Interventional Cardiology & Surgery

Atrial fibrillation has been known to confer an increased risk for poor outcomes after transcatheter aortic valve replacement, but there’s been no evidence of how the etiology of AFib can influence post-TAVR outcomes.

enot-poloskun/Getty Images

Now, a group of researchers from Bern (Switzerland) University are reporting that valvular AFib almost triples the risk of death or debilitating stroke, compared with patients with no AFib, and significantly increases the risk over nonvalvular AFib.*

“The present findings may have implications for risk stratification in patients undergoing TAVR,” wrote Taishi Okuno, MD, and colleagues in what they said is the first study “to appreciate the combined effect” of AFib and mitral stenosis in TAVR. “The identification of valvular AFib may refine the estimated risk for adverse clinical outcomes in patients undergoing TAVR,” they wrote in JACC: Cardiovascular Interventions.

“The fact that valvular AFib seems to confer a higher risk is an interesting finding,” Fred Welt, MD, professor of cardiology at the University of Utah, Salt Lake City, said in an interview. “I think it helps to a certain extent in prognostication because we can say to patients who have concomitant mitral valve disease that they are at higher risk.” Dr. Welt is also chair of the American College of Cardiology Interventional Council.

The analysis included 1,472 patients with aortic stenosis who had TAVR at Bern University Hospital between August 2007 and June 2018, 32% of whom (465) had atrial fibrillation, subcategorized as nonvalvular (26%, 376) and valvular (6%, 89). The primary endpoint, a composite of cardiovascular death or disabling stroke 1 year after TAVR, occurred in 9.3% of patients with no AFib, 14.5% of those with nonvalvular AFib and 24.2% of patients with valvular AFib.

In terms of hazard ratios, patients with nonvalvular AFib had a 57% greater risk of poor outcomes (P = .009) and those with valvular AFib had a 275% greater risk (P < .001), compared with patients with no AFib. Patients with valvular AFib had a 77% higher rate of cardiovascular death or stroke than those with nonvalvular AFib (P = .027).**

In their analysis, Dr. Okuno and colleagues acknowledged that the definition of valvular AFib used in guidelines and clinical trials isn’t uniform. Valvular atrial fibrillation was defined as AFib with mitral stenosis or a mitral valve prosthesis.

To account for the varying definitions of valvular and nonvalvular AFib, the researchers performed a sensitivity analysis of AFib patients with significant valve disease other than mitral stenosis; 42% of patients in the nonvalvular group fit this definition. Patients with AFib and valvular disease other than mitral stenosis had almost twice the risk of cardiovascular death or disabling stroke at 1 year, compared with patients who had AFib but no significant disease of any valve (20.1% vs. 10.9%, P = .03).

Furthermore, when they excluded patients with mild mitral stenosis from the valvular AFib group, “the effect of an increased risk for cardiovascular death or disabling stroke was no longer statistically significant.”

When the researchers separated out the two elements of the composite endpoint, they found valvular AFib carried a significantly higher risk of cardiovascular death – 21.1% (P < .002) vs. 7% for no AFib and 12.3% (P = .003) for nonvalvular AFib. However, the incidence of cardiovascular events – disabling stroke, nondisabling stroke and transient ischemic attack – showed no significant difference across the three groups, Dr. Okuno and colleagues noted. Specifically, the rates of disabling stroke were 3.8%, 3.7% and 5.7% in the no-AFib, nonvalvular-AFib, and valvular-AFib groups, respectively

In an invited editorial, Bernard Iung, MD, and Vincent Algalarrondo, MD, PhD, noted the problems with the definitions for valvular and nonvalvular AFib. “The term valvular AFib now frequently refers to patients with AFib associated with moderate or severe mitral stenosis or a mechanical heart valve,” they wrote. The definition is justified, they noted, because there’s little evidence on the use of non–vitamin K antagonist oral anticoagulants (NOACs) in patients with mitral stenosis.

They noted the term nonvalvular is “ambiguous” because it doesn’t exclude valvular disease but rather only a subset defined by the restrictive use of a class of anticoagulants. Hence, the definition of valvular AFib “is subject to criticisms and remains not standardized.”

“The individualization of valvular AFib in patients undergoing TAVR is debatable, and the definition used in the present study also included mild mitral stenosis and bioprostheses, thereby highlighting again the lack of a clear and uniform definition of the concept of valvular AFib,” they wrote.

While Dr. Welt said the findings may help in stratifying risk in patients with valvular AFib, he’s not certain how that would influence treatment decisions. “In most cases when we’re considering TAVR in these patients it’s because they have severe symptomatic aortic stenosis,” he said.

Surgery as an alternative is fraught with consequences, he said. “Would it be because you would want to repair the mitral valve as well?” he said. “And once you get into that territory, you’re talking about double-valve surgery, which is a much riskier operation than isolated aortic valve replacement.”

The study raises important questions about patients with valvular AFib, Dr. Welt added. “Why are these patients dying at higher rate? Is it some other arrhythmia or some other hemodynamic problem? Are there other things we can learn about these patients that would help us to better treat patients?”

But exploring these findings further with a randomized clinical trial may not be practical, he added. “The number of patients in whom this is an issue is in the scheme of things rather low: 6%,” he said.

Dr. Okuno has no relevant financial disclosures. Dr. Iung is a consultant for Edwards Lifesciences. Dr. Algalarrondo has been a consultant for Pfizer and Alnylam. Dr. Welt disclosed a relationship with Medtronic.

SOURCE: Okuno T et al. JACC Cardiovasc Interv. 2020 Sep 21. doi: 10.1016/j.jcin.2020.05.049.

Corrections, 9/29/20: An earlier version of this article misstated the increase in risk of (*) death or debilitating stroke and of (**) a poor outcome in those with valvular Afib.

Atrial fibrillation has been known to confer an increased risk for poor outcomes after transcatheter aortic valve replacement, but there’s been no evidence of how the etiology of AFib can influence post-TAVR outcomes.

enot-poloskun/Getty Images

Now, a group of researchers from Bern (Switzerland) University are reporting that valvular AFib almost triples the risk of death or debilitating stroke, compared with patients with no AFib, and significantly increases the risk over nonvalvular AFib.*

“The present findings may have implications for risk stratification in patients undergoing TAVR,” wrote Taishi Okuno, MD, and colleagues in what they said is the first study “to appreciate the combined effect” of AFib and mitral stenosis in TAVR. “The identification of valvular AFib may refine the estimated risk for adverse clinical outcomes in patients undergoing TAVR,” they wrote in JACC: Cardiovascular Interventions.

“The fact that valvular AFib seems to confer a higher risk is an interesting finding,” Fred Welt, MD, professor of cardiology at the University of Utah, Salt Lake City, said in an interview. “I think it helps to a certain extent in prognostication because we can say to patients who have concomitant mitral valve disease that they are at higher risk.” Dr. Welt is also chair of the American College of Cardiology Interventional Council.

The analysis included 1,472 patients with aortic stenosis who had TAVR at Bern University Hospital between August 2007 and June 2018, 32% of whom (465) had atrial fibrillation, subcategorized as nonvalvular (26%, 376) and valvular (6%, 89). The primary endpoint, a composite of cardiovascular death or disabling stroke 1 year after TAVR, occurred in 9.3% of patients with no AFib, 14.5% of those with nonvalvular AFib and 24.2% of patients with valvular AFib.

In terms of hazard ratios, patients with nonvalvular AFib had a 57% greater risk of poor outcomes (P = .009) and those with valvular AFib had a 275% greater risk (P < .001), compared with patients with no AFib. Patients with valvular AFib had a 77% higher rate of cardiovascular death or stroke than those with nonvalvular AFib (P = .027).**

In their analysis, Dr. Okuno and colleagues acknowledged that the definition of valvular AFib used in guidelines and clinical trials isn’t uniform. Valvular atrial fibrillation was defined as AFib with mitral stenosis or a mitral valve prosthesis.

To account for the varying definitions of valvular and nonvalvular AFib, the researchers performed a sensitivity analysis of AFib patients with significant valve disease other than mitral stenosis; 42% of patients in the nonvalvular group fit this definition. Patients with AFib and valvular disease other than mitral stenosis had almost twice the risk of cardiovascular death or disabling stroke at 1 year, compared with patients who had AFib but no significant disease of any valve (20.1% vs. 10.9%, P = .03).

Furthermore, when they excluded patients with mild mitral stenosis from the valvular AFib group, “the effect of an increased risk for cardiovascular death or disabling stroke was no longer statistically significant.”

When the researchers separated out the two elements of the composite endpoint, they found valvular AFib carried a significantly higher risk of cardiovascular death – 21.1% (P < .002) vs. 7% for no AFib and 12.3% (P = .003) for nonvalvular AFib. However, the incidence of cardiovascular events – disabling stroke, nondisabling stroke and transient ischemic attack – showed no significant difference across the three groups, Dr. Okuno and colleagues noted. Specifically, the rates of disabling stroke were 3.8%, 3.7% and 5.7% in the no-AFib, nonvalvular-AFib, and valvular-AFib groups, respectively

In an invited editorial, Bernard Iung, MD, and Vincent Algalarrondo, MD, PhD, noted the problems with the definitions for valvular and nonvalvular AFib. “The term valvular AFib now frequently refers to patients with AFib associated with moderate or severe mitral stenosis or a mechanical heart valve,” they wrote. The definition is justified, they noted, because there’s little evidence on the use of non–vitamin K antagonist oral anticoagulants (NOACs) in patients with mitral stenosis.

They noted the term nonvalvular is “ambiguous” because it doesn’t exclude valvular disease but rather only a subset defined by the restrictive use of a class of anticoagulants. Hence, the definition of valvular AFib “is subject to criticisms and remains not standardized.”

“The individualization of valvular AFib in patients undergoing TAVR is debatable, and the definition used in the present study also included mild mitral stenosis and bioprostheses, thereby highlighting again the lack of a clear and uniform definition of the concept of valvular AFib,” they wrote.

While Dr. Welt said the findings may help in stratifying risk in patients with valvular AFib, he’s not certain how that would influence treatment decisions. “In most cases when we’re considering TAVR in these patients it’s because they have severe symptomatic aortic stenosis,” he said.

Surgery as an alternative is fraught with consequences, he said. “Would it be because you would want to repair the mitral valve as well?” he said. “And once you get into that territory, you’re talking about double-valve surgery, which is a much riskier operation than isolated aortic valve replacement.”

The study raises important questions about patients with valvular AFib, Dr. Welt added. “Why are these patients dying at higher rate? Is it some other arrhythmia or some other hemodynamic problem? Are there other things we can learn about these patients that would help us to better treat patients?”

But exploring these findings further with a randomized clinical trial may not be practical, he added. “The number of patients in whom this is an issue is in the scheme of things rather low: 6%,” he said.

Dr. Okuno has no relevant financial disclosures. Dr. Iung is a consultant for Edwards Lifesciences. Dr. Algalarrondo has been a consultant for Pfizer and Alnylam. Dr. Welt disclosed a relationship with Medtronic.

SOURCE: Okuno T et al. JACC Cardiovasc Interv. 2020 Sep 21. doi: 10.1016/j.jcin.2020.05.049.

Corrections, 9/29/20: An earlier version of this article misstated the increase in risk of (*) death or debilitating stroke and of (**) a poor outcome in those with valvular Afib.

Atrial fibrillation has been known to confer an increased risk for poor outcomes after transcatheter aortic valve replacement, but there’s been no evidence of how the etiology of AFib can influence post-TAVR outcomes.

enot-poloskun/Getty Images

Now, a group of researchers from Bern (Switzerland) University are reporting that valvular AFib almost triples the risk of death or debilitating stroke, compared with patients with no AFib, and significantly increases the risk over nonvalvular AFib.*

“The present findings may have implications for risk stratification in patients undergoing TAVR,” wrote Taishi Okuno, MD, and colleagues in what they said is the first study “to appreciate the combined effect” of AFib and mitral stenosis in TAVR. “The identification of valvular AFib may refine the estimated risk for adverse clinical outcomes in patients undergoing TAVR,” they wrote in JACC: Cardiovascular Interventions.

“The fact that valvular AFib seems to confer a higher risk is an interesting finding,” Fred Welt, MD, professor of cardiology at the University of Utah, Salt Lake City, said in an interview. “I think it helps to a certain extent in prognostication because we can say to patients who have concomitant mitral valve disease that they are at higher risk.” Dr. Welt is also chair of the American College of Cardiology Interventional Council.

The analysis included 1,472 patients with aortic stenosis who had TAVR at Bern University Hospital between August 2007 and June 2018, 32% of whom (465) had atrial fibrillation, subcategorized as nonvalvular (26%, 376) and valvular (6%, 89). The primary endpoint, a composite of cardiovascular death or disabling stroke 1 year after TAVR, occurred in 9.3% of patients with no AFib, 14.5% of those with nonvalvular AFib and 24.2% of patients with valvular AFib.

In terms of hazard ratios, patients with nonvalvular AFib had a 57% greater risk of poor outcomes (P = .009) and those with valvular AFib had a 275% greater risk (P < .001), compared with patients with no AFib. Patients with valvular AFib had a 77% higher rate of cardiovascular death or stroke than those with nonvalvular AFib (P = .027).**

In their analysis, Dr. Okuno and colleagues acknowledged that the definition of valvular AFib used in guidelines and clinical trials isn’t uniform. Valvular atrial fibrillation was defined as AFib with mitral stenosis or a mitral valve prosthesis.

To account for the varying definitions of valvular and nonvalvular AFib, the researchers performed a sensitivity analysis of AFib patients with significant valve disease other than mitral stenosis; 42% of patients in the nonvalvular group fit this definition. Patients with AFib and valvular disease other than mitral stenosis had almost twice the risk of cardiovascular death or disabling stroke at 1 year, compared with patients who had AFib but no significant disease of any valve (20.1% vs. 10.9%, P = .03).

Furthermore, when they excluded patients with mild mitral stenosis from the valvular AFib group, “the effect of an increased risk for cardiovascular death or disabling stroke was no longer statistically significant.”

When the researchers separated out the two elements of the composite endpoint, they found valvular AFib carried a significantly higher risk of cardiovascular death – 21.1% (P < .002) vs. 7% for no AFib and 12.3% (P = .003) for nonvalvular AFib. However, the incidence of cardiovascular events – disabling stroke, nondisabling stroke and transient ischemic attack – showed no significant difference across the three groups, Dr. Okuno and colleagues noted. Specifically, the rates of disabling stroke were 3.8%, 3.7% and 5.7% in the no-AFib, nonvalvular-AFib, and valvular-AFib groups, respectively

In an invited editorial, Bernard Iung, MD, and Vincent Algalarrondo, MD, PhD, noted the problems with the definitions for valvular and nonvalvular AFib. “The term valvular AFib now frequently refers to patients with AFib associated with moderate or severe mitral stenosis or a mechanical heart valve,” they wrote. The definition is justified, they noted, because there’s little evidence on the use of non–vitamin K antagonist oral anticoagulants (NOACs) in patients with mitral stenosis.

They noted the term nonvalvular is “ambiguous” because it doesn’t exclude valvular disease but rather only a subset defined by the restrictive use of a class of anticoagulants. Hence, the definition of valvular AFib “is subject to criticisms and remains not standardized.”

“The individualization of valvular AFib in patients undergoing TAVR is debatable, and the definition used in the present study also included mild mitral stenosis and bioprostheses, thereby highlighting again the lack of a clear and uniform definition of the concept of valvular AFib,” they wrote.

While Dr. Welt said the findings may help in stratifying risk in patients with valvular AFib, he’s not certain how that would influence treatment decisions. “In most cases when we’re considering TAVR in these patients it’s because they have severe symptomatic aortic stenosis,” he said.

Surgery as an alternative is fraught with consequences, he said. “Would it be because you would want to repair the mitral valve as well?” he said. “And once you get into that territory, you’re talking about double-valve surgery, which is a much riskier operation than isolated aortic valve replacement.”

The study raises important questions about patients with valvular AFib, Dr. Welt added. “Why are these patients dying at higher rate? Is it some other arrhythmia or some other hemodynamic problem? Are there other things we can learn about these patients that would help us to better treat patients?”

But exploring these findings further with a randomized clinical trial may not be practical, he added. “The number of patients in whom this is an issue is in the scheme of things rather low: 6%,” he said.

Dr. Okuno has no relevant financial disclosures. Dr. Iung is a consultant for Edwards Lifesciences. Dr. Algalarrondo has been a consultant for Pfizer and Alnylam. Dr. Welt disclosed a relationship with Medtronic.

SOURCE: Okuno T et al. JACC Cardiovasc Interv. 2020 Sep 21. doi: 10.1016/j.jcin.2020.05.049.

Corrections, 9/29/20: An earlier version of this article misstated the increase in risk of (*) death or debilitating stroke and of (**) a poor outcome in those with valvular Afib.

The landmark ISCHEMIA trial rattled the cardiology world with its message that clinical outcomes weren’t significantly better with a routine initial invasive strategy than with medical therapy alone in patients with stable coronary artery disease and moderate or severe myocardial ischemia on noninvasive testing. But a new prespecified subanalysis from the randomized trial points to a subgroup that might actually benefit from immediate revascularization.

European Society of Cardiology

ISCHEMIA participants in the sweet spot for an initial invasive strategy were the ones with a baseline history of mild to moderate heart failure symptoms and a left ventricular ejection fraction (LVEF) of 35%-45%, Renato Lopes, MD, PhD, reported at the virtual annual congress of the European Society of Cardiology.

“An invasive approach may be beneficial in this subgroup of high-risk patients with moderate to severe ischemia and a history of heart failure and left ventricular dysfunction,” declared Dr. Lopes, professor of medicine at Duke University, Durham, N.C.

He was quick to add, however, that this finding from ISCHEMIA should be considered hypothesis generating in light of the small sample size in the subgroup analysis.

The ISCHEMIA trial randomized 5,179 patients with stable CAD and at least moderate myocardial ischemia on noninvasive testing to a routine invasive or conservative management strategy. At 4 years of follow-up there was no significant between-group difference in cardiovascular outcomes (N Engl J Med. 2020 Apr 9;382[15]:1395-407).

Patients with a baseline LVEF below 35% weren’t eligible for enrollment in ISCHEMIA. That’s because the prior Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) showed patients with ischemic cardiomyopathy and an LVEF below 35% had a significantly lower cardiovascular death rate with surgical revascularization plus medical therapy than optimal medical therapy alone at 10 years of follow-up (N Engl J Med. 2016 Apr 21;374[16]:1511-20).

But what about the impact of immediate revascularization as compared with medical management alone in patients with milder impairment of LVEF in the 35%-45% range and/or a history of symptomatic heart failure? Theoretically, the improved blood flow to ischemic myocardium obtained via revascularization in such patients might activate hibernating myocardium and reduce ventricular dysfunction, thereby reducing the risk of cardiovascular events. The ISCHEMIA trial provided a unique opportunity to prospectively examine this question in 398 affected study participants, Dr. Lopes explained.

This 398-patient subgroup with a baseline history of heart failure and/or left ventricular dysfunction (HF/LVD) was at higher risk than patients without those features. Indeed, the primary outcome in ISCHEMIA – a composite of cardiovascular death, nonfatal MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest – occurred in 22.7% of the HF/LVD group at 4 years of follow-up, compared with 13.8% of the much larger group without HF/LVD. The HF/LVD group also had significantly higher rates of the secondary composite endpoints of cardiovascular death or MI (19.7% vs. 12.3%) and all-cause mortality or heart failure (15% vs. 6.9%).

The provocative central finding in this new subanalysis was that patients in the HF/LVD subgroup fared significantly better in terms of cardiovascular events if randomized to the initial invasive approach. Indeed, their 4-year rate of the primary outcome was 17.2%, compared with 29.3% with an initial conservative approach. The various secondary outcomes followed suit. In contrast, the primary outcome occurred in 13% of patients without HF/LVD who were randomized to the invasive strategy, not significantly different from the 14.6% rate with conservative management.

Drilling deeper into the data, Dr. Lopes and coinvestigators found that the enhanced event-free survival benefit of an initial invasive strategy was restricted to the 28 patients having both a baseline history of symptomatic heart failure and an LVEF of 35%-45%. There was no significant difference in outcomes with an invasive versus conservative strategy in the 177 patients with a history of heart failure whose LVEF was greater than 50% – that is, patients with heart failure with preserved ejection fraction – nor in the 193 participants with an LVEF of 35%-45% but no history of symptomatic heart failure.

In an interview, Mark H. Drazner, MD, commented, “this is an interesting hypothesis, for sure, that warrants further study to confirm whether it’s valid. And if it is valid, there could be real implications. If this is true, I think there could be a decent number of patients out there that this would have implications for.

“The ISCHEMIA trial was a heroic effort. While there are certainly logistical hurdles involved in anybody doing an ISCHEMIA 2 trial based on this small subgroup analysis, other people could start looking at retrospective datasets and see if they can confirm these findings to build momentum to study this further,” said Dr. Drazner, professor of medicine and chief of clinical cardiology at the University of Texas Southwestern Medical Center, Dallas, as well as an associate editor at Circulation.

Dr. Lopes reported receiving research grants from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi-Aventis as well as serving as a consultant to a handful of pharmaceutical companies, none relevant to his presentation.

Simultaneous with his presentation at ESC Congress 2020, Dr. Lopes’ study was published online in Circulation.

[email protected]

SOURCE: Lopes R et al. Circulation. 2020 Aug 29. doi: 10.1161/CIRCULATIONAHA.120.050304.

The landmark ISCHEMIA trial rattled the cardiology world with its message that clinical outcomes weren’t significantly better with a routine initial invasive strategy than with medical therapy alone in patients with stable coronary artery disease and moderate or severe myocardial ischemia on noninvasive testing. But a new prespecified subanalysis from the randomized trial points to a subgroup that might actually benefit from immediate revascularization.

European Society of Cardiology

ISCHEMIA participants in the sweet spot for an initial invasive strategy were the ones with a baseline history of mild to moderate heart failure symptoms and a left ventricular ejection fraction (LVEF) of 35%-45%, Renato Lopes, MD, PhD, reported at the virtual annual congress of the European Society of Cardiology.

“An invasive approach may be beneficial in this subgroup of high-risk patients with moderate to severe ischemia and a history of heart failure and left ventricular dysfunction,” declared Dr. Lopes, professor of medicine at Duke University, Durham, N.C.

He was quick to add, however, that this finding from ISCHEMIA should be considered hypothesis generating in light of the small sample size in the subgroup analysis.

The ISCHEMIA trial randomized 5,179 patients with stable CAD and at least moderate myocardial ischemia on noninvasive testing to a routine invasive or conservative management strategy. At 4 years of follow-up there was no significant between-group difference in cardiovascular outcomes (N Engl J Med. 2020 Apr 9;382[15]:1395-407).

Patients with a baseline LVEF below 35% weren’t eligible for enrollment in ISCHEMIA. That’s because the prior Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) showed patients with ischemic cardiomyopathy and an LVEF below 35% had a significantly lower cardiovascular death rate with surgical revascularization plus medical therapy than optimal medical therapy alone at 10 years of follow-up (N Engl J Med. 2016 Apr 21;374[16]:1511-20).

But what about the impact of immediate revascularization as compared with medical management alone in patients with milder impairment of LVEF in the 35%-45% range and/or a history of symptomatic heart failure? Theoretically, the improved blood flow to ischemic myocardium obtained via revascularization in such patients might activate hibernating myocardium and reduce ventricular dysfunction, thereby reducing the risk of cardiovascular events. The ISCHEMIA trial provided a unique opportunity to prospectively examine this question in 398 affected study participants, Dr. Lopes explained.

This 398-patient subgroup with a baseline history of heart failure and/or left ventricular dysfunction (HF/LVD) was at higher risk than patients without those features. Indeed, the primary outcome in ISCHEMIA – a composite of cardiovascular death, nonfatal MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest – occurred in 22.7% of the HF/LVD group at 4 years of follow-up, compared with 13.8% of the much larger group without HF/LVD. The HF/LVD group also had significantly higher rates of the secondary composite endpoints of cardiovascular death or MI (19.7% vs. 12.3%) and all-cause mortality or heart failure (15% vs. 6.9%).

The provocative central finding in this new subanalysis was that patients in the HF/LVD subgroup fared significantly better in terms of cardiovascular events if randomized to the initial invasive approach. Indeed, their 4-year rate of the primary outcome was 17.2%, compared with 29.3% with an initial conservative approach. The various secondary outcomes followed suit. In contrast, the primary outcome occurred in 13% of patients without HF/LVD who were randomized to the invasive strategy, not significantly different from the 14.6% rate with conservative management.

Drilling deeper into the data, Dr. Lopes and coinvestigators found that the enhanced event-free survival benefit of an initial invasive strategy was restricted to the 28 patients having both a baseline history of symptomatic heart failure and an LVEF of 35%-45%. There was no significant difference in outcomes with an invasive versus conservative strategy in the 177 patients with a history of heart failure whose LVEF was greater than 50% – that is, patients with heart failure with preserved ejection fraction – nor in the 193 participants with an LVEF of 35%-45% but no history of symptomatic heart failure.

In an interview, Mark H. Drazner, MD, commented, “this is an interesting hypothesis, for sure, that warrants further study to confirm whether it’s valid. And if it is valid, there could be real implications. If this is true, I think there could be a decent number of patients out there that this would have implications for.

“The ISCHEMIA trial was a heroic effort. While there are certainly logistical hurdles involved in anybody doing an ISCHEMIA 2 trial based on this small subgroup analysis, other people could start looking at retrospective datasets and see if they can confirm these findings to build momentum to study this further,” said Dr. Drazner, professor of medicine and chief of clinical cardiology at the University of Texas Southwestern Medical Center, Dallas, as well as an associate editor at Circulation.

Dr. Lopes reported receiving research grants from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi-Aventis as well as serving as a consultant to a handful of pharmaceutical companies, none relevant to his presentation.

Simultaneous with his presentation at ESC Congress 2020, Dr. Lopes’ study was published online in Circulation.

[email protected]

SOURCE: Lopes R et al. Circulation. 2020 Aug 29. doi: 10.1161/CIRCULATIONAHA.120.050304.

The landmark ISCHEMIA trial rattled the cardiology world with its message that clinical outcomes weren’t significantly better with a routine initial invasive strategy than with medical therapy alone in patients with stable coronary artery disease and moderate or severe myocardial ischemia on noninvasive testing. But a new prespecified subanalysis from the randomized trial points to a subgroup that might actually benefit from immediate revascularization.

European Society of Cardiology

ISCHEMIA participants in the sweet spot for an initial invasive strategy were the ones with a baseline history of mild to moderate heart failure symptoms and a left ventricular ejection fraction (LVEF) of 35%-45%, Renato Lopes, MD, PhD, reported at the virtual annual congress of the European Society of Cardiology.

“An invasive approach may be beneficial in this subgroup of high-risk patients with moderate to severe ischemia and a history of heart failure and left ventricular dysfunction,” declared Dr. Lopes, professor of medicine at Duke University, Durham, N.C.

He was quick to add, however, that this finding from ISCHEMIA should be considered hypothesis generating in light of the small sample size in the subgroup analysis.

The ISCHEMIA trial randomized 5,179 patients with stable CAD and at least moderate myocardial ischemia on noninvasive testing to a routine invasive or conservative management strategy. At 4 years of follow-up there was no significant between-group difference in cardiovascular outcomes (N Engl J Med. 2020 Apr 9;382[15]:1395-407).

Patients with a baseline LVEF below 35% weren’t eligible for enrollment in ISCHEMIA. That’s because the prior Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) showed patients with ischemic cardiomyopathy and an LVEF below 35% had a significantly lower cardiovascular death rate with surgical revascularization plus medical therapy than optimal medical therapy alone at 10 years of follow-up (N Engl J Med. 2016 Apr 21;374[16]:1511-20).

But what about the impact of immediate revascularization as compared with medical management alone in patients with milder impairment of LVEF in the 35%-45% range and/or a history of symptomatic heart failure? Theoretically, the improved blood flow to ischemic myocardium obtained via revascularization in such patients might activate hibernating myocardium and reduce ventricular dysfunction, thereby reducing the risk of cardiovascular events. The ISCHEMIA trial provided a unique opportunity to prospectively examine this question in 398 affected study participants, Dr. Lopes explained.

This 398-patient subgroup with a baseline history of heart failure and/or left ventricular dysfunction (HF/LVD) was at higher risk than patients without those features. Indeed, the primary outcome in ISCHEMIA – a composite of cardiovascular death, nonfatal MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest – occurred in 22.7% of the HF/LVD group at 4 years of follow-up, compared with 13.8% of the much larger group without HF/LVD. The HF/LVD group also had significantly higher rates of the secondary composite endpoints of cardiovascular death or MI (19.7% vs. 12.3%) and all-cause mortality or heart failure (15% vs. 6.9%).

The provocative central finding in this new subanalysis was that patients in the HF/LVD subgroup fared significantly better in terms of cardiovascular events if randomized to the initial invasive approach. Indeed, their 4-year rate of the primary outcome was 17.2%, compared with 29.3% with an initial conservative approach. The various secondary outcomes followed suit. In contrast, the primary outcome occurred in 13% of patients without HF/LVD who were randomized to the invasive strategy, not significantly different from the 14.6% rate with conservative management.

Drilling deeper into the data, Dr. Lopes and coinvestigators found that the enhanced event-free survival benefit of an initial invasive strategy was restricted to the 28 patients having both a baseline history of symptomatic heart failure and an LVEF of 35%-45%. There was no significant difference in outcomes with an invasive versus conservative strategy in the 177 patients with a history of heart failure whose LVEF was greater than 50% – that is, patients with heart failure with preserved ejection fraction – nor in the 193 participants with an LVEF of 35%-45% but no history of symptomatic heart failure.

In an interview, Mark H. Drazner, MD, commented, “this is an interesting hypothesis, for sure, that warrants further study to confirm whether it’s valid. And if it is valid, there could be real implications. If this is true, I think there could be a decent number of patients out there that this would have implications for.

“The ISCHEMIA trial was a heroic effort. While there are certainly logistical hurdles involved in anybody doing an ISCHEMIA 2 trial based on this small subgroup analysis, other people could start looking at retrospective datasets and see if they can confirm these findings to build momentum to study this further,” said Dr. Drazner, professor of medicine and chief of clinical cardiology at the University of Texas Southwestern Medical Center, Dallas, as well as an associate editor at Circulation.

Dr. Lopes reported receiving research grants from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi-Aventis as well as serving as a consultant to a handful of pharmaceutical companies, none relevant to his presentation.

Simultaneous with his presentation at ESC Congress 2020, Dr. Lopes’ study was published online in Circulation.

[email protected]

SOURCE: Lopes R et al. Circulation. 2020 Aug 29. doi: 10.1161/CIRCULATIONAHA.120.050304.

Early administration of evolocumab significantly reduced levels of LDL cholesterol in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention, according to data from an open-label randomized trial of 102 adults in Japan.

Data from previous studies have shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can reduce LDL cholesterol in acute coronary syndrome patients, wrote Tomoaki Okada, MD, of Kagawa (Japan) Prefectural Central Hospital and colleagues.

In particular, “The EVOPACS trial [J Am Coll Cardiol 2019; 74:2452-62] reported that evolocumab therapy initiated at an early phase of ACS showed [LDL cholesterol] level reduction by 4-8 weeks,” they said.

“However, the 4-week efficacy of PCSK9 inhibitor therapy combined with a statin remains unknown,” they said.

In a study presented at the virtual annual congress of the European Society of Cardiology and published simultaneously in JACC: Cardiovascular Interventions, the researchers randomized 52 patients to receive 140 mg of evolocumab subcutaneously within 24 hours of indexed percutaneous coronary intervention and again after 2 weeks. A group of 50 controls received evolocumab after PCI only, but no additional dose after 2 weeks.

The average age of the patients was 65 years, 88% were men, and 26% had a history of statin treatment.

A total of 49 patients in each group were included in the final analysis, with a primary outcome of change in LDL cholesterol levels from baseline to 4 weeks.

Baseline LCL cholesterol levels were 120.8 mg/dL and 124.7 mg/dL in the evolocumab and control groups, respectively. Changes from baseline were significantly greater in the evolocumab group, compared with controls, at –76% and –33%, respectively.

All patients in the evolocumab group and 27% of patients in the control groups achieved LDL cholesterol levels of less than 70 mg/dL at 4 weeks. In addition, 92% and 96% of evolocumab patients achieved LDL cholesterol levels less than 55 mg/dL at 2 weeks and 4 weeks, respectively.

Overall changes in non-HDL cholesterol, HDL cholesterol, and small dense LDL in the evolocumab and control groups were –66.2% and –26.0%; 2.8% and –0.7%; and –67% and –13.8%, respectively. Of these, changes in non-HDL cholesterol and small dense LDL were significantly different between the groups.

In addition, patients in the evolocumab group showed a 3% decrease in lipoprotein, compared with an 82% increase in the control group. This finding suggests the additional benefit of including evolocumab for managing residual risk in patients with high lipoprotein(a) levels” after acute MI, the researchers noted.

Adverse events and serious adverse events were similar between the groups.

‘Early and strong’ LDL cholesterol lowering best for preventing repeat events

“By using the PCSK9 inhibitors, we have the opportunity to lower LDL cholesterol [LDL-C]” both quickly and dramatically, said Heinz Drexel, MD, in an interview.

“This Japanese study shows that very low LDL-C levels can be obtained as fast as within 4 weeks,” he said. “This fits into the concept that risk for future infarctions and strokes is best reduced by early and strong LDL-C lowering,” he explained.

Dr. Drexel said that he was not surprised by the magnitude of the decrease in LDL cholesterol in study findings in light of the EVOPACS study and other research, as well as his own clinical experience.

“The primary message for doctors is that it is now possible to achieve these low levels of LDL-C in a short time,” he said.

“Additional research must prove that this low LDL-C translates to reduction of MIs and strokes, and there is increasing evidence that this will happen,” Dr. Drexel noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Drexel had no financial conflicts to disclose.

SOURCE: Okada T et al. ESC 2020. JACC Cardiovascular Interventions. 2020 Aug 28. doi: 10.1016/j.jcin.2020.08.026.

Early administration of evolocumab significantly reduced levels of LDL cholesterol in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention, according to data from an open-label randomized trial of 102 adults in Japan.

Data from previous studies have shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can reduce LDL cholesterol in acute coronary syndrome patients, wrote Tomoaki Okada, MD, of Kagawa (Japan) Prefectural Central Hospital and colleagues.

In particular, “The EVOPACS trial [J Am Coll Cardiol 2019; 74:2452-62] reported that evolocumab therapy initiated at an early phase of ACS showed [LDL cholesterol] level reduction by 4-8 weeks,” they said.

“However, the 4-week efficacy of PCSK9 inhibitor therapy combined with a statin remains unknown,” they said.

In a study presented at the virtual annual congress of the European Society of Cardiology and published simultaneously in JACC: Cardiovascular Interventions, the researchers randomized 52 patients to receive 140 mg of evolocumab subcutaneously within 24 hours of indexed percutaneous coronary intervention and again after 2 weeks. A group of 50 controls received evolocumab after PCI only, but no additional dose after 2 weeks.

The average age of the patients was 65 years, 88% were men, and 26% had a history of statin treatment.

A total of 49 patients in each group were included in the final analysis, with a primary outcome of change in LDL cholesterol levels from baseline to 4 weeks.

Baseline LCL cholesterol levels were 120.8 mg/dL and 124.7 mg/dL in the evolocumab and control groups, respectively. Changes from baseline were significantly greater in the evolocumab group, compared with controls, at –76% and –33%, respectively.

All patients in the evolocumab group and 27% of patients in the control groups achieved LDL cholesterol levels of less than 70 mg/dL at 4 weeks. In addition, 92% and 96% of evolocumab patients achieved LDL cholesterol levels less than 55 mg/dL at 2 weeks and 4 weeks, respectively.

Overall changes in non-HDL cholesterol, HDL cholesterol, and small dense LDL in the evolocumab and control groups were –66.2% and –26.0%; 2.8% and –0.7%; and –67% and –13.8%, respectively. Of these, changes in non-HDL cholesterol and small dense LDL were significantly different between the groups.

In addition, patients in the evolocumab group showed a 3% decrease in lipoprotein, compared with an 82% increase in the control group. This finding suggests the additional benefit of including evolocumab for managing residual risk in patients with high lipoprotein(a) levels” after acute MI, the researchers noted.

Adverse events and serious adverse events were similar between the groups.

‘Early and strong’ LDL cholesterol lowering best for preventing repeat events

“By using the PCSK9 inhibitors, we have the opportunity to lower LDL cholesterol [LDL-C]” both quickly and dramatically, said Heinz Drexel, MD, in an interview.

“This Japanese study shows that very low LDL-C levels can be obtained as fast as within 4 weeks,” he said. “This fits into the concept that risk for future infarctions and strokes is best reduced by early and strong LDL-C lowering,” he explained.

Dr. Drexel said that he was not surprised by the magnitude of the decrease in LDL cholesterol in study findings in light of the EVOPACS study and other research, as well as his own clinical experience.

“The primary message for doctors is that it is now possible to achieve these low levels of LDL-C in a short time,” he said.

“Additional research must prove that this low LDL-C translates to reduction of MIs and strokes, and there is increasing evidence that this will happen,” Dr. Drexel noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Drexel had no financial conflicts to disclose.

SOURCE: Okada T et al. ESC 2020. JACC Cardiovascular Interventions. 2020 Aug 28. doi: 10.1016/j.jcin.2020.08.026.

Early administration of evolocumab significantly reduced levels of LDL cholesterol in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention, according to data from an open-label randomized trial of 102 adults in Japan.

Data from previous studies have shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can reduce LDL cholesterol in acute coronary syndrome patients, wrote Tomoaki Okada, MD, of Kagawa (Japan) Prefectural Central Hospital and colleagues.

In particular, “The EVOPACS trial [J Am Coll Cardiol 2019; 74:2452-62] reported that evolocumab therapy initiated at an early phase of ACS showed [LDL cholesterol] level reduction by 4-8 weeks,” they said.

“However, the 4-week efficacy of PCSK9 inhibitor therapy combined with a statin remains unknown,” they said.

In a study presented at the virtual annual congress of the European Society of Cardiology and published simultaneously in JACC: Cardiovascular Interventions, the researchers randomized 52 patients to receive 140 mg of evolocumab subcutaneously within 24 hours of indexed percutaneous coronary intervention and again after 2 weeks. A group of 50 controls received evolocumab after PCI only, but no additional dose after 2 weeks.

The average age of the patients was 65 years, 88% were men, and 26% had a history of statin treatment.

A total of 49 patients in each group were included in the final analysis, with a primary outcome of change in LDL cholesterol levels from baseline to 4 weeks.

Baseline LCL cholesterol levels were 120.8 mg/dL and 124.7 mg/dL in the evolocumab and control groups, respectively. Changes from baseline were significantly greater in the evolocumab group, compared with controls, at –76% and –33%, respectively.

All patients in the evolocumab group and 27% of patients in the control groups achieved LDL cholesterol levels of less than 70 mg/dL at 4 weeks. In addition, 92% and 96% of evolocumab patients achieved LDL cholesterol levels less than 55 mg/dL at 2 weeks and 4 weeks, respectively.

Overall changes in non-HDL cholesterol, HDL cholesterol, and small dense LDL in the evolocumab and control groups were –66.2% and –26.0%; 2.8% and –0.7%; and –67% and –13.8%, respectively. Of these, changes in non-HDL cholesterol and small dense LDL were significantly different between the groups.

In addition, patients in the evolocumab group showed a 3% decrease in lipoprotein, compared with an 82% increase in the control group. This finding suggests the additional benefit of including evolocumab for managing residual risk in patients with high lipoprotein(a) levels” after acute MI, the researchers noted.

Adverse events and serious adverse events were similar between the groups.

‘Early and strong’ LDL cholesterol lowering best for preventing repeat events

“By using the PCSK9 inhibitors, we have the opportunity to lower LDL cholesterol [LDL-C]” both quickly and dramatically, said Heinz Drexel, MD, in an interview.

“This Japanese study shows that very low LDL-C levels can be obtained as fast as within 4 weeks,” he said. “This fits into the concept that risk for future infarctions and strokes is best reduced by early and strong LDL-C lowering,” he explained.

Dr. Drexel said that he was not surprised by the magnitude of the decrease in LDL cholesterol in study findings in light of the EVOPACS study and other research, as well as his own clinical experience.

“The primary message for doctors is that it is now possible to achieve these low levels of LDL-C in a short time,” he said.

“Additional research must prove that this low LDL-C translates to reduction of MIs and strokes, and there is increasing evidence that this will happen,” Dr. Drexel noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Drexel had no financial conflicts to disclose.

SOURCE: Okada T et al. ESC 2020. JACC Cardiovascular Interventions. 2020 Aug 28. doi: 10.1016/j.jcin.2020.08.026.

A restrictive blood transfusion strategy in myocardial infarction patients with anemia proved safe, significantly less costly, and at least as effective as the standard liberal transfusion strategy in the landmark REALITY trial.

Randomized trial data already support a restrictive transfusion strategy in patients undergoing cardiac and noncardiac surgery, as well as in other settings. Those trials deliberately excluded patients with acute myocardial ischemia.

Cardiologists have been loath to adopt a restrictive strategy in the absence of persuasive supporting evidence because of a theoretic concern that low hemoglobin might be particularly harmful to ischemic myocardium. Anemia occurs in 5%-10% patients with MI, and clinicians have been eager for evidence-based guidance on how to best manage it.

“Blood is a precious resource and transfusion is costly, logistically cumbersome, and has side effects,” Philippe Gabriel Steg, MD, chair of the REALITY trial, noted in presenting the study results at the virtual annual congress of the European Society of Cardiology.

REALITY was the first-ever large randomized trial of a restrictive versus liberal transfusion strategy in acute MI. The study, which featured a noninferiority design, included 668 stable patients with acute MI and anemia with a hemoglobin of 7-10 g/dL at 35 hospitals in France and Spain. Participants were randomized to a restrictive strategy in which transfusion was withheld unless the hemoglobin dropped to 8 g/dL or less, or to a conventional liberal strategy triggered by a hemoglobin of 10 g/dL or lower. The transfusion target was a hemoglobin level of 8-10 g/dL in the restrictive strategy group and greater than 11 g/dL in the liberal transfusion group. In the restrictive transfusion group, 36% received at least one RBC transfusion, as did 87% in the liberal transfusion study arm. The restrictive strategy group used 414 fewer units of blood.

The two coprimary endpoints were 30-day major adverse cardiovascular events and cost-effectiveness. The 30-day composite of all-cause mortality, reinfarction, stroke, and emergency percutaneous coronary intervention for myocardial ischemia occurred in 11% of the restrictive transfusion group and 14% of the liberal transfusion group. The resultant 21% relative risk reduction established that the restrictive strategy was noninferior. Of note, all of the individual components of the composite endpoint numerically favored the restrictive approach.

In terms of safety, patients in the restrictive transfusion group were significantly less likely to develop an infection, by a margin of 0% versus 1.5%. The rate of acute lung injury was also significantly lower in the restrictive group: 0.3%, compared with 2.2%. The median hospital length of stay was identical at 7 days in both groups.

The cost-effectiveness analysis concluded that the restrictive transfusion strategy had an 84% probability of being both less expensive and more effective.

Patients were enrolled in REALITY regardless of whether they had active bleeding, as long as the bleeding wasn’t deemed massive and life-threatening. Notably, there was no difference in the results of restrictive versus liberal transfusion regardless of whether active bleeding was present, nor did baseline hemoglobin or the presence or absence of preexisting anemia affect the results.

Dr. Steg noted that a much larger randomized trial of restrictive versus liberal transfusion in the setting of acute MI with anemia is underway in the United States and Canada. The 3,000-patient MINT trial, sponsored by the National Institutes of Health, is testing the superiority of restrictive transfusion, rather than its noninferiority, as in REALITY. Results are a couple of years away.

“I think that will be an important piece of additional evidence,” he said.

Discussant Marco Roffi, MD, didn’t mince words.

“I really love the REALITY trial,” declared Dr. Roffi, professor and vice chairman of the cardiology department and director of the interventional cardiology unit at University Hospital of Geneva.

He ticked off a series of reasons: The trial addressed a common clinical dilemma about which there has been essentially no prior high-quality evidence, it provided convincing results, and it carried important implications for responsible stewardship of the blood supply.

“REALITY allows clinicians to comfortably refrain from transfusing anemic patients presenting with myocardial infarction, and this should lead to a reduction in the consumption of blood products,” Dr. Roffi said.

He applauded the investigators for their success in obtaining public funding for a study lacking a commercial hook. And as a clinical investigator, he was particularly impressed by one of the technical details about the REALITY trial: “I was amazed by the fact that the observed event rates virtually corresponded to the estimated ones used for the power calculations. This is rarely the case in such a trial.”

Dr. Roffi said the REALITY findings should have an immediate impact on clinical practice, as well as on the brand new 2020 ESC guidelines on the management of non–ST-elevation ACS issued during the ESC virtual congress.

The freshly inked guidelines state: “Based on inconsistent study results and the lack of adequately powered randomized, controlled trials, a restrictive policy of transfusion in anemic patients with MI may be considered.” As of today, Dr. Roffi argued, the phrase “may be considered” ought to be replaced by the stronger phrase “should be considered.”

During the discussion period, he was asked if it’s appropriate to extrapolate the REALITY results to patients undergoing transcatheter aortic valve replacement, among whom anemia is highly prevalent.

“I think this is a different patient population. Nevertheless, the concept of being restrictive is one that in my opinion now remains until proven otherwise. So we are being very restrictive in these patients,” he replied.

Asked about possible mechanisms by which liberal transfusion might have detrimental effects in acute MI patients, Dr. Steg cited several, including evidence that transfusion may not improve oxygen delivery to as great an extent as traditionally thought. There is also the risk of volume overload, increased blood viscosity, and enhanced platelet aggregation and activation, which could promote myocardial ischemia.

The REALITY trial was funded by the French Ministry of Health and the Spanish Ministry of Economy and Competitiveness with no commercial support. Outside the scope of the trial, Dr. Steg reported receiving research grants from Bayer, Merck, Servier, and Sanofi as well as serving as a consultant to numerous pharmaceutical companies.

[email protected]

A restrictive blood transfusion strategy in myocardial infarction patients with anemia proved safe, significantly less costly, and at least as effective as the standard liberal transfusion strategy in the landmark REALITY trial.

Randomized trial data already support a restrictive transfusion strategy in patients undergoing cardiac and noncardiac surgery, as well as in other settings. Those trials deliberately excluded patients with acute myocardial ischemia.

Cardiologists have been loath to adopt a restrictive strategy in the absence of persuasive supporting evidence because of a theoretic concern that low hemoglobin might be particularly harmful to ischemic myocardium. Anemia occurs in 5%-10% patients with MI, and clinicians have been eager for evidence-based guidance on how to best manage it.

“Blood is a precious resource and transfusion is costly, logistically cumbersome, and has side effects,” Philippe Gabriel Steg, MD, chair of the REALITY trial, noted in presenting the study results at the virtual annual congress of the European Society of Cardiology.

REALITY was the first-ever large randomized trial of a restrictive versus liberal transfusion strategy in acute MI. The study, which featured a noninferiority design, included 668 stable patients with acute MI and anemia with a hemoglobin of 7-10 g/dL at 35 hospitals in France and Spain. Participants were randomized to a restrictive strategy in which transfusion was withheld unless the hemoglobin dropped to 8 g/dL or less, or to a conventional liberal strategy triggered by a hemoglobin of 10 g/dL or lower. The transfusion target was a hemoglobin level of 8-10 g/dL in the restrictive strategy group and greater than 11 g/dL in the liberal transfusion group. In the restrictive transfusion group, 36% received at least one RBC transfusion, as did 87% in the liberal transfusion study arm. The restrictive strategy group used 414 fewer units of blood.

The two coprimary endpoints were 30-day major adverse cardiovascular events and cost-effectiveness. The 30-day composite of all-cause mortality, reinfarction, stroke, and emergency percutaneous coronary intervention for myocardial ischemia occurred in 11% of the restrictive transfusion group and 14% of the liberal transfusion group. The resultant 21% relative risk reduction established that the restrictive strategy was noninferior. Of note, all of the individual components of the composite endpoint numerically favored the restrictive approach.

In terms of safety, patients in the restrictive transfusion group were significantly less likely to develop an infection, by a margin of 0% versus 1.5%. The rate of acute lung injury was also significantly lower in the restrictive group: 0.3%, compared with 2.2%. The median hospital length of stay was identical at 7 days in both groups.

The cost-effectiveness analysis concluded that the restrictive transfusion strategy had an 84% probability of being both less expensive and more effective.

Patients were enrolled in REALITY regardless of whether they had active bleeding, as long as the bleeding wasn’t deemed massive and life-threatening. Notably, there was no difference in the results of restrictive versus liberal transfusion regardless of whether active bleeding was present, nor did baseline hemoglobin or the presence or absence of preexisting anemia affect the results.

Dr. Steg noted that a much larger randomized trial of restrictive versus liberal transfusion in the setting of acute MI with anemia is underway in the United States and Canada. The 3,000-patient MINT trial, sponsored by the National Institutes of Health, is testing the superiority of restrictive transfusion, rather than its noninferiority, as in REALITY. Results are a couple of years away.

“I think that will be an important piece of additional evidence,” he said.

Discussant Marco Roffi, MD, didn’t mince words.

“I really love the REALITY trial,” declared Dr. Roffi, professor and vice chairman of the cardiology department and director of the interventional cardiology unit at University Hospital of Geneva.

He ticked off a series of reasons: The trial addressed a common clinical dilemma about which there has been essentially no prior high-quality evidence, it provided convincing results, and it carried important implications for responsible stewardship of the blood supply.

“REALITY allows clinicians to comfortably refrain from transfusing anemic patients presenting with myocardial infarction, and this should lead to a reduction in the consumption of blood products,” Dr. Roffi said.

He applauded the investigators for their success in obtaining public funding for a study lacking a commercial hook. And as a clinical investigator, he was particularly impressed by one of the technical details about the REALITY trial: “I was amazed by the fact that the observed event rates virtually corresponded to the estimated ones used for the power calculations. This is rarely the case in such a trial.”

Dr. Roffi said the REALITY findings should have an immediate impact on clinical practice, as well as on the brand new 2020 ESC guidelines on the management of non–ST-elevation ACS issued during the ESC virtual congress.

The freshly inked guidelines state: “Based on inconsistent study results and the lack of adequately powered randomized, controlled trials, a restrictive policy of transfusion in anemic patients with MI may be considered.” As of today, Dr. Roffi argued, the phrase “may be considered” ought to be replaced by the stronger phrase “should be considered.”

During the discussion period, he was asked if it’s appropriate to extrapolate the REALITY results to patients undergoing transcatheter aortic valve replacement, among whom anemia is highly prevalent.

“I think this is a different patient population. Nevertheless, the concept of being restrictive is one that in my opinion now remains until proven otherwise. So we are being very restrictive in these patients,” he replied.

Asked about possible mechanisms by which liberal transfusion might have detrimental effects in acute MI patients, Dr. Steg cited several, including evidence that transfusion may not improve oxygen delivery to as great an extent as traditionally thought. There is also the risk of volume overload, increased blood viscosity, and enhanced platelet aggregation and activation, which could promote myocardial ischemia.

The REALITY trial was funded by the French Ministry of Health and the Spanish Ministry of Economy and Competitiveness with no commercial support. Outside the scope of the trial, Dr. Steg reported receiving research grants from Bayer, Merck, Servier, and Sanofi as well as serving as a consultant to numerous pharmaceutical companies.

[email protected]

A restrictive blood transfusion strategy in myocardial infarction patients with anemia proved safe, significantly less costly, and at least as effective as the standard liberal transfusion strategy in the landmark REALITY trial.

Randomized trial data already support a restrictive transfusion strategy in patients undergoing cardiac and noncardiac surgery, as well as in other settings. Those trials deliberately excluded patients with acute myocardial ischemia.

Cardiologists have been loath to adopt a restrictive strategy in the absence of persuasive supporting evidence because of a theoretic concern that low hemoglobin might be particularly harmful to ischemic myocardium. Anemia occurs in 5%-10% patients with MI, and clinicians have been eager for evidence-based guidance on how to best manage it.

“Blood is a precious resource and transfusion is costly, logistically cumbersome, and has side effects,” Philippe Gabriel Steg, MD, chair of the REALITY trial, noted in presenting the study results at the virtual annual congress of the European Society of Cardiology.

REALITY was the first-ever large randomized trial of a restrictive versus liberal transfusion strategy in acute MI. The study, which featured a noninferiority design, included 668 stable patients with acute MI and anemia with a hemoglobin of 7-10 g/dL at 35 hospitals in France and Spain. Participants were randomized to a restrictive strategy in which transfusion was withheld unless the hemoglobin dropped to 8 g/dL or less, or to a conventional liberal strategy triggered by a hemoglobin of 10 g/dL or lower. The transfusion target was a hemoglobin level of 8-10 g/dL in the restrictive strategy group and greater than 11 g/dL in the liberal transfusion group. In the restrictive transfusion group, 36% received at least one RBC transfusion, as did 87% in the liberal transfusion study arm. The restrictive strategy group used 414 fewer units of blood.

The two coprimary endpoints were 30-day major adverse cardiovascular events and cost-effectiveness. The 30-day composite of all-cause mortality, reinfarction, stroke, and emergency percutaneous coronary intervention for myocardial ischemia occurred in 11% of the restrictive transfusion group and 14% of the liberal transfusion group. The resultant 21% relative risk reduction established that the restrictive strategy was noninferior. Of note, all of the individual components of the composite endpoint numerically favored the restrictive approach.

In terms of safety, patients in the restrictive transfusion group were significantly less likely to develop an infection, by a margin of 0% versus 1.5%. The rate of acute lung injury was also significantly lower in the restrictive group: 0.3%, compared with 2.2%. The median hospital length of stay was identical at 7 days in both groups.

The cost-effectiveness analysis concluded that the restrictive transfusion strategy had an 84% probability of being both less expensive and more effective.

Patients were enrolled in REALITY regardless of whether they had active bleeding, as long as the bleeding wasn’t deemed massive and life-threatening. Notably, there was no difference in the results of restrictive versus liberal transfusion regardless of whether active bleeding was present, nor did baseline hemoglobin or the presence or absence of preexisting anemia affect the results.

Dr. Steg noted that a much larger randomized trial of restrictive versus liberal transfusion in the setting of acute MI with anemia is underway in the United States and Canada. The 3,000-patient MINT trial, sponsored by the National Institutes of Health, is testing the superiority of restrictive transfusion, rather than its noninferiority, as in REALITY. Results are a couple of years away.

“I think that will be an important piece of additional evidence,” he said.

Discussant Marco Roffi, MD, didn’t mince words.

“I really love the REALITY trial,” declared Dr. Roffi, professor and vice chairman of the cardiology department and director of the interventional cardiology unit at University Hospital of Geneva.

He ticked off a series of reasons: The trial addressed a common clinical dilemma about which there has been essentially no prior high-quality evidence, it provided convincing results, and it carried important implications for responsible stewardship of the blood supply.

“REALITY allows clinicians to comfortably refrain from transfusing anemic patients presenting with myocardial infarction, and this should lead to a reduction in the consumption of blood products,” Dr. Roffi said.

He applauded the investigators for their success in obtaining public funding for a study lacking a commercial hook. And as a clinical investigator, he was particularly impressed by one of the technical details about the REALITY trial: “I was amazed by the fact that the observed event rates virtually corresponded to the estimated ones used for the power calculations. This is rarely the case in such a trial.”

Dr. Roffi said the REALITY findings should have an immediate impact on clinical practice, as well as on the brand new 2020 ESC guidelines on the management of non–ST-elevation ACS issued during the ESC virtual congress.

The freshly inked guidelines state: “Based on inconsistent study results and the lack of adequately powered randomized, controlled trials, a restrictive policy of transfusion in anemic patients with MI may be considered.” As of today, Dr. Roffi argued, the phrase “may be considered” ought to be replaced by the stronger phrase “should be considered.”

During the discussion period, he was asked if it’s appropriate to extrapolate the REALITY results to patients undergoing transcatheter aortic valve replacement, among whom anemia is highly prevalent.

“I think this is a different patient population. Nevertheless, the concept of being restrictive is one that in my opinion now remains until proven otherwise. So we are being very restrictive in these patients,” he replied.

Asked about possible mechanisms by which liberal transfusion might have detrimental effects in acute MI patients, Dr. Steg cited several, including evidence that transfusion may not improve oxygen delivery to as great an extent as traditionally thought. There is also the risk of volume overload, increased blood viscosity, and enhanced platelet aggregation and activation, which could promote myocardial ischemia.

The REALITY trial was funded by the French Ministry of Health and the Spanish Ministry of Economy and Competitiveness with no commercial support. Outside the scope of the trial, Dr. Steg reported receiving research grants from Bayer, Merck, Servier, and Sanofi as well as serving as a consultant to numerous pharmaceutical companies.

[email protected]

Adding trimetazidine to optimal medical therapy does not improve outcomes following successful percutaneous coronary intervention (PCI) for stable angina or a non–ST-elevated myocardial infarction, results of the ATPCI trial show.

There was no benefit for the composite primary endpoint of cardiac death, hospitalization for cardiac events, or recurrent/persistent angina requiring an addition, switch, or increased dose of antianginal therapies, or requiring coronary angiography (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09).

• Cardiac death: 2.1% vs. 2.6% (HR, 0.81)
• Hospital admission for cardiac events: 13.4% vs. 13.4% (HR, 1.01)
• Angina leading to coronary angiography: 16.9% vs. 16.6% (HR, 1.02)
• Angina leading to increase/switch in antianginal drugs (HR, 1.01)

There was no between-group difference in the composite major secondary endpoint, which included the primary endpoint components plus ischemia leading to coronary angiography and an increase or switch in antianginal therapies. This outcome occurred in 23.5% and 24.0% of patients in the trimetazidine and control groups, respectively (HR, 0.98; 95% CI, 0.88-1.08).

Results were also similar when the primary endpoint was analyzed based on whether patients underwent elective PCI (HR, 0.94; 95% CI, 0.82-1.08) or urgent PCI (HR, 1.04; 95% CI, 0.88-1.22), Dr. Ferrari reported.

Given the lack of observed efficacy, trimetazidine has no use or place in the population studied, said Stephan Windecker, MD, the formal discussant for the study and chair of cardiology at Bern (Switzerland) University Hospital. “Notwithstanding, I think we have to recognize that the optimal medical therapy is so potent and has been well implemented in this trial that any additional medication beyond this is just unable to exploit additional benefit.”

The study was supported by Servier. Dr. Ferrari received fees, honoraria, and travel expenses from Servier. Dr. Ohman reports no relevant financial conflicts of interest. Dr. Windecker is an unpaid member of the steering/executive group for trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliancé, Medtronic, Polares, Sinomed, V-Wave, and Xeltis but has not received personal payments from any pharmaceutical or device company.

This article first appeared on Medscape.com.

Adding trimetazidine to optimal medical therapy does not improve outcomes following successful percutaneous coronary intervention (PCI) for stable angina or a non–ST-elevated myocardial infarction, results of the ATPCI trial show.

There was no benefit for the composite primary endpoint of cardiac death, hospitalization for cardiac events, or recurrent/persistent angina requiring an addition, switch, or increased dose of antianginal therapies, or requiring coronary angiography (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09).

• Cardiac death: 2.1% vs. 2.6% (HR, 0.81)
• Hospital admission for cardiac events: 13.4% vs. 13.4% (HR, 1.01)
• Angina leading to coronary angiography: 16.9% vs. 16.6% (HR, 1.02)
• Angina leading to increase/switch in antianginal drugs (HR, 1.01)

There was no between-group difference in the composite major secondary endpoint, which included the primary endpoint components plus ischemia leading to coronary angiography and an increase or switch in antianginal therapies. This outcome occurred in 23.5% and 24.0% of patients in the trimetazidine and control groups, respectively (HR, 0.98; 95% CI, 0.88-1.08).

Results were also similar when the primary endpoint was analyzed based on whether patients underwent elective PCI (HR, 0.94; 95% CI, 0.82-1.08) or urgent PCI (HR, 1.04; 95% CI, 0.88-1.22), Dr. Ferrari reported.

Given the lack of observed efficacy, trimetazidine has no use or place in the population studied, said Stephan Windecker, MD, the formal discussant for the study and chair of cardiology at Bern (Switzerland) University Hospital. “Notwithstanding, I think we have to recognize that the optimal medical therapy is so potent and has been well implemented in this trial that any additional medication beyond this is just unable to exploit additional benefit.”

The study was supported by Servier. Dr. Ferrari received fees, honoraria, and travel expenses from Servier. Dr. Ohman reports no relevant financial conflicts of interest. Dr. Windecker is an unpaid member of the steering/executive group for trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliancé, Medtronic, Polares, Sinomed, V-Wave, and Xeltis but has not received personal payments from any pharmaceutical or device company.

This article first appeared on Medscape.com.

Adding trimetazidine to optimal medical therapy does not improve outcomes following successful percutaneous coronary intervention (PCI) for stable angina or a non–ST-elevated myocardial infarction, results of the ATPCI trial show.

There was no benefit for the composite primary endpoint of cardiac death, hospitalization for cardiac events, or recurrent/persistent angina requiring an addition, switch, or increased dose of antianginal therapies, or requiring coronary angiography (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09).

• Cardiac death: 2.1% vs. 2.6% (HR, 0.81)
• Hospital admission for cardiac events: 13.4% vs. 13.4% (HR, 1.01)
• Angina leading to coronary angiography: 16.9% vs. 16.6% (HR, 1.02)
• Angina leading to increase/switch in antianginal drugs (HR, 1.01)

There was no between-group difference in the composite major secondary endpoint, which included the primary endpoint components plus ischemia leading to coronary angiography and an increase or switch in antianginal therapies. This outcome occurred in 23.5% and 24.0% of patients in the trimetazidine and control groups, respectively (HR, 0.98; 95% CI, 0.88-1.08).

Results were also similar when the primary endpoint was analyzed based on whether patients underwent elective PCI (HR, 0.94; 95% CI, 0.82-1.08) or urgent PCI (HR, 1.04; 95% CI, 0.88-1.22), Dr. Ferrari reported.

Given the lack of observed efficacy, trimetazidine has no use or place in the population studied, said Stephan Windecker, MD, the formal discussant for the study and chair of cardiology at Bern (Switzerland) University Hospital. “Notwithstanding, I think we have to recognize that the optimal medical therapy is so potent and has been well implemented in this trial that any additional medication beyond this is just unable to exploit additional benefit.”

The study was supported by Servier. Dr. Ferrari received fees, honoraria, and travel expenses from Servier. Dr. Ohman reports no relevant financial conflicts of interest. Dr. Windecker is an unpaid member of the steering/executive group for trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliancé, Medtronic, Polares, Sinomed, V-Wave, and Xeltis but has not received personal payments from any pharmaceutical or device company.

This article first appeared on Medscape.com.

Aspirin alone after transcatheter aortic valve implantation (TAVI) significantly reduced bleeding, compared with aspirin plus clopidogrel, without increasing thromboembolic events, in the latest results from the POPular TAVI study.

“Physicians can easily and safely reduce rate of bleeding by omitting clopidogrel after TAVI,” lead author, Jorn Brouwer, MD, St Antonius Hospital, Nieuwegein, the Netherlands, said.

“Aspirin alone should be used in patients undergoing TAVI who are not on oral anticoagulants and have not recently undergone coronary stenting,” he concluded.

Senior author, Jurriën ten Berg, MD, PhD, also from St Antonius Hospital, said in an interview: “I think we can say for TAVI patients, when it comes to antithrombotic therapy, less is definitely more.”

“This is a major change to clinical practice, with current guidelines recommending 3-6 months of dual antiplatelet therapy after a TAVI procedure,” he added. “We expected that these guidelines will change after our results.”

These latest results from POPular TAVI were presented at the virtual European Society of Cardiology Congress 2020 and simultaneously published online in The New England Journal of Medicine.

The trial was conducted in two cohorts of patients undergoing TAVI. The results from cohort B – in patients who were already taking an anticoagulant for another indication – were reported earlier this year and showed no benefit of adding clopidogrel and an increase in bleeding. Now the current results in cohort A – patients undergoing TAVI who do not have an established indication for long-term anticoagulation – show similar results, with aspirin alone preferred over aspirin plus clopidogrel.

Dr. ten Berg explained that the recommendation for dual antiplatelet therapy (DAPT) was adopted mainly because this has been shown to be beneficial in patients undergoing percutaneous coronary intervention (PCI) with stenting; it was thought the same benefits would be seen in TAVI, which also uses a stent-based delivery system.

“However, TAVI patients are a different population – they are generally much older than PCI patients, with an average age of 80 plus, and they have many more comorbidities, so they are much higher bleeding risk,” Dr. ten Berg explained. “In addition, the catheters used for TAVI are larger than those used for PCI, forcing the femoral route to be employed, and both of these factors increases bleeding risk.”

“We saw that, in the trial, patients on dual antiplatelet therapy had a much greater rate of major bleeding and the addition of clopidogrel did not reduce the risk of major thrombotic events,” such as stroke, myocardial infarction (MI), or cardiovascular (CV) death.

Given that the TAVI procedure is associated with an increase in stroke in the immediate few days after the procedure, it would seem logical that increased antiplatelet therapy would be beneficial in reducing this, Dr. ten Berg noted.

“But this is not what we are seeing,” he said. “The stroke incidence was similar in the two groups in POPular TAVI. This suggests that the strokes may not be platelet mediated. They might be caused by another mechanism, such as dislodgement of calcium from the valve or tissue from the aorta.”

For the current part of the study, 690 patients who were undergoing TAVI and did not have an indication for long-term anticoagulation were randomly assigned to receive aspirin alone or aspirin plus clopidogrel for 3 months.

The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non–procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as not procedure related.

Results showed that a bleeding event occurred in 15.1% of patients receiving aspirin alone and 26.6% of those receiving aspirin plus clopidogrel (risk ratio, 0.57; P = .001). Non–procedure-related bleeding occurred 15.1% of patients receiving aspirin alone vs 24.9% of those receiving aspirin plus clopidogrel (risk ratio, 0.61; P = .005). Major, life-threatening, or disabling bleeding occurred in 5.1% of the aspirin-alone group versus 10.8% of those in the aspirin plus clopidogrel group.

Two secondary outcomes included thromboembolic events. The secondary composite one endpoint of death from cardiovascular causes, non–procedure-related bleeding, stroke, or MI at 1 year occurred in 23.0% of those receiving aspirin alone and in 31.1% of those receiving aspirin plus clopidogrel (difference, −8.2 percentage points; P for noninferiority < .001; risk ratio, 0.74; P for superiority = .04).

The secondary composite two endpoint of death from cardiovascular causes, ischemic stroke, or MI at 1 year occurred in 9.7% of the aspirin-alone group versus 9.9% of the dual-antiplatelet group (difference, −0.2 percentage points; P for noninferiority = .004; risk ratio, 0.98; P for superiority = .93).

Dr. ten Berg pointed out that the trial was not strictly powered to look at thrombotic events, but he added: “There was no hint of an increase in the aspirin-alone group and there was quite a high event rate, so we should have seen something if it was there.”

The group has also performed a meta-analysis of these results, with some previous smaller studies also comparing aspirin and DAPT in TAVI which again showed no reduction in thrombotic events with dual-antiplatelet therapy.

Dr. ten Berg noted that the trial included all-comer TAVI patients. “The overall risk was quite a low [STS score, 2.5]. This is a reflection of the typical TAVI patient we are seeing but I would say our results apply to patients of all risk.”
 

Simplifies and clarifies

Discussant of the trial at the ESC Hotline session, Anna Sonia Petronio, MD, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, said, “This was an excellent and essential study that simplifies and clarifies aspects of TAVI treatment and needs to change the guidelines.”

“These results will have a large impact on clinical practice in this elderly population,” she said. But she added that more data are needed for younger patients and more complicated cases, such as valve-in-valve and bicuspid valves.

Commenting on the results, Robert Bonow, MD, Northwestern University, Chicago, said, “The optimal antithrombotic management of patients undergoing TAVI who do not otherwise have an indication for anticoagulation [such as atrial fibrillation] has been uncertain and debatable. Aspirin plus clopidogrel for 3-6 months has been the standard, based on the experience with coronary stents.”

“Thus, the current results of cohort A of the POPular TAVI trial showing significant reduction in bleeding events with aspirin alone compared to DAPT for 3 months, with no difference in ischemic events, are important observations,” he said. “It is noteworthy that most of the bleeding events occurred in the first 30 days.

“This is a relatively small randomized trial, so whether these results will be practice changing will depend on confirmation by additional studies, but it is reassuring to know that patients at higher risk for bleeding would appear to do well with low-dose aspirin alone after TAVI,” Dr. Bonow added.

“These results complete the circle in terms of antithrombotic therapy after TAVI,” commented Michael Reardon, MD, Houston Methodist DeBakey Heart & Vascular Institute, Texas.

“I would add two caveats: First is that most of the difference in the primary endpoint occurs in the first month and levels out between the groups after that,” Dr. Reardon said. “Second is that this does not address the issue of leaflet thickening and immobility.”

Ashish Pershad, MD, Banner – University Medicine Heart Institute, Phoenix, added: “This trial answers a very important question and shows dual-antiplatelet therapy is hazardous in TAVI patients. Clopidogrel is not needed.”

Dr. Pershad says he still wonders about patients who receive very small valves who may have a higher risk for valve-induced thrombosis. “While there were some of these patients in the trial, the numbers were small, so we need more data on this group,” he commented.

“But for bread-and-butter TAVI, aspirin alone is the best choice, and the previous results showed, for patients already taking oral anticoagulation, no additional antithrombotic therapy is required,” Dr. Pershad concluded. “This is a big deal and will change the way we treat patients.”

 The POPular trial was supported by the Netherlands Organization for Health Research and Development. Brouwer reports no disclosures.
 

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

Aspirin alone after transcatheter aortic valve implantation (TAVI) significantly reduced bleeding, compared with aspirin plus clopidogrel, without increasing thromboembolic events, in the latest results from the POPular TAVI study.

“Physicians can easily and safely reduce rate of bleeding by omitting clopidogrel after TAVI,” lead author, Jorn Brouwer, MD, St Antonius Hospital, Nieuwegein, the Netherlands, said.

“Aspirin alone should be used in patients undergoing TAVI who are not on oral anticoagulants and have not recently undergone coronary stenting,” he concluded.

Senior author, Jurriën ten Berg, MD, PhD, also from St Antonius Hospital, said in an interview: “I think we can say for TAVI patients, when it comes to antithrombotic therapy, less is definitely more.”

“This is a major change to clinical practice, with current guidelines recommending 3-6 months of dual antiplatelet therapy after a TAVI procedure,” he added. “We expected that these guidelines will change after our results.”

These latest results from POPular TAVI were presented at the virtual European Society of Cardiology Congress 2020 and simultaneously published online in The New England Journal of Medicine.

The trial was conducted in two cohorts of patients undergoing TAVI. The results from cohort B – in patients who were already taking an anticoagulant for another indication – were reported earlier this year and showed no benefit of adding clopidogrel and an increase in bleeding. Now the current results in cohort A – patients undergoing TAVI who do not have an established indication for long-term anticoagulation – show similar results, with aspirin alone preferred over aspirin plus clopidogrel.

Dr. ten Berg explained that the recommendation for dual antiplatelet therapy (DAPT) was adopted mainly because this has been shown to be beneficial in patients undergoing percutaneous coronary intervention (PCI) with stenting; it was thought the same benefits would be seen in TAVI, which also uses a stent-based delivery system.

“However, TAVI patients are a different population – they are generally much older than PCI patients, with an average age of 80 plus, and they have many more comorbidities, so they are much higher bleeding risk,” Dr. ten Berg explained. “In addition, the catheters used for TAVI are larger than those used for PCI, forcing the femoral route to be employed, and both of these factors increases bleeding risk.”

“We saw that, in the trial, patients on dual antiplatelet therapy had a much greater rate of major bleeding and the addition of clopidogrel did not reduce the risk of major thrombotic events,” such as stroke, myocardial infarction (MI), or cardiovascular (CV) death.

Given that the TAVI procedure is associated with an increase in stroke in the immediate few days after the procedure, it would seem logical that increased antiplatelet therapy would be beneficial in reducing this, Dr. ten Berg noted.

“But this is not what we are seeing,” he said. “The stroke incidence was similar in the two groups in POPular TAVI. This suggests that the strokes may not be platelet mediated. They might be caused by another mechanism, such as dislodgement of calcium from the valve or tissue from the aorta.”

For the current part of the study, 690 patients who were undergoing TAVI and did not have an indication for long-term anticoagulation were randomly assigned to receive aspirin alone or aspirin plus clopidogrel for 3 months.

The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non–procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as not procedure related.

Results showed that a bleeding event occurred in 15.1% of patients receiving aspirin alone and 26.6% of those receiving aspirin plus clopidogrel (risk ratio, 0.57; P = .001). Non–procedure-related bleeding occurred 15.1% of patients receiving aspirin alone vs 24.9% of those receiving aspirin plus clopidogrel (risk ratio, 0.61; P = .005). Major, life-threatening, or disabling bleeding occurred in 5.1% of the aspirin-alone group versus 10.8% of those in the aspirin plus clopidogrel group.

Two secondary outcomes included thromboembolic events. The secondary composite one endpoint of death from cardiovascular causes, non–procedure-related bleeding, stroke, or MI at 1 year occurred in 23.0% of those receiving aspirin alone and in 31.1% of those receiving aspirin plus clopidogrel (difference, −8.2 percentage points; P for noninferiority < .001; risk ratio, 0.74; P for superiority = .04).

The secondary composite two endpoint of death from cardiovascular causes, ischemic stroke, or MI at 1 year occurred in 9.7% of the aspirin-alone group versus 9.9% of the dual-antiplatelet group (difference, −0.2 percentage points; P for noninferiority = .004; risk ratio, 0.98; P for superiority = .93).

Dr. ten Berg pointed out that the trial was not strictly powered to look at thrombotic events, but he added: “There was no hint of an increase in the aspirin-alone group and there was quite a high event rate, so we should have seen something if it was there.”

The group has also performed a meta-analysis of these results, with some previous smaller studies also comparing aspirin and DAPT in TAVI which again showed no reduction in thrombotic events with dual-antiplatelet therapy.

Dr. ten Berg noted that the trial included all-comer TAVI patients. “The overall risk was quite a low [STS score, 2.5]. This is a reflection of the typical TAVI patient we are seeing but I would say our results apply to patients of all risk.”
 

Simplifies and clarifies

Discussant of the trial at the ESC Hotline session, Anna Sonia Petronio, MD, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, said, “This was an excellent and essential study that simplifies and clarifies aspects of TAVI treatment and needs to change the guidelines.”

“These results will have a large impact on clinical practice in this elderly population,” she said. But she added that more data are needed for younger patients and more complicated cases, such as valve-in-valve and bicuspid valves.

Commenting on the results, Robert Bonow, MD, Northwestern University, Chicago, said, “The optimal antithrombotic management of patients undergoing TAVI who do not otherwise have an indication for anticoagulation [such as atrial fibrillation] has been uncertain and debatable. Aspirin plus clopidogrel for 3-6 months has been the standard, based on the experience with coronary stents.”

“Thus, the current results of cohort A of the POPular TAVI trial showing significant reduction in bleeding events with aspirin alone compared to DAPT for 3 months, with no difference in ischemic events, are important observations,” he said. “It is noteworthy that most of the bleeding events occurred in the first 30 days.

“This is a relatively small randomized trial, so whether these results will be practice changing will depend on confirmation by additional studies, but it is reassuring to know that patients at higher risk for bleeding would appear to do well with low-dose aspirin alone after TAVI,” Dr. Bonow added.

“These results complete the circle in terms of antithrombotic therapy after TAVI,” commented Michael Reardon, MD, Houston Methodist DeBakey Heart & Vascular Institute, Texas.

“I would add two caveats: First is that most of the difference in the primary endpoint occurs in the first month and levels out between the groups after that,” Dr. Reardon said. “Second is that this does not address the issue of leaflet thickening and immobility.”

Ashish Pershad, MD, Banner – University Medicine Heart Institute, Phoenix, added: “This trial answers a very important question and shows dual-antiplatelet therapy is hazardous in TAVI patients. Clopidogrel is not needed.”

Dr. Pershad says he still wonders about patients who receive very small valves who may have a higher risk for valve-induced thrombosis. “While there were some of these patients in the trial, the numbers were small, so we need more data on this group,” he commented.

“But for bread-and-butter TAVI, aspirin alone is the best choice, and the previous results showed, for patients already taking oral anticoagulation, no additional antithrombotic therapy is required,” Dr. Pershad concluded. “This is a big deal and will change the way we treat patients.”

 The POPular trial was supported by the Netherlands Organization for Health Research and Development. Brouwer reports no disclosures.
 

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

Aspirin alone after transcatheter aortic valve implantation (TAVI) significantly reduced bleeding, compared with aspirin plus clopidogrel, without increasing thromboembolic events, in the latest results from the POPular TAVI study.

“Physicians can easily and safely reduce rate of bleeding by omitting clopidogrel after TAVI,” lead author, Jorn Brouwer, MD, St Antonius Hospital, Nieuwegein, the Netherlands, said.

“Aspirin alone should be used in patients undergoing TAVI who are not on oral anticoagulants and have not recently undergone coronary stenting,” he concluded.

Senior author, Jurriën ten Berg, MD, PhD, also from St Antonius Hospital, said in an interview: “I think we can say for TAVI patients, when it comes to antithrombotic therapy, less is definitely more.”

“This is a major change to clinical practice, with current guidelines recommending 3-6 months of dual antiplatelet therapy after a TAVI procedure,” he added. “We expected that these guidelines will change after our results.”

These latest results from POPular TAVI were presented at the virtual European Society of Cardiology Congress 2020 and simultaneously published online in The New England Journal of Medicine.

The trial was conducted in two cohorts of patients undergoing TAVI. The results from cohort B – in patients who were already taking an anticoagulant for another indication – were reported earlier this year and showed no benefit of adding clopidogrel and an increase in bleeding. Now the current results in cohort A – patients undergoing TAVI who do not have an established indication for long-term anticoagulation – show similar results, with aspirin alone preferred over aspirin plus clopidogrel.

Dr. ten Berg explained that the recommendation for dual antiplatelet therapy (DAPT) was adopted mainly because this has been shown to be beneficial in patients undergoing percutaneous coronary intervention (PCI) with stenting; it was thought the same benefits would be seen in TAVI, which also uses a stent-based delivery system.

“However, TAVI patients are a different population – they are generally much older than PCI patients, with an average age of 80 plus, and they have many more comorbidities, so they are much higher bleeding risk,” Dr. ten Berg explained. “In addition, the catheters used for TAVI are larger than those used for PCI, forcing the femoral route to be employed, and both of these factors increases bleeding risk.”

“We saw that, in the trial, patients on dual antiplatelet therapy had a much greater rate of major bleeding and the addition of clopidogrel did not reduce the risk of major thrombotic events,” such as stroke, myocardial infarction (MI), or cardiovascular (CV) death.

Given that the TAVI procedure is associated with an increase in stroke in the immediate few days after the procedure, it would seem logical that increased antiplatelet therapy would be beneficial in reducing this, Dr. ten Berg noted.

“But this is not what we are seeing,” he said. “The stroke incidence was similar in the two groups in POPular TAVI. This suggests that the strokes may not be platelet mediated. They might be caused by another mechanism, such as dislodgement of calcium from the valve or tissue from the aorta.”

For the current part of the study, 690 patients who were undergoing TAVI and did not have an indication for long-term anticoagulation were randomly assigned to receive aspirin alone or aspirin plus clopidogrel for 3 months.

The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non–procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as not procedure related.

Results showed that a bleeding event occurred in 15.1% of patients receiving aspirin alone and 26.6% of those receiving aspirin plus clopidogrel (risk ratio, 0.57; P = .001). Non–procedure-related bleeding occurred 15.1% of patients receiving aspirin alone vs 24.9% of those receiving aspirin plus clopidogrel (risk ratio, 0.61; P = .005). Major, life-threatening, or disabling bleeding occurred in 5.1% of the aspirin-alone group versus 10.8% of those in the aspirin plus clopidogrel group.

Two secondary outcomes included thromboembolic events. The secondary composite one endpoint of death from cardiovascular causes, non–procedure-related bleeding, stroke, or MI at 1 year occurred in 23.0% of those receiving aspirin alone and in 31.1% of those receiving aspirin plus clopidogrel (difference, −8.2 percentage points; P for noninferiority < .001; risk ratio, 0.74; P for superiority = .04).

The secondary composite two endpoint of death from cardiovascular causes, ischemic stroke, or MI at 1 year occurred in 9.7% of the aspirin-alone group versus 9.9% of the dual-antiplatelet group (difference, −0.2 percentage points; P for noninferiority = .004; risk ratio, 0.98; P for superiority = .93).

Dr. ten Berg pointed out that the trial was not strictly powered to look at thrombotic events, but he added: “There was no hint of an increase in the aspirin-alone group and there was quite a high event rate, so we should have seen something if it was there.”

The group has also performed a meta-analysis of these results, with some previous smaller studies also comparing aspirin and DAPT in TAVI which again showed no reduction in thrombotic events with dual-antiplatelet therapy.

Dr. ten Berg noted that the trial included all-comer TAVI patients. “The overall risk was quite a low [STS score, 2.5]. This is a reflection of the typical TAVI patient we are seeing but I would say our results apply to patients of all risk.”
 

Simplifies and clarifies

Discussant of the trial at the ESC Hotline session, Anna Sonia Petronio, MD, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, said, “This was an excellent and essential study that simplifies and clarifies aspects of TAVI treatment and needs to change the guidelines.”

“These results will have a large impact on clinical practice in this elderly population,” she said. But she added that more data are needed for younger patients and more complicated cases, such as valve-in-valve and bicuspid valves.

Commenting on the results, Robert Bonow, MD, Northwestern University, Chicago, said, “The optimal antithrombotic management of patients undergoing TAVI who do not otherwise have an indication for anticoagulation [such as atrial fibrillation] has been uncertain and debatable. Aspirin plus clopidogrel for 3-6 months has been the standard, based on the experience with coronary stents.”

“Thus, the current results of cohort A of the POPular TAVI trial showing significant reduction in bleeding events with aspirin alone compared to DAPT for 3 months, with no difference in ischemic events, are important observations,” he said. “It is noteworthy that most of the bleeding events occurred in the first 30 days.

“This is a relatively small randomized trial, so whether these results will be practice changing will depend on confirmation by additional studies, but it is reassuring to know that patients at higher risk for bleeding would appear to do well with low-dose aspirin alone after TAVI,” Dr. Bonow added.

“These results complete the circle in terms of antithrombotic therapy after TAVI,” commented Michael Reardon, MD, Houston Methodist DeBakey Heart & Vascular Institute, Texas.

“I would add two caveats: First is that most of the difference in the primary endpoint occurs in the first month and levels out between the groups after that,” Dr. Reardon said. “Second is that this does not address the issue of leaflet thickening and immobility.”

Ashish Pershad, MD, Banner – University Medicine Heart Institute, Phoenix, added: “This trial answers a very important question and shows dual-antiplatelet therapy is hazardous in TAVI patients. Clopidogrel is not needed.”

Dr. Pershad says he still wonders about patients who receive very small valves who may have a higher risk for valve-induced thrombosis. “While there were some of these patients in the trial, the numbers were small, so we need more data on this group,” he commented.

“But for bread-and-butter TAVI, aspirin alone is the best choice, and the previous results showed, for patients already taking oral anticoagulation, no additional antithrombotic therapy is required,” Dr. Pershad concluded. “This is a big deal and will change the way we treat patients.”

 The POPular trial was supported by the Netherlands Organization for Health Research and Development. Brouwer reports no disclosures.
 

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

A new report recommends the surgical closure of patent foramen ovale (PFO) in high-risk divers, but physicians in the United States urged caution about widespread use of the procedure in this population.

“PFO closure is recommended in divers with a high-grade PFO, with a history of unprovoked decompression sickness [DCS], or at the diver’s preference. Besides protection from DCS, PFO closure also offers the diver life-long protection from PFO-associated stroke,” write the authors of an analysis of the DIVE-PFO Registry.

The investigators, led by Jakub Honêk, MD, PhD, of Motol University Hospital in Prague, based that advice on results of their analysis, which compared two groups of divers with high-grade PFO: 55 who underwent catheter-based PFO closure, and 98 who were urged to dive cautiously.

Over a mean of about 7 years, the divers who underwent catheter-based PFO closure had no unprovoked decompression sickness (DCS), while the condition occurred in 11% of those who hadn’t had the procedure, according to the report, a research letter published online in the Journal of the American College of Cardiology.Decompression sickness, also known as the bends, can occur as gas bubbles pass through the circulatory system as divers ascend. In divers with PFO, which affects about 25% of the population, the bubbles can bypass filtration in the lungs and cause strokes, said neurologist David Thaler, MD, PhD, of Tufts Medical Center, Boston.

PFO closure via surgery is one option for divers with PFO, but there’s debate over whether the procedure should be widespread. For the new research letter, researchers prospectively tracked 748 divers in the DIVE-PFO (Decompression Illness Prevention in Divers with a Patent Foramen Ovale) registry during 2006-2018. Twenty-two percent had high-grade PFO.

In divers with PFO of grade 3 or above, procedures were performed if patients had a history of DCS or if they couldn’t adapt to conservative diving recommendations. The researchers said this population included commercial divers.

The groups that did or didn’t undergo surgery were similar in age (40.0 and 37.3 years, respectively, P = 0.079), and sex (78.2% and 79.6% male, respectively, P = 0.893), but differed in number of new dives (30,684 vs. 25,328, respectively, P < 0.001,), ). They were tracked for a mean of 7.1 years and 6.5 years, respectively.

It’s not clear whether the divers who underwent the closure procedure had fewer DCSs because they were more cautious about dive safety than the other diver group. The research letter doesn’t mention whether strokes occurred in divers in the two groups.

The study authors write that the results are consistent with previous findings that “PFO closure eliminates arterial gas emboli, “PFO is a major risk factor for unprovoked DCS,” and “PFO closure is a safe procedure with a very low complication rate.”

In interviews, physicians who are familiar with diver safety questioned the value of the findings and said medical professionals shouldn’t change practice.
 

Not so fast, experts say

Dr. Thaler, the Tufts Medical Center neurologist, questioned why the report explored a link between PFO and DCS. Overall, he said, the findings are too incomplete to inform practice. Anesthesiologist Richard Moon, MD, of Duke University, Durham, N.C., also questioned the study’s examination of DCS. “Most DCS cases are uncorrelated with PFO. It is only serious cases, a minority, that could conceivably be related to PFO, and even then, many serious cases that occur in divers with PFO are unrelated to it.” He added that “numerous divers with mild DCS ... have been mistakenly evaluated for PFO. Such practice is unsubstantiated by data.”

Should more closures be performed in this population? “I would be hesitant to make the recommended closures in divers,” said cardiologist David C. Peritz, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. “There are probably other ways that you can decrease your chances of getting decompression illness and make your dives more safe.”

Cardiologist Clifford J. Kavinsky, MD, PhD, of Rush University Medical Center, Chicago, said the closure procedure is “relatively safe” when performed by experienced surgeons. He noted that it is “only approved to prevent recurrent ischemic stroke in patients predominantly between the ages of 18 and 60 years who have experienced a cortical stroke presumed to be of embolic nature and for which no obvious cause can be found.”

As for high-risk divers, he said PFO closures “can be considered, but the data as yet are not strong enough to strongly recommend it.”

The Czech Republic’s Ministry of Health funded the study. The authors report no relevant disclosures. Dr. Thaler, Dr. Kavinsky, Dr. Moon and Dr. Peritz report no relevant disclosures.

SOURCE: Honěk J et al. J Am Coll Cardiol. 2020 Sep 1;76(9):1149-50.

A new report recommends the surgical closure of patent foramen ovale (PFO) in high-risk divers, but physicians in the United States urged caution about widespread use of the procedure in this population.

“PFO closure is recommended in divers with a high-grade PFO, with a history of unprovoked decompression sickness [DCS], or at the diver’s preference. Besides protection from DCS, PFO closure also offers the diver life-long protection from PFO-associated stroke,” write the authors of an analysis of the DIVE-PFO Registry.

The investigators, led by Jakub Honêk, MD, PhD, of Motol University Hospital in Prague, based that advice on results of their analysis, which compared two groups of divers with high-grade PFO: 55 who underwent catheter-based PFO closure, and 98 who were urged to dive cautiously.

Over a mean of about 7 years, the divers who underwent catheter-based PFO closure had no unprovoked decompression sickness (DCS), while the condition occurred in 11% of those who hadn’t had the procedure, according to the report, a research letter published online in the Journal of the American College of Cardiology.Decompression sickness, also known as the bends, can occur as gas bubbles pass through the circulatory system as divers ascend. In divers with PFO, which affects about 25% of the population, the bubbles can bypass filtration in the lungs and cause strokes, said neurologist David Thaler, MD, PhD, of Tufts Medical Center, Boston.

PFO closure via surgery is one option for divers with PFO, but there’s debate over whether the procedure should be widespread. For the new research letter, researchers prospectively tracked 748 divers in the DIVE-PFO (Decompression Illness Prevention in Divers with a Patent Foramen Ovale) registry during 2006-2018. Twenty-two percent had high-grade PFO.

In divers with PFO of grade 3 or above, procedures were performed if patients had a history of DCS or if they couldn’t adapt to conservative diving recommendations. The researchers said this population included commercial divers.

The groups that did or didn’t undergo surgery were similar in age (40.0 and 37.3 years, respectively, P = 0.079), and sex (78.2% and 79.6% male, respectively, P = 0.893), but differed in number of new dives (30,684 vs. 25,328, respectively, P < 0.001,), ). They were tracked for a mean of 7.1 years and 6.5 years, respectively.

It’s not clear whether the divers who underwent the closure procedure had fewer DCSs because they were more cautious about dive safety than the other diver group. The research letter doesn’t mention whether strokes occurred in divers in the two groups.

The study authors write that the results are consistent with previous findings that “PFO closure eliminates arterial gas emboli, “PFO is a major risk factor for unprovoked DCS,” and “PFO closure is a safe procedure with a very low complication rate.”

In interviews, physicians who are familiar with diver safety questioned the value of the findings and said medical professionals shouldn’t change practice.
 

Not so fast, experts say

Dr. Thaler, the Tufts Medical Center neurologist, questioned why the report explored a link between PFO and DCS. Overall, he said, the findings are too incomplete to inform practice. Anesthesiologist Richard Moon, MD, of Duke University, Durham, N.C., also questioned the study’s examination of DCS. “Most DCS cases are uncorrelated with PFO. It is only serious cases, a minority, that could conceivably be related to PFO, and even then, many serious cases that occur in divers with PFO are unrelated to it.” He added that “numerous divers with mild DCS ... have been mistakenly evaluated for PFO. Such practice is unsubstantiated by data.”

Should more closures be performed in this population? “I would be hesitant to make the recommended closures in divers,” said cardiologist David C. Peritz, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. “There are probably other ways that you can decrease your chances of getting decompression illness and make your dives more safe.”

Cardiologist Clifford J. Kavinsky, MD, PhD, of Rush University Medical Center, Chicago, said the closure procedure is “relatively safe” when performed by experienced surgeons. He noted that it is “only approved to prevent recurrent ischemic stroke in patients predominantly between the ages of 18 and 60 years who have experienced a cortical stroke presumed to be of embolic nature and for which no obvious cause can be found.”

As for high-risk divers, he said PFO closures “can be considered, but the data as yet are not strong enough to strongly recommend it.”

The Czech Republic’s Ministry of Health funded the study. The authors report no relevant disclosures. Dr. Thaler, Dr. Kavinsky, Dr. Moon and Dr. Peritz report no relevant disclosures.

SOURCE: Honěk J et al. J Am Coll Cardiol. 2020 Sep 1;76(9):1149-50.

A new report recommends the surgical closure of patent foramen ovale (PFO) in high-risk divers, but physicians in the United States urged caution about widespread use of the procedure in this population.

“PFO closure is recommended in divers with a high-grade PFO, with a history of unprovoked decompression sickness [DCS], or at the diver’s preference. Besides protection from DCS, PFO closure also offers the diver life-long protection from PFO-associated stroke,” write the authors of an analysis of the DIVE-PFO Registry.

The investigators, led by Jakub Honêk, MD, PhD, of Motol University Hospital in Prague, based that advice on results of their analysis, which compared two groups of divers with high-grade PFO: 55 who underwent catheter-based PFO closure, and 98 who were urged to dive cautiously.

Over a mean of about 7 years, the divers who underwent catheter-based PFO closure had no unprovoked decompression sickness (DCS), while the condition occurred in 11% of those who hadn’t had the procedure, according to the report, a research letter published online in the Journal of the American College of Cardiology.Decompression sickness, also known as the bends, can occur as gas bubbles pass through the circulatory system as divers ascend. In divers with PFO, which affects about 25% of the population, the bubbles can bypass filtration in the lungs and cause strokes, said neurologist David Thaler, MD, PhD, of Tufts Medical Center, Boston.

PFO closure via surgery is one option for divers with PFO, but there’s debate over whether the procedure should be widespread. For the new research letter, researchers prospectively tracked 748 divers in the DIVE-PFO (Decompression Illness Prevention in Divers with a Patent Foramen Ovale) registry during 2006-2018. Twenty-two percent had high-grade PFO.

In divers with PFO of grade 3 or above, procedures were performed if patients had a history of DCS or if they couldn’t adapt to conservative diving recommendations. The researchers said this population included commercial divers.

The groups that did or didn’t undergo surgery were similar in age (40.0 and 37.3 years, respectively, P = 0.079), and sex (78.2% and 79.6% male, respectively, P = 0.893), but differed in number of new dives (30,684 vs. 25,328, respectively, P < 0.001,), ). They were tracked for a mean of 7.1 years and 6.5 years, respectively.

It’s not clear whether the divers who underwent the closure procedure had fewer DCSs because they were more cautious about dive safety than the other diver group. The research letter doesn’t mention whether strokes occurred in divers in the two groups.

The study authors write that the results are consistent with previous findings that “PFO closure eliminates arterial gas emboli, “PFO is a major risk factor for unprovoked DCS,” and “PFO closure is a safe procedure with a very low complication rate.”

In interviews, physicians who are familiar with diver safety questioned the value of the findings and said medical professionals shouldn’t change practice.
 

Not so fast, experts say

Dr. Thaler, the Tufts Medical Center neurologist, questioned why the report explored a link between PFO and DCS. Overall, he said, the findings are too incomplete to inform practice. Anesthesiologist Richard Moon, MD, of Duke University, Durham, N.C., also questioned the study’s examination of DCS. “Most DCS cases are uncorrelated with PFO. It is only serious cases, a minority, that could conceivably be related to PFO, and even then, many serious cases that occur in divers with PFO are unrelated to it.” He added that “numerous divers with mild DCS ... have been mistakenly evaluated for PFO. Such practice is unsubstantiated by data.”

Should more closures be performed in this population? “I would be hesitant to make the recommended closures in divers,” said cardiologist David C. Peritz, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. “There are probably other ways that you can decrease your chances of getting decompression illness and make your dives more safe.”

Cardiologist Clifford J. Kavinsky, MD, PhD, of Rush University Medical Center, Chicago, said the closure procedure is “relatively safe” when performed by experienced surgeons. He noted that it is “only approved to prevent recurrent ischemic stroke in patients predominantly between the ages of 18 and 60 years who have experienced a cortical stroke presumed to be of embolic nature and for which no obvious cause can be found.”

As for high-risk divers, he said PFO closures “can be considered, but the data as yet are not strong enough to strongly recommend it.”

The Czech Republic’s Ministry of Health funded the study. The authors report no relevant disclosures. Dr. Thaler, Dr. Kavinsky, Dr. Moon and Dr. Peritz report no relevant disclosures.

SOURCE: Honěk J et al. J Am Coll Cardiol. 2020 Sep 1;76(9):1149-50.

The coronavirus may have quashed plans to socialize and stroll the canals of Amsterdam while at this year’s European Society of Cardiology (ESC) Congress, but organizers are promising a historic digital experience that will “once again, be a celebration of discovery and ground-breaking science.”

“My message — if I have to choose only one thing why ESC 2020 will be a historic event — is that the physician working at the Cleveland Clinic, who was planning to attend this year in Amsterdam, as well as the colleague in a bush hospital in Uganda, who would have never have dreamed to be part of the ESC Congress, both will have for the first time the same access at the same time to knowledge shared at the worldwide leading cardiovascular meeting,” Marco Roffi, MD, co-chair of the scientific program, told theheart.org | Medscape Cardiology.

Taking a page from the American College of Cardiology, which set the virtual bar early in the pandemic with its highly interactive ACC 2020, ESC is taking some 80 Hot Line, clinical practice guidelines, and special sessions live with question-and-answer interactions and panel discussions.

The latest COVID-19 research and four new guideline documents — including recommendations on atrial fibrillation (AF), non-ST-segment elevation acute coronary syndromes, sports cardiology and exercise in patients with cardiovascular disease, and adult congenital heart disease — will be featured at the ESC Congress 2020, scheduled for August 29 to September 1.

Presentations will be shorter and sessions more focused, but more than 500 scientific and educational sessions will be streamed in addition to more than 4000 abstracts available live or on demand as full presentations or e-posters, said Roffi, University Hospital of Geneva, Switzerland.

To pull off the virtual event, a digital studio in Amsterdam will host hundreds of key opinion leaders, and ESC employed more than 1000 satellite studios around the world to gather contributions from scientists and experts with the help of 70 behind-the-scenes experts.

Nevertheless, a “strategic decision” was made to provide free access to the event and its content for 30 days — a strategy that has attracted some 58,000 registrants thus far, up from a record 32,000 attendees at last year’s congress in Paris, Roffi said.

“Obviously, the income will not be the same as a physical congress, but we felt there was too much at stake to make a compromise,” he said. “We believe we are the leaders in cardiovascular meetings in the physical ones and we want to keep this position even in the new era. And we believe this is the beginning of a new era in whatever form will be.”

Hot Line Sessions 1-3, Saturday (14:00 CEST)

The Hot Line sessions will feature 13 clinical trials and kick off with EMPEROR-Reduced, which compared the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) added to standard care in patients with heart failure with reduced ejection fraction (HFrEF), with and without diabetes.

Eli Lilly and Boehringer Ingelheim already announced the trial met its composite primary endpoint of reducing cardiovascular (CV) death or HF hospitalization risk but the details will be important given the SGLT2 inhibitors› rapid shift beyond diabetes to HF and chronic kidney disease (CKD).

Results presented at ESC 2019 from the landmark DAPA-HF trial led to the recent new indication for dapagliflozin (Farxiga, AstraZeneca) for HFrEF in the absence of diabetes. New data will be released in a Sunday Hot Line session looking at the SGLT2 inhibitor among diabetic and nondiabetic CKD patients in DAPA-CKD, which was halted early because of overwhelming efficacy.

As the indication evolved, the SGLT2 inhibitors became truly cardiovascular disease drugs, Roffi said, “so all the cardiologists will have to become familiar with these agents.”

Hot Line 2 will look at the oral cardiac myosin inhibitor mavacamten as an alternative to surgery or percutaneous interventions to treat obstructive hypertrophic cardiomyopathy (HCM). The first-in-class investigational agent is thought to reduce the hypercontractility characteristic of HCM by inhibiting excessive actin-myosin cross-bridges, and it showed promise in the recent phase 2 dose-finding MAVERICK HCM trial.

Investigators are expected to flesh out details from the 251-patient phase 3 EXPLORER-HCM trial, which reported functional and symptomatic gains with once-daily dosing in top-line results released by developer MyoKardia.

“This is really a revolutionary way to treat — hopefully successfully — this very complex disease,” Roffi said.

Rounding out the day is the EAST-AFNET 4 trial, which has been almost 10 years in the making and examined whether early rhythm control with antiarrhythmic drugs and catheter ablation can prevent adverse outcomes in patients with AF compared with usual care alone based on the ESC 2010 AF treatment guidelines.

Hot Line Sessions 4-6, Sunday (14:00 CEST)

Hot Line 4 features the ATPCI study examining the addition of the oral antianginal agent trimetazidine to standard of care in 6007 patients with angina after recent successful percutaneous coronary intervention.

Next up is POPULAR-TAVI looking at aspirin with or without clopidogrel in patients undergoing transcatheter aortic valve implantation (TAVI).

“This is a dilemma that we have every day in the cath lab when we perform a TAVI because we have in front of us patients who, by definition, are at high bleeding risk, are old, and have comorbidities such as renal insufficiencies,” Roffi said. “I like this very much because it’s a very practical study. Whatever the response will be of this study, it will impact clinical practice.”

Hot Line 6 is devoted to the PARALLAX trial comparing sacubitril/valsartan (Entresto, Novartis) with individualized medical therapy in 2569 heart failure with preserved ejection fraction (HFpEF) patients. The primary outcomes are 12-week change in N-terminal pro-brain natriuretic peptide and 24-week change in 6-minute walk distance.

Hot Line Sessions 7-9, Monday (14:00 CEST)

The next day starts with the timely topic of inflammation with the LoDoCo2 trial, in which 5522 patients with stable coronary artery disease were randomized to low-dose colchicine 0.5 mg daily or placebo on top of optimal medical therapy. The primary composite endpoint is CV death, myocardial infarction (MI), ischemic stroke, and ischemia-driven revascularization.

Additional colchicine data also will be presented in a late-breaking science session on Saturday that includes the Australian COPS trial in acute coronary syndromes and new analyses from COLCOT, which demonstrated a 23% reduction in the risk of first ischemic CV events following an MI but no mortality benefit. The low-cost anti-inflammatory drug is also being tested in the mammoth 6000-patient phase 3 Colchicine Coronavirus SARS-CoV-2 (COLCORONA) trial, expected to be completed by the end of September.

Hot Line 8 switches gears with the open-label randomized HOME-PE trial comparing outpatient management of pulmonary embolism (PE) in 1975 select patients based on either the simplified Pulmonary Embolism Severity Index (PESI) score, featured in the most recent ESC acute PE guidelines, or the HESTIA criteria, developed in the HESTIA study. The event-driven primary end point is the composite of recurrent venous thromboembolism, major bleeding, and all-cause death at 30 days.

Last up on Monday is a new analysis on the effects of lowering blood pressure for prevention of CV events across various BP levels from the BPLTTC, which is the largest resource of patient-level randomized clinical trial data, at more than 350,000 patients.


Tuesday Hot Line Sessions 10-12 (14:00 CEST)

The final day of the Congress ends with bang, with the randomized BRACE-CORONA trial examining the effect of continuing or suspending angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in 700 patients with SARS-CoV-2 infection.

Although several cardiovascular societies including ESC recommend continuation of renin-angiotensin-aldosterone system (RAAS) antagonists in COVID-19 patients, randomized data are lacking and patients have been rattled by early observations suggesting that ACE2 upregulation from RAAS antagonists could increase the risk of developing severe COVID-19.

“BRACE-CORONA will answer the question that everybody’s been asking, whether or not you should continue ARBs and ACE inhibitors in COVID-19 patients. This is a randomized trial and we are all very excited about it,” Roffi said.

COVID-19 will also be discussed in a late-breaking science session on Sunday and in three industry Q&A sessions scattered over the 4 days.

Rounding out the last Hot Line session is IMPACT-AFib, a claims database analysis of early vs delayed educational interventions to improve oral anticoagulation use in a whopping 80,000 patients with AF, and REALITY, a much-needed cost-effectiveness analysis of liberal vs restrictive transfusion strategies in 630 patients with acute MI and anemia.
 

This article first appeared on Medscape.com.

The coronavirus may have quashed plans to socialize and stroll the canals of Amsterdam while at this year’s European Society of Cardiology (ESC) Congress, but organizers are promising a historic digital experience that will “once again, be a celebration of discovery and ground-breaking science.”

“My message — if I have to choose only one thing why ESC 2020 will be a historic event — is that the physician working at the Cleveland Clinic, who was planning to attend this year in Amsterdam, as well as the colleague in a bush hospital in Uganda, who would have never have dreamed to be part of the ESC Congress, both will have for the first time the same access at the same time to knowledge shared at the worldwide leading cardiovascular meeting,” Marco Roffi, MD, co-chair of the scientific program, told theheart.org | Medscape Cardiology.

Taking a page from the American College of Cardiology, which set the virtual bar early in the pandemic with its highly interactive ACC 2020, ESC is taking some 80 Hot Line, clinical practice guidelines, and special sessions live with question-and-answer interactions and panel discussions.

The latest COVID-19 research and four new guideline documents — including recommendations on atrial fibrillation (AF), non-ST-segment elevation acute coronary syndromes, sports cardiology and exercise in patients with cardiovascular disease, and adult congenital heart disease — will be featured at the ESC Congress 2020, scheduled for August 29 to September 1.

Presentations will be shorter and sessions more focused, but more than 500 scientific and educational sessions will be streamed in addition to more than 4000 abstracts available live or on demand as full presentations or e-posters, said Roffi, University Hospital of Geneva, Switzerland.

To pull off the virtual event, a digital studio in Amsterdam will host hundreds of key opinion leaders, and ESC employed more than 1000 satellite studios around the world to gather contributions from scientists and experts with the help of 70 behind-the-scenes experts.

Nevertheless, a “strategic decision” was made to provide free access to the event and its content for 30 days — a strategy that has attracted some 58,000 registrants thus far, up from a record 32,000 attendees at last year’s congress in Paris, Roffi said.

“Obviously, the income will not be the same as a physical congress, but we felt there was too much at stake to make a compromise,” he said. “We believe we are the leaders in cardiovascular meetings in the physical ones and we want to keep this position even in the new era. And we believe this is the beginning of a new era in whatever form will be.”

Hot Line Sessions 1-3, Saturday (14:00 CEST)

The Hot Line sessions will feature 13 clinical trials and kick off with EMPEROR-Reduced, which compared the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) added to standard care in patients with heart failure with reduced ejection fraction (HFrEF), with and without diabetes.

Eli Lilly and Boehringer Ingelheim already announced the trial met its composite primary endpoint of reducing cardiovascular (CV) death or HF hospitalization risk but the details will be important given the SGLT2 inhibitors› rapid shift beyond diabetes to HF and chronic kidney disease (CKD).

Results presented at ESC 2019 from the landmark DAPA-HF trial led to the recent new indication for dapagliflozin (Farxiga, AstraZeneca) for HFrEF in the absence of diabetes. New data will be released in a Sunday Hot Line session looking at the SGLT2 inhibitor among diabetic and nondiabetic CKD patients in DAPA-CKD, which was halted early because of overwhelming efficacy.

As the indication evolved, the SGLT2 inhibitors became truly cardiovascular disease drugs, Roffi said, “so all the cardiologists will have to become familiar with these agents.”

Hot Line 2 will look at the oral cardiac myosin inhibitor mavacamten as an alternative to surgery or percutaneous interventions to treat obstructive hypertrophic cardiomyopathy (HCM). The first-in-class investigational agent is thought to reduce the hypercontractility characteristic of HCM by inhibiting excessive actin-myosin cross-bridges, and it showed promise in the recent phase 2 dose-finding MAVERICK HCM trial.

Investigators are expected to flesh out details from the 251-patient phase 3 EXPLORER-HCM trial, which reported functional and symptomatic gains with once-daily dosing in top-line results released by developer MyoKardia.

“This is really a revolutionary way to treat — hopefully successfully — this very complex disease,” Roffi said.

Rounding out the day is the EAST-AFNET 4 trial, which has been almost 10 years in the making and examined whether early rhythm control with antiarrhythmic drugs and catheter ablation can prevent adverse outcomes in patients with AF compared with usual care alone based on the ESC 2010 AF treatment guidelines.

Hot Line Sessions 4-6, Sunday (14:00 CEST)

Hot Line 4 features the ATPCI study examining the addition of the oral antianginal agent trimetazidine to standard of care in 6007 patients with angina after recent successful percutaneous coronary intervention.

Next up is POPULAR-TAVI looking at aspirin with or without clopidogrel in patients undergoing transcatheter aortic valve implantation (TAVI).

“This is a dilemma that we have every day in the cath lab when we perform a TAVI because we have in front of us patients who, by definition, are at high bleeding risk, are old, and have comorbidities such as renal insufficiencies,” Roffi said. “I like this very much because it’s a very practical study. Whatever the response will be of this study, it will impact clinical practice.”

Hot Line 6 is devoted to the PARALLAX trial comparing sacubitril/valsartan (Entresto, Novartis) with individualized medical therapy in 2569 heart failure with preserved ejection fraction (HFpEF) patients. The primary outcomes are 12-week change in N-terminal pro-brain natriuretic peptide and 24-week change in 6-minute walk distance.

Hot Line Sessions 7-9, Monday (14:00 CEST)

The next day starts with the timely topic of inflammation with the LoDoCo2 trial, in which 5522 patients with stable coronary artery disease were randomized to low-dose colchicine 0.5 mg daily or placebo on top of optimal medical therapy. The primary composite endpoint is CV death, myocardial infarction (MI), ischemic stroke, and ischemia-driven revascularization.

Additional colchicine data also will be presented in a late-breaking science session on Saturday that includes the Australian COPS trial in acute coronary syndromes and new analyses from COLCOT, which demonstrated a 23% reduction in the risk of first ischemic CV events following an MI but no mortality benefit. The low-cost anti-inflammatory drug is also being tested in the mammoth 6000-patient phase 3 Colchicine Coronavirus SARS-CoV-2 (COLCORONA) trial, expected to be completed by the end of September.

Hot Line 8 switches gears with the open-label randomized HOME-PE trial comparing outpatient management of pulmonary embolism (PE) in 1975 select patients based on either the simplified Pulmonary Embolism Severity Index (PESI) score, featured in the most recent ESC acute PE guidelines, or the HESTIA criteria, developed in the HESTIA study. The event-driven primary end point is the composite of recurrent venous thromboembolism, major bleeding, and all-cause death at 30 days.

Last up on Monday is a new analysis on the effects of lowering blood pressure for prevention of CV events across various BP levels from the BPLTTC, which is the largest resource of patient-level randomized clinical trial data, at more than 350,000 patients.


Tuesday Hot Line Sessions 10-12 (14:00 CEST)

The final day of the Congress ends with bang, with the randomized BRACE-CORONA trial examining the effect of continuing or suspending angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in 700 patients with SARS-CoV-2 infection.

Although several cardiovascular societies including ESC recommend continuation of renin-angiotensin-aldosterone system (RAAS) antagonists in COVID-19 patients, randomized data are lacking and patients have been rattled by early observations suggesting that ACE2 upregulation from RAAS antagonists could increase the risk of developing severe COVID-19.

“BRACE-CORONA will answer the question that everybody’s been asking, whether or not you should continue ARBs and ACE inhibitors in COVID-19 patients. This is a randomized trial and we are all very excited about it,” Roffi said.

COVID-19 will also be discussed in a late-breaking science session on Sunday and in three industry Q&A sessions scattered over the 4 days.

Rounding out the last Hot Line session is IMPACT-AFib, a claims database analysis of early vs delayed educational interventions to improve oral anticoagulation use in a whopping 80,000 patients with AF, and REALITY, a much-needed cost-effectiveness analysis of liberal vs restrictive transfusion strategies in 630 patients with acute MI and anemia.
 

This article first appeared on Medscape.com.

The coronavirus may have quashed plans to socialize and stroll the canals of Amsterdam while at this year’s European Society of Cardiology (ESC) Congress, but organizers are promising a historic digital experience that will “once again, be a celebration of discovery and ground-breaking science.”

“My message — if I have to choose only one thing why ESC 2020 will be a historic event — is that the physician working at the Cleveland Clinic, who was planning to attend this year in Amsterdam, as well as the colleague in a bush hospital in Uganda, who would have never have dreamed to be part of the ESC Congress, both will have for the first time the same access at the same time to knowledge shared at the worldwide leading cardiovascular meeting,” Marco Roffi, MD, co-chair of the scientific program, told theheart.org | Medscape Cardiology.

Taking a page from the American College of Cardiology, which set the virtual bar early in the pandemic with its highly interactive ACC 2020, ESC is taking some 80 Hot Line, clinical practice guidelines, and special sessions live with question-and-answer interactions and panel discussions.

The latest COVID-19 research and four new guideline documents — including recommendations on atrial fibrillation (AF), non-ST-segment elevation acute coronary syndromes, sports cardiology and exercise in patients with cardiovascular disease, and adult congenital heart disease — will be featured at the ESC Congress 2020, scheduled for August 29 to September 1.

Presentations will be shorter and sessions more focused, but more than 500 scientific and educational sessions will be streamed in addition to more than 4000 abstracts available live or on demand as full presentations or e-posters, said Roffi, University Hospital of Geneva, Switzerland.

To pull off the virtual event, a digital studio in Amsterdam will host hundreds of key opinion leaders, and ESC employed more than 1000 satellite studios around the world to gather contributions from scientists and experts with the help of 70 behind-the-scenes experts.

Nevertheless, a “strategic decision” was made to provide free access to the event and its content for 30 days — a strategy that has attracted some 58,000 registrants thus far, up from a record 32,000 attendees at last year’s congress in Paris, Roffi said.

“Obviously, the income will not be the same as a physical congress, but we felt there was too much at stake to make a compromise,” he said. “We believe we are the leaders in cardiovascular meetings in the physical ones and we want to keep this position even in the new era. And we believe this is the beginning of a new era in whatever form will be.”

Hot Line Sessions 1-3, Saturday (14:00 CEST)

The Hot Line sessions will feature 13 clinical trials and kick off with EMPEROR-Reduced, which compared the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) added to standard care in patients with heart failure with reduced ejection fraction (HFrEF), with and without diabetes.

Eli Lilly and Boehringer Ingelheim already announced the trial met its composite primary endpoint of reducing cardiovascular (CV) death or HF hospitalization risk but the details will be important given the SGLT2 inhibitors› rapid shift beyond diabetes to HF and chronic kidney disease (CKD).

Results presented at ESC 2019 from the landmark DAPA-HF trial led to the recent new indication for dapagliflozin (Farxiga, AstraZeneca) for HFrEF in the absence of diabetes. New data will be released in a Sunday Hot Line session looking at the SGLT2 inhibitor among diabetic and nondiabetic CKD patients in DAPA-CKD, which was halted early because of overwhelming efficacy.

As the indication evolved, the SGLT2 inhibitors became truly cardiovascular disease drugs, Roffi said, “so all the cardiologists will have to become familiar with these agents.”

Hot Line 2 will look at the oral cardiac myosin inhibitor mavacamten as an alternative to surgery or percutaneous interventions to treat obstructive hypertrophic cardiomyopathy (HCM). The first-in-class investigational agent is thought to reduce the hypercontractility characteristic of HCM by inhibiting excessive actin-myosin cross-bridges, and it showed promise in the recent phase 2 dose-finding MAVERICK HCM trial.

Investigators are expected to flesh out details from the 251-patient phase 3 EXPLORER-HCM trial, which reported functional and symptomatic gains with once-daily dosing in top-line results released by developer MyoKardia.

“This is really a revolutionary way to treat — hopefully successfully — this very complex disease,” Roffi said.

Rounding out the day is the EAST-AFNET 4 trial, which has been almost 10 years in the making and examined whether early rhythm control with antiarrhythmic drugs and catheter ablation can prevent adverse outcomes in patients with AF compared with usual care alone based on the ESC 2010 AF treatment guidelines.

Hot Line Sessions 4-6, Sunday (14:00 CEST)

Hot Line 4 features the ATPCI study examining the addition of the oral antianginal agent trimetazidine to standard of care in 6007 patients with angina after recent successful percutaneous coronary intervention.

Next up is POPULAR-TAVI looking at aspirin with or without clopidogrel in patients undergoing transcatheter aortic valve implantation (TAVI).

“This is a dilemma that we have every day in the cath lab when we perform a TAVI because we have in front of us patients who, by definition, are at high bleeding risk, are old, and have comorbidities such as renal insufficiencies,” Roffi said. “I like this very much because it’s a very practical study. Whatever the response will be of this study, it will impact clinical practice.”

Hot Line 6 is devoted to the PARALLAX trial comparing sacubitril/valsartan (Entresto, Novartis) with individualized medical therapy in 2569 heart failure with preserved ejection fraction (HFpEF) patients. The primary outcomes are 12-week change in N-terminal pro-brain natriuretic peptide and 24-week change in 6-minute walk distance.

Hot Line Sessions 7-9, Monday (14:00 CEST)

The next day starts with the timely topic of inflammation with the LoDoCo2 trial, in which 5522 patients with stable coronary artery disease were randomized to low-dose colchicine 0.5 mg daily or placebo on top of optimal medical therapy. The primary composite endpoint is CV death, myocardial infarction (MI), ischemic stroke, and ischemia-driven revascularization.

Additional colchicine data also will be presented in a late-breaking science session on Saturday that includes the Australian COPS trial in acute coronary syndromes and new analyses from COLCOT, which demonstrated a 23% reduction in the risk of first ischemic CV events following an MI but no mortality benefit. The low-cost anti-inflammatory drug is also being tested in the mammoth 6000-patient phase 3 Colchicine Coronavirus SARS-CoV-2 (COLCORONA) trial, expected to be completed by the end of September.

Hot Line 8 switches gears with the open-label randomized HOME-PE trial comparing outpatient management of pulmonary embolism (PE) in 1975 select patients based on either the simplified Pulmonary Embolism Severity Index (PESI) score, featured in the most recent ESC acute PE guidelines, or the HESTIA criteria, developed in the HESTIA study. The event-driven primary end point is the composite of recurrent venous thromboembolism, major bleeding, and all-cause death at 30 days.

Last up on Monday is a new analysis on the effects of lowering blood pressure for prevention of CV events across various BP levels from the BPLTTC, which is the largest resource of patient-level randomized clinical trial data, at more than 350,000 patients.


Tuesday Hot Line Sessions 10-12 (14:00 CEST)

The final day of the Congress ends with bang, with the randomized BRACE-CORONA trial examining the effect of continuing or suspending angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in 700 patients with SARS-CoV-2 infection.

Although several cardiovascular societies including ESC recommend continuation of renin-angiotensin-aldosterone system (RAAS) antagonists in COVID-19 patients, randomized data are lacking and patients have been rattled by early observations suggesting that ACE2 upregulation from RAAS antagonists could increase the risk of developing severe COVID-19.

“BRACE-CORONA will answer the question that everybody’s been asking, whether or not you should continue ARBs and ACE inhibitors in COVID-19 patients. This is a randomized trial and we are all very excited about it,” Roffi said.

COVID-19 will also be discussed in a late-breaking science session on Sunday and in three industry Q&A sessions scattered over the 4 days.

Rounding out the last Hot Line session is IMPACT-AFib, a claims database analysis of early vs delayed educational interventions to improve oral anticoagulation use in a whopping 80,000 patients with AF, and REALITY, a much-needed cost-effectiveness analysis of liberal vs restrictive transfusion strategies in 630 patients with acute MI and anemia.
 

This article first appeared on Medscape.com.

The beneficial effect on all-cause mortality of coronary artery bypass grafting surgery observed at 4 and 5 years in women with complex coronary disease seen in the SYNTAX trial is gone at 10 years.

If anything, the results suggest a mortality benefit for coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) mainly for men (adjusted hazard ratio, 0.76; 95% confidence interval, 0.56-1.02) and not for women (adjusted HR, 0.90; 95% CI, 0.54-1.51) in the SYNTAX Extended Survival (SYNTAXES) study.

The sex-treatment interaction for all-cause mortality was significant at 5 years (P = .025) but not at 10 years (P = .952).

“I’m becoming very humble with trials because I’m not expecting the convergence of the curve. I was expecting like a surge, a further divergence,” senior author Patrick Serruys, MD, PhD, National University of Ireland, Galway, said in an interview. “You could say, at the end of the day, everybody dies. And that’s the life expectancy factor.”

Although female patients had slightly lower anatomic SYNTAX scores at randomization (27.0 vs. 29.2), they were on average 4 years older than men (mean age, 68 years) and had higher prevalence rates of diabetes, hypertension, and chronic kidney disease, he noted. “The other explanation is that we know that the bypass graft, the saphenous bypass graft, became vulnerable around 7 years; that’s probably the half-life.”

Overall, mortality in both men and women tended to be lower after CABG than after PCI, although the differences were not statistically significant, the authors reported August 17 in the Journal of the American College of Cardiology.

The 1,800-patient SYNTAX trial showed no difference in all-cause mortality at 5 years between CABG and PCI, although CABG was associated with fewer major adverse cardiac and cerebrovascular events (MACCE) and more favorable results among those with complex, three-vessel disease.

The findings were confirmed in 10-year follow-up reported last year from SYNTAXES, which analyzed only all-cause mortality.

Female sex, however, was an independent predictor of mortality with PCI at 4-years follow-up (HR, 2.87) in SYNTAX and led to sex being incorporated into the SYNTAX II score to help guide revascularization decisions. Notably, this interaction for all-cause mortality has not been seen in other studies.

Treatment effect by sex

In the new prespecified subgroup analysis, women had a higher crude rate of all-cause mortality at 10 years than men (32.8% vs. 24.7%; log-rank P = .002). This held true whether women were in the PCI group (33.0% vs. 27.0%; log-rank P = .053) or the CABG group (32.5% vs. 22.5%; log-rank P = .017).

In women, the mortality rate was significantly higher with PCI than with CABG at 5 years, but was no longer different at 10 years (33.0% vs. 32.5%; log-rank P = .601). This was largely caused by an uptick in deaths between 5 and 10 years in those treated with CABG, compared with PCI.

In men, the mortality rate was similar between PCI and CABG at 5 years, but tended to be higher with PCI at 10 years (27.0% vs. 22.5%; log-rank P = .082).

Asked about the possible late benefit for CABG in men, Dr. Serruys replied: “Of course, everyone had made a hypothesis – ‘let’s look at the use of internal mammary arteries in these patients, etc.’ – but I must be honest, we don’t have an explanation so far.”

Roxana Mehran, MD, Mount Sinai School of Medicine, New York City, said with just 402 women and using a no-longer-available, first-generation (Taxus) stent, the findings are, unfortunately, not informative.

“For me, it would be important for these investigators to share their data for women so we can do a patient-based analysis to better figure out the differential between first-generation stents and how well we’re doing,” Dr. Mehran said.

“What’s really important is to have a study where you actually collect female-specific risk factors that are never, ever looked at, [such as] age at menopause or having had pregnancy-related complications, that predispose these women to more of an atherosclerotic risk. And, even so, to better understand their anatomy and what suits them better,” she said. “I just don’t think we know enough or have put enough effort into understanding the biology that is sex specific and different for men and women.”
 

Revising SYNTAX II score

Given the lack of a sex-treatment interaction in the analysis, Dr. Serruys and colleagues suggest that the SYNTAX II score “should be reevaluated for the prediction of all-cause mortality at 10 years.”

Lending further support to this is the fact that SYNTAX II score was similar between women who died at 5-10 years and those who died in the first 5 years after CABG (31.8 vs. 31.6).

“The authors rightfully ask whether the SYNTAX II score should be revised to remove female sex, and given the current study result this appears warranted,” Arnold H. Seto, MD, MPA, Long Beach (Calif.) Veterans Administration Hospital, said in a related editorial.

He pointed out that women in SYNTAXES treated with CABG tended to have a survival time 0.51 years longer than women treated with PCI (P = .07). Nonetheless, the lack of confirmation for a sex-specific treatment interaction in any other study – EXCEL, FREEDOM, BEST, PRECOMBAT, BARI, or MASS – strongly suggests that the interaction seen in SYNTAX is likely a “type 1 error.”

Rather than focusing on early mortality, which may represent relatively rare events that are susceptible to chance, Dr. Seto suggested “other endpoints such years of life saved, quality adjusted life-years, and MACE may better capture the benefits of different revascularization decisions, even if they have a higher risk for bias.”

A new risk model, SYNTAX score 2020, has been developed and will be published imminently, Dr. Serruys said in an interview.

The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research. The SYNTAX trial, during 0- to 5-years of follow-up, was funded by Boston Scientific. Both sponsors had no role in study design or data collection, analyses, and interpretation, nor were they involved in the decision to publish the final manuscript. Dr. Serruys has received personal fees from Biosensors, Micel Technologies, Sinomedical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Seto reported research grants from Philips and Acist, and honoraria from Terumo, Getinge, Boston Scientific, General Electric, and Janssen.

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

The beneficial effect on all-cause mortality of coronary artery bypass grafting surgery observed at 4 and 5 years in women with complex coronary disease seen in the SYNTAX trial is gone at 10 years.

If anything, the results suggest a mortality benefit for coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) mainly for men (adjusted hazard ratio, 0.76; 95% confidence interval, 0.56-1.02) and not for women (adjusted HR, 0.90; 95% CI, 0.54-1.51) in the SYNTAX Extended Survival (SYNTAXES) study.

The sex-treatment interaction for all-cause mortality was significant at 5 years (P = .025) but not at 10 years (P = .952).

“I’m becoming very humble with trials because I’m not expecting the convergence of the curve. I was expecting like a surge, a further divergence,” senior author Patrick Serruys, MD, PhD, National University of Ireland, Galway, said in an interview. “You could say, at the end of the day, everybody dies. And that’s the life expectancy factor.”

Although female patients had slightly lower anatomic SYNTAX scores at randomization (27.0 vs. 29.2), they were on average 4 years older than men (mean age, 68 years) and had higher prevalence rates of diabetes, hypertension, and chronic kidney disease, he noted. “The other explanation is that we know that the bypass graft, the saphenous bypass graft, became vulnerable around 7 years; that’s probably the half-life.”

Overall, mortality in both men and women tended to be lower after CABG than after PCI, although the differences were not statistically significant, the authors reported August 17 in the Journal of the American College of Cardiology.

The 1,800-patient SYNTAX trial showed no difference in all-cause mortality at 5 years between CABG and PCI, although CABG was associated with fewer major adverse cardiac and cerebrovascular events (MACCE) and more favorable results among those with complex, three-vessel disease.

The findings were confirmed in 10-year follow-up reported last year from SYNTAXES, which analyzed only all-cause mortality.

Female sex, however, was an independent predictor of mortality with PCI at 4-years follow-up (HR, 2.87) in SYNTAX and led to sex being incorporated into the SYNTAX II score to help guide revascularization decisions. Notably, this interaction for all-cause mortality has not been seen in other studies.

Treatment effect by sex

In the new prespecified subgroup analysis, women had a higher crude rate of all-cause mortality at 10 years than men (32.8% vs. 24.7%; log-rank P = .002). This held true whether women were in the PCI group (33.0% vs. 27.0%; log-rank P = .053) or the CABG group (32.5% vs. 22.5%; log-rank P = .017).

In women, the mortality rate was significantly higher with PCI than with CABG at 5 years, but was no longer different at 10 years (33.0% vs. 32.5%; log-rank P = .601). This was largely caused by an uptick in deaths between 5 and 10 years in those treated with CABG, compared with PCI.

In men, the mortality rate was similar between PCI and CABG at 5 years, but tended to be higher with PCI at 10 years (27.0% vs. 22.5%; log-rank P = .082).

Asked about the possible late benefit for CABG in men, Dr. Serruys replied: “Of course, everyone had made a hypothesis – ‘let’s look at the use of internal mammary arteries in these patients, etc.’ – but I must be honest, we don’t have an explanation so far.”

Roxana Mehran, MD, Mount Sinai School of Medicine, New York City, said with just 402 women and using a no-longer-available, first-generation (Taxus) stent, the findings are, unfortunately, not informative.

“For me, it would be important for these investigators to share their data for women so we can do a patient-based analysis to better figure out the differential between first-generation stents and how well we’re doing,” Dr. Mehran said.

“What’s really important is to have a study where you actually collect female-specific risk factors that are never, ever looked at, [such as] age at menopause or having had pregnancy-related complications, that predispose these women to more of an atherosclerotic risk. And, even so, to better understand their anatomy and what suits them better,” she said. “I just don’t think we know enough or have put enough effort into understanding the biology that is sex specific and different for men and women.”
 

Revising SYNTAX II score

Given the lack of a sex-treatment interaction in the analysis, Dr. Serruys and colleagues suggest that the SYNTAX II score “should be reevaluated for the prediction of all-cause mortality at 10 years.”

Lending further support to this is the fact that SYNTAX II score was similar between women who died at 5-10 years and those who died in the first 5 years after CABG (31.8 vs. 31.6).

“The authors rightfully ask whether the SYNTAX II score should be revised to remove female sex, and given the current study result this appears warranted,” Arnold H. Seto, MD, MPA, Long Beach (Calif.) Veterans Administration Hospital, said in a related editorial.

He pointed out that women in SYNTAXES treated with CABG tended to have a survival time 0.51 years longer than women treated with PCI (P = .07). Nonetheless, the lack of confirmation for a sex-specific treatment interaction in any other study – EXCEL, FREEDOM, BEST, PRECOMBAT, BARI, or MASS – strongly suggests that the interaction seen in SYNTAX is likely a “type 1 error.”

Rather than focusing on early mortality, which may represent relatively rare events that are susceptible to chance, Dr. Seto suggested “other endpoints such years of life saved, quality adjusted life-years, and MACE may better capture the benefits of different revascularization decisions, even if they have a higher risk for bias.”

A new risk model, SYNTAX score 2020, has been developed and will be published imminently, Dr. Serruys said in an interview.

The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research. The SYNTAX trial, during 0- to 5-years of follow-up, was funded by Boston Scientific. Both sponsors had no role in study design or data collection, analyses, and interpretation, nor were they involved in the decision to publish the final manuscript. Dr. Serruys has received personal fees from Biosensors, Micel Technologies, Sinomedical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Seto reported research grants from Philips and Acist, and honoraria from Terumo, Getinge, Boston Scientific, General Electric, and Janssen.

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

The beneficial effect on all-cause mortality of coronary artery bypass grafting surgery observed at 4 and 5 years in women with complex coronary disease seen in the SYNTAX trial is gone at 10 years.

If anything, the results suggest a mortality benefit for coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) mainly for men (adjusted hazard ratio, 0.76; 95% confidence interval, 0.56-1.02) and not for women (adjusted HR, 0.90; 95% CI, 0.54-1.51) in the SYNTAX Extended Survival (SYNTAXES) study.

The sex-treatment interaction for all-cause mortality was significant at 5 years (P = .025) but not at 10 years (P = .952).

“I’m becoming very humble with trials because I’m not expecting the convergence of the curve. I was expecting like a surge, a further divergence,” senior author Patrick Serruys, MD, PhD, National University of Ireland, Galway, said in an interview. “You could say, at the end of the day, everybody dies. And that’s the life expectancy factor.”

Although female patients had slightly lower anatomic SYNTAX scores at randomization (27.0 vs. 29.2), they were on average 4 years older than men (mean age, 68 years) and had higher prevalence rates of diabetes, hypertension, and chronic kidney disease, he noted. “The other explanation is that we know that the bypass graft, the saphenous bypass graft, became vulnerable around 7 years; that’s probably the half-life.”

Overall, mortality in both men and women tended to be lower after CABG than after PCI, although the differences were not statistically significant, the authors reported August 17 in the Journal of the American College of Cardiology.

The 1,800-patient SYNTAX trial showed no difference in all-cause mortality at 5 years between CABG and PCI, although CABG was associated with fewer major adverse cardiac and cerebrovascular events (MACCE) and more favorable results among those with complex, three-vessel disease.

The findings were confirmed in 10-year follow-up reported last year from SYNTAXES, which analyzed only all-cause mortality.

Female sex, however, was an independent predictor of mortality with PCI at 4-years follow-up (HR, 2.87) in SYNTAX and led to sex being incorporated into the SYNTAX II score to help guide revascularization decisions. Notably, this interaction for all-cause mortality has not been seen in other studies.

Treatment effect by sex

In the new prespecified subgroup analysis, women had a higher crude rate of all-cause mortality at 10 years than men (32.8% vs. 24.7%; log-rank P = .002). This held true whether women were in the PCI group (33.0% vs. 27.0%; log-rank P = .053) or the CABG group (32.5% vs. 22.5%; log-rank P = .017).

In women, the mortality rate was significantly higher with PCI than with CABG at 5 years, but was no longer different at 10 years (33.0% vs. 32.5%; log-rank P = .601). This was largely caused by an uptick in deaths between 5 and 10 years in those treated with CABG, compared with PCI.

In men, the mortality rate was similar between PCI and CABG at 5 years, but tended to be higher with PCI at 10 years (27.0% vs. 22.5%; log-rank P = .082).

Asked about the possible late benefit for CABG in men, Dr. Serruys replied: “Of course, everyone had made a hypothesis – ‘let’s look at the use of internal mammary arteries in these patients, etc.’ – but I must be honest, we don’t have an explanation so far.”

Roxana Mehran, MD, Mount Sinai School of Medicine, New York City, said with just 402 women and using a no-longer-available, first-generation (Taxus) stent, the findings are, unfortunately, not informative.

“For me, it would be important for these investigators to share their data for women so we can do a patient-based analysis to better figure out the differential between first-generation stents and how well we’re doing,” Dr. Mehran said.

“What’s really important is to have a study where you actually collect female-specific risk factors that are never, ever looked at, [such as] age at menopause or having had pregnancy-related complications, that predispose these women to more of an atherosclerotic risk. And, even so, to better understand their anatomy and what suits them better,” she said. “I just don’t think we know enough or have put enough effort into understanding the biology that is sex specific and different for men and women.”
 

Revising SYNTAX II score

Given the lack of a sex-treatment interaction in the analysis, Dr. Serruys and colleagues suggest that the SYNTAX II score “should be reevaluated for the prediction of all-cause mortality at 10 years.”

Lending further support to this is the fact that SYNTAX II score was similar between women who died at 5-10 years and those who died in the first 5 years after CABG (31.8 vs. 31.6).

“The authors rightfully ask whether the SYNTAX II score should be revised to remove female sex, and given the current study result this appears warranted,” Arnold H. Seto, MD, MPA, Long Beach (Calif.) Veterans Administration Hospital, said in a related editorial.

He pointed out that women in SYNTAXES treated with CABG tended to have a survival time 0.51 years longer than women treated with PCI (P = .07). Nonetheless, the lack of confirmation for a sex-specific treatment interaction in any other study – EXCEL, FREEDOM, BEST, PRECOMBAT, BARI, or MASS – strongly suggests that the interaction seen in SYNTAX is likely a “type 1 error.”

Rather than focusing on early mortality, which may represent relatively rare events that are susceptible to chance, Dr. Seto suggested “other endpoints such years of life saved, quality adjusted life-years, and MACE may better capture the benefits of different revascularization decisions, even if they have a higher risk for bias.”

A new risk model, SYNTAX score 2020, has been developed and will be published imminently, Dr. Serruys said in an interview.

The SYNTAX Extended Survival study was supported by the German Foundation of Heart Research. The SYNTAX trial, during 0- to 5-years of follow-up, was funded by Boston Scientific. Both sponsors had no role in study design or data collection, analyses, and interpretation, nor were they involved in the decision to publish the final manuscript. Dr. Serruys has received personal fees from Biosensors, Micel Technologies, Sinomedical Sciences Technology, Philips/Volcano, Xeltis, and HeartFlow, outside the submitted work. Dr. Seto reported research grants from Philips and Acist, and honoraria from Terumo, Getinge, Boston Scientific, General Electric, and Janssen.

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

Pulmonary artery denervation (PADN) provides persistent and clinically significant hemodynamic improvements in patients with persistent chronic thromboembolic hypertension (CTEPH) after pulmonary endarterectomy (PEA), according to a randomized, sham-controlled trial.

“PADN in patients with CTEPH after PEA was safe and effective,” according to an investigating team led by Alexander Romanov, MD, PhD.

The mean reduction in pulmonary vascular resistance (PVR) was 258 dyn/sec per cm^–5 for those randomized to PADN versus 149 dyn/sec per cm^–5 (P = .001) for those randomized to the sham procedure, according to the newly published findings.

For the 6-minute walk test (6MWT), the mean distance was 470 m for the experimental group versus 399 m (P = .03) for the controls.

Several secondary endpoints measuring hemodynamics also favored PADN relative to the sham procedure at 12 months. This included the relative increase in tricuspid annular systolic excursion (P = .03) and the increase in the right ventricular fraction area (P < .001).

A total of 50 patients with residual CTEPH for at least 6 months after PEA despite medical therapy were enrolled and randomized. Entry criteria included a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater or PVR greater than 400 dyn/sec per cm^–5 on right heart catheterization. Patients with comorbidities associated with a life expectancy of less than 1 year were excluded.

Those randomized to the sham group were treated with riociguat over the course of follow-up. This therapy was not offered to patients in the PADN group, but all patients were blinded to the procedure and told that riociguat might or might not be administered.

Following the procedure, participating clinicians, who were also blinded to the procedure, were instructed to provide standard therapies for heart failure, such beta-blockers, diuretics, or digoxin, as needed. All patients were placed on an oral anticoagulant.

At 12 months the mean PAP (26 vs. 35 mm Hg; P < .001) and the mean systolic PAP (46 vs. 54 mm Hg; P = .01) were significantly lower in the PADN group versus those who underwent a sham procedure.

About 52% of the PADN group versus 12% of the sham group were classified as responders by the definition of a PVR reduction of at least 150 dyn/sec per cm^–5 and 6MWT improvement of at least 20%, compared with baseline, reported Dr. Romanov, of the E. Meshalkin National Medical Research Center, ministry of health, Novosibirsk, Russia, and coinvestigators.

Of the three deaths caused by heart failure over the course of follow-up, two occurred in the sham group. Of the eight hospitalizations for heart failure, seven (29% of the sham group) occurred among controls versus one in those treated with PADN (4% of this group; P = .049).

There was one groin hematoma at the puncture site in each group. Both resolved without any consequences prior to hospital discharge. There were no other significant procedure-related complications in either group.

Larger multicenter trials are needed to confirm these findings, according to both the trial investigators and Marius M. Hoeper, MD, who is charge of the pulmonary hypertension program at the Hannover (Germany) Medical School.

In an editorial that accompanied publication of these findings, Dr. Hoeper identified the small sample size of this study as one of its limitations, but he said the results are consistent with several other small studies associating pulmonary artery denervation with benefit in pulmonary hypertension.

“It appears as if we are currently witnessing the emergence of a new treatment option for various forms of pulmonary hypertension,” Dr. Hoeper wrote. In his critique of the study, he suggested that it would have been “more informative” if both groups were on background riociguat, but the data from this and other studies so far indicates that ablation to achieve denervation “is safe and feasible.”

The PADN technique used in this study might be relevant to the results. Dr. Hoeper noted that the investigators employed catheter tip–based electroanatomic mapping with a novel remote navigation system with three-dimensional imaging of the right ventricle and central pulmonary arteries.

“Apparently, this approach minimizes radiation exposure and provides precise location of ablation sites,” Dr. Hoeper observed. However, he called for direct comparisons of this tool to the guidance systems used in other studies.

In an interview, Dr. Hoeper acknowledged that it is not yet clear that a large-scale trial of pulmonary artery denervation for the indication evaluated in this study is coming. He noted several strategies in CTEPH are widely used without trials confirming a reduction in clinical events.

“Balloon pulmonary angioplasty for CTEPH has become an established treatment around the world without any randomized, controlled trial and without demonstration of improved outcomes. A couple of well-conducted observational trials might be sufficient to convince physicians to introduce PADN as well,” he said. If such studies associated PADN with “improvements in hemodynamics, exercise capacity, and patient-reported outcomes, it might be sufficient.”

Currently, Dr. Hoeper is most concerned about obtaining further evidence of safety, which he characterized as a “major issue.”

If a multicenter trial is conducted “the primary endpoint should be focused on clinical events,” according to Dr. Romanov, who was asked to comment on the next steps in validating PADN for the treatment of CTEPH-associated pulmonary hypertension persisting after endarterectomy.

“The mortality rate during 1-year long-term follow-up is not so high, but heart failure progression is a problem. So in my view, the primary endpoint should be a composite of death and heart failure hospitalization,” he said. He called for follow-up duration of 2-3 years.

Jonathan Steinberg, MD, director of cardiac clinical trials and education, Summit Medical Group, Montclair, N.J., also called a trial with hard endpoints, such as death, the ideal.

In the meantime, hemodynamic and functional measures “are still quite valuable and move the ball forward for this intervention,” he said in an interview. Senior author of this trial and principle investigator of the recent ERADICATE-AF trial, which evaluated renal denervation in preventing recurrence of atrial fibrillation (JAMA. 2020;323:248-55), Dr. Steinberg predicted, “I do indeed suspect we will see trials that are more accomplishable [than a large-scale, randomized, controlled trial] in the not too distant future.”

Dr. Romanov received funding from Biosense Webster. Dr. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, Janssen, Merck Sharp & Dohme, and Pfizer.

SOURCE: Romanov A et al. J Am Coll Cardiol. 2020 Aug 17;76:916-26.

Pulmonary artery denervation (PADN) provides persistent and clinically significant hemodynamic improvements in patients with persistent chronic thromboembolic hypertension (CTEPH) after pulmonary endarterectomy (PEA), according to a randomized, sham-controlled trial.

“PADN in patients with CTEPH after PEA was safe and effective,” according to an investigating team led by Alexander Romanov, MD, PhD.

The mean reduction in pulmonary vascular resistance (PVR) was 258 dyn/sec per cm^–5 for those randomized to PADN versus 149 dyn/sec per cm^–5 (P = .001) for those randomized to the sham procedure, according to the newly published findings.

For the 6-minute walk test (6MWT), the mean distance was 470 m for the experimental group versus 399 m (P = .03) for the controls.

Several secondary endpoints measuring hemodynamics also favored PADN relative to the sham procedure at 12 months. This included the relative increase in tricuspid annular systolic excursion (P = .03) and the increase in the right ventricular fraction area (P < .001).

A total of 50 patients with residual CTEPH for at least 6 months after PEA despite medical therapy were enrolled and randomized. Entry criteria included a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater or PVR greater than 400 dyn/sec per cm^–5 on right heart catheterization. Patients with comorbidities associated with a life expectancy of less than 1 year were excluded.

Those randomized to the sham group were treated with riociguat over the course of follow-up. This therapy was not offered to patients in the PADN group, but all patients were blinded to the procedure and told that riociguat might or might not be administered.

Following the procedure, participating clinicians, who were also blinded to the procedure, were instructed to provide standard therapies for heart failure, such beta-blockers, diuretics, or digoxin, as needed. All patients were placed on an oral anticoagulant.

At 12 months the mean PAP (26 vs. 35 mm Hg; P < .001) and the mean systolic PAP (46 vs. 54 mm Hg; P = .01) were significantly lower in the PADN group versus those who underwent a sham procedure.

About 52% of the PADN group versus 12% of the sham group were classified as responders by the definition of a PVR reduction of at least 150 dyn/sec per cm^–5 and 6MWT improvement of at least 20%, compared with baseline, reported Dr. Romanov, of the E. Meshalkin National Medical Research Center, ministry of health, Novosibirsk, Russia, and coinvestigators.

Of the three deaths caused by heart failure over the course of follow-up, two occurred in the sham group. Of the eight hospitalizations for heart failure, seven (29% of the sham group) occurred among controls versus one in those treated with PADN (4% of this group; P = .049).

There was one groin hematoma at the puncture site in each group. Both resolved without any consequences prior to hospital discharge. There were no other significant procedure-related complications in either group.

Larger multicenter trials are needed to confirm these findings, according to both the trial investigators and Marius M. Hoeper, MD, who is charge of the pulmonary hypertension program at the Hannover (Germany) Medical School.

In an editorial that accompanied publication of these findings, Dr. Hoeper identified the small sample size of this study as one of its limitations, but he said the results are consistent with several other small studies associating pulmonary artery denervation with benefit in pulmonary hypertension.

“It appears as if we are currently witnessing the emergence of a new treatment option for various forms of pulmonary hypertension,” Dr. Hoeper wrote. In his critique of the study, he suggested that it would have been “more informative” if both groups were on background riociguat, but the data from this and other studies so far indicates that ablation to achieve denervation “is safe and feasible.”

The PADN technique used in this study might be relevant to the results. Dr. Hoeper noted that the investigators employed catheter tip–based electroanatomic mapping with a novel remote navigation system with three-dimensional imaging of the right ventricle and central pulmonary arteries.

“Apparently, this approach minimizes radiation exposure and provides precise location of ablation sites,” Dr. Hoeper observed. However, he called for direct comparisons of this tool to the guidance systems used in other studies.

In an interview, Dr. Hoeper acknowledged that it is not yet clear that a large-scale trial of pulmonary artery denervation for the indication evaluated in this study is coming. He noted several strategies in CTEPH are widely used without trials confirming a reduction in clinical events.

“Balloon pulmonary angioplasty for CTEPH has become an established treatment around the world without any randomized, controlled trial and without demonstration of improved outcomes. A couple of well-conducted observational trials might be sufficient to convince physicians to introduce PADN as well,” he said. If such studies associated PADN with “improvements in hemodynamics, exercise capacity, and patient-reported outcomes, it might be sufficient.”

Currently, Dr. Hoeper is most concerned about obtaining further evidence of safety, which he characterized as a “major issue.”

If a multicenter trial is conducted “the primary endpoint should be focused on clinical events,” according to Dr. Romanov, who was asked to comment on the next steps in validating PADN for the treatment of CTEPH-associated pulmonary hypertension persisting after endarterectomy.

“The mortality rate during 1-year long-term follow-up is not so high, but heart failure progression is a problem. So in my view, the primary endpoint should be a composite of death and heart failure hospitalization,” he said. He called for follow-up duration of 2-3 years.

Jonathan Steinberg, MD, director of cardiac clinical trials and education, Summit Medical Group, Montclair, N.J., also called a trial with hard endpoints, such as death, the ideal.

In the meantime, hemodynamic and functional measures “are still quite valuable and move the ball forward for this intervention,” he said in an interview. Senior author of this trial and principle investigator of the recent ERADICATE-AF trial, which evaluated renal denervation in preventing recurrence of atrial fibrillation (JAMA. 2020;323:248-55), Dr. Steinberg predicted, “I do indeed suspect we will see trials that are more accomplishable [than a large-scale, randomized, controlled trial] in the not too distant future.”

Dr. Romanov received funding from Biosense Webster. Dr. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, Janssen, Merck Sharp & Dohme, and Pfizer.

SOURCE: Romanov A et al. J Am Coll Cardiol. 2020 Aug 17;76:916-26.

Pulmonary artery denervation (PADN) provides persistent and clinically significant hemodynamic improvements in patients with persistent chronic thromboembolic hypertension (CTEPH) after pulmonary endarterectomy (PEA), according to a randomized, sham-controlled trial.

“PADN in patients with CTEPH after PEA was safe and effective,” according to an investigating team led by Alexander Romanov, MD, PhD.

The mean reduction in pulmonary vascular resistance (PVR) was 258 dyn/sec per cm^–5 for those randomized to PADN versus 149 dyn/sec per cm^–5 (P = .001) for those randomized to the sham procedure, according to the newly published findings.

For the 6-minute walk test (6MWT), the mean distance was 470 m for the experimental group versus 399 m (P = .03) for the controls.

Several secondary endpoints measuring hemodynamics also favored PADN relative to the sham procedure at 12 months. This included the relative increase in tricuspid annular systolic excursion (P = .03) and the increase in the right ventricular fraction area (P < .001).

A total of 50 patients with residual CTEPH for at least 6 months after PEA despite medical therapy were enrolled and randomized. Entry criteria included a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater or PVR greater than 400 dyn/sec per cm^–5 on right heart catheterization. Patients with comorbidities associated with a life expectancy of less than 1 year were excluded.

Those randomized to the sham group were treated with riociguat over the course of follow-up. This therapy was not offered to patients in the PADN group, but all patients were blinded to the procedure and told that riociguat might or might not be administered.

Following the procedure, participating clinicians, who were also blinded to the procedure, were instructed to provide standard therapies for heart failure, such beta-blockers, diuretics, or digoxin, as needed. All patients were placed on an oral anticoagulant.

At 12 months the mean PAP (26 vs. 35 mm Hg; P < .001) and the mean systolic PAP (46 vs. 54 mm Hg; P = .01) were significantly lower in the PADN group versus those who underwent a sham procedure.

About 52% of the PADN group versus 12% of the sham group were classified as responders by the definition of a PVR reduction of at least 150 dyn/sec per cm^–5 and 6MWT improvement of at least 20%, compared with baseline, reported Dr. Romanov, of the E. Meshalkin National Medical Research Center, ministry of health, Novosibirsk, Russia, and coinvestigators.

Of the three deaths caused by heart failure over the course of follow-up, two occurred in the sham group. Of the eight hospitalizations for heart failure, seven (29% of the sham group) occurred among controls versus one in those treated with PADN (4% of this group; P = .049).

There was one groin hematoma at the puncture site in each group. Both resolved without any consequences prior to hospital discharge. There were no other significant procedure-related complications in either group.

Larger multicenter trials are needed to confirm these findings, according to both the trial investigators and Marius M. Hoeper, MD, who is charge of the pulmonary hypertension program at the Hannover (Germany) Medical School.

In an editorial that accompanied publication of these findings, Dr. Hoeper identified the small sample size of this study as one of its limitations, but he said the results are consistent with several other small studies associating pulmonary artery denervation with benefit in pulmonary hypertension.

“It appears as if we are currently witnessing the emergence of a new treatment option for various forms of pulmonary hypertension,” Dr. Hoeper wrote. In his critique of the study, he suggested that it would have been “more informative” if both groups were on background riociguat, but the data from this and other studies so far indicates that ablation to achieve denervation “is safe and feasible.”

The PADN technique used in this study might be relevant to the results. Dr. Hoeper noted that the investigators employed catheter tip–based electroanatomic mapping with a novel remote navigation system with three-dimensional imaging of the right ventricle and central pulmonary arteries.

“Apparently, this approach minimizes radiation exposure and provides precise location of ablation sites,” Dr. Hoeper observed. However, he called for direct comparisons of this tool to the guidance systems used in other studies.

In an interview, Dr. Hoeper acknowledged that it is not yet clear that a large-scale trial of pulmonary artery denervation for the indication evaluated in this study is coming. He noted several strategies in CTEPH are widely used without trials confirming a reduction in clinical events.

“Balloon pulmonary angioplasty for CTEPH has become an established treatment around the world without any randomized, controlled trial and without demonstration of improved outcomes. A couple of well-conducted observational trials might be sufficient to convince physicians to introduce PADN as well,” he said. If such studies associated PADN with “improvements in hemodynamics, exercise capacity, and patient-reported outcomes, it might be sufficient.”

Currently, Dr. Hoeper is most concerned about obtaining further evidence of safety, which he characterized as a “major issue.”

If a multicenter trial is conducted “the primary endpoint should be focused on clinical events,” according to Dr. Romanov, who was asked to comment on the next steps in validating PADN for the treatment of CTEPH-associated pulmonary hypertension persisting after endarterectomy.

“The mortality rate during 1-year long-term follow-up is not so high, but heart failure progression is a problem. So in my view, the primary endpoint should be a composite of death and heart failure hospitalization,” he said. He called for follow-up duration of 2-3 years.

Jonathan Steinberg, MD, director of cardiac clinical trials and education, Summit Medical Group, Montclair, N.J., also called a trial with hard endpoints, such as death, the ideal.

In the meantime, hemodynamic and functional measures “are still quite valuable and move the ball forward for this intervention,” he said in an interview. Senior author of this trial and principle investigator of the recent ERADICATE-AF trial, which evaluated renal denervation in preventing recurrence of atrial fibrillation (JAMA. 2020;323:248-55), Dr. Steinberg predicted, “I do indeed suspect we will see trials that are more accomplishable [than a large-scale, randomized, controlled trial] in the not too distant future.”

Dr. Romanov received funding from Biosense Webster. Dr. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, Janssen, Merck Sharp & Dohme, and Pfizer.

SOURCE: Romanov A et al. J Am Coll Cardiol. 2020 Aug 17;76:916-26.