceuticals provided the study medication and placebo. Dr. Yeap has received speaker honoraria and conference support from Bayer, Eli Lilly, and Besins Healthcare; research support from Bayer, Lily, and Lawley; and served as an adviser for Lily, Besins Healthcare, Ferring, and Lawley. Dr. Shalender reports consultation or advisement for GTx, Pfizer, and TAP; grant or other research support from Solvay and GlaxoSmithKline; and honoraria from Solvay and Auxilium. Dr. Evans reported having no relevant conflicts of interest.

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