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Novel percutaneous therapy for HOCM in development
SNOWMASS, COLO. – Percutaneous mitral valve plication shows early promise as a primary therapy for severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM), Paul Sorajja, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
He and his coworkers at the Minneapolis Heart Institute developed the novel procedure and published the first experience in the world with it. But further study in a much larger patient population is needed before percutaneous mitral plication is ready for prime time as a treatment for symptomatic HOCM, according to Dr. Sorajja, director of the Center of Valve and Structural Heart Disease at the institute.
Surgical myectomy is the guideline-recommended standard for treatment of patients with disabling symptoms caused by left ventricular outflow tract obstruction in the setting of hypertrophic cardiomyopathy. Alcohol septal ablation is a widely utilized alternative in patients who are frail and elderly or otherwise high-risk surgical candidates, or who lack ready access to an experienced surgical myectomy center, where the best outcomes are achieved. But roughly 20% of patients evaluated for alcohol septal ablation don’t have a septal artery anatomy amenable to the procedure. Other patients are put off by the 10%-50% risk that they will require a permanent pacemaker after alcohol septal ablation, depending upon their baseline ECG. And a small percentage of well-chosen patients – less than 10% – will experience inadequate gradient relief following alcohol septal ablation. So there is room for a novel therapeutic approach.
A percutaneous mitral clip–based solution, while technically challenging, offers several advantages over surgical myectomy and alcohol septal ablation. It’s less invasive, doesn’t create a potentially arrhythmogenic ablation scar requiring a permanent pacemaker, and it targets the mitral valve directly, addressing the mitral regurgitation that causes the left ventricular outflow tract obstruction. In contrast, both surgical myectomy and alcohol septal ablation target the ventricular septum.
Dr. Sorajja summarized his experience to date with percutaneous mitral valve plication for symptomatic HOCM, which encompasses the six patients in the published study (J Am Coll Cardiol. 2016 Jun 21;67[24]:2811-8) and the four others treated since then. The procedure was completed with placement of a single MitraClip in 9 of 10 patients. One patient experienced cardiac tamponade, resulting in a halt of the procedure; in the other nine, the intervention eliminated systolic anterior motion and markedly decreased the intraoperative left ventricular outflow tract gradient and mitral regurgitation.
At 2-5 years of follow-up, all patients have improved from New York Heart Association functional class III preprocedurally to class I or II. One patient required alcohol septal ablation. High systolic left ventricular outflow tract velocities in excess of 4 cm/s have been documented via follow-up echocardiography in some patients, the significance of which is under study.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Percutaneous mitral valve plication shows early promise as a primary therapy for severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM), Paul Sorajja, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
He and his coworkers at the Minneapolis Heart Institute developed the novel procedure and published the first experience in the world with it. But further study in a much larger patient population is needed before percutaneous mitral plication is ready for prime time as a treatment for symptomatic HOCM, according to Dr. Sorajja, director of the Center of Valve and Structural Heart Disease at the institute.
Surgical myectomy is the guideline-recommended standard for treatment of patients with disabling symptoms caused by left ventricular outflow tract obstruction in the setting of hypertrophic cardiomyopathy. Alcohol septal ablation is a widely utilized alternative in patients who are frail and elderly or otherwise high-risk surgical candidates, or who lack ready access to an experienced surgical myectomy center, where the best outcomes are achieved. But roughly 20% of patients evaluated for alcohol septal ablation don’t have a septal artery anatomy amenable to the procedure. Other patients are put off by the 10%-50% risk that they will require a permanent pacemaker after alcohol septal ablation, depending upon their baseline ECG. And a small percentage of well-chosen patients – less than 10% – will experience inadequate gradient relief following alcohol septal ablation. So there is room for a novel therapeutic approach.
A percutaneous mitral clip–based solution, while technically challenging, offers several advantages over surgical myectomy and alcohol septal ablation. It’s less invasive, doesn’t create a potentially arrhythmogenic ablation scar requiring a permanent pacemaker, and it targets the mitral valve directly, addressing the mitral regurgitation that causes the left ventricular outflow tract obstruction. In contrast, both surgical myectomy and alcohol septal ablation target the ventricular septum.
Dr. Sorajja summarized his experience to date with percutaneous mitral valve plication for symptomatic HOCM, which encompasses the six patients in the published study (J Am Coll Cardiol. 2016 Jun 21;67[24]:2811-8) and the four others treated since then. The procedure was completed with placement of a single MitraClip in 9 of 10 patients. One patient experienced cardiac tamponade, resulting in a halt of the procedure; in the other nine, the intervention eliminated systolic anterior motion and markedly decreased the intraoperative left ventricular outflow tract gradient and mitral regurgitation.
At 2-5 years of follow-up, all patients have improved from New York Heart Association functional class III preprocedurally to class I or II. One patient required alcohol septal ablation. High systolic left ventricular outflow tract velocities in excess of 4 cm/s have been documented via follow-up echocardiography in some patients, the significance of which is under study.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Percutaneous mitral valve plication shows early promise as a primary therapy for severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM), Paul Sorajja, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
He and his coworkers at the Minneapolis Heart Institute developed the novel procedure and published the first experience in the world with it. But further study in a much larger patient population is needed before percutaneous mitral plication is ready for prime time as a treatment for symptomatic HOCM, according to Dr. Sorajja, director of the Center of Valve and Structural Heart Disease at the institute.
Surgical myectomy is the guideline-recommended standard for treatment of patients with disabling symptoms caused by left ventricular outflow tract obstruction in the setting of hypertrophic cardiomyopathy. Alcohol septal ablation is a widely utilized alternative in patients who are frail and elderly or otherwise high-risk surgical candidates, or who lack ready access to an experienced surgical myectomy center, where the best outcomes are achieved. But roughly 20% of patients evaluated for alcohol septal ablation don’t have a septal artery anatomy amenable to the procedure. Other patients are put off by the 10%-50% risk that they will require a permanent pacemaker after alcohol septal ablation, depending upon their baseline ECG. And a small percentage of well-chosen patients – less than 10% – will experience inadequate gradient relief following alcohol septal ablation. So there is room for a novel therapeutic approach.
A percutaneous mitral clip–based solution, while technically challenging, offers several advantages over surgical myectomy and alcohol septal ablation. It’s less invasive, doesn’t create a potentially arrhythmogenic ablation scar requiring a permanent pacemaker, and it targets the mitral valve directly, addressing the mitral regurgitation that causes the left ventricular outflow tract obstruction. In contrast, both surgical myectomy and alcohol septal ablation target the ventricular septum.
Dr. Sorajja summarized his experience to date with percutaneous mitral valve plication for symptomatic HOCM, which encompasses the six patients in the published study (J Am Coll Cardiol. 2016 Jun 21;67[24]:2811-8) and the four others treated since then. The procedure was completed with placement of a single MitraClip in 9 of 10 patients. One patient experienced cardiac tamponade, resulting in a halt of the procedure; in the other nine, the intervention eliminated systolic anterior motion and markedly decreased the intraoperative left ventricular outflow tract gradient and mitral regurgitation.
At 2-5 years of follow-up, all patients have improved from New York Heart Association functional class III preprocedurally to class I or II. One patient required alcohol septal ablation. High systolic left ventricular outflow tract velocities in excess of 4 cm/s have been documented via follow-up echocardiography in some patients, the significance of which is under study.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
REPORTING FROM ACC SNOWMASS 2019
Look for alcohol septal ablation in the next HOCM guideline
SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.
Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.
The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.
The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).
In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”
The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).
The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.
The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.
One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).
However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.
“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.
At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.
Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.
The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.
The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).
In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”
The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).
The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.
The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.
One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).
However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.
“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.
At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.
Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.
The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.
The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).
In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”
The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).
The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.
The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.
One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).
However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.
“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.
At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.
Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.
EXPERT ANALYSIS FROM ACC SNOWMASS 2019
Adjunctive devices for transcatheter valve replacement improve outcomes
WASHINGTON – One transcatheter device designed to prevent left ventricular outflow tract (LVOT) obstruction relevant to transcatheter mitral valve replacement (TMVR) and another designed to prevent coronary obstruction relevant to transcatheter aortic valve replacement (TAVR) performed well in feasibility studies, according to data presented in two separate late breaking clinical trial sessions at the CRT 2019, sponsored by MedStar Heart & Vascular Institute.
LVOT obstruction prevention
“The 30-day survival in subjects with an increased risk of LVOT obstruction was significantly better than that previously reported in registries,” said Jaffar M. Khan, BM BCh, of the National Heart, Lung, and Blood Institute, who addressing results with the LAMPOON device prior to TMVR,.
LAMPOON is an acronym for intentional Laceration of the Anterior Mitral valve leaflet to Prevent LVOT ObstructioN. Introduced percutaneously and guided to the valve with wires, it was designed to tear existing mitral valve leaflets to prevent them from causing life-threatening LVOT obstruction. It is used immediately prior to TMVR in patients at risk for this complication.
In a feasibility study, delivery, deployment, and retrieval of the device was achieved in all 30 patients. On the basis of the primary endpoint of LVOT gradients of less than 50 mm Hg and no emergency surgery, the procedural success was 73%. The 30-day survival was 93%.
Citing data from registries, Dr. Khan said that the expected survival in TMVR patients with LVOT obstruction caused by a native mitral valve leaflet has been less than 40%. With few existing options to prevent this complication, none of which are reliable, LAMPOON is poised to permit patients who are poor candidates or are contraindicated for TMVR to undergo this treatment, according to Dr. Khan.
“LAMPOON is feasible in all anatomies and calcium patterns,” said Dr. Khan, who noted that gradients of less than 30 mm Hg was achieved in 29 of the 30 patients. Although Dr. Khan acknowledged that this study was small and uncontrolled, and he further cautioned that current strategies for predicting mitral valve leaflet LVOT obstruction are “imprecise,” he believes larger studies of LAMPOON are warranted based on these results.
Coronary artery obstruction prevention
Dr. Khan also presented data on the BASILICA device from a second feasibility study. The device is employed immediately prior to TAVR in order to prevent large aortic valve leaflets, whether native or from an existing bioprosthetic valve, from producing coronary obstruction. BASILICA is an acronym for Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction.
This device is also introduced percutaneously and uses radiofrequency ablation to split leaflets that are considered to pose a risk for coronary obstruction. Even though Dr. Khan acknowledged that there is also a lack of precision for predicting which TAVR candidates require an intervention to prevent coronary obstruction, he cited mortality rates exceeding 40% when this complication occurs.
In the feasibility study, 30 patients, of whom 80% were female, were enrolled. In half of the cases, the target for BASILICA was a native valve. The remainder was treated for risk of coronary obstruction posed by a bioprosthetic valve. Multiple comorbidities, including a high proportion with prior stroke, made those selected for enrollment poor candidates for surgery.
The BASILICA intervention was successful in 28 of the 30 participants and in 35 of the 37 leaflets treated. At 30 days, there was one death and one disabling stroke. The overall success rate of the procedure was 93%, according to Dr. Khan.
“One hundred percent of patients were discharged from the cath lab without coronary obstruction despite the high baseline risk,” Dr. Khan said. Again, larger studies are needed to validate the safety and efficacy of this approach, but Dr. Khan believes the outcomes in this study warrant expanded clinical studies.
WASHINGTON – One transcatheter device designed to prevent left ventricular outflow tract (LVOT) obstruction relevant to transcatheter mitral valve replacement (TMVR) and another designed to prevent coronary obstruction relevant to transcatheter aortic valve replacement (TAVR) performed well in feasibility studies, according to data presented in two separate late breaking clinical trial sessions at the CRT 2019, sponsored by MedStar Heart & Vascular Institute.
LVOT obstruction prevention
“The 30-day survival in subjects with an increased risk of LVOT obstruction was significantly better than that previously reported in registries,” said Jaffar M. Khan, BM BCh, of the National Heart, Lung, and Blood Institute, who addressing results with the LAMPOON device prior to TMVR,.
LAMPOON is an acronym for intentional Laceration of the Anterior Mitral valve leaflet to Prevent LVOT ObstructioN. Introduced percutaneously and guided to the valve with wires, it was designed to tear existing mitral valve leaflets to prevent them from causing life-threatening LVOT obstruction. It is used immediately prior to TMVR in patients at risk for this complication.
In a feasibility study, delivery, deployment, and retrieval of the device was achieved in all 30 patients. On the basis of the primary endpoint of LVOT gradients of less than 50 mm Hg and no emergency surgery, the procedural success was 73%. The 30-day survival was 93%.
Citing data from registries, Dr. Khan said that the expected survival in TMVR patients with LVOT obstruction caused by a native mitral valve leaflet has been less than 40%. With few existing options to prevent this complication, none of which are reliable, LAMPOON is poised to permit patients who are poor candidates or are contraindicated for TMVR to undergo this treatment, according to Dr. Khan.
“LAMPOON is feasible in all anatomies and calcium patterns,” said Dr. Khan, who noted that gradients of less than 30 mm Hg was achieved in 29 of the 30 patients. Although Dr. Khan acknowledged that this study was small and uncontrolled, and he further cautioned that current strategies for predicting mitral valve leaflet LVOT obstruction are “imprecise,” he believes larger studies of LAMPOON are warranted based on these results.
Coronary artery obstruction prevention
Dr. Khan also presented data on the BASILICA device from a second feasibility study. The device is employed immediately prior to TAVR in order to prevent large aortic valve leaflets, whether native or from an existing bioprosthetic valve, from producing coronary obstruction. BASILICA is an acronym for Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction.
This device is also introduced percutaneously and uses radiofrequency ablation to split leaflets that are considered to pose a risk for coronary obstruction. Even though Dr. Khan acknowledged that there is also a lack of precision for predicting which TAVR candidates require an intervention to prevent coronary obstruction, he cited mortality rates exceeding 40% when this complication occurs.
In the feasibility study, 30 patients, of whom 80% were female, were enrolled. In half of the cases, the target for BASILICA was a native valve. The remainder was treated for risk of coronary obstruction posed by a bioprosthetic valve. Multiple comorbidities, including a high proportion with prior stroke, made those selected for enrollment poor candidates for surgery.
The BASILICA intervention was successful in 28 of the 30 participants and in 35 of the 37 leaflets treated. At 30 days, there was one death and one disabling stroke. The overall success rate of the procedure was 93%, according to Dr. Khan.
“One hundred percent of patients were discharged from the cath lab without coronary obstruction despite the high baseline risk,” Dr. Khan said. Again, larger studies are needed to validate the safety and efficacy of this approach, but Dr. Khan believes the outcomes in this study warrant expanded clinical studies.
WASHINGTON – One transcatheter device designed to prevent left ventricular outflow tract (LVOT) obstruction relevant to transcatheter mitral valve replacement (TMVR) and another designed to prevent coronary obstruction relevant to transcatheter aortic valve replacement (TAVR) performed well in feasibility studies, according to data presented in two separate late breaking clinical trial sessions at the CRT 2019, sponsored by MedStar Heart & Vascular Institute.
LVOT obstruction prevention
“The 30-day survival in subjects with an increased risk of LVOT obstruction was significantly better than that previously reported in registries,” said Jaffar M. Khan, BM BCh, of the National Heart, Lung, and Blood Institute, who addressing results with the LAMPOON device prior to TMVR,.
LAMPOON is an acronym for intentional Laceration of the Anterior Mitral valve leaflet to Prevent LVOT ObstructioN. Introduced percutaneously and guided to the valve with wires, it was designed to tear existing mitral valve leaflets to prevent them from causing life-threatening LVOT obstruction. It is used immediately prior to TMVR in patients at risk for this complication.
In a feasibility study, delivery, deployment, and retrieval of the device was achieved in all 30 patients. On the basis of the primary endpoint of LVOT gradients of less than 50 mm Hg and no emergency surgery, the procedural success was 73%. The 30-day survival was 93%.
Citing data from registries, Dr. Khan said that the expected survival in TMVR patients with LVOT obstruction caused by a native mitral valve leaflet has been less than 40%. With few existing options to prevent this complication, none of which are reliable, LAMPOON is poised to permit patients who are poor candidates or are contraindicated for TMVR to undergo this treatment, according to Dr. Khan.
“LAMPOON is feasible in all anatomies and calcium patterns,” said Dr. Khan, who noted that gradients of less than 30 mm Hg was achieved in 29 of the 30 patients. Although Dr. Khan acknowledged that this study was small and uncontrolled, and he further cautioned that current strategies for predicting mitral valve leaflet LVOT obstruction are “imprecise,” he believes larger studies of LAMPOON are warranted based on these results.
Coronary artery obstruction prevention
Dr. Khan also presented data on the BASILICA device from a second feasibility study. The device is employed immediately prior to TAVR in order to prevent large aortic valve leaflets, whether native or from an existing bioprosthetic valve, from producing coronary obstruction. BASILICA is an acronym for Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction.
This device is also introduced percutaneously and uses radiofrequency ablation to split leaflets that are considered to pose a risk for coronary obstruction. Even though Dr. Khan acknowledged that there is also a lack of precision for predicting which TAVR candidates require an intervention to prevent coronary obstruction, he cited mortality rates exceeding 40% when this complication occurs.
In the feasibility study, 30 patients, of whom 80% were female, were enrolled. In half of the cases, the target for BASILICA was a native valve. The remainder was treated for risk of coronary obstruction posed by a bioprosthetic valve. Multiple comorbidities, including a high proportion with prior stroke, made those selected for enrollment poor candidates for surgery.
The BASILICA intervention was successful in 28 of the 30 participants and in 35 of the 37 leaflets treated. At 30 days, there was one death and one disabling stroke. The overall success rate of the procedure was 93%, according to Dr. Khan.
“One hundred percent of patients were discharged from the cath lab without coronary obstruction despite the high baseline risk,” Dr. Khan said. Again, larger studies are needed to validate the safety and efficacy of this approach, but Dr. Khan believes the outcomes in this study warrant expanded clinical studies.
REPORTING FROM CRT 2019
Hospital TAVR volume matters to patient survival
Hospitals that performed more transcatheter aortic valve replacements continued to outperform low-volume centers for 30-day postprocedure survival, in data collected from more than 113,000 transcatheter aortic valves replaced during 2015-2017.
During that time, 113,662 transcatheter aortic valve replacement (TAVR) procedures occurred in the United States and were entered into a registry maintained by the Society of Thoracic Surgeons and American College of Cardiology. The new analysis focused on the more than 96,000 valve placements done via a transfemoral approach. The analysis divided these patients into quartiles based on total annual TAVR volume at each of the 554 centers where the procedures occurred, and this showed that 30-day mortality, after adjustment for 39 demographic and clinical variables, was 3.19% among patients treated at centers in the lowest-volume quartile and 2.66% in patients treated at centers in the highest-volume quartile. This translated to a 21% relative risk increase in 30-day mortality at the lowest volume centers that was statistically significant, Sreekanth Vemulapalli, MD, and his associates reported in an article published online on April 3 in the New England Journal of Medicine.
The mean annual volume among centers in the lowest-volume quartile during the 3 years studied was 27 procedures/year, while the average volume among the 25% highest-volume centers was 143 TAVRs each year, reported Dr. Vemulapalli, an interventional cardiologist at Duke University in Durham, N.C., and his associates. After excluding the first 12 months of TAVR performance for each center during the study period, the adjusted 30-day mortality averaged 3.10% in the lowest-volume tertile and 2.61% in centers in the highest-volume tertile. That meant the lowest-volume centers saw a 19% relative increase in mortality that was statistically significant.
This is not the first study to show a significant link between TAVR procedure volumes at individual centers and patient outcomes, and since 2012 the Centers for Medicare & Medicaid Services has stipulated that eligibility for Medicare coverage of TAVR requires that it be done at a center that performs at least 20 TAVR procedures annually or at least 40 during the most recent 2 years. A prior report showing a similar volume-outcome link looked at U.S. TAVR cases during 2011-2015 (J Am Coll Cardiol. 2017 July;70[1]:29-41), and reports of volume-outcome relationships have also come out for other catheter-based intravascular procedures.
“Our results suggest that raising the minimum volume requirements for TAVR centers may improve the quality of outcomes. However, this potential improvement in quality needs to be balanced against access to care in general, and for underserved and underrepresented populations in particular,” Dr. Vemulapalli said in an interview. The data suggested that a significant number of patients from underserved populations are treated at lower-volume TAVR centers. It’s unclear what impact raising the threshold volume [by CMS] might have on these underserved populations,” he explained.
Dr. Vemulapalli conceded that his analysis may have been affected by several potential confounding variables that did not receive adjustment in the analyses he and his associates ran. The variables of hospital size and teaching status both showed an association with TAVR volume. Hospitals with a greater number of beds and those that were teaching hospitals were also the places where TAVR volumes were highest, while lower-volume centers tended to be smaller, nonteaching institutions. But the variables of size and teaching status did not receive adjustment. Both are “difficult to tease apart from TAVR volume,” he noted.
The CMS mandated Transcatheter Valve Therapy Registry also functions as a quality-improvement mechanism in which U.S. TAVR sites receive quarterly feedback on their performance and are benchmarked against other programs in a risk-adjusted way. The registry also disseminates best practices as part of the quality improvement process, Dr. Vemulapalli said.
Results from two TAVR trials reported at the American College of Cardiology’s annual meeting in March, PARTNER 3 and Evolut Low Risk, documented the efficacy and safety of TAVR compared with surgery in low-risk patients, findings that will soon substantially increase the volume of TAVR cases performed (N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052 and doi: 10.1056/NEJMoa1816885).
When the impact of TAVR moving to low-risk patients starts to kick in, “the findings from our analysis will become even more relevant,” Dr. Vemulapalli predicted. “As TAVR moves to low-risk, healthier patients, and more patients undergo the procedure, a firm commitment to measuring and ensuring quality while balancing access to care will be pivotal. The data in our study regarding the association between TAVR volume and outcomes and the characteristics of low- and high-volume hospitals and the patients they treat are fundamental to striking this balance.”
SOURCE: Vemulapalli S. et al. N Engl J Med. 2019 Apr 3.doi: 10.1056/NEJMsa1901109.
Hospitals that performed more transcatheter aortic valve replacements continued to outperform low-volume centers for 30-day postprocedure survival, in data collected from more than 113,000 transcatheter aortic valves replaced during 2015-2017.
During that time, 113,662 transcatheter aortic valve replacement (TAVR) procedures occurred in the United States and were entered into a registry maintained by the Society of Thoracic Surgeons and American College of Cardiology. The new analysis focused on the more than 96,000 valve placements done via a transfemoral approach. The analysis divided these patients into quartiles based on total annual TAVR volume at each of the 554 centers where the procedures occurred, and this showed that 30-day mortality, after adjustment for 39 demographic and clinical variables, was 3.19% among patients treated at centers in the lowest-volume quartile and 2.66% in patients treated at centers in the highest-volume quartile. This translated to a 21% relative risk increase in 30-day mortality at the lowest volume centers that was statistically significant, Sreekanth Vemulapalli, MD, and his associates reported in an article published online on April 3 in the New England Journal of Medicine.
The mean annual volume among centers in the lowest-volume quartile during the 3 years studied was 27 procedures/year, while the average volume among the 25% highest-volume centers was 143 TAVRs each year, reported Dr. Vemulapalli, an interventional cardiologist at Duke University in Durham, N.C., and his associates. After excluding the first 12 months of TAVR performance for each center during the study period, the adjusted 30-day mortality averaged 3.10% in the lowest-volume tertile and 2.61% in centers in the highest-volume tertile. That meant the lowest-volume centers saw a 19% relative increase in mortality that was statistically significant.
This is not the first study to show a significant link between TAVR procedure volumes at individual centers and patient outcomes, and since 2012 the Centers for Medicare & Medicaid Services has stipulated that eligibility for Medicare coverage of TAVR requires that it be done at a center that performs at least 20 TAVR procedures annually or at least 40 during the most recent 2 years. A prior report showing a similar volume-outcome link looked at U.S. TAVR cases during 2011-2015 (J Am Coll Cardiol. 2017 July;70[1]:29-41), and reports of volume-outcome relationships have also come out for other catheter-based intravascular procedures.
“Our results suggest that raising the minimum volume requirements for TAVR centers may improve the quality of outcomes. However, this potential improvement in quality needs to be balanced against access to care in general, and for underserved and underrepresented populations in particular,” Dr. Vemulapalli said in an interview. The data suggested that a significant number of patients from underserved populations are treated at lower-volume TAVR centers. It’s unclear what impact raising the threshold volume [by CMS] might have on these underserved populations,” he explained.
Dr. Vemulapalli conceded that his analysis may have been affected by several potential confounding variables that did not receive adjustment in the analyses he and his associates ran. The variables of hospital size and teaching status both showed an association with TAVR volume. Hospitals with a greater number of beds and those that were teaching hospitals were also the places where TAVR volumes were highest, while lower-volume centers tended to be smaller, nonteaching institutions. But the variables of size and teaching status did not receive adjustment. Both are “difficult to tease apart from TAVR volume,” he noted.
The CMS mandated Transcatheter Valve Therapy Registry also functions as a quality-improvement mechanism in which U.S. TAVR sites receive quarterly feedback on their performance and are benchmarked against other programs in a risk-adjusted way. The registry also disseminates best practices as part of the quality improvement process, Dr. Vemulapalli said.
Results from two TAVR trials reported at the American College of Cardiology’s annual meeting in March, PARTNER 3 and Evolut Low Risk, documented the efficacy and safety of TAVR compared with surgery in low-risk patients, findings that will soon substantially increase the volume of TAVR cases performed (N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052 and doi: 10.1056/NEJMoa1816885).
When the impact of TAVR moving to low-risk patients starts to kick in, “the findings from our analysis will become even more relevant,” Dr. Vemulapalli predicted. “As TAVR moves to low-risk, healthier patients, and more patients undergo the procedure, a firm commitment to measuring and ensuring quality while balancing access to care will be pivotal. The data in our study regarding the association between TAVR volume and outcomes and the characteristics of low- and high-volume hospitals and the patients they treat are fundamental to striking this balance.”
SOURCE: Vemulapalli S. et al. N Engl J Med. 2019 Apr 3.doi: 10.1056/NEJMsa1901109.
Hospitals that performed more transcatheter aortic valve replacements continued to outperform low-volume centers for 30-day postprocedure survival, in data collected from more than 113,000 transcatheter aortic valves replaced during 2015-2017.
During that time, 113,662 transcatheter aortic valve replacement (TAVR) procedures occurred in the United States and were entered into a registry maintained by the Society of Thoracic Surgeons and American College of Cardiology. The new analysis focused on the more than 96,000 valve placements done via a transfemoral approach. The analysis divided these patients into quartiles based on total annual TAVR volume at each of the 554 centers where the procedures occurred, and this showed that 30-day mortality, after adjustment for 39 demographic and clinical variables, was 3.19% among patients treated at centers in the lowest-volume quartile and 2.66% in patients treated at centers in the highest-volume quartile. This translated to a 21% relative risk increase in 30-day mortality at the lowest volume centers that was statistically significant, Sreekanth Vemulapalli, MD, and his associates reported in an article published online on April 3 in the New England Journal of Medicine.
The mean annual volume among centers in the lowest-volume quartile during the 3 years studied was 27 procedures/year, while the average volume among the 25% highest-volume centers was 143 TAVRs each year, reported Dr. Vemulapalli, an interventional cardiologist at Duke University in Durham, N.C., and his associates. After excluding the first 12 months of TAVR performance for each center during the study period, the adjusted 30-day mortality averaged 3.10% in the lowest-volume tertile and 2.61% in centers in the highest-volume tertile. That meant the lowest-volume centers saw a 19% relative increase in mortality that was statistically significant.
This is not the first study to show a significant link between TAVR procedure volumes at individual centers and patient outcomes, and since 2012 the Centers for Medicare & Medicaid Services has stipulated that eligibility for Medicare coverage of TAVR requires that it be done at a center that performs at least 20 TAVR procedures annually or at least 40 during the most recent 2 years. A prior report showing a similar volume-outcome link looked at U.S. TAVR cases during 2011-2015 (J Am Coll Cardiol. 2017 July;70[1]:29-41), and reports of volume-outcome relationships have also come out for other catheter-based intravascular procedures.
“Our results suggest that raising the minimum volume requirements for TAVR centers may improve the quality of outcomes. However, this potential improvement in quality needs to be balanced against access to care in general, and for underserved and underrepresented populations in particular,” Dr. Vemulapalli said in an interview. The data suggested that a significant number of patients from underserved populations are treated at lower-volume TAVR centers. It’s unclear what impact raising the threshold volume [by CMS] might have on these underserved populations,” he explained.
Dr. Vemulapalli conceded that his analysis may have been affected by several potential confounding variables that did not receive adjustment in the analyses he and his associates ran. The variables of hospital size and teaching status both showed an association with TAVR volume. Hospitals with a greater number of beds and those that were teaching hospitals were also the places where TAVR volumes were highest, while lower-volume centers tended to be smaller, nonteaching institutions. But the variables of size and teaching status did not receive adjustment. Both are “difficult to tease apart from TAVR volume,” he noted.
The CMS mandated Transcatheter Valve Therapy Registry also functions as a quality-improvement mechanism in which U.S. TAVR sites receive quarterly feedback on their performance and are benchmarked against other programs in a risk-adjusted way. The registry also disseminates best practices as part of the quality improvement process, Dr. Vemulapalli said.
Results from two TAVR trials reported at the American College of Cardiology’s annual meeting in March, PARTNER 3 and Evolut Low Risk, documented the efficacy and safety of TAVR compared with surgery in low-risk patients, findings that will soon substantially increase the volume of TAVR cases performed (N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052 and doi: 10.1056/NEJMoa1816885).
When the impact of TAVR moving to low-risk patients starts to kick in, “the findings from our analysis will become even more relevant,” Dr. Vemulapalli predicted. “As TAVR moves to low-risk, healthier patients, and more patients undergo the procedure, a firm commitment to measuring and ensuring quality while balancing access to care will be pivotal. The data in our study regarding the association between TAVR volume and outcomes and the characteristics of low- and high-volume hospitals and the patients they treat are fundamental to striking this balance.”
SOURCE: Vemulapalli S. et al. N Engl J Med. 2019 Apr 3.doi: 10.1056/NEJMsa1901109.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: U.S. centers that performed the most TAVR procedures had the best rates of 30-day patient survival.
Major finding: .
Study details: Analysis of data from 113,622 TAVR procedures done at U.S. hospitals during 2015-2017.
Disclosures: Dr. Vemulapalli has received personal fees from Boston Scientific, Janssen, Novella, Premiere, and Zafgen, and he has received research funding from Abbott Vascular and Boston Scientific.
Source: Vemulapalli S et al. N Engl J Med. 2019 Apr 3. doi: 10.1056/NEJMsa1901109.
No further amplification of signal for benefit from ultrathin stent at 3 years
WASHINGTON – In the latest analysis of data from a randomized trial comparing three different thin polymer-coated drug-eluting stents, the signal at 1 year that the thinnest device might reduce risk of target lesion revascularization has been lost at 3 years, according to an update of results from the BIO-RESORT trial presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“At 3-year follow-up, all three drug-eluting stents were associated with favorable outcomes and both very thin strut polymer-coated devices showed safety and patency similar to the thin-strut durable polymer drug-eluting stent,” reported Clemons von Birgelen, MD, PhD, professor of cardiology, University of Twente, Enschede, the Netherlands.
In order of strut thickness, the stents tested in BIO-RESORT were Orsiro (60 mcm), Synergy (74 mcm), and Resolute Integrity (90 mcm). Although the study had a noninferiority design, the potential for the biodegradable polymer coatings of the two thinner stents to provide faster healing than the durable polymer of the Resolute stent was one of the driving hypotheses of the trial (Lancet. 2016 Nov 26;388[10060]:2607-17).
Some support for this hypothesis was provided by 2-year results presented at EuroPCR 2018 last year. At that time, it was reported that the risk of target lesion revascularization between the end of year 1 and end of year 2 was significantly lower for the Orsiro stent (1.3%) than the Resolute stent (2.3%). Target lesion revascularization also was lower in the Synergy stent group (1.8%), but this rate did not differ significantly from that of the other two stents in the trial.
Now, reassessed at 3 years, the target lesion revascularization rates are 2.9%, 3.3%, and 3.8% for the Orsiro, Synergy, and Resolute stents, respectively. Although the numerical hierarchy is preserved, the differences are no longer significant.
Other outcomes, including the primary outcome of target lesion failure, show the same numerical hierarchy but, again, without differences reaching significance. For target lesion failure, these rates are 8.5%, 8.8%, and 10.0%, respectively.
The difference in the rates of stent thrombosis at 3 years was even smaller with rates of less than 1% for all three stents. A catch-up phenomenon between years 2 and 3 of follow-up largely eliminated a numerical advantage seen earlier for the Orsiro stent.
The BIO-RESORT trial randomized 3,514 patients, of whom 70% had an acute coronary syndrome. Nearly one-third had an ST-elevated myocardial infarction. Dr. von Birgelen emphasized that this was “a very complex study population.” For example, roughly 20% had severely calcified lesions. Follow-up data were available on 97% of the randomized patients at 3 years.
There are differences between these stents other than thickness and the durability of the polymer. In particular, Orsiro is coated with sirolimus, Synergy with everolimus, and Resolute with zotarolimus. While the metals of the frame also differ, the estimated time to resorption of the polymer is faster with the Synergy stent (4 months) than the Orsiro stent (24 months).
Despite the loss of a difference in target vessel revascularization in the most recent follow-up, the potential for the differences in designs and materials to influence risk of late complications, including revascularization and thrombosis, persists.
“Follow-up beyond 3 years is of interest to definitely answer the question of whether one of these drug-eluting stents might improve outcome at a later stage,” Dr. von Birgelen said.
WASHINGTON – In the latest analysis of data from a randomized trial comparing three different thin polymer-coated drug-eluting stents, the signal at 1 year that the thinnest device might reduce risk of target lesion revascularization has been lost at 3 years, according to an update of results from the BIO-RESORT trial presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“At 3-year follow-up, all three drug-eluting stents were associated with favorable outcomes and both very thin strut polymer-coated devices showed safety and patency similar to the thin-strut durable polymer drug-eluting stent,” reported Clemons von Birgelen, MD, PhD, professor of cardiology, University of Twente, Enschede, the Netherlands.
In order of strut thickness, the stents tested in BIO-RESORT were Orsiro (60 mcm), Synergy (74 mcm), and Resolute Integrity (90 mcm). Although the study had a noninferiority design, the potential for the biodegradable polymer coatings of the two thinner stents to provide faster healing than the durable polymer of the Resolute stent was one of the driving hypotheses of the trial (Lancet. 2016 Nov 26;388[10060]:2607-17).
Some support for this hypothesis was provided by 2-year results presented at EuroPCR 2018 last year. At that time, it was reported that the risk of target lesion revascularization between the end of year 1 and end of year 2 was significantly lower for the Orsiro stent (1.3%) than the Resolute stent (2.3%). Target lesion revascularization also was lower in the Synergy stent group (1.8%), but this rate did not differ significantly from that of the other two stents in the trial.
Now, reassessed at 3 years, the target lesion revascularization rates are 2.9%, 3.3%, and 3.8% for the Orsiro, Synergy, and Resolute stents, respectively. Although the numerical hierarchy is preserved, the differences are no longer significant.
Other outcomes, including the primary outcome of target lesion failure, show the same numerical hierarchy but, again, without differences reaching significance. For target lesion failure, these rates are 8.5%, 8.8%, and 10.0%, respectively.
The difference in the rates of stent thrombosis at 3 years was even smaller with rates of less than 1% for all three stents. A catch-up phenomenon between years 2 and 3 of follow-up largely eliminated a numerical advantage seen earlier for the Orsiro stent.
The BIO-RESORT trial randomized 3,514 patients, of whom 70% had an acute coronary syndrome. Nearly one-third had an ST-elevated myocardial infarction. Dr. von Birgelen emphasized that this was “a very complex study population.” For example, roughly 20% had severely calcified lesions. Follow-up data were available on 97% of the randomized patients at 3 years.
There are differences between these stents other than thickness and the durability of the polymer. In particular, Orsiro is coated with sirolimus, Synergy with everolimus, and Resolute with zotarolimus. While the metals of the frame also differ, the estimated time to resorption of the polymer is faster with the Synergy stent (4 months) than the Orsiro stent (24 months).
Despite the loss of a difference in target vessel revascularization in the most recent follow-up, the potential for the differences in designs and materials to influence risk of late complications, including revascularization and thrombosis, persists.
“Follow-up beyond 3 years is of interest to definitely answer the question of whether one of these drug-eluting stents might improve outcome at a later stage,” Dr. von Birgelen said.
WASHINGTON – In the latest analysis of data from a randomized trial comparing three different thin polymer-coated drug-eluting stents, the signal at 1 year that the thinnest device might reduce risk of target lesion revascularization has been lost at 3 years, according to an update of results from the BIO-RESORT trial presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“At 3-year follow-up, all three drug-eluting stents were associated with favorable outcomes and both very thin strut polymer-coated devices showed safety and patency similar to the thin-strut durable polymer drug-eluting stent,” reported Clemons von Birgelen, MD, PhD, professor of cardiology, University of Twente, Enschede, the Netherlands.
In order of strut thickness, the stents tested in BIO-RESORT were Orsiro (60 mcm), Synergy (74 mcm), and Resolute Integrity (90 mcm). Although the study had a noninferiority design, the potential for the biodegradable polymer coatings of the two thinner stents to provide faster healing than the durable polymer of the Resolute stent was one of the driving hypotheses of the trial (Lancet. 2016 Nov 26;388[10060]:2607-17).
Some support for this hypothesis was provided by 2-year results presented at EuroPCR 2018 last year. At that time, it was reported that the risk of target lesion revascularization between the end of year 1 and end of year 2 was significantly lower for the Orsiro stent (1.3%) than the Resolute stent (2.3%). Target lesion revascularization also was lower in the Synergy stent group (1.8%), but this rate did not differ significantly from that of the other two stents in the trial.
Now, reassessed at 3 years, the target lesion revascularization rates are 2.9%, 3.3%, and 3.8% for the Orsiro, Synergy, and Resolute stents, respectively. Although the numerical hierarchy is preserved, the differences are no longer significant.
Other outcomes, including the primary outcome of target lesion failure, show the same numerical hierarchy but, again, without differences reaching significance. For target lesion failure, these rates are 8.5%, 8.8%, and 10.0%, respectively.
The difference in the rates of stent thrombosis at 3 years was even smaller with rates of less than 1% for all three stents. A catch-up phenomenon between years 2 and 3 of follow-up largely eliminated a numerical advantage seen earlier for the Orsiro stent.
The BIO-RESORT trial randomized 3,514 patients, of whom 70% had an acute coronary syndrome. Nearly one-third had an ST-elevated myocardial infarction. Dr. von Birgelen emphasized that this was “a very complex study population.” For example, roughly 20% had severely calcified lesions. Follow-up data were available on 97% of the randomized patients at 3 years.
There are differences between these stents other than thickness and the durability of the polymer. In particular, Orsiro is coated with sirolimus, Synergy with everolimus, and Resolute with zotarolimus. While the metals of the frame also differ, the estimated time to resorption of the polymer is faster with the Synergy stent (4 months) than the Orsiro stent (24 months).
Despite the loss of a difference in target vessel revascularization in the most recent follow-up, the potential for the differences in designs and materials to influence risk of late complications, including revascularization and thrombosis, persists.
“Follow-up beyond 3 years is of interest to definitely answer the question of whether one of these drug-eluting stents might improve outcome at a later stage,” Dr. von Birgelen said.
REPORTING FROM CRT 2019
Has radial access PCI been overhyped?
NEW ORLEANS – , Michel R. Le May, MD, reported at the annual meeting of the American College of Cardiology.
Our findings suggest that adequately trained operators should be able to achieve similar results using either radial or femoral access for primary PCI,” declared Dr. Le May, professor of medicine at the University of Ottawa Heart Institute.
This is a controversial issue. European cardiologists have led a strong push for preferential use of radial access, citing reduced bleeding risk and an associated reduction in 30-day mortality. And this movement has spread to North America. But the evidence doesn’t convincingly support this position, the cardiologist said. He noted that of nine prior RCTs of radial versus the more traditional femoral access for primary PCI in STEMI, seven showed no difference in mortality. Nor did SAFARI-STEMI, which at 2,292 randomized STEMI patients was the second-largest trial to date.
SAFARI-STEMI was conducted at five high-volume Canadian PCI centers. Participating interventional cardiologists averaged 250 PCIs per year and were proficient in both access approaches. The study plan was to enroll 5,000 STEMI patients, but the trial was stopped after results were in for the first 2,292 because outcomes in the two study arms were so similar that the trial’s data safety monitoring board deemed it futile to continue.
The primary outcome was 30-day mortality. The rate was 1.5% in the radial access group and 1.3% in the femoral access group, with no differences among various subgroups.
Nor were there any between-group significant difference in the secondary endpoints of reinfarction (1.8% with radial, 1.6% with femoral), stroke (1.0% versus 0.4%), or the composite of death, reinfarction, or stroke, which occurred in 4.0% of the radial access group and 3.4% of the femoral group. Rates of non-CABG TIMI major or minor bleeding at 30 days were closely similar, as was need for transfusion. Definite or probable stent thrombosis occurred in 1.5% of the radial and 1.1% of the femoral groups.
Time from arrival at the PCI center to first balloon inflation was 47 minutes in the radial access group and significantly shorter at 44 minutes with femoral access, a noteworthy finding in the setting of STEMI, where time is myocardium. Fluoroscopy time was 1.2 minutes shorter in the femoral access group as well.
The reaction
Discussant Jacqueline E. Tamis-Holland, MD, said that, although she recently switched over to a radial access-first approach, her take away from SAFARI-STEMI is “It’s okay to do femoral.
“I think it’s comforting to the femoralists who are struggling to say, ‘I do a good femoral job and I don’t necessarily want to transition my STEMI patients to radial,’ ” said Dr. Tamis-Holland, associate director for the Mount Sinai St. Luke’s cardiac cath labs in New York.
Session cochair Martin B. Leon, MD, embraced the SAFARI-STEMI results with gusto.
“I’ve been tortured over the past 5 years by my junior interventional colleagues saying that, unless you’re doing transradial for STEMIs, that you’re not only out of step with the modern era of PCI, but you’re really moving against the evidence. And this study brings it back to a center position, where if you do a very-high-quality transfemoral approach, it is no different from transradial, not just from the standpoint of mortality but also bleeding complications. So I think we should aspire to be better transfemoral interventionalists, and if we do then there probably isn’t that much of a difference,” said Dr. Leon, professor of medicine at Columbia University in New York.
But discussant Sunil V. Rao, MD, who has championed radial access in the United States, was skeptical. “I think the results you achieved with femoral access in this trial are quite remarkable. We know from the registry data that those results are difficult to achieve in clinical practice.
“I would caution that the trial was stopped early, so I think it’s very challenging to try to apply this so as to influence our practice definitively,” said Dr. Rao of Duke University, Durham, N.C.
He asked Dr. Le May what advice he could give to femoralists in community practice to up their game and achieve results comparable to those in SAFARI-STEMI.
“We have to pay attention to their puncture,” Dr. Le May replied. “We use fluoroscopic guidance, and there are others who use ultrasound. We pay attention to the anticoagulation and antiplatelet therapy we use for these patients. We use GP IIb/IIIa inhibitors less today, and smaller sheaths. More than 90% of patients got ticagrelor before going to the cath lab. We’ve borrowed some of the techniques that the radial access people use.”
At a postpresentation ACC press conference, he indicated that it was difficult to recruit patients for the trial in the current strongly pro–radial access climate.
“I think there are people who think that, seriously, the horse is out of the barn, and it’s game over for the femoral. There is a mindset out there where people think that it’s just wrong to do a femoral approach,” said Dr. Le May. “We had comments that it’s not even ethical to randomize such patients.”
In fact, the issue is “very debatable,” he asserted, noting that radial artery occlusion is emerging as an important complication. And he suspects that cardiologists who strive to do 80%-90% of their percutaneous coronary interventions via the transradial route may become deskilled at using the femoral approach. That becomes a real concern when there is a problem in accessing the radial artery or need arises for a device that requires femoral access.
“I am of the school of thought that, given the results of our trial, we should teach people that you’re not a femoralist or a radialist. You should be an interventionalist that can do either and flip from one side to the other and be comfortable in doing that,” Dr. Le May concluded.
He reported having no conflicts regarding the study, funded by the Canadian Institutes of Health Research.
NEW ORLEANS – , Michel R. Le May, MD, reported at the annual meeting of the American College of Cardiology.
Our findings suggest that adequately trained operators should be able to achieve similar results using either radial or femoral access for primary PCI,” declared Dr. Le May, professor of medicine at the University of Ottawa Heart Institute.
This is a controversial issue. European cardiologists have led a strong push for preferential use of radial access, citing reduced bleeding risk and an associated reduction in 30-day mortality. And this movement has spread to North America. But the evidence doesn’t convincingly support this position, the cardiologist said. He noted that of nine prior RCTs of radial versus the more traditional femoral access for primary PCI in STEMI, seven showed no difference in mortality. Nor did SAFARI-STEMI, which at 2,292 randomized STEMI patients was the second-largest trial to date.
SAFARI-STEMI was conducted at five high-volume Canadian PCI centers. Participating interventional cardiologists averaged 250 PCIs per year and were proficient in both access approaches. The study plan was to enroll 5,000 STEMI patients, but the trial was stopped after results were in for the first 2,292 because outcomes in the two study arms were so similar that the trial’s data safety monitoring board deemed it futile to continue.
The primary outcome was 30-day mortality. The rate was 1.5% in the radial access group and 1.3% in the femoral access group, with no differences among various subgroups.
Nor were there any between-group significant difference in the secondary endpoints of reinfarction (1.8% with radial, 1.6% with femoral), stroke (1.0% versus 0.4%), or the composite of death, reinfarction, or stroke, which occurred in 4.0% of the radial access group and 3.4% of the femoral group. Rates of non-CABG TIMI major or minor bleeding at 30 days were closely similar, as was need for transfusion. Definite or probable stent thrombosis occurred in 1.5% of the radial and 1.1% of the femoral groups.
Time from arrival at the PCI center to first balloon inflation was 47 minutes in the radial access group and significantly shorter at 44 minutes with femoral access, a noteworthy finding in the setting of STEMI, where time is myocardium. Fluoroscopy time was 1.2 minutes shorter in the femoral access group as well.
The reaction
Discussant Jacqueline E. Tamis-Holland, MD, said that, although she recently switched over to a radial access-first approach, her take away from SAFARI-STEMI is “It’s okay to do femoral.
“I think it’s comforting to the femoralists who are struggling to say, ‘I do a good femoral job and I don’t necessarily want to transition my STEMI patients to radial,’ ” said Dr. Tamis-Holland, associate director for the Mount Sinai St. Luke’s cardiac cath labs in New York.
Session cochair Martin B. Leon, MD, embraced the SAFARI-STEMI results with gusto.
“I’ve been tortured over the past 5 years by my junior interventional colleagues saying that, unless you’re doing transradial for STEMIs, that you’re not only out of step with the modern era of PCI, but you’re really moving against the evidence. And this study brings it back to a center position, where if you do a very-high-quality transfemoral approach, it is no different from transradial, not just from the standpoint of mortality but also bleeding complications. So I think we should aspire to be better transfemoral interventionalists, and if we do then there probably isn’t that much of a difference,” said Dr. Leon, professor of medicine at Columbia University in New York.
But discussant Sunil V. Rao, MD, who has championed radial access in the United States, was skeptical. “I think the results you achieved with femoral access in this trial are quite remarkable. We know from the registry data that those results are difficult to achieve in clinical practice.
“I would caution that the trial was stopped early, so I think it’s very challenging to try to apply this so as to influence our practice definitively,” said Dr. Rao of Duke University, Durham, N.C.
He asked Dr. Le May what advice he could give to femoralists in community practice to up their game and achieve results comparable to those in SAFARI-STEMI.
“We have to pay attention to their puncture,” Dr. Le May replied. “We use fluoroscopic guidance, and there are others who use ultrasound. We pay attention to the anticoagulation and antiplatelet therapy we use for these patients. We use GP IIb/IIIa inhibitors less today, and smaller sheaths. More than 90% of patients got ticagrelor before going to the cath lab. We’ve borrowed some of the techniques that the radial access people use.”
At a postpresentation ACC press conference, he indicated that it was difficult to recruit patients for the trial in the current strongly pro–radial access climate.
“I think there are people who think that, seriously, the horse is out of the barn, and it’s game over for the femoral. There is a mindset out there where people think that it’s just wrong to do a femoral approach,” said Dr. Le May. “We had comments that it’s not even ethical to randomize such patients.”
In fact, the issue is “very debatable,” he asserted, noting that radial artery occlusion is emerging as an important complication. And he suspects that cardiologists who strive to do 80%-90% of their percutaneous coronary interventions via the transradial route may become deskilled at using the femoral approach. That becomes a real concern when there is a problem in accessing the radial artery or need arises for a device that requires femoral access.
“I am of the school of thought that, given the results of our trial, we should teach people that you’re not a femoralist or a radialist. You should be an interventionalist that can do either and flip from one side to the other and be comfortable in doing that,” Dr. Le May concluded.
He reported having no conflicts regarding the study, funded by the Canadian Institutes of Health Research.
NEW ORLEANS – , Michel R. Le May, MD, reported at the annual meeting of the American College of Cardiology.
Our findings suggest that adequately trained operators should be able to achieve similar results using either radial or femoral access for primary PCI,” declared Dr. Le May, professor of medicine at the University of Ottawa Heart Institute.
This is a controversial issue. European cardiologists have led a strong push for preferential use of radial access, citing reduced bleeding risk and an associated reduction in 30-day mortality. And this movement has spread to North America. But the evidence doesn’t convincingly support this position, the cardiologist said. He noted that of nine prior RCTs of radial versus the more traditional femoral access for primary PCI in STEMI, seven showed no difference in mortality. Nor did SAFARI-STEMI, which at 2,292 randomized STEMI patients was the second-largest trial to date.
SAFARI-STEMI was conducted at five high-volume Canadian PCI centers. Participating interventional cardiologists averaged 250 PCIs per year and were proficient in both access approaches. The study plan was to enroll 5,000 STEMI patients, but the trial was stopped after results were in for the first 2,292 because outcomes in the two study arms were so similar that the trial’s data safety monitoring board deemed it futile to continue.
The primary outcome was 30-day mortality. The rate was 1.5% in the radial access group and 1.3% in the femoral access group, with no differences among various subgroups.
Nor were there any between-group significant difference in the secondary endpoints of reinfarction (1.8% with radial, 1.6% with femoral), stroke (1.0% versus 0.4%), or the composite of death, reinfarction, or stroke, which occurred in 4.0% of the radial access group and 3.4% of the femoral group. Rates of non-CABG TIMI major or minor bleeding at 30 days were closely similar, as was need for transfusion. Definite or probable stent thrombosis occurred in 1.5% of the radial and 1.1% of the femoral groups.
Time from arrival at the PCI center to first balloon inflation was 47 minutes in the radial access group and significantly shorter at 44 minutes with femoral access, a noteworthy finding in the setting of STEMI, where time is myocardium. Fluoroscopy time was 1.2 minutes shorter in the femoral access group as well.
The reaction
Discussant Jacqueline E. Tamis-Holland, MD, said that, although she recently switched over to a radial access-first approach, her take away from SAFARI-STEMI is “It’s okay to do femoral.
“I think it’s comforting to the femoralists who are struggling to say, ‘I do a good femoral job and I don’t necessarily want to transition my STEMI patients to radial,’ ” said Dr. Tamis-Holland, associate director for the Mount Sinai St. Luke’s cardiac cath labs in New York.
Session cochair Martin B. Leon, MD, embraced the SAFARI-STEMI results with gusto.
“I’ve been tortured over the past 5 years by my junior interventional colleagues saying that, unless you’re doing transradial for STEMIs, that you’re not only out of step with the modern era of PCI, but you’re really moving against the evidence. And this study brings it back to a center position, where if you do a very-high-quality transfemoral approach, it is no different from transradial, not just from the standpoint of mortality but also bleeding complications. So I think we should aspire to be better transfemoral interventionalists, and if we do then there probably isn’t that much of a difference,” said Dr. Leon, professor of medicine at Columbia University in New York.
But discussant Sunil V. Rao, MD, who has championed radial access in the United States, was skeptical. “I think the results you achieved with femoral access in this trial are quite remarkable. We know from the registry data that those results are difficult to achieve in clinical practice.
“I would caution that the trial was stopped early, so I think it’s very challenging to try to apply this so as to influence our practice definitively,” said Dr. Rao of Duke University, Durham, N.C.
He asked Dr. Le May what advice he could give to femoralists in community practice to up their game and achieve results comparable to those in SAFARI-STEMI.
“We have to pay attention to their puncture,” Dr. Le May replied. “We use fluoroscopic guidance, and there are others who use ultrasound. We pay attention to the anticoagulation and antiplatelet therapy we use for these patients. We use GP IIb/IIIa inhibitors less today, and smaller sheaths. More than 90% of patients got ticagrelor before going to the cath lab. We’ve borrowed some of the techniques that the radial access people use.”
At a postpresentation ACC press conference, he indicated that it was difficult to recruit patients for the trial in the current strongly pro–radial access climate.
“I think there are people who think that, seriously, the horse is out of the barn, and it’s game over for the femoral. There is a mindset out there where people think that it’s just wrong to do a femoral approach,” said Dr. Le May. “We had comments that it’s not even ethical to randomize such patients.”
In fact, the issue is “very debatable,” he asserted, noting that radial artery occlusion is emerging as an important complication. And he suspects that cardiologists who strive to do 80%-90% of their percutaneous coronary interventions via the transradial route may become deskilled at using the femoral approach. That becomes a real concern when there is a problem in accessing the radial artery or need arises for a device that requires femoral access.
“I am of the school of thought that, given the results of our trial, we should teach people that you’re not a femoralist or a radialist. You should be an interventionalist that can do either and flip from one side to the other and be comfortable in doing that,” Dr. Le May concluded.
He reported having no conflicts regarding the study, funded by the Canadian Institutes of Health Research.
REPORTING FROM ACC 19
Ticagrelor reversal agent looks promising
NEW ORLEANS – A novel targeted ticagrelor reversal agent demonstrated rapid and sustained reversal of the potent antiplatelet agent in a phase 1 proof-of-concept study, Deepak L. Bhatt, MD, reported at the annual meeting of the American College of Cardiology.
“Hopefully the FDA will view this as something that really is a breakthrough,” commented Dr. Bhatt, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard University, both in Boston.
Why a breakthrough? Because despite recent major advances in the ability to reverse the action of the direct-acting oral anticoagulants and thereby greatly improve their safety margin, there have been no parallel developments with regard to the potent antiplatelet agents ticagrelor (Brilinta), prasugrel (Effient), and clopidogrel. The effects of these antiplatelet drugs take 3-5 days to dissipate after they’ve been stopped, which is highly problematic when they’ve induced catastrophic bleeding or a patient requires emergent or urgent surgery, the cardiologist explained.
“The ability to reverse tigracelor’s antiplatelet effects rapidly could distinguish it from other antiplatelet agents such as prasugrel or even generic clopidogrel and, for that matter, even aspirin,” Dr. Bhatt said.
The ticagrelor reversal agent, known for now as PB2452, is an intravenously administered recombinant human immunoglobulin G1 monoclonal antibody antigen-binding fragment. It binds specifically and with high affinity to ticagrelor and its active metabolite. In the phase 1, placebo-controlled, double-blind study conducted in 64 healthy volunteers pretreated with ticagrelor for 48 hours, it reversed oral ticagrelor’s antiplatelet effects within 5 minutes and, with prolonged infusion, showed sustained effect for at least 20 hours.
The only adverse events observed in blinded assessment were minor injection site issues.
PB2452 is specific to ticagrelor and will not reverse the activity of other potent antiplatelet agents. Indeed, because of their chemical structure, neither prasugrel nor clopidogrel is reversible, according to Dr. Bhatt.
He said the developmental game plan for the ticagrelor reversal agent is initially to get it approved by the Food and Drug Administration for ticagrelor-related catastrophic bleeding, such as intracranial hemorrhage, since there is a recognized major unmet need in such situations. But as shown in the phase 1 study, BP2452 is potentially titratable by varying the size of the initial bolus dose and the dosing and duration of the subsequent infusion. So after initial approval for catastrophic bleeding, it makes sense to branch out and conduct further studies establishing the reversal agent’s value for prevention of bleeding complications caused by ticagrelor. An example might be a patient on ticagrelor because she recently received a stent in her left main coronary artery who falls and breaks her hip, and her surgeon says she needs surgery right away.
“If someone on ticagrelor came in with an intracranial hemorrhage, you’d want rapid reversal and have it sustained for as many days as the neurologist advises, whereas maybe if someone came in on ticagrelor after placement of a left main stent and you needed to do a lumbar puncture, you’d want to reverse the antiplatelet effect for the LP, and then if things go smoothly you’d want to get the ticagrelor back on board so the stent doesn’t thrombose. But that type of more precise dosing will require further work,” according to the cardiologist.
Discussant Barbara S. Wiggins, PharmD, commented, “We’ve been fortunate to have reversal agents come out for oral anticoagulants, but in terms of antiplatelet activity we’ve not been able to be successful with platelet transfusions. So having a reversal agent added to our armamentarium certainly is something that’s desirable.”
The phase 1 study of PB2452 indicates the monoclonal antibody checks the key boxes one looks for in a reversal agent: quick onset, long duration of effect, lack of a rebound in platelet activity after drug cessation, and potential for tailored titration. Of course, data on efficacy outcomes will also be necessary, noted Dr. Wiggins, a clinical pharmacologist at the Medical University of South Carolina, Charleston.
She added that she was favorably impressed that Dr. Bhatt and his coinvestigators went to the trouble of convincingly demonstrating reversal of ticagrelor’s antiplatelet effects using three different assays: light transmission aggregometry, which is considered the standard, as well as the point-of-care VerifyNow P2Y12 assay and the modified CY-QUANT assay.
The phase 1 study was funded by PhaseBio Pharmaceuticals. Dr. Bhatt reported the company provided a research grant directly to Brigham and Women’s Hospital.
Simultaneous with Dr. Bhatt’s presentation, the study results were published online (N Engl J Med. 2019 Mar 17. doi: 10.1056/NEJMoa1901778).
NEW ORLEANS – A novel targeted ticagrelor reversal agent demonstrated rapid and sustained reversal of the potent antiplatelet agent in a phase 1 proof-of-concept study, Deepak L. Bhatt, MD, reported at the annual meeting of the American College of Cardiology.
“Hopefully the FDA will view this as something that really is a breakthrough,” commented Dr. Bhatt, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard University, both in Boston.
Why a breakthrough? Because despite recent major advances in the ability to reverse the action of the direct-acting oral anticoagulants and thereby greatly improve their safety margin, there have been no parallel developments with regard to the potent antiplatelet agents ticagrelor (Brilinta), prasugrel (Effient), and clopidogrel. The effects of these antiplatelet drugs take 3-5 days to dissipate after they’ve been stopped, which is highly problematic when they’ve induced catastrophic bleeding or a patient requires emergent or urgent surgery, the cardiologist explained.
“The ability to reverse tigracelor’s antiplatelet effects rapidly could distinguish it from other antiplatelet agents such as prasugrel or even generic clopidogrel and, for that matter, even aspirin,” Dr. Bhatt said.
The ticagrelor reversal agent, known for now as PB2452, is an intravenously administered recombinant human immunoglobulin G1 monoclonal antibody antigen-binding fragment. It binds specifically and with high affinity to ticagrelor and its active metabolite. In the phase 1, placebo-controlled, double-blind study conducted in 64 healthy volunteers pretreated with ticagrelor for 48 hours, it reversed oral ticagrelor’s antiplatelet effects within 5 minutes and, with prolonged infusion, showed sustained effect for at least 20 hours.
The only adverse events observed in blinded assessment were minor injection site issues.
PB2452 is specific to ticagrelor and will not reverse the activity of other potent antiplatelet agents. Indeed, because of their chemical structure, neither prasugrel nor clopidogrel is reversible, according to Dr. Bhatt.
He said the developmental game plan for the ticagrelor reversal agent is initially to get it approved by the Food and Drug Administration for ticagrelor-related catastrophic bleeding, such as intracranial hemorrhage, since there is a recognized major unmet need in such situations. But as shown in the phase 1 study, BP2452 is potentially titratable by varying the size of the initial bolus dose and the dosing and duration of the subsequent infusion. So after initial approval for catastrophic bleeding, it makes sense to branch out and conduct further studies establishing the reversal agent’s value for prevention of bleeding complications caused by ticagrelor. An example might be a patient on ticagrelor because she recently received a stent in her left main coronary artery who falls and breaks her hip, and her surgeon says she needs surgery right away.
“If someone on ticagrelor came in with an intracranial hemorrhage, you’d want rapid reversal and have it sustained for as many days as the neurologist advises, whereas maybe if someone came in on ticagrelor after placement of a left main stent and you needed to do a lumbar puncture, you’d want to reverse the antiplatelet effect for the LP, and then if things go smoothly you’d want to get the ticagrelor back on board so the stent doesn’t thrombose. But that type of more precise dosing will require further work,” according to the cardiologist.
Discussant Barbara S. Wiggins, PharmD, commented, “We’ve been fortunate to have reversal agents come out for oral anticoagulants, but in terms of antiplatelet activity we’ve not been able to be successful with platelet transfusions. So having a reversal agent added to our armamentarium certainly is something that’s desirable.”
The phase 1 study of PB2452 indicates the monoclonal antibody checks the key boxes one looks for in a reversal agent: quick onset, long duration of effect, lack of a rebound in platelet activity after drug cessation, and potential for tailored titration. Of course, data on efficacy outcomes will also be necessary, noted Dr. Wiggins, a clinical pharmacologist at the Medical University of South Carolina, Charleston.
She added that she was favorably impressed that Dr. Bhatt and his coinvestigators went to the trouble of convincingly demonstrating reversal of ticagrelor’s antiplatelet effects using three different assays: light transmission aggregometry, which is considered the standard, as well as the point-of-care VerifyNow P2Y12 assay and the modified CY-QUANT assay.
The phase 1 study was funded by PhaseBio Pharmaceuticals. Dr. Bhatt reported the company provided a research grant directly to Brigham and Women’s Hospital.
Simultaneous with Dr. Bhatt’s presentation, the study results were published online (N Engl J Med. 2019 Mar 17. doi: 10.1056/NEJMoa1901778).
NEW ORLEANS – A novel targeted ticagrelor reversal agent demonstrated rapid and sustained reversal of the potent antiplatelet agent in a phase 1 proof-of-concept study, Deepak L. Bhatt, MD, reported at the annual meeting of the American College of Cardiology.
“Hopefully the FDA will view this as something that really is a breakthrough,” commented Dr. Bhatt, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard University, both in Boston.
Why a breakthrough? Because despite recent major advances in the ability to reverse the action of the direct-acting oral anticoagulants and thereby greatly improve their safety margin, there have been no parallel developments with regard to the potent antiplatelet agents ticagrelor (Brilinta), prasugrel (Effient), and clopidogrel. The effects of these antiplatelet drugs take 3-5 days to dissipate after they’ve been stopped, which is highly problematic when they’ve induced catastrophic bleeding or a patient requires emergent or urgent surgery, the cardiologist explained.
“The ability to reverse tigracelor’s antiplatelet effects rapidly could distinguish it from other antiplatelet agents such as prasugrel or even generic clopidogrel and, for that matter, even aspirin,” Dr. Bhatt said.
The ticagrelor reversal agent, known for now as PB2452, is an intravenously administered recombinant human immunoglobulin G1 monoclonal antibody antigen-binding fragment. It binds specifically and with high affinity to ticagrelor and its active metabolite. In the phase 1, placebo-controlled, double-blind study conducted in 64 healthy volunteers pretreated with ticagrelor for 48 hours, it reversed oral ticagrelor’s antiplatelet effects within 5 minutes and, with prolonged infusion, showed sustained effect for at least 20 hours.
The only adverse events observed in blinded assessment were minor injection site issues.
PB2452 is specific to ticagrelor and will not reverse the activity of other potent antiplatelet agents. Indeed, because of their chemical structure, neither prasugrel nor clopidogrel is reversible, according to Dr. Bhatt.
He said the developmental game plan for the ticagrelor reversal agent is initially to get it approved by the Food and Drug Administration for ticagrelor-related catastrophic bleeding, such as intracranial hemorrhage, since there is a recognized major unmet need in such situations. But as shown in the phase 1 study, BP2452 is potentially titratable by varying the size of the initial bolus dose and the dosing and duration of the subsequent infusion. So after initial approval for catastrophic bleeding, it makes sense to branch out and conduct further studies establishing the reversal agent’s value for prevention of bleeding complications caused by ticagrelor. An example might be a patient on ticagrelor because she recently received a stent in her left main coronary artery who falls and breaks her hip, and her surgeon says she needs surgery right away.
“If someone on ticagrelor came in with an intracranial hemorrhage, you’d want rapid reversal and have it sustained for as many days as the neurologist advises, whereas maybe if someone came in on ticagrelor after placement of a left main stent and you needed to do a lumbar puncture, you’d want to reverse the antiplatelet effect for the LP, and then if things go smoothly you’d want to get the ticagrelor back on board so the stent doesn’t thrombose. But that type of more precise dosing will require further work,” according to the cardiologist.
Discussant Barbara S. Wiggins, PharmD, commented, “We’ve been fortunate to have reversal agents come out for oral anticoagulants, but in terms of antiplatelet activity we’ve not been able to be successful with platelet transfusions. So having a reversal agent added to our armamentarium certainly is something that’s desirable.”
The phase 1 study of PB2452 indicates the monoclonal antibody checks the key boxes one looks for in a reversal agent: quick onset, long duration of effect, lack of a rebound in platelet activity after drug cessation, and potential for tailored titration. Of course, data on efficacy outcomes will also be necessary, noted Dr. Wiggins, a clinical pharmacologist at the Medical University of South Carolina, Charleston.
She added that she was favorably impressed that Dr. Bhatt and his coinvestigators went to the trouble of convincingly demonstrating reversal of ticagrelor’s antiplatelet effects using three different assays: light transmission aggregometry, which is considered the standard, as well as the point-of-care VerifyNow P2Y12 assay and the modified CY-QUANT assay.
The phase 1 study was funded by PhaseBio Pharmaceuticals. Dr. Bhatt reported the company provided a research grant directly to Brigham and Women’s Hospital.
Simultaneous with Dr. Bhatt’s presentation, the study results were published online (N Engl J Med. 2019 Mar 17. doi: 10.1056/NEJMoa1901778).
REPORTING FROM ACC 19
Key clinical point: Oral ticagrelor’s antiplatelet effect was reversed within 5 minutes by a novel targeted monoclonal antibody.
Major finding: A novel targeted monoclonal antibody reversed oral ticagrelor’s antiplatelet effects within 5 minutes and, with prolonged infusion, showed sustained effect for at least 20 hours.
Study details: This phase 1 study included 64 healthy subjects pretreated with 48 hours of ticagrelor before receiving various doses of the reversal agent or placebo.
Disclosures: The study was funded by PhaseBio Pharmaceuticals, which provided a research grant directly to Brigham and Women’s Hospital.
Low-flow, low-gradient aortic stenosis with preserved LVEF: a special situation
SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The first question is, What happens to the patient’s symptoms upon control of the hypertension?
“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
An aortic valve area of less than 1.0 cm2 is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?
“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm2. You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.
These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.
“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.
Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.
This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.
The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm2 or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”
Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.
“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.
Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.
“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.
One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).
This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.
When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.
“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The first question is, What happens to the patient’s symptoms upon control of the hypertension?
“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
An aortic valve area of less than 1.0 cm2 is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?
“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm2. You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.
These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.
“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.
Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.
This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.
The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm2 or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”
Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.
“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.
Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.
“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.
One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).
This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.
When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.
“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The first question is, What happens to the patient’s symptoms upon control of the hypertension?
“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
An aortic valve area of less than 1.0 cm2 is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?
“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm2. You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.
These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.
“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.
Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.
This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.
The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm2 or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”
Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.
“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.
Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.
“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.
One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).
This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.
When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.
“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
REPORTING FROM ACC SNOWMASS 2019
TAVR tops surgery in low-risk patients
NEW ORLEANS – Patients with severely symptomatic aortic stenosis at low surgical risk had significantly better key outcomes with transcatheter aortic valve replacement than with surgical valve replacement through 1 year of follow-up in the landmark PARTNER 3 and Evolut Low Risk randomized trials presented at the annual meeting of the American College of Cardiology.
As the two study presenters stepped down from the stage after sharing their results, the packed audience in the meeting’s main arena rose to shower them with a prolonged standing ovation.
“This is a historic moment, and all of us here should recognize it as such,” thundered discussant Eugene Braunwald, MD, professor of medicine at Harvard Medical School, Boston. “We’re going to remember it. We’re going to tell our grandchildren and great grandchildren that we were there at the time these incredible advances in the care of patients with aortic stenosis were presented.”
This was in fact the day that transcatheter aortic valve replacement (TAVR), a relatively young, rapidly evolving nonsurgical technique, finally overtook surgical aortic valve replacement (SAVR), a mature operation first successfully performed back in 1962. Previous large, randomized trials had established that TAVR was superior to SAVR in extreme-risk patients and noninferior to surgery in high- and intermediate-risk patients, yet with the advantage of much quicker recovery. The only remaining question was how TAVR would stack up in low-risk patients, who comprise 80% of those who currently undergo SAVR for aortic stenosis.
“Two separate groups using two separate valves have come to very similar conclusions. This doesn’t double the acceptability, it quadruples it,” Dr. Braunwald said.
PARTNER 3
Martin B. Leon, MD, presented the findings of the PARTNER 3 (Placement of Aortic Transcatheter Valves) trial, in which 1,000 low-risk patients at 71 centers were randomized to TAVR with transfemoral placement of the balloon-expandable Edwards Lifesciences Sapien 3 bioprosthetic valve or to SAVR. The mean age of the patients was 73 years, with a mean Society of Thoracic Surgeons risk score of 1.9%. Operators had to have more than 1 year of experience using the Sapien 3 valve in order to participate in the trial.
At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with SAVR, for a highly significant 46% relative risk reduction. All three components of the primary endpoint occurred significantly less often in the TAVR group. And the rate of the key endpoint of death or disabling stroke was 1.0% with TAVR, compared with 2.9% with SAVR, reported Dr. Leon, coprincipal investigator in PARTNER 3 and professor of medicine at Columbia University, New York.
TAVR also outperformed SAVR on all six prespecified major secondary endpoints. These included new-onset atrial fibrillation within 30 days, at 5.0% with TAVR and 39.5% with SAVR; length of index hospitalization at 3 versus 7 days; all stroke at 30 days at 0.6% versus 2.4%; and death or a significant deterioration in quality of life at 30 days as measured by the Kansas City Cardiomyopathy Questionnaire at 3.9% versus 30.6%. There was significantly less life-threatening or major bleeding within 30 days in the TAVR group, by a margin of 3.6% versus 24.5%, and similarly low rates of new pacemaker implantation at 6.5% versus 4.0%. There was, however, a higher 30-day incidence of new left bundle branch block with TAVR, by a margin of 22% versus 8%, which may eventually translate into need for a pacemaker.
“Based upon these findings, TAVR, through 1 year, should be considered the preferred therapy in low-surgical-risk aortic stenosis patients. The PARTNER randomized trials over the past 12 years clearly indicate that the relative value of TAVR, compared with surgery, is independent of surgical risk profiles,” Dr. Leon declared.
Evolut Low Risk
Michael J. Reardon, MD, coprincipal investigator for the Evolut Low Risk study and professor of cardiovascular surgery at Houston Methodist Hospital, reported on 1,468 patients randomized to TAVR with a Medtronic self-expanding, supra-annular bioprosthetic valve or to SAVR. Of them, 22% of patients got the most recent version of the valve, known as the Evolut PRO, 74% got the Evolut R, and the remainder received the first-generation CoreValve.
The primary endpoint – death or disabling stroke – was slightly different from that in PARTNER 3. At 1 year, the rate was 2.9% in the TAVR arm and 4.6% with SAVR, a statistically significant difference, while at 2 years the rate was 5.3% with TAVR and 6.7% with SAVR, a difference that was not significant. Impressively, the rate of the composite of death, disabling stroke, or heart failure hospitalizations through 1 year was 5.6% with TAVR versus 10.2% with SAVR.
“We’ve shown that, with TAVR, you’re more likely to be alive, without a stroke, and outside the hospital. This is exactly what my patients tell me they want when we sit down for shared decision-making and talk about their expectations,” Dr. Reardon said.
Noting the striking similarity of across-the-board outcomes in the two trials, Dr. Reardon concluded, “I think what we’re seeing here is a class effect of TAVR, and we have to recognize it as such.”
Dr. Leon agreed, with a caveat. “I think the class effect for these two versions of TAVR systems is very real. I wouldn’t presume to think that every TAVR device will perform the same way, so I think we need a lot more data on the newer devices that are being introduced.”
The reaction
During the question-and-answer session, the two investigators were asked about stroke rates, which were significantly lower in the TAVR patients even though in the early randomized trials in high-risk patients the stroke rates were twice as high with TAVR than SAVR. The explanation probably lies in a mix of device refinements over time, better techniques, standardized procedures, and careful patient selection, they said.
“If you look at stroke in the TAVR arm in both these trials, we’re almost approaching the background stroke rate in a group of 74-year-olds sitting around in a room,” Dr. Reardon observed.
Both trials will continue to assess participants both clinically and by echocardiography through 10 years, in part to assess TAVR valve durability, but also to evaluate the durability of surgical valves, which isn’t nearly as well established as most people think, according to the investigators.
“There is a myth of surgical bioprosthetic valve immortality. It’s based upon relatively few numbers of patients, largely sponsor-based studies, with numbers at risk at 15-20 years that are extremely low,” Dr. Leon asserted. “The majority of surgical valves being used today and touted as being durable are backed by only 2-4 years of data.”
In contrast, he added, “We have 5-year TAVR data which is absolutely definitive of no early structural valve deterioration.”
Discussant Mayra E. Guerrero, MD, of the Mayo Clinic in Rochester, Minn., expressed concern that “this paradigm shift to ‘TAVR for all’ ” could break the bank for many institutions because the cost of TAVR valves is far greater than for SAVR valves. But she was heartened by the fresh PARTNER 3 and Evolut Low Risk data showing TAVR patients had fewer ICU days, shorter hospital stays, fewer strokes, more frequent discharge home, and a lower rehospitalization rate.
Dr. Reardon was reassuring on this score.
“I am 100% convinced that when we do the financials for these two trials, TAVR is going to be a cost saver and a huge winner,” the surgeon said.
He reported serving as a consultant to Medtronic and receiving research grants from Medtronic and Boston Scientific. Dr. Leon reported receiving research grants from Edwards Lifesciences and St. Jude Medical and acting as a consultant to several medical device companies.
The two trials have been published online by the New England Journal of Medicine.
SOURCES: Leon MB et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052; Reardon MJ et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1816885.
NEW ORLEANS – Patients with severely symptomatic aortic stenosis at low surgical risk had significantly better key outcomes with transcatheter aortic valve replacement than with surgical valve replacement through 1 year of follow-up in the landmark PARTNER 3 and Evolut Low Risk randomized trials presented at the annual meeting of the American College of Cardiology.
As the two study presenters stepped down from the stage after sharing their results, the packed audience in the meeting’s main arena rose to shower them with a prolonged standing ovation.
“This is a historic moment, and all of us here should recognize it as such,” thundered discussant Eugene Braunwald, MD, professor of medicine at Harvard Medical School, Boston. “We’re going to remember it. We’re going to tell our grandchildren and great grandchildren that we were there at the time these incredible advances in the care of patients with aortic stenosis were presented.”
This was in fact the day that transcatheter aortic valve replacement (TAVR), a relatively young, rapidly evolving nonsurgical technique, finally overtook surgical aortic valve replacement (SAVR), a mature operation first successfully performed back in 1962. Previous large, randomized trials had established that TAVR was superior to SAVR in extreme-risk patients and noninferior to surgery in high- and intermediate-risk patients, yet with the advantage of much quicker recovery. The only remaining question was how TAVR would stack up in low-risk patients, who comprise 80% of those who currently undergo SAVR for aortic stenosis.
“Two separate groups using two separate valves have come to very similar conclusions. This doesn’t double the acceptability, it quadruples it,” Dr. Braunwald said.
PARTNER 3
Martin B. Leon, MD, presented the findings of the PARTNER 3 (Placement of Aortic Transcatheter Valves) trial, in which 1,000 low-risk patients at 71 centers were randomized to TAVR with transfemoral placement of the balloon-expandable Edwards Lifesciences Sapien 3 bioprosthetic valve or to SAVR. The mean age of the patients was 73 years, with a mean Society of Thoracic Surgeons risk score of 1.9%. Operators had to have more than 1 year of experience using the Sapien 3 valve in order to participate in the trial.
At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with SAVR, for a highly significant 46% relative risk reduction. All three components of the primary endpoint occurred significantly less often in the TAVR group. And the rate of the key endpoint of death or disabling stroke was 1.0% with TAVR, compared with 2.9% with SAVR, reported Dr. Leon, coprincipal investigator in PARTNER 3 and professor of medicine at Columbia University, New York.
TAVR also outperformed SAVR on all six prespecified major secondary endpoints. These included new-onset atrial fibrillation within 30 days, at 5.0% with TAVR and 39.5% with SAVR; length of index hospitalization at 3 versus 7 days; all stroke at 30 days at 0.6% versus 2.4%; and death or a significant deterioration in quality of life at 30 days as measured by the Kansas City Cardiomyopathy Questionnaire at 3.9% versus 30.6%. There was significantly less life-threatening or major bleeding within 30 days in the TAVR group, by a margin of 3.6% versus 24.5%, and similarly low rates of new pacemaker implantation at 6.5% versus 4.0%. There was, however, a higher 30-day incidence of new left bundle branch block with TAVR, by a margin of 22% versus 8%, which may eventually translate into need for a pacemaker.
“Based upon these findings, TAVR, through 1 year, should be considered the preferred therapy in low-surgical-risk aortic stenosis patients. The PARTNER randomized trials over the past 12 years clearly indicate that the relative value of TAVR, compared with surgery, is independent of surgical risk profiles,” Dr. Leon declared.
Evolut Low Risk
Michael J. Reardon, MD, coprincipal investigator for the Evolut Low Risk study and professor of cardiovascular surgery at Houston Methodist Hospital, reported on 1,468 patients randomized to TAVR with a Medtronic self-expanding, supra-annular bioprosthetic valve or to SAVR. Of them, 22% of patients got the most recent version of the valve, known as the Evolut PRO, 74% got the Evolut R, and the remainder received the first-generation CoreValve.
The primary endpoint – death or disabling stroke – was slightly different from that in PARTNER 3. At 1 year, the rate was 2.9% in the TAVR arm and 4.6% with SAVR, a statistically significant difference, while at 2 years the rate was 5.3% with TAVR and 6.7% with SAVR, a difference that was not significant. Impressively, the rate of the composite of death, disabling stroke, or heart failure hospitalizations through 1 year was 5.6% with TAVR versus 10.2% with SAVR.
“We’ve shown that, with TAVR, you’re more likely to be alive, without a stroke, and outside the hospital. This is exactly what my patients tell me they want when we sit down for shared decision-making and talk about their expectations,” Dr. Reardon said.
Noting the striking similarity of across-the-board outcomes in the two trials, Dr. Reardon concluded, “I think what we’re seeing here is a class effect of TAVR, and we have to recognize it as such.”
Dr. Leon agreed, with a caveat. “I think the class effect for these two versions of TAVR systems is very real. I wouldn’t presume to think that every TAVR device will perform the same way, so I think we need a lot more data on the newer devices that are being introduced.”
The reaction
During the question-and-answer session, the two investigators were asked about stroke rates, which were significantly lower in the TAVR patients even though in the early randomized trials in high-risk patients the stroke rates were twice as high with TAVR than SAVR. The explanation probably lies in a mix of device refinements over time, better techniques, standardized procedures, and careful patient selection, they said.
“If you look at stroke in the TAVR arm in both these trials, we’re almost approaching the background stroke rate in a group of 74-year-olds sitting around in a room,” Dr. Reardon observed.
Both trials will continue to assess participants both clinically and by echocardiography through 10 years, in part to assess TAVR valve durability, but also to evaluate the durability of surgical valves, which isn’t nearly as well established as most people think, according to the investigators.
“There is a myth of surgical bioprosthetic valve immortality. It’s based upon relatively few numbers of patients, largely sponsor-based studies, with numbers at risk at 15-20 years that are extremely low,” Dr. Leon asserted. “The majority of surgical valves being used today and touted as being durable are backed by only 2-4 years of data.”
In contrast, he added, “We have 5-year TAVR data which is absolutely definitive of no early structural valve deterioration.”
Discussant Mayra E. Guerrero, MD, of the Mayo Clinic in Rochester, Minn., expressed concern that “this paradigm shift to ‘TAVR for all’ ” could break the bank for many institutions because the cost of TAVR valves is far greater than for SAVR valves. But she was heartened by the fresh PARTNER 3 and Evolut Low Risk data showing TAVR patients had fewer ICU days, shorter hospital stays, fewer strokes, more frequent discharge home, and a lower rehospitalization rate.
Dr. Reardon was reassuring on this score.
“I am 100% convinced that when we do the financials for these two trials, TAVR is going to be a cost saver and a huge winner,” the surgeon said.
He reported serving as a consultant to Medtronic and receiving research grants from Medtronic and Boston Scientific. Dr. Leon reported receiving research grants from Edwards Lifesciences and St. Jude Medical and acting as a consultant to several medical device companies.
The two trials have been published online by the New England Journal of Medicine.
SOURCES: Leon MB et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052; Reardon MJ et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1816885.
NEW ORLEANS – Patients with severely symptomatic aortic stenosis at low surgical risk had significantly better key outcomes with transcatheter aortic valve replacement than with surgical valve replacement through 1 year of follow-up in the landmark PARTNER 3 and Evolut Low Risk randomized trials presented at the annual meeting of the American College of Cardiology.
As the two study presenters stepped down from the stage after sharing their results, the packed audience in the meeting’s main arena rose to shower them with a prolonged standing ovation.
“This is a historic moment, and all of us here should recognize it as such,” thundered discussant Eugene Braunwald, MD, professor of medicine at Harvard Medical School, Boston. “We’re going to remember it. We’re going to tell our grandchildren and great grandchildren that we were there at the time these incredible advances in the care of patients with aortic stenosis were presented.”
This was in fact the day that transcatheter aortic valve replacement (TAVR), a relatively young, rapidly evolving nonsurgical technique, finally overtook surgical aortic valve replacement (SAVR), a mature operation first successfully performed back in 1962. Previous large, randomized trials had established that TAVR was superior to SAVR in extreme-risk patients and noninferior to surgery in high- and intermediate-risk patients, yet with the advantage of much quicker recovery. The only remaining question was how TAVR would stack up in low-risk patients, who comprise 80% of those who currently undergo SAVR for aortic stenosis.
“Two separate groups using two separate valves have come to very similar conclusions. This doesn’t double the acceptability, it quadruples it,” Dr. Braunwald said.
PARTNER 3
Martin B. Leon, MD, presented the findings of the PARTNER 3 (Placement of Aortic Transcatheter Valves) trial, in which 1,000 low-risk patients at 71 centers were randomized to TAVR with transfemoral placement of the balloon-expandable Edwards Lifesciences Sapien 3 bioprosthetic valve or to SAVR. The mean age of the patients was 73 years, with a mean Society of Thoracic Surgeons risk score of 1.9%. Operators had to have more than 1 year of experience using the Sapien 3 valve in order to participate in the trial.
At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with SAVR, for a highly significant 46% relative risk reduction. All three components of the primary endpoint occurred significantly less often in the TAVR group. And the rate of the key endpoint of death or disabling stroke was 1.0% with TAVR, compared with 2.9% with SAVR, reported Dr. Leon, coprincipal investigator in PARTNER 3 and professor of medicine at Columbia University, New York.
TAVR also outperformed SAVR on all six prespecified major secondary endpoints. These included new-onset atrial fibrillation within 30 days, at 5.0% with TAVR and 39.5% with SAVR; length of index hospitalization at 3 versus 7 days; all stroke at 30 days at 0.6% versus 2.4%; and death or a significant deterioration in quality of life at 30 days as measured by the Kansas City Cardiomyopathy Questionnaire at 3.9% versus 30.6%. There was significantly less life-threatening or major bleeding within 30 days in the TAVR group, by a margin of 3.6% versus 24.5%, and similarly low rates of new pacemaker implantation at 6.5% versus 4.0%. There was, however, a higher 30-day incidence of new left bundle branch block with TAVR, by a margin of 22% versus 8%, which may eventually translate into need for a pacemaker.
“Based upon these findings, TAVR, through 1 year, should be considered the preferred therapy in low-surgical-risk aortic stenosis patients. The PARTNER randomized trials over the past 12 years clearly indicate that the relative value of TAVR, compared with surgery, is independent of surgical risk profiles,” Dr. Leon declared.
Evolut Low Risk
Michael J. Reardon, MD, coprincipal investigator for the Evolut Low Risk study and professor of cardiovascular surgery at Houston Methodist Hospital, reported on 1,468 patients randomized to TAVR with a Medtronic self-expanding, supra-annular bioprosthetic valve or to SAVR. Of them, 22% of patients got the most recent version of the valve, known as the Evolut PRO, 74% got the Evolut R, and the remainder received the first-generation CoreValve.
The primary endpoint – death or disabling stroke – was slightly different from that in PARTNER 3. At 1 year, the rate was 2.9% in the TAVR arm and 4.6% with SAVR, a statistically significant difference, while at 2 years the rate was 5.3% with TAVR and 6.7% with SAVR, a difference that was not significant. Impressively, the rate of the composite of death, disabling stroke, or heart failure hospitalizations through 1 year was 5.6% with TAVR versus 10.2% with SAVR.
“We’ve shown that, with TAVR, you’re more likely to be alive, without a stroke, and outside the hospital. This is exactly what my patients tell me they want when we sit down for shared decision-making and talk about their expectations,” Dr. Reardon said.
Noting the striking similarity of across-the-board outcomes in the two trials, Dr. Reardon concluded, “I think what we’re seeing here is a class effect of TAVR, and we have to recognize it as such.”
Dr. Leon agreed, with a caveat. “I think the class effect for these two versions of TAVR systems is very real. I wouldn’t presume to think that every TAVR device will perform the same way, so I think we need a lot more data on the newer devices that are being introduced.”
The reaction
During the question-and-answer session, the two investigators were asked about stroke rates, which were significantly lower in the TAVR patients even though in the early randomized trials in high-risk patients the stroke rates were twice as high with TAVR than SAVR. The explanation probably lies in a mix of device refinements over time, better techniques, standardized procedures, and careful patient selection, they said.
“If you look at stroke in the TAVR arm in both these trials, we’re almost approaching the background stroke rate in a group of 74-year-olds sitting around in a room,” Dr. Reardon observed.
Both trials will continue to assess participants both clinically and by echocardiography through 10 years, in part to assess TAVR valve durability, but also to evaluate the durability of surgical valves, which isn’t nearly as well established as most people think, according to the investigators.
“There is a myth of surgical bioprosthetic valve immortality. It’s based upon relatively few numbers of patients, largely sponsor-based studies, with numbers at risk at 15-20 years that are extremely low,” Dr. Leon asserted. “The majority of surgical valves being used today and touted as being durable are backed by only 2-4 years of data.”
In contrast, he added, “We have 5-year TAVR data which is absolutely definitive of no early structural valve deterioration.”
Discussant Mayra E. Guerrero, MD, of the Mayo Clinic in Rochester, Minn., expressed concern that “this paradigm shift to ‘TAVR for all’ ” could break the bank for many institutions because the cost of TAVR valves is far greater than for SAVR valves. But she was heartened by the fresh PARTNER 3 and Evolut Low Risk data showing TAVR patients had fewer ICU days, shorter hospital stays, fewer strokes, more frequent discharge home, and a lower rehospitalization rate.
Dr. Reardon was reassuring on this score.
“I am 100% convinced that when we do the financials for these two trials, TAVR is going to be a cost saver and a huge winner,” the surgeon said.
He reported serving as a consultant to Medtronic and receiving research grants from Medtronic and Boston Scientific. Dr. Leon reported receiving research grants from Edwards Lifesciences and St. Jude Medical and acting as a consultant to several medical device companies.
The two trials have been published online by the New England Journal of Medicine.
SOURCES: Leon MB et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052; Reardon MJ et al. N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1816885.
REPORTING FROM ACC 19
Immediate angiography after non-STEMI cardiac arrest confers no survival benefit
Immediate angiography after resuscitation from out-of-hospital cardiac arrest does not improve survival compared to delaying angiography until neurologic recovery in patients with no evidence of ST-segment elevation myocardial infarction, according to data presented at the annual meeting of the American College of Cardiology.
The Coronary Angiography after Cardiac Arrest (COACT) trial involved 552 patients who had been successfully resuscitated after out-of-hospital cardiac arrest, without signs of ST-segment elevation myocardial infarction. The study also excluded patients with shock and severe renal dysfunction, and was not blinded, so this may have influenced treatment decisions.
Patients were randomized either to immediate coronary angiography after resuscitation, while still unconscious, or delayed coronary angiography until they had recovered neurologically, which was generally after discharge from intensive care.
Overall, 97.1% of patients in the immediate angiography group and 64.9% of the delayed angiography group underwent coronary angiography, with the median time until angiography being 0.8 hours in the immediate group and 119.9 hours in the delayed group.
In the immediate angiography group, 3.4% of patients were found to have an acute coronary occlusion, while in the delayed group that figure was 7.6%. Percutaneous coronary intervention was performed in 33% of the immediate angiography group and 24.2% of the delayed angiography group.
Survival rates at 90 days were not significantly different between the two groups; 64.5% of the immediate angiography group and 67.2% of the delayed angiography group survived to 90 days (OR 0.89, P = 0.51). The two groups also did not significantly differ in the secondary endpoints of survival with good cerebral performance or mild-to-moderate disability (62.9% vs. 64.4%).
“Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI,” wrote Dr. Jorrit S. Lemkes, from the department of cardiology at Amsterdam University Medical Center VUmc, and co-authors. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favored treating patients who had a presumed better prognosis with a strategy of immediate angiography.”
They also suggested the lack of benefit from early coronary angiography could relate to the fact that majority of those who died did so as a result of neurological complications, as has been seen in other studies of resuscitation.
The authors did note that the vast majority of patients in the study had stable coronary artery lesions, and only 5% showed thrombotic occlusions. They suggested this could explain their results, as percutaneous coronary intervention was not associated with improved outcomes in patients with stable coronary artery lesions – only in patients with acute thrombotic coronary occlusions.
However, they did see the suggestion of a treatment effect in patients over 70 years old and those with a history of coronary artery disease.
The study also revealed differences in subsequent treatment between patients who underwent immediate coronary angiography and those who had delayed angiography. Those in the delayed group were significantly more likely to be treated with salicylates or a P2Y12 inhibitor than those in the immediate angiography group.
“This observation illustrates how the result of immediate coronary angiography can influence treatment, since patients who did not have evidence of coronary artery disease on angiography do not require antiplatelet therapy,” the authors wrote.
Conversely, patients in the immediate angiography were more likely to receive a glycoprotein IIb/IIIa inhibitor. However the authors said these different strategies did not translate to any significant difference in major bleeding.
The COACT trial results were published in the New England Journal of Medicine simultaneously with Dr.Lemkes's presentation.
COACT was supported by the Netherlands Heart Institute, Biotronik and AstraZeneca. Two authors declared grants and support from the study supporters, both in and outside the context of the study. One author declared grants from private industry outside the study. No other conflicts of interest were declared.
SOURCE: Lemkes J et al. NEJM, 2019, March 18. DOI: 10.1056/NEJMoa1816897
The results of the COACT trial are consistent with other studies in patients with acute coronary syndromes but without evidence of STEMI or cardiac arrest, showing that immediate coronary angiography is not associated with improved outcomes.
However, less than 20% of the COACT cohort had unstable coronary lesions and less than 40% underwent coronary interventions, so relatively few patients would have been affected by the timing of coronary angiography or the procedure itself. In this trial, more than 60% of deaths were due to neurologic injury rather than cardiac complications.
Enriching the study population with patients with probable coronary disease might have led to a different result. A substudy analysis of patients over age 70 with a history of coronary disease showed they were more likely to benefit from immediate coronary angiography than were younger patients without a history of coronary disease.
Prioritizing interventions also had an impact on targeted temperature managemen, which also may have played into the results. The median time to achieve target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group.
Additional insights may come from two ongoing clinical trials, ACCESS and DISCO (Direct or Subacute Coronary Angiography in Out-of-hospital Cardiac Arrest), may shed additional light on how interventions after out-of-hospital cardiac arrest affect patient outcomes.
Dr. Benjamin S. Abella is from the Center for Resuscitation Science and Department of Emergency Medicine at the University of Pennsylvania Perelman School of Medicine and Dr. David F. Gaieski is from the Department of Emergency Medicine at Jefferson Medical College. These comments are adapted from an accompanying editorial (NEJM 2019, March 18. DOI: 10.1056/NEJMe1901651). Both authors declared grants, personal support and other support from private industry outside the submitted work.
The results of the COACT trial are consistent with other studies in patients with acute coronary syndromes but without evidence of STEMI or cardiac arrest, showing that immediate coronary angiography is not associated with improved outcomes.
However, less than 20% of the COACT cohort had unstable coronary lesions and less than 40% underwent coronary interventions, so relatively few patients would have been affected by the timing of coronary angiography or the procedure itself. In this trial, more than 60% of deaths were due to neurologic injury rather than cardiac complications.
Enriching the study population with patients with probable coronary disease might have led to a different result. A substudy analysis of patients over age 70 with a history of coronary disease showed they were more likely to benefit from immediate coronary angiography than were younger patients without a history of coronary disease.
Prioritizing interventions also had an impact on targeted temperature managemen, which also may have played into the results. The median time to achieve target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group.
Additional insights may come from two ongoing clinical trials, ACCESS and DISCO (Direct or Subacute Coronary Angiography in Out-of-hospital Cardiac Arrest), may shed additional light on how interventions after out-of-hospital cardiac arrest affect patient outcomes.
Dr. Benjamin S. Abella is from the Center for Resuscitation Science and Department of Emergency Medicine at the University of Pennsylvania Perelman School of Medicine and Dr. David F. Gaieski is from the Department of Emergency Medicine at Jefferson Medical College. These comments are adapted from an accompanying editorial (NEJM 2019, March 18. DOI: 10.1056/NEJMe1901651). Both authors declared grants, personal support and other support from private industry outside the submitted work.
The results of the COACT trial are consistent with other studies in patients with acute coronary syndromes but without evidence of STEMI or cardiac arrest, showing that immediate coronary angiography is not associated with improved outcomes.
However, less than 20% of the COACT cohort had unstable coronary lesions and less than 40% underwent coronary interventions, so relatively few patients would have been affected by the timing of coronary angiography or the procedure itself. In this trial, more than 60% of deaths were due to neurologic injury rather than cardiac complications.
Enriching the study population with patients with probable coronary disease might have led to a different result. A substudy analysis of patients over age 70 with a history of coronary disease showed they were more likely to benefit from immediate coronary angiography than were younger patients without a history of coronary disease.
Prioritizing interventions also had an impact on targeted temperature managemen, which also may have played into the results. The median time to achieve target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group.
Additional insights may come from two ongoing clinical trials, ACCESS and DISCO (Direct or Subacute Coronary Angiography in Out-of-hospital Cardiac Arrest), may shed additional light on how interventions after out-of-hospital cardiac arrest affect patient outcomes.
Dr. Benjamin S. Abella is from the Center for Resuscitation Science and Department of Emergency Medicine at the University of Pennsylvania Perelman School of Medicine and Dr. David F. Gaieski is from the Department of Emergency Medicine at Jefferson Medical College. These comments are adapted from an accompanying editorial (NEJM 2019, March 18. DOI: 10.1056/NEJMe1901651). Both authors declared grants, personal support and other support from private industry outside the submitted work.
Immediate angiography after resuscitation from out-of-hospital cardiac arrest does not improve survival compared to delaying angiography until neurologic recovery in patients with no evidence of ST-segment elevation myocardial infarction, according to data presented at the annual meeting of the American College of Cardiology.
The Coronary Angiography after Cardiac Arrest (COACT) trial involved 552 patients who had been successfully resuscitated after out-of-hospital cardiac arrest, without signs of ST-segment elevation myocardial infarction. The study also excluded patients with shock and severe renal dysfunction, and was not blinded, so this may have influenced treatment decisions.
Patients were randomized either to immediate coronary angiography after resuscitation, while still unconscious, or delayed coronary angiography until they had recovered neurologically, which was generally after discharge from intensive care.
Overall, 97.1% of patients in the immediate angiography group and 64.9% of the delayed angiography group underwent coronary angiography, with the median time until angiography being 0.8 hours in the immediate group and 119.9 hours in the delayed group.
In the immediate angiography group, 3.4% of patients were found to have an acute coronary occlusion, while in the delayed group that figure was 7.6%. Percutaneous coronary intervention was performed in 33% of the immediate angiography group and 24.2% of the delayed angiography group.
Survival rates at 90 days were not significantly different between the two groups; 64.5% of the immediate angiography group and 67.2% of the delayed angiography group survived to 90 days (OR 0.89, P = 0.51). The two groups also did not significantly differ in the secondary endpoints of survival with good cerebral performance or mild-to-moderate disability (62.9% vs. 64.4%).
“Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI,” wrote Dr. Jorrit S. Lemkes, from the department of cardiology at Amsterdam University Medical Center VUmc, and co-authors. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favored treating patients who had a presumed better prognosis with a strategy of immediate angiography.”
They also suggested the lack of benefit from early coronary angiography could relate to the fact that majority of those who died did so as a result of neurological complications, as has been seen in other studies of resuscitation.
The authors did note that the vast majority of patients in the study had stable coronary artery lesions, and only 5% showed thrombotic occlusions. They suggested this could explain their results, as percutaneous coronary intervention was not associated with improved outcomes in patients with stable coronary artery lesions – only in patients with acute thrombotic coronary occlusions.
However, they did see the suggestion of a treatment effect in patients over 70 years old and those with a history of coronary artery disease.
The study also revealed differences in subsequent treatment between patients who underwent immediate coronary angiography and those who had delayed angiography. Those in the delayed group were significantly more likely to be treated with salicylates or a P2Y12 inhibitor than those in the immediate angiography group.
“This observation illustrates how the result of immediate coronary angiography can influence treatment, since patients who did not have evidence of coronary artery disease on angiography do not require antiplatelet therapy,” the authors wrote.
Conversely, patients in the immediate angiography were more likely to receive a glycoprotein IIb/IIIa inhibitor. However the authors said these different strategies did not translate to any significant difference in major bleeding.
The COACT trial results were published in the New England Journal of Medicine simultaneously with Dr.Lemkes's presentation.
COACT was supported by the Netherlands Heart Institute, Biotronik and AstraZeneca. Two authors declared grants and support from the study supporters, both in and outside the context of the study. One author declared grants from private industry outside the study. No other conflicts of interest were declared.
SOURCE: Lemkes J et al. NEJM, 2019, March 18. DOI: 10.1056/NEJMoa1816897
Immediate angiography after resuscitation from out-of-hospital cardiac arrest does not improve survival compared to delaying angiography until neurologic recovery in patients with no evidence of ST-segment elevation myocardial infarction, according to data presented at the annual meeting of the American College of Cardiology.
The Coronary Angiography after Cardiac Arrest (COACT) trial involved 552 patients who had been successfully resuscitated after out-of-hospital cardiac arrest, without signs of ST-segment elevation myocardial infarction. The study also excluded patients with shock and severe renal dysfunction, and was not blinded, so this may have influenced treatment decisions.
Patients were randomized either to immediate coronary angiography after resuscitation, while still unconscious, or delayed coronary angiography until they had recovered neurologically, which was generally after discharge from intensive care.
Overall, 97.1% of patients in the immediate angiography group and 64.9% of the delayed angiography group underwent coronary angiography, with the median time until angiography being 0.8 hours in the immediate group and 119.9 hours in the delayed group.
In the immediate angiography group, 3.4% of patients were found to have an acute coronary occlusion, while in the delayed group that figure was 7.6%. Percutaneous coronary intervention was performed in 33% of the immediate angiography group and 24.2% of the delayed angiography group.
Survival rates at 90 days were not significantly different between the two groups; 64.5% of the immediate angiography group and 67.2% of the delayed angiography group survived to 90 days (OR 0.89, P = 0.51). The two groups also did not significantly differ in the secondary endpoints of survival with good cerebral performance or mild-to-moderate disability (62.9% vs. 64.4%).
“Our findings do not corroborate findings of previous observational studies, which showed a survival benefit with immediate coronary angiography in patients who had cardiac arrest without STEMI,” wrote Dr. Jorrit S. Lemkes, from the department of cardiology at Amsterdam University Medical Center VUmc, and co-authors. “This difference could be related to the observational nature of the previous studies, which may have resulted in selection bias that favored treating patients who had a presumed better prognosis with a strategy of immediate angiography.”
They also suggested the lack of benefit from early coronary angiography could relate to the fact that majority of those who died did so as a result of neurological complications, as has been seen in other studies of resuscitation.
The authors did note that the vast majority of patients in the study had stable coronary artery lesions, and only 5% showed thrombotic occlusions. They suggested this could explain their results, as percutaneous coronary intervention was not associated with improved outcomes in patients with stable coronary artery lesions – only in patients with acute thrombotic coronary occlusions.
However, they did see the suggestion of a treatment effect in patients over 70 years old and those with a history of coronary artery disease.
The study also revealed differences in subsequent treatment between patients who underwent immediate coronary angiography and those who had delayed angiography. Those in the delayed group were significantly more likely to be treated with salicylates or a P2Y12 inhibitor than those in the immediate angiography group.
“This observation illustrates how the result of immediate coronary angiography can influence treatment, since patients who did not have evidence of coronary artery disease on angiography do not require antiplatelet therapy,” the authors wrote.
Conversely, patients in the immediate angiography were more likely to receive a glycoprotein IIb/IIIa inhibitor. However the authors said these different strategies did not translate to any significant difference in major bleeding.
The COACT trial results were published in the New England Journal of Medicine simultaneously with Dr.Lemkes's presentation.
COACT was supported by the Netherlands Heart Institute, Biotronik and AstraZeneca. Two authors declared grants and support from the study supporters, both in and outside the context of the study. One author declared grants from private industry outside the study. No other conflicts of interest were declared.
SOURCE: Lemkes J et al. NEJM, 2019, March 18. DOI: 10.1056/NEJMoa1816897
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