Interventional Cardiology & Surgery

The U.S. Food and Drug Administration has approved 1-month – as short as 28 days – dual antiplatelet therapy (DAPT) labeling for Xience stents in patients at high risk for bleeding, Abbott announced on June 30.

Patients who receive stents are typically on DAPT regimens such as aspirin and P2Y12 inhibitors for 6 to 12 months to prevent blood clots, but high-bleeding risk patients can experience bleeding during prolonged DAPT.

“The new FDA approval for DAPT for the XIENCE family of stents provides interventional cardiologists confidence they are delivering the best care to patients with high bleeding risk. A short DAPT duration minimizes risks for high bleeding risk patients and allows them to return to daily life sooner and with more assurance,” Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York and the global principal investigator for Abbott’s Short DAPT program (XIENCE 28 and XIENCE 90), said in a news release.

The new labeling comes on the heels of European CE Mark approval for the Xience stents with DAPT as short as 28 days, “giving Xience stents the shortest DAPT indication in the world,” the company noted.

Results of the XIENCE 28 trial were used to support the new CE Mark DAPT indication. The trial showed no increase in death of myocardial infarction between 1 and 6 months and a significantly lower risk for severe bleeding with the Xience stent and 1-month DAPT, compared with 6-month DAPT in more than 1,600 high-bleeding risk patients.

The XIENCE 90 trial involving more than 2,000 high-bleeding risk patients reported no difference in death or MI between 3 and 12 months with Xience and 3-month DAPT versus 12-month DAPT.

Abbott scored a second win, also announcing FDA and CE Mark approval of its next-generation Xience Skypoint stent in high-bleeding risk patients with 1-month DAPT.

“XIENCE Skypoint is easier to place and allows physicians to treat larger blood vessels through improved stent expansion that can open clogged vessels more effectively,” the company said.

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

The U.S. Food and Drug Administration has approved 1-month – as short as 28 days – dual antiplatelet therapy (DAPT) labeling for Xience stents in patients at high risk for bleeding, Abbott announced on June 30.

Patients who receive stents are typically on DAPT regimens such as aspirin and P2Y12 inhibitors for 6 to 12 months to prevent blood clots, but high-bleeding risk patients can experience bleeding during prolonged DAPT.

“The new FDA approval for DAPT for the XIENCE family of stents provides interventional cardiologists confidence they are delivering the best care to patients with high bleeding risk. A short DAPT duration minimizes risks for high bleeding risk patients and allows them to return to daily life sooner and with more assurance,” Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York and the global principal investigator for Abbott’s Short DAPT program (XIENCE 28 and XIENCE 90), said in a news release.

The new labeling comes on the heels of European CE Mark approval for the Xience stents with DAPT as short as 28 days, “giving Xience stents the shortest DAPT indication in the world,” the company noted.

Results of the XIENCE 28 trial were used to support the new CE Mark DAPT indication. The trial showed no increase in death of myocardial infarction between 1 and 6 months and a significantly lower risk for severe bleeding with the Xience stent and 1-month DAPT, compared with 6-month DAPT in more than 1,600 high-bleeding risk patients.

The XIENCE 90 trial involving more than 2,000 high-bleeding risk patients reported no difference in death or MI between 3 and 12 months with Xience and 3-month DAPT versus 12-month DAPT.

Abbott scored a second win, also announcing FDA and CE Mark approval of its next-generation Xience Skypoint stent in high-bleeding risk patients with 1-month DAPT.

“XIENCE Skypoint is easier to place and allows physicians to treat larger blood vessels through improved stent expansion that can open clogged vessels more effectively,” the company said.

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

The U.S. Food and Drug Administration has approved 1-month – as short as 28 days – dual antiplatelet therapy (DAPT) labeling for Xience stents in patients at high risk for bleeding, Abbott announced on June 30.

Patients who receive stents are typically on DAPT regimens such as aspirin and P2Y12 inhibitors for 6 to 12 months to prevent blood clots, but high-bleeding risk patients can experience bleeding during prolonged DAPT.

“The new FDA approval for DAPT for the XIENCE family of stents provides interventional cardiologists confidence they are delivering the best care to patients with high bleeding risk. A short DAPT duration minimizes risks for high bleeding risk patients and allows them to return to daily life sooner and with more assurance,” Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York and the global principal investigator for Abbott’s Short DAPT program (XIENCE 28 and XIENCE 90), said in a news release.

The new labeling comes on the heels of European CE Mark approval for the Xience stents with DAPT as short as 28 days, “giving Xience stents the shortest DAPT indication in the world,” the company noted.

Results of the XIENCE 28 trial were used to support the new CE Mark DAPT indication. The trial showed no increase in death of myocardial infarction between 1 and 6 months and a significantly lower risk for severe bleeding with the Xience stent and 1-month DAPT, compared with 6-month DAPT in more than 1,600 high-bleeding risk patients.

The XIENCE 90 trial involving more than 2,000 high-bleeding risk patients reported no difference in death or MI between 3 and 12 months with Xience and 3-month DAPT versus 12-month DAPT.

Abbott scored a second win, also announcing FDA and CE Mark approval of its next-generation Xience Skypoint stent in high-bleeding risk patients with 1-month DAPT.

“XIENCE Skypoint is easier to place and allows physicians to treat larger blood vessels through improved stent expansion that can open clogged vessels more effectively,” the company said.

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

When it comes to medical therapy after a coronary revascularization procedure, more is better. Patients started and then maintained indefinitely on more rather than fewer of the drugs identified as optimal medical therapy (OMT) achieve a major survival benefit 10 years later, according to long-term follow-up from an extended analysis of the SYNTAX trial.

Courtesy Cardiovascular Research Foundation

For the survival benefit at 10 years, “the present study suggests that at least three types of optimal medical therapy should be maintained for at least 5 years after revascularization,” reported a multinational team of cardiovascular specialists led by Hideyuki Kawashima, MD and Patrick Serruys, MD, who both have affiliations with the department of cardiology of the National University of Ireland, Galway.

The SYNTAX trial was conducted to compare percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) for patients with previously untreated three-vessel and/or left main disease (N Engl J Med 2009;360:961-72). The conclusion from that study, published in 2009 and subsequently reinforced by a 5-year follow-up, was that CABG should remain the standard of care for complex lesions.
 

Optimal medical therapy defined

In the course of SYNTAX, the impact of OMT on outcome was also evaluated in a subanalysis. At 5 years, there was a mortality advantage for those receiving an antiplatelet drug, a statin, a renin-angiotensin system inhibitor (ACE inhibitor or angiotensin receptor blocker), and a beta-blocker when compared with fewer of these agents.

When an investigator-initiated extension of SYNTAX, called SYNTAXES, was conducted to compare the outcomes of PCI and CABG at 10 years, it also permitted an extended analysis of OMT. Although the primary comparison of SYNTAXES, reported 2 years ago, did not show a significant difference between PCI and CABG for mortality at 10 years, there was a difference for OMT.

When investigators compared treatment with three or more OMT agents with that with two or fewer OMT drugs at 5 years, the result for all-cause death at 10 years translated into a more than 50% relative reduction (hazard ratio, 0.47; P = .002). The absolute difference in mortality was a more than 6% reduction (13.1% vs. 19.9%).
 

OMT data offer major message

The current study is considered to have a major message for patients as well as physicians.

“OMT even outweighs the survival benefit from revascularization alone, so our patients should convince themselves of the value of rigorous adherence and compliance,” Dr. Serruys said in an interview. According to him, these are compelling data for telling patients that OMT “is the best insurance for extended survival.” We now know from these data “the longer, the better.”

The same message from these data extends to physicians.

“I wish I could understand the apparent blind spot physicians have with respect to prescribing OMT despite the overwhelming benefit from multiple clinical trials,” said William E. Boden, MD, professor of medicine, Boston University.

Dr. Boden was a coauthor of an editorial accompanying the newly published SYNTAXES subanalysis. In the editorial, he noted that OMT following revascularization and in other high-risk patients “has been unacceptably low,” but he was asked to expand on the lessons from the newly released SYNTAXES subanalysis in an interview.

“There has often been a belief that revascularization negates the need for OMT and that’s why the SYNTAXES trial 10-year mortality reduction – which builds upon an earlier 5-year mortality reduction analysis – is so important,” he said.
 

Patients should take OMT long term

These data “should be both a motivator for physicians to prescribe OMT and for patients to remain adherent to OMT,” he said. “It is the best warranty to blunt the progression of atherosclerosis and to reduce subsequent cardiac events.”

For the 10-year subanalysis of OMT in SYNTAXES, the patients were stratified by the number of OMTs they were taking at 5 years after revascularization and then evaluated for survival at 10 years. Of the 1,472 patients available for analysis at 5 years, only 678 (46%) were on OMT. The other 794 patients were not.

Graphically, the Kaplan-Meier survival curve for those on three types of OMT was consistently beneath that of those on four OMTs, but the gap narrowed over time. At the end of 10 years, the advantage of the four-drug OMT was not statistically significant relative to three or fewer (13.1% vs. 12.7%).
 

Statins and antiplatelets show largest effect

When analyzed individually and in different combinations, the agents with OMT did not appear to be equal. For example, the biggest survival gap at 10 years was for those who were on an antiplatelet therapy and a statin at 5 years relative to those who were not on either (13.2% vs. 22.6%; P = .006). Even after adjustment, there was nearly 45% survival benefit for these two agents (HR, 0.556; P = .02).

Conversely, the 10-year survival advantage for being on a renin-angiotensin system inhibitor at 5 years versus not being exposed to this therapy was small and nonsignificant (14.7% vs. 13.7%; P = .651).

The precise proportion of patients who were prescribed and adhered to OMT between 5 years and 10 years is unknown, acknowledged the authors, so conclusions are limited about the added benefit of 10- versus 5-year OMT, although the authors presume that a substantial proportion of those adherent for 5 years would likely continue on these therapies.

It can be said with confidence that those adherent for at least 5 years are more likely to be alive at 10 years than those who are not, according to Dr. Boden. He considers these data a call for physicians and all high-risk patients, not just those who have undergone revascularization, to take these standard therapies.

There are plenty of data to “show how poorly we treat patients with OMT,” said Dr. Boden, citing several studies. In one, which looked at OMT in a nationally representative sample in the United States, only a third of patients with angina were taking an antiplatelet, a statin, and a beta-blocker, all of which are indicated.

“Hospitalization for revascularization provides an opportune time to capture the attention of patients and their physicians,” he wrote in his editorial. He called OMT “an imperative to optimize clinical outcomes.”

Many of the investigators involved in the SYNTAXES subanalysis, including Dr. Serruys, have financial relationships with multiple pharmaceutical companies, including Boston Scientific, which provided the initial funding for the SYNTAX trial. Dr. Boden reports no potential conflicts of interest.

When it comes to medical therapy after a coronary revascularization procedure, more is better. Patients started and then maintained indefinitely on more rather than fewer of the drugs identified as optimal medical therapy (OMT) achieve a major survival benefit 10 years later, according to long-term follow-up from an extended analysis of the SYNTAX trial.

Courtesy Cardiovascular Research Foundation

For the survival benefit at 10 years, “the present study suggests that at least three types of optimal medical therapy should be maintained for at least 5 years after revascularization,” reported a multinational team of cardiovascular specialists led by Hideyuki Kawashima, MD and Patrick Serruys, MD, who both have affiliations with the department of cardiology of the National University of Ireland, Galway.

The SYNTAX trial was conducted to compare percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) for patients with previously untreated three-vessel and/or left main disease (N Engl J Med 2009;360:961-72). The conclusion from that study, published in 2009 and subsequently reinforced by a 5-year follow-up, was that CABG should remain the standard of care for complex lesions.
 

Optimal medical therapy defined

In the course of SYNTAX, the impact of OMT on outcome was also evaluated in a subanalysis. At 5 years, there was a mortality advantage for those receiving an antiplatelet drug, a statin, a renin-angiotensin system inhibitor (ACE inhibitor or angiotensin receptor blocker), and a beta-blocker when compared with fewer of these agents.

When an investigator-initiated extension of SYNTAX, called SYNTAXES, was conducted to compare the outcomes of PCI and CABG at 10 years, it also permitted an extended analysis of OMT. Although the primary comparison of SYNTAXES, reported 2 years ago, did not show a significant difference between PCI and CABG for mortality at 10 years, there was a difference for OMT.

When investigators compared treatment with three or more OMT agents with that with two or fewer OMT drugs at 5 years, the result for all-cause death at 10 years translated into a more than 50% relative reduction (hazard ratio, 0.47; P = .002). The absolute difference in mortality was a more than 6% reduction (13.1% vs. 19.9%).
 

OMT data offer major message

The current study is considered to have a major message for patients as well as physicians.

“OMT even outweighs the survival benefit from revascularization alone, so our patients should convince themselves of the value of rigorous adherence and compliance,” Dr. Serruys said in an interview. According to him, these are compelling data for telling patients that OMT “is the best insurance for extended survival.” We now know from these data “the longer, the better.”

The same message from these data extends to physicians.

“I wish I could understand the apparent blind spot physicians have with respect to prescribing OMT despite the overwhelming benefit from multiple clinical trials,” said William E. Boden, MD, professor of medicine, Boston University.

Dr. Boden was a coauthor of an editorial accompanying the newly published SYNTAXES subanalysis. In the editorial, he noted that OMT following revascularization and in other high-risk patients “has been unacceptably low,” but he was asked to expand on the lessons from the newly released SYNTAXES subanalysis in an interview.

“There has often been a belief that revascularization negates the need for OMT and that’s why the SYNTAXES trial 10-year mortality reduction – which builds upon an earlier 5-year mortality reduction analysis – is so important,” he said.
 

Patients should take OMT long term

These data “should be both a motivator for physicians to prescribe OMT and for patients to remain adherent to OMT,” he said. “It is the best warranty to blunt the progression of atherosclerosis and to reduce subsequent cardiac events.”

For the 10-year subanalysis of OMT in SYNTAXES, the patients were stratified by the number of OMTs they were taking at 5 years after revascularization and then evaluated for survival at 10 years. Of the 1,472 patients available for analysis at 5 years, only 678 (46%) were on OMT. The other 794 patients were not.

Graphically, the Kaplan-Meier survival curve for those on three types of OMT was consistently beneath that of those on four OMTs, but the gap narrowed over time. At the end of 10 years, the advantage of the four-drug OMT was not statistically significant relative to three or fewer (13.1% vs. 12.7%).
 

Statins and antiplatelets show largest effect

When analyzed individually and in different combinations, the agents with OMT did not appear to be equal. For example, the biggest survival gap at 10 years was for those who were on an antiplatelet therapy and a statin at 5 years relative to those who were not on either (13.2% vs. 22.6%; P = .006). Even after adjustment, there was nearly 45% survival benefit for these two agents (HR, 0.556; P = .02).

Conversely, the 10-year survival advantage for being on a renin-angiotensin system inhibitor at 5 years versus not being exposed to this therapy was small and nonsignificant (14.7% vs. 13.7%; P = .651).

The precise proportion of patients who were prescribed and adhered to OMT between 5 years and 10 years is unknown, acknowledged the authors, so conclusions are limited about the added benefit of 10- versus 5-year OMT, although the authors presume that a substantial proportion of those adherent for 5 years would likely continue on these therapies.

It can be said with confidence that those adherent for at least 5 years are more likely to be alive at 10 years than those who are not, according to Dr. Boden. He considers these data a call for physicians and all high-risk patients, not just those who have undergone revascularization, to take these standard therapies.

There are plenty of data to “show how poorly we treat patients with OMT,” said Dr. Boden, citing several studies. In one, which looked at OMT in a nationally representative sample in the United States, only a third of patients with angina were taking an antiplatelet, a statin, and a beta-blocker, all of which are indicated.

“Hospitalization for revascularization provides an opportune time to capture the attention of patients and their physicians,” he wrote in his editorial. He called OMT “an imperative to optimize clinical outcomes.”

Many of the investigators involved in the SYNTAXES subanalysis, including Dr. Serruys, have financial relationships with multiple pharmaceutical companies, including Boston Scientific, which provided the initial funding for the SYNTAX trial. Dr. Boden reports no potential conflicts of interest.

When it comes to medical therapy after a coronary revascularization procedure, more is better. Patients started and then maintained indefinitely on more rather than fewer of the drugs identified as optimal medical therapy (OMT) achieve a major survival benefit 10 years later, according to long-term follow-up from an extended analysis of the SYNTAX trial.

Courtesy Cardiovascular Research Foundation

For the survival benefit at 10 years, “the present study suggests that at least three types of optimal medical therapy should be maintained for at least 5 years after revascularization,” reported a multinational team of cardiovascular specialists led by Hideyuki Kawashima, MD and Patrick Serruys, MD, who both have affiliations with the department of cardiology of the National University of Ireland, Galway.

The SYNTAX trial was conducted to compare percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) for patients with previously untreated three-vessel and/or left main disease (N Engl J Med 2009;360:961-72). The conclusion from that study, published in 2009 and subsequently reinforced by a 5-year follow-up, was that CABG should remain the standard of care for complex lesions.
 

Optimal medical therapy defined

In the course of SYNTAX, the impact of OMT on outcome was also evaluated in a subanalysis. At 5 years, there was a mortality advantage for those receiving an antiplatelet drug, a statin, a renin-angiotensin system inhibitor (ACE inhibitor or angiotensin receptor blocker), and a beta-blocker when compared with fewer of these agents.

When an investigator-initiated extension of SYNTAX, called SYNTAXES, was conducted to compare the outcomes of PCI and CABG at 10 years, it also permitted an extended analysis of OMT. Although the primary comparison of SYNTAXES, reported 2 years ago, did not show a significant difference between PCI and CABG for mortality at 10 years, there was a difference for OMT.

When investigators compared treatment with three or more OMT agents with that with two or fewer OMT drugs at 5 years, the result for all-cause death at 10 years translated into a more than 50% relative reduction (hazard ratio, 0.47; P = .002). The absolute difference in mortality was a more than 6% reduction (13.1% vs. 19.9%).
 

OMT data offer major message

The current study is considered to have a major message for patients as well as physicians.

“OMT even outweighs the survival benefit from revascularization alone, so our patients should convince themselves of the value of rigorous adherence and compliance,” Dr. Serruys said in an interview. According to him, these are compelling data for telling patients that OMT “is the best insurance for extended survival.” We now know from these data “the longer, the better.”

The same message from these data extends to physicians.

“I wish I could understand the apparent blind spot physicians have with respect to prescribing OMT despite the overwhelming benefit from multiple clinical trials,” said William E. Boden, MD, professor of medicine, Boston University.

Dr. Boden was a coauthor of an editorial accompanying the newly published SYNTAXES subanalysis. In the editorial, he noted that OMT following revascularization and in other high-risk patients “has been unacceptably low,” but he was asked to expand on the lessons from the newly released SYNTAXES subanalysis in an interview.

“There has often been a belief that revascularization negates the need for OMT and that’s why the SYNTAXES trial 10-year mortality reduction – which builds upon an earlier 5-year mortality reduction analysis – is so important,” he said.
 

Patients should take OMT long term

These data “should be both a motivator for physicians to prescribe OMT and for patients to remain adherent to OMT,” he said. “It is the best warranty to blunt the progression of atherosclerosis and to reduce subsequent cardiac events.”

For the 10-year subanalysis of OMT in SYNTAXES, the patients were stratified by the number of OMTs they were taking at 5 years after revascularization and then evaluated for survival at 10 years. Of the 1,472 patients available for analysis at 5 years, only 678 (46%) were on OMT. The other 794 patients were not.

Graphically, the Kaplan-Meier survival curve for those on three types of OMT was consistently beneath that of those on four OMTs, but the gap narrowed over time. At the end of 10 years, the advantage of the four-drug OMT was not statistically significant relative to three or fewer (13.1% vs. 12.7%).
 

Statins and antiplatelets show largest effect

When analyzed individually and in different combinations, the agents with OMT did not appear to be equal. For example, the biggest survival gap at 10 years was for those who were on an antiplatelet therapy and a statin at 5 years relative to those who were not on either (13.2% vs. 22.6%; P = .006). Even after adjustment, there was nearly 45% survival benefit for these two agents (HR, 0.556; P = .02).

Conversely, the 10-year survival advantage for being on a renin-angiotensin system inhibitor at 5 years versus not being exposed to this therapy was small and nonsignificant (14.7% vs. 13.7%; P = .651).

The precise proportion of patients who were prescribed and adhered to OMT between 5 years and 10 years is unknown, acknowledged the authors, so conclusions are limited about the added benefit of 10- versus 5-year OMT, although the authors presume that a substantial proportion of those adherent for 5 years would likely continue on these therapies.

It can be said with confidence that those adherent for at least 5 years are more likely to be alive at 10 years than those who are not, according to Dr. Boden. He considers these data a call for physicians and all high-risk patients, not just those who have undergone revascularization, to take these standard therapies.

There are plenty of data to “show how poorly we treat patients with OMT,” said Dr. Boden, citing several studies. In one, which looked at OMT in a nationally representative sample in the United States, only a third of patients with angina were taking an antiplatelet, a statin, and a beta-blocker, all of which are indicated.

“Hospitalization for revascularization provides an opportune time to capture the attention of patients and their physicians,” he wrote in his editorial. He called OMT “an imperative to optimize clinical outcomes.”

Many of the investigators involved in the SYNTAXES subanalysis, including Dr. Serruys, have financial relationships with multiple pharmaceutical companies, including Boston Scientific, which provided the initial funding for the SYNTAX trial. Dr. Boden reports no potential conflicts of interest.

A patient’s risk for ischemic events, but not bleeding, after percutaneous coronary intervention (PCI) can be predicted simply based on whether they have one or more guideline-based standardized risk criteria, a large-scale real-world analysis suggests.

Haoyu Wang, MD, and colleagues showed that having at least one high-risk feature, as outlined in the 2018 European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) Guidelines on Myocardial Revascularization, was associated with an increased risk for target vessel failure by 48% and for a patient-oriented composite outcome by 44%.

Moreover, they showed that implantation of at least three stents and the presence of diabetes and diffuse multivessel disease were the only high-risk features from the guidelines that were independent predictors of the two outcomes.

The study of more than 10,000 PCI patients also showed that determining whether patients were at high bleeding risk (HBR) did not modify their ischemic risk.

This, said Dr. Wang, from the National Center for Cardiovascular Diseases, Fuwai Hospital, Beijing, underscores the importance of applying the high ischemic risk (HIR) criteria from the ESC/EACTS guidelines when tailoring dual antiplatelet therapy (DAPT).

The research was presented at the European Atherosclerosis Society 2021 Virtual Congress on June 2, and published online in the Journal of Atherosclerosis and Thrombosis.

Dr. Wang told theheart.org | Medscape Cardiology that they conducted the study to determine which – HIR or HBR – is “most important to balance when treating patients undergoing PCI and then having dual antiplatelet therapy.”

The results showed that when patients have both a HIR and HBR, it is the ESC/EACTS guideline HIR criteria that have “a higher impact” than the bleeding risk, and that this can be “used to guide our choice of the duration of dual anti-platelet therapy.”

“Maybe we can extend, or use more potent, P2Y12 inhibitors” in those situations, he said.

S. Lale Tokgözoglu, MD, PhD, professor of cardiology, Hacettepe University, Ankara, Turkey, who was not involved in the study, said the HIR assessment “performed well,” adding that the HBR score might have been expected to attenuate its “prognostic advantage.”

She told this news organization that the results “are interesting since previous observations have suggested that Asian patients may be more prone to medication side effects and bleeding.”

These findings emphasize the importance of assessing HIR in daily PCI practice and confirm that it “performs well in different populations in real life,” added Dr. Tokgözoglu, a former president of the EAS.

The ESC/EACTS guidelines aimed to standardize the definition of HIR, Dr. Wang said during the presentation.

They set out 10 high-risk features for ischemic events for patients undergoing revascularization, which included patient medical history, comorbid conditions, and the characteristics of the PCI procedure.

Although the goals of the criteria are to inform decision-making and stimulate research, Dr. Wang said that their “prevalence and prognostic association with clinical outcomes are yet to be established in real-world PCI practice.”

Alongside, the Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score was developed to predict out-of-hospital bleeding in patients receiving DAPT after stent implantation.

Although a PRECISE-DAPT score of at least 25 constitutes a patient at high bleeding risk, Dr. Wang pointed out that such patients are typically also at risk for ischemic events after PCI, and it is “unclear” whether being at HBR modifies this risk.

To investigate further, they used the prospective, real-world Fuwai PCI registry to collate an all-comer patient population with unselected use of drug-eluting stents at the National Center for Cardiovascular Diseases at Fuwai Hospital.

They excluded individuals who were treated with balloon angioplasty alone, bioresorbable scaffolds, or bare metal stents, leaving a total population of 10,167 patients who were treated in 2013.

In that cohort, 5,149 patients (50.6%) met at least one risk criterion from the ESC/EACTS guidelines (HIR patients) and 5,018 (49.4%) met none of the risk criteria (non-HIR patients).

The most common criteria were implantation of at least three stents (23.5%); total stent length greater than 60 mm (20.2%); diffuse multivessel disease, especially in diabetic patients (18.5%); and a history of ST-segment elevation myocardial infarction (13.9%).

HIR patients were significantly older than non-HIR patients (average age, 58.86 vs. 57.77 years; P < .001), were more likely to have diabetes mellitus (42.6% vs. 16.9%; P < .001); and were more likely to have already had a myocardial infarction (32.2% vs. 5.2%; P < .001).

HIR patients also had higher average PRECISE-ADAPT scores than those without HIR (11.22 vs. 9.94; P < .001), and were conversely less likely to have the left anterior descending artery as the target vessel than non-HIR patients (86.0% vs. 94.6%; P < .001).

Cox regression analysis taking into account a range of patient and clinical factors revealed that HIR patients were significantly more likely than their non-HIR counterparts to experience target vessel failure (hazard ratio, 1.48; 95% confidence interval, 1.25-1.74; P < .001).

They were also significantly more likely to have a patient-oriented composite outcome, defined as all-cause death, any myocardial infarction, or any revascularization (HR, 1.44; 95% CI, 1.28-1.63; P < .001).

There was also a significantly higher risk for cardiac death in HIR than in non-HIR patients (HR, 1.95; 95% CI, 1.16-3.29; P = .012).

However, there was no significant association between HIR status and clinically relevant bleeding (HR, 0.84; 95% CI, 0.66-1.06; P = .143).

When the researchers looked at individual ischemic risk features, they found that, on fully adjusted analyses, only two were independent predictors of target vessel failure and the patient-oriented composite outcome.

Having at least three stents implanted was significantly associated with target vessel failure (HR, 1.36; 95% CI, 1.02-1.80; P = .038), and borderline significantly associated with the patient oriented composite outcome (HR, 1.23; 95% CI, 1.00-1.53; P = .056).

Diffuse multivessel disease, especially in diabetic patients, was significantly associated with both target vessel failure (HR, 1.24; 95% CI, 1.02-1.51; P = .035) and with the patient-oriented composite outcome (HR, 1.20; 95% CI, 1.04-1.39; P = .012).

Neither risk feature was significantly associated with clinically relevant bleeding, Dr. Wang noted.

Stratifying the patients by HBR status, the team found that rates of target vessel failure, the patient-oriented composite outcome, cardiac death, myocardial infarction, and definite/probable stent thrombosis were higher in patients with both HIR and HBR than those with neither HIR nor HBR (P < .001).

Further stratifying patients by PRECISE-ADAPT scores – 10 or less indicating very low risk, 11-17 indicating low risk, 18-24 indicating moderate risk, and at least 25 indicating high risk – showed that HIR features had a consistent effect on ischemic and bleeding outcomes, regardless of bleeding risk.

No funding declared. No relevant financial relationships declared.

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

A patient’s risk for ischemic events, but not bleeding, after percutaneous coronary intervention (PCI) can be predicted simply based on whether they have one or more guideline-based standardized risk criteria, a large-scale real-world analysis suggests.

Haoyu Wang, MD, and colleagues showed that having at least one high-risk feature, as outlined in the 2018 European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) Guidelines on Myocardial Revascularization, was associated with an increased risk for target vessel failure by 48% and for a patient-oriented composite outcome by 44%.

Moreover, they showed that implantation of at least three stents and the presence of diabetes and diffuse multivessel disease were the only high-risk features from the guidelines that were independent predictors of the two outcomes.

The study of more than 10,000 PCI patients also showed that determining whether patients were at high bleeding risk (HBR) did not modify their ischemic risk.

This, said Dr. Wang, from the National Center for Cardiovascular Diseases, Fuwai Hospital, Beijing, underscores the importance of applying the high ischemic risk (HIR) criteria from the ESC/EACTS guidelines when tailoring dual antiplatelet therapy (DAPT).

The research was presented at the European Atherosclerosis Society 2021 Virtual Congress on June 2, and published online in the Journal of Atherosclerosis and Thrombosis.

Dr. Wang told theheart.org | Medscape Cardiology that they conducted the study to determine which – HIR or HBR – is “most important to balance when treating patients undergoing PCI and then having dual antiplatelet therapy.”

The results showed that when patients have both a HIR and HBR, it is the ESC/EACTS guideline HIR criteria that have “a higher impact” than the bleeding risk, and that this can be “used to guide our choice of the duration of dual anti-platelet therapy.”

“Maybe we can extend, or use more potent, P2Y12 inhibitors” in those situations, he said.

S. Lale Tokgözoglu, MD, PhD, professor of cardiology, Hacettepe University, Ankara, Turkey, who was not involved in the study, said the HIR assessment “performed well,” adding that the HBR score might have been expected to attenuate its “prognostic advantage.”

She told this news organization that the results “are interesting since previous observations have suggested that Asian patients may be more prone to medication side effects and bleeding.”

These findings emphasize the importance of assessing HIR in daily PCI practice and confirm that it “performs well in different populations in real life,” added Dr. Tokgözoglu, a former president of the EAS.

The ESC/EACTS guidelines aimed to standardize the definition of HIR, Dr. Wang said during the presentation.

They set out 10 high-risk features for ischemic events for patients undergoing revascularization, which included patient medical history, comorbid conditions, and the characteristics of the PCI procedure.

Although the goals of the criteria are to inform decision-making and stimulate research, Dr. Wang said that their “prevalence and prognostic association with clinical outcomes are yet to be established in real-world PCI practice.”

Alongside, the Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score was developed to predict out-of-hospital bleeding in patients receiving DAPT after stent implantation.

Although a PRECISE-DAPT score of at least 25 constitutes a patient at high bleeding risk, Dr. Wang pointed out that such patients are typically also at risk for ischemic events after PCI, and it is “unclear” whether being at HBR modifies this risk.

To investigate further, they used the prospective, real-world Fuwai PCI registry to collate an all-comer patient population with unselected use of drug-eluting stents at the National Center for Cardiovascular Diseases at Fuwai Hospital.

They excluded individuals who were treated with balloon angioplasty alone, bioresorbable scaffolds, or bare metal stents, leaving a total population of 10,167 patients who were treated in 2013.

In that cohort, 5,149 patients (50.6%) met at least one risk criterion from the ESC/EACTS guidelines (HIR patients) and 5,018 (49.4%) met none of the risk criteria (non-HIR patients).

The most common criteria were implantation of at least three stents (23.5%); total stent length greater than 60 mm (20.2%); diffuse multivessel disease, especially in diabetic patients (18.5%); and a history of ST-segment elevation myocardial infarction (13.9%).

HIR patients were significantly older than non-HIR patients (average age, 58.86 vs. 57.77 years; P < .001), were more likely to have diabetes mellitus (42.6% vs. 16.9%; P < .001); and were more likely to have already had a myocardial infarction (32.2% vs. 5.2%; P < .001).

HIR patients also had higher average PRECISE-ADAPT scores than those without HIR (11.22 vs. 9.94; P < .001), and were conversely less likely to have the left anterior descending artery as the target vessel than non-HIR patients (86.0% vs. 94.6%; P < .001).

Cox regression analysis taking into account a range of patient and clinical factors revealed that HIR patients were significantly more likely than their non-HIR counterparts to experience target vessel failure (hazard ratio, 1.48; 95% confidence interval, 1.25-1.74; P < .001).

They were also significantly more likely to have a patient-oriented composite outcome, defined as all-cause death, any myocardial infarction, or any revascularization (HR, 1.44; 95% CI, 1.28-1.63; P < .001).

There was also a significantly higher risk for cardiac death in HIR than in non-HIR patients (HR, 1.95; 95% CI, 1.16-3.29; P = .012).

However, there was no significant association between HIR status and clinically relevant bleeding (HR, 0.84; 95% CI, 0.66-1.06; P = .143).

When the researchers looked at individual ischemic risk features, they found that, on fully adjusted analyses, only two were independent predictors of target vessel failure and the patient-oriented composite outcome.

Having at least three stents implanted was significantly associated with target vessel failure (HR, 1.36; 95% CI, 1.02-1.80; P = .038), and borderline significantly associated with the patient oriented composite outcome (HR, 1.23; 95% CI, 1.00-1.53; P = .056).

Diffuse multivessel disease, especially in diabetic patients, was significantly associated with both target vessel failure (HR, 1.24; 95% CI, 1.02-1.51; P = .035) and with the patient-oriented composite outcome (HR, 1.20; 95% CI, 1.04-1.39; P = .012).

Neither risk feature was significantly associated with clinically relevant bleeding, Dr. Wang noted.

Stratifying the patients by HBR status, the team found that rates of target vessel failure, the patient-oriented composite outcome, cardiac death, myocardial infarction, and definite/probable stent thrombosis were higher in patients with both HIR and HBR than those with neither HIR nor HBR (P < .001).

Further stratifying patients by PRECISE-ADAPT scores – 10 or less indicating very low risk, 11-17 indicating low risk, 18-24 indicating moderate risk, and at least 25 indicating high risk – showed that HIR features had a consistent effect on ischemic and bleeding outcomes, regardless of bleeding risk.

No funding declared. No relevant financial relationships declared.

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

A patient’s risk for ischemic events, but not bleeding, after percutaneous coronary intervention (PCI) can be predicted simply based on whether they have one or more guideline-based standardized risk criteria, a large-scale real-world analysis suggests.

Haoyu Wang, MD, and colleagues showed that having at least one high-risk feature, as outlined in the 2018 European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) Guidelines on Myocardial Revascularization, was associated with an increased risk for target vessel failure by 48% and for a patient-oriented composite outcome by 44%.

Moreover, they showed that implantation of at least three stents and the presence of diabetes and diffuse multivessel disease were the only high-risk features from the guidelines that were independent predictors of the two outcomes.

The study of more than 10,000 PCI patients also showed that determining whether patients were at high bleeding risk (HBR) did not modify their ischemic risk.

This, said Dr. Wang, from the National Center for Cardiovascular Diseases, Fuwai Hospital, Beijing, underscores the importance of applying the high ischemic risk (HIR) criteria from the ESC/EACTS guidelines when tailoring dual antiplatelet therapy (DAPT).

The research was presented at the European Atherosclerosis Society 2021 Virtual Congress on June 2, and published online in the Journal of Atherosclerosis and Thrombosis.

Dr. Wang told theheart.org | Medscape Cardiology that they conducted the study to determine which – HIR or HBR – is “most important to balance when treating patients undergoing PCI and then having dual antiplatelet therapy.”

The results showed that when patients have both a HIR and HBR, it is the ESC/EACTS guideline HIR criteria that have “a higher impact” than the bleeding risk, and that this can be “used to guide our choice of the duration of dual anti-platelet therapy.”

“Maybe we can extend, or use more potent, P2Y12 inhibitors” in those situations, he said.

S. Lale Tokgözoglu, MD, PhD, professor of cardiology, Hacettepe University, Ankara, Turkey, who was not involved in the study, said the HIR assessment “performed well,” adding that the HBR score might have been expected to attenuate its “prognostic advantage.”

She told this news organization that the results “are interesting since previous observations have suggested that Asian patients may be more prone to medication side effects and bleeding.”

These findings emphasize the importance of assessing HIR in daily PCI practice and confirm that it “performs well in different populations in real life,” added Dr. Tokgözoglu, a former president of the EAS.

The ESC/EACTS guidelines aimed to standardize the definition of HIR, Dr. Wang said during the presentation.

They set out 10 high-risk features for ischemic events for patients undergoing revascularization, which included patient medical history, comorbid conditions, and the characteristics of the PCI procedure.

Although the goals of the criteria are to inform decision-making and stimulate research, Dr. Wang said that their “prevalence and prognostic association with clinical outcomes are yet to be established in real-world PCI practice.”

Alongside, the Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score was developed to predict out-of-hospital bleeding in patients receiving DAPT after stent implantation.

Although a PRECISE-DAPT score of at least 25 constitutes a patient at high bleeding risk, Dr. Wang pointed out that such patients are typically also at risk for ischemic events after PCI, and it is “unclear” whether being at HBR modifies this risk.

To investigate further, they used the prospective, real-world Fuwai PCI registry to collate an all-comer patient population with unselected use of drug-eluting stents at the National Center for Cardiovascular Diseases at Fuwai Hospital.

They excluded individuals who were treated with balloon angioplasty alone, bioresorbable scaffolds, or bare metal stents, leaving a total population of 10,167 patients who were treated in 2013.

In that cohort, 5,149 patients (50.6%) met at least one risk criterion from the ESC/EACTS guidelines (HIR patients) and 5,018 (49.4%) met none of the risk criteria (non-HIR patients).

The most common criteria were implantation of at least three stents (23.5%); total stent length greater than 60 mm (20.2%); diffuse multivessel disease, especially in diabetic patients (18.5%); and a history of ST-segment elevation myocardial infarction (13.9%).

HIR patients were significantly older than non-HIR patients (average age, 58.86 vs. 57.77 years; P < .001), were more likely to have diabetes mellitus (42.6% vs. 16.9%; P < .001); and were more likely to have already had a myocardial infarction (32.2% vs. 5.2%; P < .001).

HIR patients also had higher average PRECISE-ADAPT scores than those without HIR (11.22 vs. 9.94; P < .001), and were conversely less likely to have the left anterior descending artery as the target vessel than non-HIR patients (86.0% vs. 94.6%; P < .001).

Cox regression analysis taking into account a range of patient and clinical factors revealed that HIR patients were significantly more likely than their non-HIR counterparts to experience target vessel failure (hazard ratio, 1.48; 95% confidence interval, 1.25-1.74; P < .001).

They were also significantly more likely to have a patient-oriented composite outcome, defined as all-cause death, any myocardial infarction, or any revascularization (HR, 1.44; 95% CI, 1.28-1.63; P < .001).

There was also a significantly higher risk for cardiac death in HIR than in non-HIR patients (HR, 1.95; 95% CI, 1.16-3.29; P = .012).

However, there was no significant association between HIR status and clinically relevant bleeding (HR, 0.84; 95% CI, 0.66-1.06; P = .143).

When the researchers looked at individual ischemic risk features, they found that, on fully adjusted analyses, only two were independent predictors of target vessel failure and the patient-oriented composite outcome.

Having at least three stents implanted was significantly associated with target vessel failure (HR, 1.36; 95% CI, 1.02-1.80; P = .038), and borderline significantly associated with the patient oriented composite outcome (HR, 1.23; 95% CI, 1.00-1.53; P = .056).

Diffuse multivessel disease, especially in diabetic patients, was significantly associated with both target vessel failure (HR, 1.24; 95% CI, 1.02-1.51; P = .035) and with the patient-oriented composite outcome (HR, 1.20; 95% CI, 1.04-1.39; P = .012).

Neither risk feature was significantly associated with clinically relevant bleeding, Dr. Wang noted.

Stratifying the patients by HBR status, the team found that rates of target vessel failure, the patient-oriented composite outcome, cardiac death, myocardial infarction, and definite/probable stent thrombosis were higher in patients with both HIR and HBR than those with neither HIR nor HBR (P < .001).

Further stratifying patients by PRECISE-ADAPT scores – 10 or less indicating very low risk, 11-17 indicating low risk, 18-24 indicating moderate risk, and at least 25 indicating high risk – showed that HIR features had a consistent effect on ischemic and bleeding outcomes, regardless of bleeding risk.

No funding declared. No relevant financial relationships declared.

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

A new clinical score has been developed, and externally validated, to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR).

“Despite the TAVR iterations, we recognize that bleeding remains a very important and perhaps also neglected issue. Indeed, no specifically developed standard algorithm existed before this to assess bleeding risk post-TAVR,” lead author Eliano Pio Navarese, MD, PhD, said in an interview.

Although bleeding rates can be as high as 9% at 30 days and between 3% and 11% in the first year, only a few studies have applied existing scores to TAVR patients, he noted.

The PREDICT-TAVR score includes six common variables and can be calculated by hand using a simple nomogram or a web-based calculator, with a dedicated website in the works, said Dr. Navarese, Nicolaus Copernicus University and SIRO MEDICINE Network, Bydgoszcz, Poland, and the University of Alberta, Edmonton.

A strength of the score is that machine-learning methods were used and the choice of variables optimized through recursive feature elimination and cross validation to remove the weakest variables, he said. Artificial intelligence, including use of random forest, naïve Bayes, and logistic regression classifiers, was also applied to the algorithms and the results cross-checked with standard multivariate analysis.

“It was a tremendous effort in terms of the analytics conducted,” Dr. Navarese said. “This is not a simple score but the integration of the most sophisticated machine learning methods and algorithms.”

Details are published in the June 14 issue of JACC: Cardiovascular Interventions.

The six variables used to calculate 30-day bleeding risk after TAVR and the points assigned to each are:

• blood hemoglobin (0-10 points)
• serum iron concentration (0-5 points)
• common femoral artery diameter (0-3 points)
•  (0-3 points)
• dual antiplatelet therapy (DAPT; 0-2 points)
• oral anticoagulation therapy (0-2 points)

The six items were selected among 104 baseline variables from 5,185 consecutive patients undergoing transfemoral TAVR in the prospective RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea) registry between March 2012 and December 2019, then validated in 5,043 patients in the prospective POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) between January 2013 and December 2019.

In the derivation cohort, 216 patients (4.2%) experienced bleeding events at 1 year, with 169 events (78%) occurring during the first 30 days.

PREDICT-TAVR exhibited high discriminatory power for bleeding events at 30 days, as reflected by an area under the curve (AUC) of 0.80 (95% confidence interval, 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was consistent at 0.79 (95% CI, 0.75-0.83).

PREDICT-TAVR also outperformed scores not developed for TAVR, such as the PARIS score for patients undergoing percutaneous coronary intervention (AUC, 0.69) and the well-validated HAS-BLED for patients receiving anticoagulation (AUC, 0.58; P < .001 for both).

In the validation cohort, the AUC for bleeding complications at 30 days was 0.78 (95% CI, 0.72-0.82) versus an AUC of 0.68 for PARIS and 0.66 for HAS-BLED.

A HAS-BLED score of 4 predicted a higher rate of severe bleeding and mortality in the year after transfemoral TAVR in the 2018 Japanese OCEAN-TAVI study.
 

Bleeding events by risk categories

Risk score quartiles identified as low risk were 8 points or less, as moderate risk were 8 to less than 10 points, as high risk were 10 to less than 12 points, and as very-high-risk score were above 12 points.

In the derivation cohort, 30-day bleeding events across quartiles were 0.8%, 1.1%, 2.5%, and 8.5%, respectively (overall P < .001).

Compared with the lowest quartile, bleeding risk was numerically higher for the second quartile (odds ratio, 1.75) and significantly higher in the third (OR, 2.0) and fourth (OR, 2.49) quartiles (P < .001 for both).

A landmark cumulative-event analysis showed a significantly greater risk of bleeding for the two highest quartiles up to 30 days; however, these differences were no longer significant from 30 days to 1 year, likely because of a limited number of events, the authors suggest. Similar results were seen in the validation cohort.

The number of patients in the high- and very-high-risk groups isn’t trivial, and bleeding rates reached as high as 12.6% in the highest quartile, Dr. Navarese observed. Guidelines recommend DAPT for 3 to 6 months after TAVR; however, emerging data, including a recent meta-analysis, suggest monotherapy may be a very good option.

“So, if you had a high bleeding risk and are considering postprocedural DAPT or anticoagulation, I would think twice rather than administering dual antiplatelet therapy or anticoagulation for a long time, or at least, I would consider the impact of this score on this choice,” he said.

Subgroup analyses showed AUCs ranging from 0.77 to 0.81 for subgroups such as age older than 80 years, diabetes, obesity, female sex, previous PCI, and New York Heart Association class III or IV.

Serum iron showed the highest AUC in the primary PREDICT-TAVR model; however, should iron levels be unavailable, a simplified score modeled without iron levels retained predictive power, yielding AUCs for 30-day bleeding of 0.78 in the derivation cohort and 0.75 in the validation cohort.

“PREDICT-TAVR score can impact clinical practice, not only selecting the optimal thrombotic regimen in certain high bleeding-risk populations but also to treat pre-TAVR anemia and iron deficiencies, which may affect outcomes,” Dr. Navarese said. “Of course, future prospective biological and clinical investigations are needed to elucidate the score and the role of the score’s treatable risk traits in reducing post-TAVR bleeding complications.”

Commenting for this news organization, Sunil Rao, MD, Duke University, Durham, N.C., said anemia is a covariant in many risk models for bleeding and vascular complications in PCI and acute coronary syndrome, but hemoglobin and iron levels are collinear.

“The problem I think is when you throw hemoglobin and iron in the same model, just by play of chance, one variable can knock out the other one,” he said. “So I don’t know necessarily if we need to start measuring iron on everyone. We certainly should be measuring hemoglobin, which I think most people will have, and if a patient has pre-existing anemia, that should be a red flag for us.”

Age and Society of Thoracic Surgeons (STS) risk score did not reach statistical significance in the model – likely reflecting the high-/extremely-high-risk patient population with an average STS score of 7.7 and average age of 82 years – but may become more important as TAVR is applied more widely, Dr. Rao and Zachary Wegermann, MD, Duke Clinical Research Institute, write in an accompanying editorial.

They also point out that the study was limited by a low rate of bleeding events, and, importantly, the score can’t distinguish between minor or major bleeding.

“It’s worth trying to repeat the analyses in lower-risk patients because we may find other covariates that are important,” Dr. Rao said in an interview. “The other thing we need to get to is probably being a little bit more sophisticated. The variables included in these models are the ones that are measured; they’re also the ones that are clinically apparent.”

“But there’s a whole area of genomic medicine, proteomic medicine, metabolomic medicine that, as it starts developing and becomes more and more sophisticated, my suspicion is that we’re going to get even more precise and accurate about patients’ risk, and it’s going to become more individualized, rather than just measuring variables like age and lab values,” he said.

In the meantime, having variables documented in the electronic health record, with hard stops deployed if variables aren’t measured, is “a step in the right direction,” he added.

Dr. Navarese has received research grants from Abbott, Amgen, and Medtronic and received lecture fees and honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. Dr. Rao and Dr. Wegermann report no relevant financial disclosures.

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

A new clinical score has been developed, and externally validated, to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR).

“Despite the TAVR iterations, we recognize that bleeding remains a very important and perhaps also neglected issue. Indeed, no specifically developed standard algorithm existed before this to assess bleeding risk post-TAVR,” lead author Eliano Pio Navarese, MD, PhD, said in an interview.

Although bleeding rates can be as high as 9% at 30 days and between 3% and 11% in the first year, only a few studies have applied existing scores to TAVR patients, he noted.

The PREDICT-TAVR score includes six common variables and can be calculated by hand using a simple nomogram or a web-based calculator, with a dedicated website in the works, said Dr. Navarese, Nicolaus Copernicus University and SIRO MEDICINE Network, Bydgoszcz, Poland, and the University of Alberta, Edmonton.

A strength of the score is that machine-learning methods were used and the choice of variables optimized through recursive feature elimination and cross validation to remove the weakest variables, he said. Artificial intelligence, including use of random forest, naïve Bayes, and logistic regression classifiers, was also applied to the algorithms and the results cross-checked with standard multivariate analysis.

“It was a tremendous effort in terms of the analytics conducted,” Dr. Navarese said. “This is not a simple score but the integration of the most sophisticated machine learning methods and algorithms.”

Details are published in the June 14 issue of JACC: Cardiovascular Interventions.

The six variables used to calculate 30-day bleeding risk after TAVR and the points assigned to each are:

• blood hemoglobin (0-10 points)
• serum iron concentration (0-5 points)
• common femoral artery diameter (0-3 points)
•  (0-3 points)
• dual antiplatelet therapy (DAPT; 0-2 points)
• oral anticoagulation therapy (0-2 points)

The six items were selected among 104 baseline variables from 5,185 consecutive patients undergoing transfemoral TAVR in the prospective RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea) registry between March 2012 and December 2019, then validated in 5,043 patients in the prospective POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) between January 2013 and December 2019.

In the derivation cohort, 216 patients (4.2%) experienced bleeding events at 1 year, with 169 events (78%) occurring during the first 30 days.

PREDICT-TAVR exhibited high discriminatory power for bleeding events at 30 days, as reflected by an area under the curve (AUC) of 0.80 (95% confidence interval, 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was consistent at 0.79 (95% CI, 0.75-0.83).

PREDICT-TAVR also outperformed scores not developed for TAVR, such as the PARIS score for patients undergoing percutaneous coronary intervention (AUC, 0.69) and the well-validated HAS-BLED for patients receiving anticoagulation (AUC, 0.58; P < .001 for both).

In the validation cohort, the AUC for bleeding complications at 30 days was 0.78 (95% CI, 0.72-0.82) versus an AUC of 0.68 for PARIS and 0.66 for HAS-BLED.

A HAS-BLED score of 4 predicted a higher rate of severe bleeding and mortality in the year after transfemoral TAVR in the 2018 Japanese OCEAN-TAVI study.
 

Bleeding events by risk categories

Risk score quartiles identified as low risk were 8 points or less, as moderate risk were 8 to less than 10 points, as high risk were 10 to less than 12 points, and as very-high-risk score were above 12 points.

In the derivation cohort, 30-day bleeding events across quartiles were 0.8%, 1.1%, 2.5%, and 8.5%, respectively (overall P < .001).

Compared with the lowest quartile, bleeding risk was numerically higher for the second quartile (odds ratio, 1.75) and significantly higher in the third (OR, 2.0) and fourth (OR, 2.49) quartiles (P < .001 for both).

A landmark cumulative-event analysis showed a significantly greater risk of bleeding for the two highest quartiles up to 30 days; however, these differences were no longer significant from 30 days to 1 year, likely because of a limited number of events, the authors suggest. Similar results were seen in the validation cohort.

The number of patients in the high- and very-high-risk groups isn’t trivial, and bleeding rates reached as high as 12.6% in the highest quartile, Dr. Navarese observed. Guidelines recommend DAPT for 3 to 6 months after TAVR; however, emerging data, including a recent meta-analysis, suggest monotherapy may be a very good option.

“So, if you had a high bleeding risk and are considering postprocedural DAPT or anticoagulation, I would think twice rather than administering dual antiplatelet therapy or anticoagulation for a long time, or at least, I would consider the impact of this score on this choice,” he said.

Subgroup analyses showed AUCs ranging from 0.77 to 0.81 for subgroups such as age older than 80 years, diabetes, obesity, female sex, previous PCI, and New York Heart Association class III or IV.

Serum iron showed the highest AUC in the primary PREDICT-TAVR model; however, should iron levels be unavailable, a simplified score modeled without iron levels retained predictive power, yielding AUCs for 30-day bleeding of 0.78 in the derivation cohort and 0.75 in the validation cohort.

“PREDICT-TAVR score can impact clinical practice, not only selecting the optimal thrombotic regimen in certain high bleeding-risk populations but also to treat pre-TAVR anemia and iron deficiencies, which may affect outcomes,” Dr. Navarese said. “Of course, future prospective biological and clinical investigations are needed to elucidate the score and the role of the score’s treatable risk traits in reducing post-TAVR bleeding complications.”

Commenting for this news organization, Sunil Rao, MD, Duke University, Durham, N.C., said anemia is a covariant in many risk models for bleeding and vascular complications in PCI and acute coronary syndrome, but hemoglobin and iron levels are collinear.

“The problem I think is when you throw hemoglobin and iron in the same model, just by play of chance, one variable can knock out the other one,” he said. “So I don’t know necessarily if we need to start measuring iron on everyone. We certainly should be measuring hemoglobin, which I think most people will have, and if a patient has pre-existing anemia, that should be a red flag for us.”

Age and Society of Thoracic Surgeons (STS) risk score did not reach statistical significance in the model – likely reflecting the high-/extremely-high-risk patient population with an average STS score of 7.7 and average age of 82 years – but may become more important as TAVR is applied more widely, Dr. Rao and Zachary Wegermann, MD, Duke Clinical Research Institute, write in an accompanying editorial.

They also point out that the study was limited by a low rate of bleeding events, and, importantly, the score can’t distinguish between minor or major bleeding.

“It’s worth trying to repeat the analyses in lower-risk patients because we may find other covariates that are important,” Dr. Rao said in an interview. “The other thing we need to get to is probably being a little bit more sophisticated. The variables included in these models are the ones that are measured; they’re also the ones that are clinically apparent.”

“But there’s a whole area of genomic medicine, proteomic medicine, metabolomic medicine that, as it starts developing and becomes more and more sophisticated, my suspicion is that we’re going to get even more precise and accurate about patients’ risk, and it’s going to become more individualized, rather than just measuring variables like age and lab values,” he said.

In the meantime, having variables documented in the electronic health record, with hard stops deployed if variables aren’t measured, is “a step in the right direction,” he added.

Dr. Navarese has received research grants from Abbott, Amgen, and Medtronic and received lecture fees and honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. Dr. Rao and Dr. Wegermann report no relevant financial disclosures.

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

A new clinical score has been developed, and externally validated, to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR).

“Despite the TAVR iterations, we recognize that bleeding remains a very important and perhaps also neglected issue. Indeed, no specifically developed standard algorithm existed before this to assess bleeding risk post-TAVR,” lead author Eliano Pio Navarese, MD, PhD, said in an interview.

Although bleeding rates can be as high as 9% at 30 days and between 3% and 11% in the first year, only a few studies have applied existing scores to TAVR patients, he noted.

The PREDICT-TAVR score includes six common variables and can be calculated by hand using a simple nomogram or a web-based calculator, with a dedicated website in the works, said Dr. Navarese, Nicolaus Copernicus University and SIRO MEDICINE Network, Bydgoszcz, Poland, and the University of Alberta, Edmonton.

A strength of the score is that machine-learning methods were used and the choice of variables optimized through recursive feature elimination and cross validation to remove the weakest variables, he said. Artificial intelligence, including use of random forest, naïve Bayes, and logistic regression classifiers, was also applied to the algorithms and the results cross-checked with standard multivariate analysis.

“It was a tremendous effort in terms of the analytics conducted,” Dr. Navarese said. “This is not a simple score but the integration of the most sophisticated machine learning methods and algorithms.”

Details are published in the June 14 issue of JACC: Cardiovascular Interventions.

The six variables used to calculate 30-day bleeding risk after TAVR and the points assigned to each are:

• blood hemoglobin (0-10 points)
• serum iron concentration (0-5 points)
• common femoral artery diameter (0-3 points)
•  (0-3 points)
• dual antiplatelet therapy (DAPT; 0-2 points)
• oral anticoagulation therapy (0-2 points)

The six items were selected among 104 baseline variables from 5,185 consecutive patients undergoing transfemoral TAVR in the prospective RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea) registry between March 2012 and December 2019, then validated in 5,043 patients in the prospective POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) between January 2013 and December 2019.

In the derivation cohort, 216 patients (4.2%) experienced bleeding events at 1 year, with 169 events (78%) occurring during the first 30 days.

PREDICT-TAVR exhibited high discriminatory power for bleeding events at 30 days, as reflected by an area under the curve (AUC) of 0.80 (95% confidence interval, 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was consistent at 0.79 (95% CI, 0.75-0.83).

PREDICT-TAVR also outperformed scores not developed for TAVR, such as the PARIS score for patients undergoing percutaneous coronary intervention (AUC, 0.69) and the well-validated HAS-BLED for patients receiving anticoagulation (AUC, 0.58; P < .001 for both).

In the validation cohort, the AUC for bleeding complications at 30 days was 0.78 (95% CI, 0.72-0.82) versus an AUC of 0.68 for PARIS and 0.66 for HAS-BLED.

A HAS-BLED score of 4 predicted a higher rate of severe bleeding and mortality in the year after transfemoral TAVR in the 2018 Japanese OCEAN-TAVI study.
 

Bleeding events by risk categories

Risk score quartiles identified as low risk were 8 points or less, as moderate risk were 8 to less than 10 points, as high risk were 10 to less than 12 points, and as very-high-risk score were above 12 points.

In the derivation cohort, 30-day bleeding events across quartiles were 0.8%, 1.1%, 2.5%, and 8.5%, respectively (overall P < .001).

Compared with the lowest quartile, bleeding risk was numerically higher for the second quartile (odds ratio, 1.75) and significantly higher in the third (OR, 2.0) and fourth (OR, 2.49) quartiles (P < .001 for both).

A landmark cumulative-event analysis showed a significantly greater risk of bleeding for the two highest quartiles up to 30 days; however, these differences were no longer significant from 30 days to 1 year, likely because of a limited number of events, the authors suggest. Similar results were seen in the validation cohort.

The number of patients in the high- and very-high-risk groups isn’t trivial, and bleeding rates reached as high as 12.6% in the highest quartile, Dr. Navarese observed. Guidelines recommend DAPT for 3 to 6 months after TAVR; however, emerging data, including a recent meta-analysis, suggest monotherapy may be a very good option.

“So, if you had a high bleeding risk and are considering postprocedural DAPT or anticoagulation, I would think twice rather than administering dual antiplatelet therapy or anticoagulation for a long time, or at least, I would consider the impact of this score on this choice,” he said.

Subgroup analyses showed AUCs ranging from 0.77 to 0.81 for subgroups such as age older than 80 years, diabetes, obesity, female sex, previous PCI, and New York Heart Association class III or IV.

Serum iron showed the highest AUC in the primary PREDICT-TAVR model; however, should iron levels be unavailable, a simplified score modeled without iron levels retained predictive power, yielding AUCs for 30-day bleeding of 0.78 in the derivation cohort and 0.75 in the validation cohort.

“PREDICT-TAVR score can impact clinical practice, not only selecting the optimal thrombotic regimen in certain high bleeding-risk populations but also to treat pre-TAVR anemia and iron deficiencies, which may affect outcomes,” Dr. Navarese said. “Of course, future prospective biological and clinical investigations are needed to elucidate the score and the role of the score’s treatable risk traits in reducing post-TAVR bleeding complications.”

Commenting for this news organization, Sunil Rao, MD, Duke University, Durham, N.C., said anemia is a covariant in many risk models for bleeding and vascular complications in PCI and acute coronary syndrome, but hemoglobin and iron levels are collinear.

“The problem I think is when you throw hemoglobin and iron in the same model, just by play of chance, one variable can knock out the other one,” he said. “So I don’t know necessarily if we need to start measuring iron on everyone. We certainly should be measuring hemoglobin, which I think most people will have, and if a patient has pre-existing anemia, that should be a red flag for us.”

Age and Society of Thoracic Surgeons (STS) risk score did not reach statistical significance in the model – likely reflecting the high-/extremely-high-risk patient population with an average STS score of 7.7 and average age of 82 years – but may become more important as TAVR is applied more widely, Dr. Rao and Zachary Wegermann, MD, Duke Clinical Research Institute, write in an accompanying editorial.

They also point out that the study was limited by a low rate of bleeding events, and, importantly, the score can’t distinguish between minor or major bleeding.

“It’s worth trying to repeat the analyses in lower-risk patients because we may find other covariates that are important,” Dr. Rao said in an interview. “The other thing we need to get to is probably being a little bit more sophisticated. The variables included in these models are the ones that are measured; they’re also the ones that are clinically apparent.”

“But there’s a whole area of genomic medicine, proteomic medicine, metabolomic medicine that, as it starts developing and becomes more and more sophisticated, my suspicion is that we’re going to get even more precise and accurate about patients’ risk, and it’s going to become more individualized, rather than just measuring variables like age and lab values,” he said.

In the meantime, having variables documented in the electronic health record, with hard stops deployed if variables aren’t measured, is “a step in the right direction,” he added.

Dr. Navarese has received research grants from Abbott, Amgen, and Medtronic and received lecture fees and honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. Dr. Rao and Dr. Wegermann report no relevant financial disclosures.

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

Further evidence that powerful magnets in some Apple iPhones can interfere with cardiac implantable electronic devices (CIEDs) comes from a small study that also suggests some devices are more susceptible than others.

The iPhone 12 Pro Max with MagSafe technology interfered with CIEDs implanted in three consecutive patients presenting to an electrophysiology lab and in 8 of 11 implantable cardioverter defibrillators (ICDs) and pacemakers (72.7%) still in their original packaging.

The results, published in the Journal of the American Heart Association, are consistent with a widely publicized single-patient report this February and evidence of electromagnetic interference with fitness wristbands and e-cigarettes.

The MagSafe technology supports wireless charging and is optimized by a ring-shaped array of magnets. Although magnet mode activation has been shown to occur in CIEDs with exposure to a magnetic field as low as 10 gauss, the field strength of the iPhone 12 Pro Max can be greater than 50 G when in direct contact, the researchers determined.

“If this becomes a standard in a lot of the new smartphones or companies start to use stronger magnets ... then we will see more and more of these consumer electronic and device interactions,” senior author Michael Wu, MD, Brown University, Providence, R.I., told this news organization.

In a May advisory on these device interactions, the U.S. Food and Drug Administration also cautioned that the number of consumer electronics with strong magnets is expected to increase over time.

That trend appears to be already underway, with Forbes reporting in February that the MagSafe batteries will be “getting stronger” as part of upgrades to the iPhone 13 and Bloomberg reporting in advance of Apple’s annual developers conference this week that an upgraded version of MagSafe is in the works to support wireless charging for its iPad. MagSafe has not been used previously in iPads.

Although Apple has acknowledged that the iPhone 12 contains more magnets than previous iPhone models, it says “they’re not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” The company maintains a page that specifically warns about the potential for interactions and advises that consumers keep the iPhone and MagSafe accessories more than 15 cm (6 inches) away from medical devices.

Older-generation iPhones have not shown this risk, with only one case of interference reported with the iPhone 6 and an Apple Watch in 1,352 tests among 148 patients with CIEDs and leads from four different manufacturers.

In the present study, magnet reversion mode was triggered in all three patients when the iPhone 12 Pro Max was placed on the skin over the device.

The phone inhibited tachycardia therapies in Medtronic’s Amplia MRI Quad CRT-D and Abbott’s 1231-40 Fortify VR device.

The Boston Scientific V273 Intua CRT-P device, however, “appeared to be less susceptible, as we were only able to elicit transient temporary asynchronous pacing but no sustained response by the iPhone 12 Pro Max magnet,” Dr. Wu and colleagues note.

Among the 11 ex vivo CIEDs tested, placing the iPhone 12 Pro Max directly over the packaged device inhibited tachytherapies in Medtronic’s Visia AF MRI ICD and Abbott’s Fortify Assura DR ICD and Ellipse DR ICD.

The phone also led to asynchronous pacing in Medtronic’s Azure, Advisa MRI, and Adapta pacemakers and in Abbott’s Assurity MRI pacemaker.

Boston Scientific devices again “appeared to be less susceptible, as no clear magnet interference” was noted in the Dynagen ICD, Emblem MRI S-ICD, or Accolade MRI pacemaker, Dr. Wu reported. There was temporary asynchronous pacing but no sustained response in the company’s U125 Valitude pacemaker.

Using the Medtronic Visia AF MRI ICD, the researchers found that the iPhone 12 Pro Max was able to trigger magnet reversion mode at a distance up to 1.5 cm (0.6 inch) from the anterior aspect of the device ex vivo.

The difference in magnet response to the iPhone 12 Pro Max among the different devices is likely due to different hall-sensor magnet sensitivity, as all of the devices were susceptible to a standard donut magnet, Dr. Wu noted. Boston Scientific’s Accolade MRI pacemaker, for example, requires a magnet stronger than 70 G to activate magnet mode, according to the product manual.

“Even so, sometimes with our test, we were able to trigger a brief response,” he said. “The response isn’t as lasting as some of the other companies, but with the small sample size, I can only speculate and suggest that maybe it’s possible. But we always want a formal study through the company or other agencies to really pinpoint which company has more susceptible devices.”

As to whether manufacturers should build CIEDs less susceptible to today’s stronger magnets, Dr. Wu said it’s worth exploring, but there are pros and cons.

Although magnets in consumer devices have the potential to inhibit lifesaving therapies, a magnet is also very useful in certain medical settings, such as a quick way to ensure pacing without worrying about electrocautery noise during surgery or to deactivate a defibrillator if there’s noise resulting in inappropriate shocks.

“It would require an overhaul of a lot of the devices going forward, and I think that’s something that’s worth exploring, especially now that a lot of devices are using wireless communication, Bluetooth, and other communication technology,” he said.

Even though the study is small, Dr. Wu said, it does represent many of the available devices and has clinical implications, given that people often put their smartphones in a breast pocket.

“This report highlights the importance of public awareness regarding an interaction between CIEDs and a recently released smartphone model with magnetic charging capability,” Dr. Wu and colleagues conclude.

Apple was contacted for comment but had not responded at press time.

The authors reported no study funding or relevant conflicts of interests.

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

Further evidence that powerful magnets in some Apple iPhones can interfere with cardiac implantable electronic devices (CIEDs) comes from a small study that also suggests some devices are more susceptible than others.

The iPhone 12 Pro Max with MagSafe technology interfered with CIEDs implanted in three consecutive patients presenting to an electrophysiology lab and in 8 of 11 implantable cardioverter defibrillators (ICDs) and pacemakers (72.7%) still in their original packaging.

The results, published in the Journal of the American Heart Association, are consistent with a widely publicized single-patient report this February and evidence of electromagnetic interference with fitness wristbands and e-cigarettes.

The MagSafe technology supports wireless charging and is optimized by a ring-shaped array of magnets. Although magnet mode activation has been shown to occur in CIEDs with exposure to a magnetic field as low as 10 gauss, the field strength of the iPhone 12 Pro Max can be greater than 50 G when in direct contact, the researchers determined.

“If this becomes a standard in a lot of the new smartphones or companies start to use stronger magnets ... then we will see more and more of these consumer electronic and device interactions,” senior author Michael Wu, MD, Brown University, Providence, R.I., told this news organization.

In a May advisory on these device interactions, the U.S. Food and Drug Administration also cautioned that the number of consumer electronics with strong magnets is expected to increase over time.

That trend appears to be already underway, with Forbes reporting in February that the MagSafe batteries will be “getting stronger” as part of upgrades to the iPhone 13 and Bloomberg reporting in advance of Apple’s annual developers conference this week that an upgraded version of MagSafe is in the works to support wireless charging for its iPad. MagSafe has not been used previously in iPads.

Although Apple has acknowledged that the iPhone 12 contains more magnets than previous iPhone models, it says “they’re not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” The company maintains a page that specifically warns about the potential for interactions and advises that consumers keep the iPhone and MagSafe accessories more than 15 cm (6 inches) away from medical devices.

Older-generation iPhones have not shown this risk, with only one case of interference reported with the iPhone 6 and an Apple Watch in 1,352 tests among 148 patients with CIEDs and leads from four different manufacturers.

In the present study, magnet reversion mode was triggered in all three patients when the iPhone 12 Pro Max was placed on the skin over the device.

The phone inhibited tachycardia therapies in Medtronic’s Amplia MRI Quad CRT-D and Abbott’s 1231-40 Fortify VR device.

The Boston Scientific V273 Intua CRT-P device, however, “appeared to be less susceptible, as we were only able to elicit transient temporary asynchronous pacing but no sustained response by the iPhone 12 Pro Max magnet,” Dr. Wu and colleagues note.

Among the 11 ex vivo CIEDs tested, placing the iPhone 12 Pro Max directly over the packaged device inhibited tachytherapies in Medtronic’s Visia AF MRI ICD and Abbott’s Fortify Assura DR ICD and Ellipse DR ICD.

The phone also led to asynchronous pacing in Medtronic’s Azure, Advisa MRI, and Adapta pacemakers and in Abbott’s Assurity MRI pacemaker.

Boston Scientific devices again “appeared to be less susceptible, as no clear magnet interference” was noted in the Dynagen ICD, Emblem MRI S-ICD, or Accolade MRI pacemaker, Dr. Wu reported. There was temporary asynchronous pacing but no sustained response in the company’s U125 Valitude pacemaker.

Using the Medtronic Visia AF MRI ICD, the researchers found that the iPhone 12 Pro Max was able to trigger magnet reversion mode at a distance up to 1.5 cm (0.6 inch) from the anterior aspect of the device ex vivo.

The difference in magnet response to the iPhone 12 Pro Max among the different devices is likely due to different hall-sensor magnet sensitivity, as all of the devices were susceptible to a standard donut magnet, Dr. Wu noted. Boston Scientific’s Accolade MRI pacemaker, for example, requires a magnet stronger than 70 G to activate magnet mode, according to the product manual.

“Even so, sometimes with our test, we were able to trigger a brief response,” he said. “The response isn’t as lasting as some of the other companies, but with the small sample size, I can only speculate and suggest that maybe it’s possible. But we always want a formal study through the company or other agencies to really pinpoint which company has more susceptible devices.”

As to whether manufacturers should build CIEDs less susceptible to today’s stronger magnets, Dr. Wu said it’s worth exploring, but there are pros and cons.

Although magnets in consumer devices have the potential to inhibit lifesaving therapies, a magnet is also very useful in certain medical settings, such as a quick way to ensure pacing without worrying about electrocautery noise during surgery or to deactivate a defibrillator if there’s noise resulting in inappropriate shocks.

“It would require an overhaul of a lot of the devices going forward, and I think that’s something that’s worth exploring, especially now that a lot of devices are using wireless communication, Bluetooth, and other communication technology,” he said.

Even though the study is small, Dr. Wu said, it does represent many of the available devices and has clinical implications, given that people often put their smartphones in a breast pocket.

“This report highlights the importance of public awareness regarding an interaction between CIEDs and a recently released smartphone model with magnetic charging capability,” Dr. Wu and colleagues conclude.

Apple was contacted for comment but had not responded at press time.

The authors reported no study funding or relevant conflicts of interests.

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

Further evidence that powerful magnets in some Apple iPhones can interfere with cardiac implantable electronic devices (CIEDs) comes from a small study that also suggests some devices are more susceptible than others.

The iPhone 12 Pro Max with MagSafe technology interfered with CIEDs implanted in three consecutive patients presenting to an electrophysiology lab and in 8 of 11 implantable cardioverter defibrillators (ICDs) and pacemakers (72.7%) still in their original packaging.

The results, published in the Journal of the American Heart Association, are consistent with a widely publicized single-patient report this February and evidence of electromagnetic interference with fitness wristbands and e-cigarettes.

The MagSafe technology supports wireless charging and is optimized by a ring-shaped array of magnets. Although magnet mode activation has been shown to occur in CIEDs with exposure to a magnetic field as low as 10 gauss, the field strength of the iPhone 12 Pro Max can be greater than 50 G when in direct contact, the researchers determined.

“If this becomes a standard in a lot of the new smartphones or companies start to use stronger magnets ... then we will see more and more of these consumer electronic and device interactions,” senior author Michael Wu, MD, Brown University, Providence, R.I., told this news organization.

In a May advisory on these device interactions, the U.S. Food and Drug Administration also cautioned that the number of consumer electronics with strong magnets is expected to increase over time.

That trend appears to be already underway, with Forbes reporting in February that the MagSafe batteries will be “getting stronger” as part of upgrades to the iPhone 13 and Bloomberg reporting in advance of Apple’s annual developers conference this week that an upgraded version of MagSafe is in the works to support wireless charging for its iPad. MagSafe has not been used previously in iPads.

Although Apple has acknowledged that the iPhone 12 contains more magnets than previous iPhone models, it says “they’re not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” The company maintains a page that specifically warns about the potential for interactions and advises that consumers keep the iPhone and MagSafe accessories more than 15 cm (6 inches) away from medical devices.

Older-generation iPhones have not shown this risk, with only one case of interference reported with the iPhone 6 and an Apple Watch in 1,352 tests among 148 patients with CIEDs and leads from four different manufacturers.

In the present study, magnet reversion mode was triggered in all three patients when the iPhone 12 Pro Max was placed on the skin over the device.

The phone inhibited tachycardia therapies in Medtronic’s Amplia MRI Quad CRT-D and Abbott’s 1231-40 Fortify VR device.

The Boston Scientific V273 Intua CRT-P device, however, “appeared to be less susceptible, as we were only able to elicit transient temporary asynchronous pacing but no sustained response by the iPhone 12 Pro Max magnet,” Dr. Wu and colleagues note.

Among the 11 ex vivo CIEDs tested, placing the iPhone 12 Pro Max directly over the packaged device inhibited tachytherapies in Medtronic’s Visia AF MRI ICD and Abbott’s Fortify Assura DR ICD and Ellipse DR ICD.

The phone also led to asynchronous pacing in Medtronic’s Azure, Advisa MRI, and Adapta pacemakers and in Abbott’s Assurity MRI pacemaker.

Boston Scientific devices again “appeared to be less susceptible, as no clear magnet interference” was noted in the Dynagen ICD, Emblem MRI S-ICD, or Accolade MRI pacemaker, Dr. Wu reported. There was temporary asynchronous pacing but no sustained response in the company’s U125 Valitude pacemaker.

Using the Medtronic Visia AF MRI ICD, the researchers found that the iPhone 12 Pro Max was able to trigger magnet reversion mode at a distance up to 1.5 cm (0.6 inch) from the anterior aspect of the device ex vivo.

The difference in magnet response to the iPhone 12 Pro Max among the different devices is likely due to different hall-sensor magnet sensitivity, as all of the devices were susceptible to a standard donut magnet, Dr. Wu noted. Boston Scientific’s Accolade MRI pacemaker, for example, requires a magnet stronger than 70 G to activate magnet mode, according to the product manual.

“Even so, sometimes with our test, we were able to trigger a brief response,” he said. “The response isn’t as lasting as some of the other companies, but with the small sample size, I can only speculate and suggest that maybe it’s possible. But we always want a formal study through the company or other agencies to really pinpoint which company has more susceptible devices.”

As to whether manufacturers should build CIEDs less susceptible to today’s stronger magnets, Dr. Wu said it’s worth exploring, but there are pros and cons.

Although magnets in consumer devices have the potential to inhibit lifesaving therapies, a magnet is also very useful in certain medical settings, such as a quick way to ensure pacing without worrying about electrocautery noise during surgery or to deactivate a defibrillator if there’s noise resulting in inappropriate shocks.

“It would require an overhaul of a lot of the devices going forward, and I think that’s something that’s worth exploring, especially now that a lot of devices are using wireless communication, Bluetooth, and other communication technology,” he said.

Even though the study is small, Dr. Wu said, it does represent many of the available devices and has clinical implications, given that people often put their smartphones in a breast pocket.

“This report highlights the importance of public awareness regarding an interaction between CIEDs and a recently released smartphone model with magnetic charging capability,” Dr. Wu and colleagues conclude.

Apple was contacted for comment but had not responded at press time.

The authors reported no study funding or relevant conflicts of interests.

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

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.

Chalabala/iStock/Getty Images Plus

The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).

The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).

But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).

“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.

While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.

“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.

“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.

The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.

Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.

There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.

The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”

That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.

“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”

Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.

“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”

None of the authors or editorialists reported any conflicts of interest.

Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.

“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.

There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.

Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.

Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.

“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”

Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.

The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.

In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).

“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”

For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”

Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: [email protected].

Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.

Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.

Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.

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

Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.

“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.

There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.

Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.

Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.

“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”

Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.

The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.

In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).

“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”

For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”

Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: [email protected].

Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.

Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.

Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.

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

Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.

“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.

There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.

Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.

Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.

“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”

Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.

The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.

In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).

“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”

For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”

Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: [email protected].

Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.

Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.

Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.

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

Transcatheter mitral valve repair with the PASCAL device showed high rates of survival and freedom from heart failure rehospitalization at 2 years in the single-arm, safety and efficacy CLASP study.

The Heart Hospital Baylor Plano

The early reductions in mitral regurgitation (MR) were sustained with 97% of patients having MR grades of 2+ or less and 78% having MR grades of 1+ or less at 2 years.

There was also evidence of left ventricular (LV) reverse remodeling and significant improvements in functional status, Molly Szerlip, MD, Baylor Scott & White Health, Plano, Texas, reported as lead author. The results were published online May 18 in JACC: Cardiovascular Interventions.

“The PASCAL transcatheter valve repair system is a favorable option for treating patients with MR,” she said in a simultaneous virtual presentation at the 2021 Congress of European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021).

The PASCAL system is not approved in the United States, but Dr. Szerlip observed that the investigators are eagerly awaiting results from the ongoing, pivotal CLASP IID/IIF trial comparing the edge-to-edge repair system with another such device, MitraClip, in 1,275 patients with functional or degenerative MR. The primary completion date is set for December 2023.

Abbott’s MitraClip has been available in the United States since 2013 and in Europe since 2008; Edwards Lifesciences received a CE mark for the PASCAL system in 2019.

“The results of the CLASP study are remarkable and indicate an additional differentiated tool ready for clinical routine,” Georg Goliasch, MD, PhD, and Philipp Bartko, MD, both from the Medical University of Vienna, write in an accompanying editorial.

As both systems target similar lesions, there might be “significant overlap in this particular patient population,” Dr. Goliasch told this news organization. From a technical perspective, the separate leaflet grasping was initially one of the advantages of the PASCAL, but this has also been recently introduced for the MitraClip.

That said, the “PASCAL device may offer a leaflet repair with decreased mechanical leaflet traction – specifically appealing to treat ventricular secondary MR – because mechanical forces applied to leaflets remain low, and the [central] spacer augments the leaflet surface in a way that reduces restrictive diastolic opening,” he added. “However, this remains highly speculative.”

The CLASP study enrolled 124 patients (56% male) with symptomatic MR grade of at least 3+ who were receiving optimal medical therapy at 14 sites in five countries. Their mean age was 75 years, 69% had functional MR (FMR), 31% had degenerative MR (DMR), and 60% were NYHA functional class III to IVa.

The primary endpoints of procedural and clinical success and adverse events at 30 days and 1-year outcomes were published last year. Echocardiographic data were available for 36 patients at 2 years with follow-up ongoing.

Composite major adverse event rates were 8.1% at 30 days, 18.5% at 1 year, and 16.9% at 2 years, driven mostly by severe bleeding at 7.3%, 11.3%, and 7.3%, respectively, Dr. Szerlip said.

Kaplan-Meier estimates showed 80.3% survival at 2 years (72.3% FMR, 94.3% DMR) and 84.3% freedom from heart failure rehospitalization (77.5% FMR, 97.3% DMR). The annualized HF rehospitalization rate fell to 85% at 2 years.

These results, the authors noted, hinged on minimizing residual MR. In the FMR group, 100% and 95% of patients achieved MR of 2+ or less at 1 year and 2 years, respectively, compared with 95% and 99% treated with the MitraClip in the COAPT study.

In the DMR group, 100% of patients achieved MR of 2+ or less at both 1 and 2 years, which “compares favorably to 94% from the EXPAND study at 1 year” with the MitraClip NTR and XTR systems, they write.

In CLASP, the LV end-diastolic volume decreased by 11 mL at 30 days and continued to decrease at 1 year (25 mL) and 2 years (33 mL; P < .001).

LV end-diastolic diameter (LVEDD) fell by 2.7 mm at 30 days, 3.9 mm at 1 year, and by 2.7 mm at 2 years (P = .002). At 2 years, 93% of patients were in NYHA class I or II (P < .001).

“The authors of the trial observed significant LV reverse remodeling with a decrease in LVEDD. These findings are indeed of particular interest and warrant further investigation by future studies as this has not been shown to such an extent in previous E2E [edge-to-edge] repair studies,” Dr. Goliasch said in an interview.

He raised an eyebrow, however, at the cross-trial comparisons, adding, “We should be very careful to draw any hasty conclusions considering the high proportion of missing echocardiographic data. Nevertheless, all these aspects might make the design of future studies for direct comparisons between E2E devices in the various structural aspects of mitral valve disease attractive to tailor treatment and optimize patient care.”

Dr. Szerlip and colleagues cited several study limitations including the absence of a control arm that may have contributed to a Hawthorne effect; not all patients had reached 2-year follow-up at the time of the analysis; and adjudication of events and assessment of the 6-minute walk test and quality-of-life measures were limited to 1 year based on the protocol.

The study was sponsored by Edwards Lifesciences. Dr. Szerlip reported serving as a proctor/speaker for Edwards; a national principal investigator for EFS; a speaker for Boston Scientific, and serving on steering committees for Medtronic and Abbott. Dr. Goliasch and Dr. Bartko have disclosed no relevant financial relationships.

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

Transcatheter mitral valve repair with the PASCAL device showed high rates of survival and freedom from heart failure rehospitalization at 2 years in the single-arm, safety and efficacy CLASP study.

The Heart Hospital Baylor Plano

The early reductions in mitral regurgitation (MR) were sustained with 97% of patients having MR grades of 2+ or less and 78% having MR grades of 1+ or less at 2 years.

There was also evidence of left ventricular (LV) reverse remodeling and significant improvements in functional status, Molly Szerlip, MD, Baylor Scott & White Health, Plano, Texas, reported as lead author. The results were published online May 18 in JACC: Cardiovascular Interventions.

“The PASCAL transcatheter valve repair system is a favorable option for treating patients with MR,” she said in a simultaneous virtual presentation at the 2021 Congress of European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021).

The PASCAL system is not approved in the United States, but Dr. Szerlip observed that the investigators are eagerly awaiting results from the ongoing, pivotal CLASP IID/IIF trial comparing the edge-to-edge repair system with another such device, MitraClip, in 1,275 patients with functional or degenerative MR. The primary completion date is set for December 2023.

Abbott’s MitraClip has been available in the United States since 2013 and in Europe since 2008; Edwards Lifesciences received a CE mark for the PASCAL system in 2019.

“The results of the CLASP study are remarkable and indicate an additional differentiated tool ready for clinical routine,” Georg Goliasch, MD, PhD, and Philipp Bartko, MD, both from the Medical University of Vienna, write in an accompanying editorial.

As both systems target similar lesions, there might be “significant overlap in this particular patient population,” Dr. Goliasch told this news organization. From a technical perspective, the separate leaflet grasping was initially one of the advantages of the PASCAL, but this has also been recently introduced for the MitraClip.

That said, the “PASCAL device may offer a leaflet repair with decreased mechanical leaflet traction – specifically appealing to treat ventricular secondary MR – because mechanical forces applied to leaflets remain low, and the [central] spacer augments the leaflet surface in a way that reduces restrictive diastolic opening,” he added. “However, this remains highly speculative.”

The CLASP study enrolled 124 patients (56% male) with symptomatic MR grade of at least 3+ who were receiving optimal medical therapy at 14 sites in five countries. Their mean age was 75 years, 69% had functional MR (FMR), 31% had degenerative MR (DMR), and 60% were NYHA functional class III to IVa.

The primary endpoints of procedural and clinical success and adverse events at 30 days and 1-year outcomes were published last year. Echocardiographic data were available for 36 patients at 2 years with follow-up ongoing.

Composite major adverse event rates were 8.1% at 30 days, 18.5% at 1 year, and 16.9% at 2 years, driven mostly by severe bleeding at 7.3%, 11.3%, and 7.3%, respectively, Dr. Szerlip said.

Kaplan-Meier estimates showed 80.3% survival at 2 years (72.3% FMR, 94.3% DMR) and 84.3% freedom from heart failure rehospitalization (77.5% FMR, 97.3% DMR). The annualized HF rehospitalization rate fell to 85% at 2 years.

These results, the authors noted, hinged on minimizing residual MR. In the FMR group, 100% and 95% of patients achieved MR of 2+ or less at 1 year and 2 years, respectively, compared with 95% and 99% treated with the MitraClip in the COAPT study.

In the DMR group, 100% of patients achieved MR of 2+ or less at both 1 and 2 years, which “compares favorably to 94% from the EXPAND study at 1 year” with the MitraClip NTR and XTR systems, they write.

In CLASP, the LV end-diastolic volume decreased by 11 mL at 30 days and continued to decrease at 1 year (25 mL) and 2 years (33 mL; P < .001).

LV end-diastolic diameter (LVEDD) fell by 2.7 mm at 30 days, 3.9 mm at 1 year, and by 2.7 mm at 2 years (P = .002). At 2 years, 93% of patients were in NYHA class I or II (P < .001).

“The authors of the trial observed significant LV reverse remodeling with a decrease in LVEDD. These findings are indeed of particular interest and warrant further investigation by future studies as this has not been shown to such an extent in previous E2E [edge-to-edge] repair studies,” Dr. Goliasch said in an interview.

He raised an eyebrow, however, at the cross-trial comparisons, adding, “We should be very careful to draw any hasty conclusions considering the high proportion of missing echocardiographic data. Nevertheless, all these aspects might make the design of future studies for direct comparisons between E2E devices in the various structural aspects of mitral valve disease attractive to tailor treatment and optimize patient care.”

Dr. Szerlip and colleagues cited several study limitations including the absence of a control arm that may have contributed to a Hawthorne effect; not all patients had reached 2-year follow-up at the time of the analysis; and adjudication of events and assessment of the 6-minute walk test and quality-of-life measures were limited to 1 year based on the protocol.

The study was sponsored by Edwards Lifesciences. Dr. Szerlip reported serving as a proctor/speaker for Edwards; a national principal investigator for EFS; a speaker for Boston Scientific, and serving on steering committees for Medtronic and Abbott. Dr. Goliasch and Dr. Bartko have disclosed no relevant financial relationships.

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

Transcatheter mitral valve repair with the PASCAL device showed high rates of survival and freedom from heart failure rehospitalization at 2 years in the single-arm, safety and efficacy CLASP study.

The Heart Hospital Baylor Plano

The early reductions in mitral regurgitation (MR) were sustained with 97% of patients having MR grades of 2+ or less and 78% having MR grades of 1+ or less at 2 years.

There was also evidence of left ventricular (LV) reverse remodeling and significant improvements in functional status, Molly Szerlip, MD, Baylor Scott & White Health, Plano, Texas, reported as lead author. The results were published online May 18 in JACC: Cardiovascular Interventions.

“The PASCAL transcatheter valve repair system is a favorable option for treating patients with MR,” she said in a simultaneous virtual presentation at the 2021 Congress of European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021).

The PASCAL system is not approved in the United States, but Dr. Szerlip observed that the investigators are eagerly awaiting results from the ongoing, pivotal CLASP IID/IIF trial comparing the edge-to-edge repair system with another such device, MitraClip, in 1,275 patients with functional or degenerative MR. The primary completion date is set for December 2023.

Abbott’s MitraClip has been available in the United States since 2013 and in Europe since 2008; Edwards Lifesciences received a CE mark for the PASCAL system in 2019.

“The results of the CLASP study are remarkable and indicate an additional differentiated tool ready for clinical routine,” Georg Goliasch, MD, PhD, and Philipp Bartko, MD, both from the Medical University of Vienna, write in an accompanying editorial.

As both systems target similar lesions, there might be “significant overlap in this particular patient population,” Dr. Goliasch told this news organization. From a technical perspective, the separate leaflet grasping was initially one of the advantages of the PASCAL, but this has also been recently introduced for the MitraClip.

That said, the “PASCAL device may offer a leaflet repair with decreased mechanical leaflet traction – specifically appealing to treat ventricular secondary MR – because mechanical forces applied to leaflets remain low, and the [central] spacer augments the leaflet surface in a way that reduces restrictive diastolic opening,” he added. “However, this remains highly speculative.”

The CLASP study enrolled 124 patients (56% male) with symptomatic MR grade of at least 3+ who were receiving optimal medical therapy at 14 sites in five countries. Their mean age was 75 years, 69% had functional MR (FMR), 31% had degenerative MR (DMR), and 60% were NYHA functional class III to IVa.

The primary endpoints of procedural and clinical success and adverse events at 30 days and 1-year outcomes were published last year. Echocardiographic data were available for 36 patients at 2 years with follow-up ongoing.

Composite major adverse event rates were 8.1% at 30 days, 18.5% at 1 year, and 16.9% at 2 years, driven mostly by severe bleeding at 7.3%, 11.3%, and 7.3%, respectively, Dr. Szerlip said.

Kaplan-Meier estimates showed 80.3% survival at 2 years (72.3% FMR, 94.3% DMR) and 84.3% freedom from heart failure rehospitalization (77.5% FMR, 97.3% DMR). The annualized HF rehospitalization rate fell to 85% at 2 years.

These results, the authors noted, hinged on minimizing residual MR. In the FMR group, 100% and 95% of patients achieved MR of 2+ or less at 1 year and 2 years, respectively, compared with 95% and 99% treated with the MitraClip in the COAPT study.

In the DMR group, 100% of patients achieved MR of 2+ or less at both 1 and 2 years, which “compares favorably to 94% from the EXPAND study at 1 year” with the MitraClip NTR and XTR systems, they write.

In CLASP, the LV end-diastolic volume decreased by 11 mL at 30 days and continued to decrease at 1 year (25 mL) and 2 years (33 mL; P < .001).

LV end-diastolic diameter (LVEDD) fell by 2.7 mm at 30 days, 3.9 mm at 1 year, and by 2.7 mm at 2 years (P = .002). At 2 years, 93% of patients were in NYHA class I or II (P < .001).

“The authors of the trial observed significant LV reverse remodeling with a decrease in LVEDD. These findings are indeed of particular interest and warrant further investigation by future studies as this has not been shown to such an extent in previous E2E [edge-to-edge] repair studies,” Dr. Goliasch said in an interview.

He raised an eyebrow, however, at the cross-trial comparisons, adding, “We should be very careful to draw any hasty conclusions considering the high proportion of missing echocardiographic data. Nevertheless, all these aspects might make the design of future studies for direct comparisons between E2E devices in the various structural aspects of mitral valve disease attractive to tailor treatment and optimize patient care.”

Dr. Szerlip and colleagues cited several study limitations including the absence of a control arm that may have contributed to a Hawthorne effect; not all patients had reached 2-year follow-up at the time of the analysis; and adjudication of events and assessment of the 6-minute walk test and quality-of-life measures were limited to 1 year based on the protocol.

The study was sponsored by Edwards Lifesciences. Dr. Szerlip reported serving as a proctor/speaker for Edwards; a national principal investigator for EFS; a speaker for Boston Scientific, and serving on steering committees for Medtronic and Abbott. Dr. Goliasch and Dr. Bartko have disclosed no relevant financial relationships.

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

A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.

Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.

The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.

The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.

Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.

“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.

RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.

In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.

The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.

The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).

The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.

“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”

The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.

MDedge News

Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”

The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.

“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.

Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.

CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.

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

A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.

Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.

The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.

The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.

Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.

“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.

RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.

In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.

The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.

The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).

The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.

“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”

The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.

MDedge News

Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”

The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.

“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.

Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.

CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.

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

A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.

Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.

The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.

The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.

Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.

“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.

RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.

In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.

The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.

The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).

The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.

“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”

The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.

MDedge News

Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”

The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.

“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.

Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.

CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.

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

After taking it on the chin for previously reporting Bayesian estimates, actual 2-year data from the EVOLUT Low Risk trial confirm that transcatheter aortic valve replacement (TAVR) is noninferior to surgery for the primary endpoint of death or disabling stroke.

Among 1,414 as-treated patients, Kaplan-Meier rates for all-cause death or disabling stroke at 24 months were 4.3% with TAVR and 6.3% with surgery (P = .084).

There was also no difference in the individual components of all-cause death (3.5% vs. 4.4%; log-rank P = .366) and disabling stroke (1.5% vs. 2.7%; log-rank P = .119).

Recent low-risk TAVR studies have raised questions about whether there’s a possible catch-up for surgery between 12 and 24 months, given the early mortality benefit from the less-invasive transcatheter procedure, prompting a landmark analysis, John K. Forrest, MD, said during the virtual presentation at the 2021 Congress of European Association of Percutaneous Cardiovascular Interventions, EuroPCR 2021.

“Between 1 and 2 years, there was no convergence of the Kaplan-Meier curves for death or disabling stroke,” with an incidence of 1.9% for the TAVR group and 2.1% for the surgery group (log-rank P = .742), said Dr. Forrest, of Yale University, New Haven, Conn. “The lines were almost superimposed upon each other.”

Session moderator Bernard Prendergast, MD, observed that the Bayesian analysis, which was reported in 2019 and used 12-month follow-up to predict 2-year outcomes, generated questions and criticism over whether this was an appropriate method, compared with traditional Kaplan-Meier analysis. “Indeed, some people accused the investigators of gaming it with this form of statistical analysis.”

To act as a “fact checker,” Dr. Prendergast called in Christopher Cook, MRC, from the PCR Clinical Research Group and Imperial College London. The key methodologic question, Dr. Cook said, is whether Bayesian methods accurately predict actual clinical outcomes in this randomized clinical trial. “The simple answer to this for me, is yes.”

He pointed out that the Kaplan-Meier data for the primary outcome at 2 years were, in fact, numerically better than Bayesian estimates of 5.3% in the TAVR group and 6.7% in the surgery group.

“This validates the use of the original Bayesian methods to estimate patient outcomes in low-risk TAVI patients and, indeed, it may act as an example of where Bayesian methods can be safely applied in order to fast track potentially transformative procedures and technologies to our patients,” Dr. Cook said.

The rate of disabling stroke with TAVR was 1.5% in the new analysis, up from 1.1% in the Bayesian analysis, and 2.7% with surgery, down from 3.5% in the Bayesian analysis.

All-cause mortality, also noted earlier, was 3.5% with TAVR and 4.4% with surgery, whereas the Bayesian estimate was 4.5% for each group.

Dr. Prendergast of St. Thomas’ Hospital, London, said the actual 2-year data are reassuring regarding the statistical tools used and supplement those recently reported from low-risk patients in PARTNER 3.

But, he asked, “what does this mean for practice, what does it mean for guidelines, and how long do we need to wait until we are comfortable and reassured that we can apply TAVI in younger and low-risk patients with a durable outcome?”

Dr. Forrest said that clinicians can be reassured that these patients “are doing very well” but that long-term follow-up is critical.

“We need to be realistic here. We’re really going to be interested in 5- and 10-year outcomes and potentially even thereafter,” he said. “What happens to these valves when they eventually fail? Are superior hemodynamics going to give us longer valve durability in some way or are there going to be other unforeseen things that come up 10 years out? We don’t know those answers.”

TAVR with a supra-annular, self-expanding valve (CoreValve , Evolut R, or Evolut PRO) had superior hemodynamics in the new 2-year analysis with lower aortic valve gradients (9.0 vs. 11.7 mm Hg) and larger valve areas (2.2 vs. 2.0 cm²).

Prosthesis-patient mismatch also favored TAVR, with moderate or severe mismatch occurring in 7.2% and 2.1%, respectively, compared with 19.1% and 4.9%, respectively, with surgery. “We know that this has an impact on long-term outcomes, so it’s important to note that significant difference here,” Dr. Forrest said.

The chink in TAVR’s armor remains paravalvular leak, particularly mild leak, which was significantly higher at 26.6%, compared with only 2.6% with surgery. Moderate to severe leaks were seen in 1.7% and 0.4%, respectively, reflecting the improvement in TAVR with new iterations, he said.

Surgery was also superior to TAVR with regard to the need for permanent pacemaker implantation (7.9% vs. 21.1%). This compares with Bayesian estimates of 6.7% and 23.0%, respectively.

Rates of myocardial infarction remained constant in the two analyses for the TAVR (2.2%) and surgery (1.6%) groups, whereas heart failure hospitalizations improved slightly, from 5.4% versus 7.9%, respectively, in the Bayesian analysis to 5.3% versus 7.1%, respectively, in the new analysis.

Fellow discussant Marie-Claude Morice, MD, Institute Hospitalier Jacques Cartier, Massy, France, highlighted several meta-analyses in different risk patients showing “a lot of good news,” including decreased stroke and mortality rates and the combined outcome clearly favoring TAVR.

“The remaining question is the longevity of the valve, but with 5 years’ follow-up we have for comparison [in high-risk patients], it is the same,” she said. “What this illustrates is that the tidal wave of TAVR is continuing, and we can look optimistically to the future. Is it the nonsymptomatic patients?”

Medtronic funded the study. Dr. Forrest reported grant support from, serving on the advisory board, and proctoring for Edwards Lifesciences and Medtronic. Dr. Prendergast has received grants from Edwards Lifesciences; and speaker/consultancy fees from Abbott, Anteris, and Edwards.

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

After taking it on the chin for previously reporting Bayesian estimates, actual 2-year data from the EVOLUT Low Risk trial confirm that transcatheter aortic valve replacement (TAVR) is noninferior to surgery for the primary endpoint of death or disabling stroke.

Among 1,414 as-treated patients, Kaplan-Meier rates for all-cause death or disabling stroke at 24 months were 4.3% with TAVR and 6.3% with surgery (P = .084).

There was also no difference in the individual components of all-cause death (3.5% vs. 4.4%; log-rank P = .366) and disabling stroke (1.5% vs. 2.7%; log-rank P = .119).

Recent low-risk TAVR studies have raised questions about whether there’s a possible catch-up for surgery between 12 and 24 months, given the early mortality benefit from the less-invasive transcatheter procedure, prompting a landmark analysis, John K. Forrest, MD, said during the virtual presentation at the 2021 Congress of European Association of Percutaneous Cardiovascular Interventions, EuroPCR 2021.

“Between 1 and 2 years, there was no convergence of the Kaplan-Meier curves for death or disabling stroke,” with an incidence of 1.9% for the TAVR group and 2.1% for the surgery group (log-rank P = .742), said Dr. Forrest, of Yale University, New Haven, Conn. “The lines were almost superimposed upon each other.”

Session moderator Bernard Prendergast, MD, observed that the Bayesian analysis, which was reported in 2019 and used 12-month follow-up to predict 2-year outcomes, generated questions and criticism over whether this was an appropriate method, compared with traditional Kaplan-Meier analysis. “Indeed, some people accused the investigators of gaming it with this form of statistical analysis.”

To act as a “fact checker,” Dr. Prendergast called in Christopher Cook, MRC, from the PCR Clinical Research Group and Imperial College London. The key methodologic question, Dr. Cook said, is whether Bayesian methods accurately predict actual clinical outcomes in this randomized clinical trial. “The simple answer to this for me, is yes.”

He pointed out that the Kaplan-Meier data for the primary outcome at 2 years were, in fact, numerically better than Bayesian estimates of 5.3% in the TAVR group and 6.7% in the surgery group.

“This validates the use of the original Bayesian methods to estimate patient outcomes in low-risk TAVI patients and, indeed, it may act as an example of where Bayesian methods can be safely applied in order to fast track potentially transformative procedures and technologies to our patients,” Dr. Cook said.

The rate of disabling stroke with TAVR was 1.5% in the new analysis, up from 1.1% in the Bayesian analysis, and 2.7% with surgery, down from 3.5% in the Bayesian analysis.

All-cause mortality, also noted earlier, was 3.5% with TAVR and 4.4% with surgery, whereas the Bayesian estimate was 4.5% for each group.

Dr. Prendergast of St. Thomas’ Hospital, London, said the actual 2-year data are reassuring regarding the statistical tools used and supplement those recently reported from low-risk patients in PARTNER 3.

But, he asked, “what does this mean for practice, what does it mean for guidelines, and how long do we need to wait until we are comfortable and reassured that we can apply TAVI in younger and low-risk patients with a durable outcome?”

Dr. Forrest said that clinicians can be reassured that these patients “are doing very well” but that long-term follow-up is critical.

“We need to be realistic here. We’re really going to be interested in 5- and 10-year outcomes and potentially even thereafter,” he said. “What happens to these valves when they eventually fail? Are superior hemodynamics going to give us longer valve durability in some way or are there going to be other unforeseen things that come up 10 years out? We don’t know those answers.”

TAVR with a supra-annular, self-expanding valve (CoreValve , Evolut R, or Evolut PRO) had superior hemodynamics in the new 2-year analysis with lower aortic valve gradients (9.0 vs. 11.7 mm Hg) and larger valve areas (2.2 vs. 2.0 cm²).

Prosthesis-patient mismatch also favored TAVR, with moderate or severe mismatch occurring in 7.2% and 2.1%, respectively, compared with 19.1% and 4.9%, respectively, with surgery. “We know that this has an impact on long-term outcomes, so it’s important to note that significant difference here,” Dr. Forrest said.

The chink in TAVR’s armor remains paravalvular leak, particularly mild leak, which was significantly higher at 26.6%, compared with only 2.6% with surgery. Moderate to severe leaks were seen in 1.7% and 0.4%, respectively, reflecting the improvement in TAVR with new iterations, he said.

Surgery was also superior to TAVR with regard to the need for permanent pacemaker implantation (7.9% vs. 21.1%). This compares with Bayesian estimates of 6.7% and 23.0%, respectively.

Rates of myocardial infarction remained constant in the two analyses for the TAVR (2.2%) and surgery (1.6%) groups, whereas heart failure hospitalizations improved slightly, from 5.4% versus 7.9%, respectively, in the Bayesian analysis to 5.3% versus 7.1%, respectively, in the new analysis.

Fellow discussant Marie-Claude Morice, MD, Institute Hospitalier Jacques Cartier, Massy, France, highlighted several meta-analyses in different risk patients showing “a lot of good news,” including decreased stroke and mortality rates and the combined outcome clearly favoring TAVR.

“The remaining question is the longevity of the valve, but with 5 years’ follow-up we have for comparison [in high-risk patients], it is the same,” she said. “What this illustrates is that the tidal wave of TAVR is continuing, and we can look optimistically to the future. Is it the nonsymptomatic patients?”

Medtronic funded the study. Dr. Forrest reported grant support from, serving on the advisory board, and proctoring for Edwards Lifesciences and Medtronic. Dr. Prendergast has received grants from Edwards Lifesciences; and speaker/consultancy fees from Abbott, Anteris, and Edwards.

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

After taking it on the chin for previously reporting Bayesian estimates, actual 2-year data from the EVOLUT Low Risk trial confirm that transcatheter aortic valve replacement (TAVR) is noninferior to surgery for the primary endpoint of death or disabling stroke.

Among 1,414 as-treated patients, Kaplan-Meier rates for all-cause death or disabling stroke at 24 months were 4.3% with TAVR and 6.3% with surgery (P = .084).

There was also no difference in the individual components of all-cause death (3.5% vs. 4.4%; log-rank P = .366) and disabling stroke (1.5% vs. 2.7%; log-rank P = .119).

Recent low-risk TAVR studies have raised questions about whether there’s a possible catch-up for surgery between 12 and 24 months, given the early mortality benefit from the less-invasive transcatheter procedure, prompting a landmark analysis, John K. Forrest, MD, said during the virtual presentation at the 2021 Congress of European Association of Percutaneous Cardiovascular Interventions, EuroPCR 2021.

“Between 1 and 2 years, there was no convergence of the Kaplan-Meier curves for death or disabling stroke,” with an incidence of 1.9% for the TAVR group and 2.1% for the surgery group (log-rank P = .742), said Dr. Forrest, of Yale University, New Haven, Conn. “The lines were almost superimposed upon each other.”

Session moderator Bernard Prendergast, MD, observed that the Bayesian analysis, which was reported in 2019 and used 12-month follow-up to predict 2-year outcomes, generated questions and criticism over whether this was an appropriate method, compared with traditional Kaplan-Meier analysis. “Indeed, some people accused the investigators of gaming it with this form of statistical analysis.”

To act as a “fact checker,” Dr. Prendergast called in Christopher Cook, MRC, from the PCR Clinical Research Group and Imperial College London. The key methodologic question, Dr. Cook said, is whether Bayesian methods accurately predict actual clinical outcomes in this randomized clinical trial. “The simple answer to this for me, is yes.”

He pointed out that the Kaplan-Meier data for the primary outcome at 2 years were, in fact, numerically better than Bayesian estimates of 5.3% in the TAVR group and 6.7% in the surgery group.

“This validates the use of the original Bayesian methods to estimate patient outcomes in low-risk TAVI patients and, indeed, it may act as an example of where Bayesian methods can be safely applied in order to fast track potentially transformative procedures and technologies to our patients,” Dr. Cook said.

The rate of disabling stroke with TAVR was 1.5% in the new analysis, up from 1.1% in the Bayesian analysis, and 2.7% with surgery, down from 3.5% in the Bayesian analysis.

All-cause mortality, also noted earlier, was 3.5% with TAVR and 4.4% with surgery, whereas the Bayesian estimate was 4.5% for each group.

Dr. Prendergast of St. Thomas’ Hospital, London, said the actual 2-year data are reassuring regarding the statistical tools used and supplement those recently reported from low-risk patients in PARTNER 3.

But, he asked, “what does this mean for practice, what does it mean for guidelines, and how long do we need to wait until we are comfortable and reassured that we can apply TAVI in younger and low-risk patients with a durable outcome?”

Dr. Forrest said that clinicians can be reassured that these patients “are doing very well” but that long-term follow-up is critical.

“We need to be realistic here. We’re really going to be interested in 5- and 10-year outcomes and potentially even thereafter,” he said. “What happens to these valves when they eventually fail? Are superior hemodynamics going to give us longer valve durability in some way or are there going to be other unforeseen things that come up 10 years out? We don’t know those answers.”

TAVR with a supra-annular, self-expanding valve (CoreValve , Evolut R, or Evolut PRO) had superior hemodynamics in the new 2-year analysis with lower aortic valve gradients (9.0 vs. 11.7 mm Hg) and larger valve areas (2.2 vs. 2.0 cm²).

Prosthesis-patient mismatch also favored TAVR, with moderate or severe mismatch occurring in 7.2% and 2.1%, respectively, compared with 19.1% and 4.9%, respectively, with surgery. “We know that this has an impact on long-term outcomes, so it’s important to note that significant difference here,” Dr. Forrest said.

The chink in TAVR’s armor remains paravalvular leak, particularly mild leak, which was significantly higher at 26.6%, compared with only 2.6% with surgery. Moderate to severe leaks were seen in 1.7% and 0.4%, respectively, reflecting the improvement in TAVR with new iterations, he said.

Surgery was also superior to TAVR with regard to the need for permanent pacemaker implantation (7.9% vs. 21.1%). This compares with Bayesian estimates of 6.7% and 23.0%, respectively.

Rates of myocardial infarction remained constant in the two analyses for the TAVR (2.2%) and surgery (1.6%) groups, whereas heart failure hospitalizations improved slightly, from 5.4% versus 7.9%, respectively, in the Bayesian analysis to 5.3% versus 7.1%, respectively, in the new analysis.

Fellow discussant Marie-Claude Morice, MD, Institute Hospitalier Jacques Cartier, Massy, France, highlighted several meta-analyses in different risk patients showing “a lot of good news,” including decreased stroke and mortality rates and the combined outcome clearly favoring TAVR.

“The remaining question is the longevity of the valve, but with 5 years’ follow-up we have for comparison [in high-risk patients], it is the same,” she said. “What this illustrates is that the tidal wave of TAVR is continuing, and we can look optimistically to the future. Is it the nonsymptomatic patients?”

Medtronic funded the study. Dr. Forrest reported grant support from, serving on the advisory board, and proctoring for Edwards Lifesciences and Medtronic. Dr. Prendergast has received grants from Edwards Lifesciences; and speaker/consultancy fees from Abbott, Anteris, and Edwards.

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