User login
COMPLETE revascularization reduces death and recurrent MI risk
Revascularization of more than just the culprit lesion in patients with ST-elevation myocardial infarctions could significantly reduce their risk of cardiovascular death or myocardial infarction, according to results of the COMPLETE trial, presented at the annual congress of the European Society of Cardiology.
The report, simultaneously published online in the New England Journal of Medicine, detailed the outcomes of COMPLETE (the Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), a study in 4,041 patients who had experienced an ST-elevation myocardial infarction (STEMI), who had multi-vessel coronary artery disease, and who had undergone successful percutaneous coronary intervention of the culprit lesion.
Participants were randomized either to complete revascularization of all angiographically significant nonculprit lesions, or to no further revascularization, and were followed for a median of 3 years.
Of the patients who underwent complete revascularization, 7.8% experienced either cardiovascular death or another myocardial infarction, compared with 10.5% of those who only had revascularization of the culprit lesion, representing a significant 26% reduction (P = .004) in the incidence of this composite coprimary outcome.
The decrease in events was driven by a significant 32% reduction in the incidence of new myocardial infarction – particularly non-STEMI, new STEMI, and myocardial infarction type 1 – in the complete revascularization group, with only a 7% reduction in the incidence of death from cardiovascular causes.
With the second coprimary outcome of a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization, this was seen in 8.9% of patients in the complete revascularization group compared with 16.7% of patients with the culprit-lesion-only group; a significant 49% reduction in incidence (P less than .001).
The authors calculated that 37 complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction. To prevent cardiovascular death, myocardial infarction, or ischemia-driven revascularization, the number needed to treat was 13.
The timing of complete revascularization did not appear to affect the benefits of the procedure, which were consistent among patients who underwent complete revascularization during their index hospitalization and in those who underwent the procedure after hospital discharge. Investigators had to specify before randomization whether the patient would undergo complete revascularization during the index hospitalization or after discharge but within 45 days.
The study also did not find any significant differences between the two groups in the risks of major bleeding, stroke, or stent thrombosis. However, the complete revascularization group did experience a nonsignificant 59% higher odds of contrast-associated acute kidney injury, which was attributed to the nonculprit lesion revascularization in seven patients in the complete revascularization group.
Dr. Shamir R. Mehta, of the Population Health Research Institute at McMaster University, Ontario, and coauthors noted that previous trials of complete-revascularization strategies in patients with STEMI were smaller and had included revascularization as part of a composite primary outcome.
“In the absence of a reduction in irreversible events such as cardiovascular death or new myocardial infarction, the clinical relevance of performing early nonculprit-lesion PCI in all patients with multivessel coronary artery disease to prevent later PCI in a smaller number of those patients is debatable,” they wrote. “We have now found that routine nonculprit-lesion PCI with the goal of complete revascularization confers a reduction in the long-term risk of cardiovascular death or myocardial infarction.”
No patients with cardiogenic shock were enrolled in the study, so the results could not be extrapolated to that patient group.
In an accompanying editorial, Dr. Lars Kober and Dr. Thomas Engstrøm, of the department of cardiology at Rigshospitalet at the University of Copenhagen, wrote that until now, there had been a lack of evidence that complete revascularization could reduce hard outcomes such as death and recurrent myocardial infarction (N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMe1910898).
However, they said, given the findings of this study, it might now be appropriate to recommend complete revascularization for patients such as those enrolled in the study.
“Better selection of high-risk patients may also refine the determination of who is most likely to benefit from complete revascularization,” they wrote.
COMPLETE was supported by the Canadian Institutes of Health Research, with additional support from AstraZeneca, Boston Scientific, and the Population Health Research Institute. Two authors declared support from AstraZeneca and Boston Scientific during the conduct of the study, and eight declared personal fees, funding, and grants from the pharmaceutical industry outside the study. One author declared employment with Medtronic, unrelated to the submitted work.
Both editorial authors declared grants and personal fees, including from the study supporters.
SOURCE: Mehta S et al. N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMoa1907775.
Revascularization of more than just the culprit lesion in patients with ST-elevation myocardial infarctions could significantly reduce their risk of cardiovascular death or myocardial infarction, according to results of the COMPLETE trial, presented at the annual congress of the European Society of Cardiology.
The report, simultaneously published online in the New England Journal of Medicine, detailed the outcomes of COMPLETE (the Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), a study in 4,041 patients who had experienced an ST-elevation myocardial infarction (STEMI), who had multi-vessel coronary artery disease, and who had undergone successful percutaneous coronary intervention of the culprit lesion.
Participants were randomized either to complete revascularization of all angiographically significant nonculprit lesions, or to no further revascularization, and were followed for a median of 3 years.
Of the patients who underwent complete revascularization, 7.8% experienced either cardiovascular death or another myocardial infarction, compared with 10.5% of those who only had revascularization of the culprit lesion, representing a significant 26% reduction (P = .004) in the incidence of this composite coprimary outcome.
The decrease in events was driven by a significant 32% reduction in the incidence of new myocardial infarction – particularly non-STEMI, new STEMI, and myocardial infarction type 1 – in the complete revascularization group, with only a 7% reduction in the incidence of death from cardiovascular causes.
With the second coprimary outcome of a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization, this was seen in 8.9% of patients in the complete revascularization group compared with 16.7% of patients with the culprit-lesion-only group; a significant 49% reduction in incidence (P less than .001).
The authors calculated that 37 complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction. To prevent cardiovascular death, myocardial infarction, or ischemia-driven revascularization, the number needed to treat was 13.
The timing of complete revascularization did not appear to affect the benefits of the procedure, which were consistent among patients who underwent complete revascularization during their index hospitalization and in those who underwent the procedure after hospital discharge. Investigators had to specify before randomization whether the patient would undergo complete revascularization during the index hospitalization or after discharge but within 45 days.
The study also did not find any significant differences between the two groups in the risks of major bleeding, stroke, or stent thrombosis. However, the complete revascularization group did experience a nonsignificant 59% higher odds of contrast-associated acute kidney injury, which was attributed to the nonculprit lesion revascularization in seven patients in the complete revascularization group.
Dr. Shamir R. Mehta, of the Population Health Research Institute at McMaster University, Ontario, and coauthors noted that previous trials of complete-revascularization strategies in patients with STEMI were smaller and had included revascularization as part of a composite primary outcome.
“In the absence of a reduction in irreversible events such as cardiovascular death or new myocardial infarction, the clinical relevance of performing early nonculprit-lesion PCI in all patients with multivessel coronary artery disease to prevent later PCI in a smaller number of those patients is debatable,” they wrote. “We have now found that routine nonculprit-lesion PCI with the goal of complete revascularization confers a reduction in the long-term risk of cardiovascular death or myocardial infarction.”
No patients with cardiogenic shock were enrolled in the study, so the results could not be extrapolated to that patient group.
In an accompanying editorial, Dr. Lars Kober and Dr. Thomas Engstrøm, of the department of cardiology at Rigshospitalet at the University of Copenhagen, wrote that until now, there had been a lack of evidence that complete revascularization could reduce hard outcomes such as death and recurrent myocardial infarction (N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMe1910898).
However, they said, given the findings of this study, it might now be appropriate to recommend complete revascularization for patients such as those enrolled in the study.
“Better selection of high-risk patients may also refine the determination of who is most likely to benefit from complete revascularization,” they wrote.
COMPLETE was supported by the Canadian Institutes of Health Research, with additional support from AstraZeneca, Boston Scientific, and the Population Health Research Institute. Two authors declared support from AstraZeneca and Boston Scientific during the conduct of the study, and eight declared personal fees, funding, and grants from the pharmaceutical industry outside the study. One author declared employment with Medtronic, unrelated to the submitted work.
Both editorial authors declared grants and personal fees, including from the study supporters.
SOURCE: Mehta S et al. N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMoa1907775.
Revascularization of more than just the culprit lesion in patients with ST-elevation myocardial infarctions could significantly reduce their risk of cardiovascular death or myocardial infarction, according to results of the COMPLETE trial, presented at the annual congress of the European Society of Cardiology.
The report, simultaneously published online in the New England Journal of Medicine, detailed the outcomes of COMPLETE (the Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), a study in 4,041 patients who had experienced an ST-elevation myocardial infarction (STEMI), who had multi-vessel coronary artery disease, and who had undergone successful percutaneous coronary intervention of the culprit lesion.
Participants were randomized either to complete revascularization of all angiographically significant nonculprit lesions, or to no further revascularization, and were followed for a median of 3 years.
Of the patients who underwent complete revascularization, 7.8% experienced either cardiovascular death or another myocardial infarction, compared with 10.5% of those who only had revascularization of the culprit lesion, representing a significant 26% reduction (P = .004) in the incidence of this composite coprimary outcome.
The decrease in events was driven by a significant 32% reduction in the incidence of new myocardial infarction – particularly non-STEMI, new STEMI, and myocardial infarction type 1 – in the complete revascularization group, with only a 7% reduction in the incidence of death from cardiovascular causes.
With the second coprimary outcome of a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization, this was seen in 8.9% of patients in the complete revascularization group compared with 16.7% of patients with the culprit-lesion-only group; a significant 49% reduction in incidence (P less than .001).
The authors calculated that 37 complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction. To prevent cardiovascular death, myocardial infarction, or ischemia-driven revascularization, the number needed to treat was 13.
The timing of complete revascularization did not appear to affect the benefits of the procedure, which were consistent among patients who underwent complete revascularization during their index hospitalization and in those who underwent the procedure after hospital discharge. Investigators had to specify before randomization whether the patient would undergo complete revascularization during the index hospitalization or after discharge but within 45 days.
The study also did not find any significant differences between the two groups in the risks of major bleeding, stroke, or stent thrombosis. However, the complete revascularization group did experience a nonsignificant 59% higher odds of contrast-associated acute kidney injury, which was attributed to the nonculprit lesion revascularization in seven patients in the complete revascularization group.
Dr. Shamir R. Mehta, of the Population Health Research Institute at McMaster University, Ontario, and coauthors noted that previous trials of complete-revascularization strategies in patients with STEMI were smaller and had included revascularization as part of a composite primary outcome.
“In the absence of a reduction in irreversible events such as cardiovascular death or new myocardial infarction, the clinical relevance of performing early nonculprit-lesion PCI in all patients with multivessel coronary artery disease to prevent later PCI in a smaller number of those patients is debatable,” they wrote. “We have now found that routine nonculprit-lesion PCI with the goal of complete revascularization confers a reduction in the long-term risk of cardiovascular death or myocardial infarction.”
No patients with cardiogenic shock were enrolled in the study, so the results could not be extrapolated to that patient group.
In an accompanying editorial, Dr. Lars Kober and Dr. Thomas Engstrøm, of the department of cardiology at Rigshospitalet at the University of Copenhagen, wrote that until now, there had been a lack of evidence that complete revascularization could reduce hard outcomes such as death and recurrent myocardial infarction (N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMe1910898).
However, they said, given the findings of this study, it might now be appropriate to recommend complete revascularization for patients such as those enrolled in the study.
“Better selection of high-risk patients may also refine the determination of who is most likely to benefit from complete revascularization,” they wrote.
COMPLETE was supported by the Canadian Institutes of Health Research, with additional support from AstraZeneca, Boston Scientific, and the Population Health Research Institute. Two authors declared support from AstraZeneca and Boston Scientific during the conduct of the study, and eight declared personal fees, funding, and grants from the pharmaceutical industry outside the study. One author declared employment with Medtronic, unrelated to the submitted work.
Both editorial authors declared grants and personal fees, including from the study supporters.
SOURCE: Mehta S et al. N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMoa1907775.
FROM THE ESC CONGRESS 2019
Key clinical point: Complete revascularization after STEMI reduces death and recurrent MI risk.
Major finding: Thirty-seven complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction.
Study details: COMPLETE, a randomized controlled trial in 4,041 patients with STEMI.
Disclosures: The study was supported by the Canadian Institutes of Health Research, with additional support from AstraZeneca, Boston Scientific, and the Population Health Research Institute. Two authors declared support from AstraZeneca and Boston Scientific during the conduct of the study, and eight declared personal fees, funding, and grants from the pharmaceutical industry outside the study. One author declared employment with Medtronic, unrelated to the submitted work.
Source: Mehta S et al. N Engl J Med. 2019 Sep 1. doi: 10.1056/NEJMoa1907775.
FDA’s low-risk TAVR okay set to propel case volume
With the Food and Drug Administration’s approval of two different pairs of transcatheter aortic valve replacement systems for patients at low surgical risk, U.S. case volume for the procedure should markedly rise given that patients at low surgical risk form the largest risk subgroup among patients with aortic stenosis severe enough to warrant valve replacement.
But even as transcatheter aortic valve replacement (TAVR) now becomes the predominant approach for fixing severely stenotic aortic valves regardless of a patient’s risk level, the procedure remains less optimal than surgical aortic valve replacement (SAVR) in selected patients, putting an onus on clinicians to identify and alert patients for whom the transcatheter approach is questionable.
The anticipated surge in TAVR cases for low-risk patients after the FDA’s Aug. 16, 2019, decision will also likely lead to more hospitals offering TAVR. That development will test whether recently enacted rules from the Centers for Medicare & Medicaid Services on procedure-volume minimums for TAVR programs – at least 20 cases a year (or 40 within 2 years) at centers that also perform at least 300 percutaneous coronary interventions annually – lead to outcomes at lower-volume centers that come reasonably close to the outcomes at higher-volume programs for low-risk patients.
“The paradigm has definitely shifted from SAVR as the gold standard to TAVR as the primary treatment for aortic stenosis. This opens TAVR to the vast majority of patients with aortic stenosis,” roughly three-quarters of patients with aortic valve stenosis severe enough to need valve replacement, said Joseph C. Cleveland Jr., MD, a cardiothoracic surgeon and professor of surgery at the University of Colorado at Denver, Aurora.
The actual, immediate increase in TAVR patients may not be quite as large as this fraction suggests. That’s in part because many patients in the low-risk category based on their surgical risk score already have been judged to have higher-risk features by heart-valve teams that has allowed such patients to undergo TAVR, said John D. Carroll, MD, professor of medicine and director of interventional cardiology at the University of Colorado.
For several years, U.S. rates of TAVR have exceeded SAVR, he noted, and in 2018 U.S. programs performed roughly 58,000 TAVR procedures and about 25,000 SAVRs, according to data collected by the Transcatheter Valve Therapy (TVT) Registry run by the Society of Thoracic Surgeons and the American College of Cardiology. Dr. Carroll is vice chair of the steering committee for this registry, which was mandated by the FDA in 2011 when the agency first allowed TAVR onto the U.S. market and is designed to capture every TAVR case performed in routine U.S. practice.
Despite this caveat, “there will be substantial growth in TAVR. Going forward, there will be more of a shift from SAVR to TAVR. That is what the results of the low-risk trials did,” Dr. Carroll predicted. In addition, the coming growth in TAVR numbers will stem from more than just low-risk patients whom a month ago would have undergone SAVR but now undergo TAVR instead. The availability of TAVR as an option for a wider range of patients should help boost public awareness that a nonsurgical way exists to treat severe aortic stenosis, plus the aging of baby boomers is on the verge of generating a substantial wave of new patients, a wave so high that Dr. Carroll called it a looming “tsunami” of patients needing TAVR.
How will low-risk TAVR affect lower-volume sites?
More TAVR patients will inevitably mean more U.S. sites offering the procedure, experts agreed. “We anticipate more low-volume programs,” Dr. Carroll said.
“Approval of TAVR for low-risk patients will result in a significant increase in the number of programs offering it. Approximately 1,100 U.S. programs offer SAVR, and as of now about 600 of these programs also offer TAVR. Health systems face the risk of losing patients if they don’t offer TAVR now that low-risk patients can be treated,” observed Sreekanth Vemulapalli, MD, a cardiologist at Duke University, Durham, N.C. who has run several studies using TVT Registry data and serves as liaison between the registry and its analytic center at Duke.
One of these studies, published earlier in 2019, showed that, among more than 96,000 registry patients who underwent transfemoral TAVR during 2015-2017 at 554 U.S. centers, those treated at sites that fell into the bottom quartile for case volume had an adjusted 30-day mortality rate that was 21% higher relative to patients treated at centers in the top quartile, a statistically significant difference (N Engl J Med. 2019 Jun 27;380[26]:2541-50). The absolute difference in adjusted 30-day mortality between the lowest and highest quartiles was 0.54%, roughly 1 additional death for every 200 patients. The TAVR centers in the lowest-volume quartile performed 5-36 cases/year, averaging 27 TAVRs/year; those in the highest quartile performed 86-371 TAVRs annually with an overall quartile average of 143 procedures/year.
Dr. Vemulapalli and others cautioned that TAVR case volume is currently serving as a surrogate, and imperfect, marker for program quality until TAVR programs generate enough data to allow a directly measured, risk-adjusted, outcome-driven assessment of performance. In the study he and his associates published in June, the 140 TAVR programs in the lowest-volume quartile showed a “high” level of variability in their adjusted mortality rates. Despite this limitation, the prospect that new TAVR programs will soon open to meet growing TAVR demand from low-risk patients poses the question of how these programs will perform during their start-up days (and possibly beyond), when case volumes may be light, especially if sites open in more remote sections of the United States.
“Will the real-world results of TAVR in low-risk patients match the fantastic results in the two low-risk TAVR trials?” wondered Dr. Carroll, referring to the PARTNER 3 (N Engl J Med. 2019 May 2;380[18]:1695-1705) and Evolut Low-Risk Patients trial (N Engl J Med. 2019 May 2;380[18]:1706-15). “It’s unknown whether a site just starting to do TAVRs will get the same results. The sites that participated in the low-risk trials were mostly high-volume sites.” On the other hand, TVT Registry data have shown that patients with surgical risk that was judged prohibitive, high, or intermediate all have had overall real-world outcomes that match what was seen in the relevant TAVR trials.
In addition, some experts view a modest drop in 30-day survival among patients treated at lower-volume TAVR sites as a reasonable trade-off for easier access for patients seeking this life-changing treatment.
“We need to ensure that patients have access to this treatment option,” said Catherine M. Otto, MD, professor of medicine and director of the Heart Valve Clinic at the University of Washington, Seattle. The potentially better outcomes produced at larger TAVR programs “need to be balanced against having a greater number of programs to ensure access for more patients and allow patients to be treated closer to home,” she said in an interview. She suggested that the potential exists to use telemedicine to link larger and more experienced TAVR programs with smaller and newer programs to help boost their performance.
“There is no perfect solution or metric to ensure high quality while also allowing for adequate access. As indications for TAVR expand we need to maintain vigilance and accountability as the therapy is dispersed to more patients at more centers,” said Brian R. Lindman, MD, medical director of the Structural Heat and Valve Center at Vanderbilt University, Nashville, Tenn. “We also need to insure that certain groups of patients have adequate access to this therapy. Adequate access to TAVR and high-quality clinical outcomes are both important goals.”
Plus, “the volume relationship may be less important,” in lower-risk patients, suggested Dr. Cleveland in an interview. Low-risk patients are younger and have fewer comorbidities and less vascular disease. “Low-volume centers should be able to treat these patients,” he said. Despite that, he personally supported the higher volume minimum for TAVR of 50 cases/year that the ACC, STS, and other U.S. professional societies recommended to CMS during public comment on the proposed rules. “We’ll see whether the increased access is worth this volume minimum.”
Who still gets SAVR?
Given the inherent attraction TAVR holds over SAVR for patients, heart-valve teams will need to convey the right message to patients who may be better served with surgical replacement despite the added trauma and recovery time it produces.
“The decision to perform TAVR or SAVR should now be based on a patient’s expected longevity as well as patient preferences and values, and not on the patient’s estimated surgical risk, except for the highest-risk patients in whom TAVR is recommended,” said Dr. Otto. A patient’s age, comorbidities, and overall life expectancy now move to center stage when deciding the TAVR or SAVR question, along with individual anatomic considerations, the possible need for concurrent procedures, and of course what the patient prefers including their willingness and ability to remain on lifelong anticoagulation if they receive a durable mechanical valve. Dr. Otto outlined this new landscape of the heart-valve team’s decision making process in an editorial she recently published (N Engl J Med. 2019 May 2;380[18]: 1769-70) that accompanied publication of PARTNER 3 and the Evolut Low-Risk Patients trial.
“For some patients there will be clear benefit from one approach, but for many patients, particularly those at low surgical risk, both TAVR and SAVR are technically feasible. For these patients it’s essential that the heart-valve team provide unbiased information to guide patients,” Dr. Otto said. The ideal person to provide this unbiased presentation of the pros and cons would be a cardiologist experienced with valve disease but not actively involved in performing valve-replacement procedures.
A big issue younger patients must confront is what remains unknown about long-term durability of TAVR valves. Dr. Otto called this “the most important missing piece of information. We only have robust data out to about 5 years. If TAVR valve will be durable for 15-20 years, then TAVR will become preferred even in younger patients.”
Even after TAVR became available to intermediate-risk patients in 2016, the median age of U.S. patients undergoing TAVR hardly budged, and has recently stood at about 81 years, Dr. Carroll noted. “With low-risk patients, we expect to see this change,” as more patients now who are in their 70s, 60s, and younger start to routinely undergo TAVR. As more younger patients with life expectancies on the order of 30 years consider TAVR, issues of valve durability “enter the discussion,” he said. “We need data to 10, 15 years,” and in its low-risk approval the FDA mandated manufacturers to follow these patients for at least 10 years. Although valve-in-valve replacement of failed TAVR valves is an option, it’s not always a smooth fix with the potential for prosthesis-patient mismatch (J Am Coll Cardiol. 2018 Dec 4;72[22]:2701-11) and resulting hemodynamic problems, Dr. Carroll said.
Bicuspid-valve replacement with TAVR is another big unknown, largely because these patients were excluded from the TAVR trials. A recently published analysis of the 2,726 patients with a bicuspid aortic valve who underwent TAVR anyway in routine U.S. practice between June 2015 and November 2018 and were in the TVT Registry (about 3% of all TAVR patients during this period) showed that these patients had similar mortality, compared with the tricuspid-valve patients, but a significantly increased stroke rate (JAMA. 2019 Jun 11;321[22]:2193-202). The authors concluded that a prospective, randomized study of TAVR, compared with SAVR, is needed for these patients, and many others in the field agree.
As availability of TAVR grows and public awareness increases, heart-valve teams may find it challenging sometimes to help patients understand the upsides of SAVR for their individual clinical needs when TAVR is superficially so much more attractive.
“The desire to avoid the prolonged hospitalization and recovery from SAVR is a huge driver of patient preference,” noted Dr. Carroll.
“It’s hard to tell a 55 year old to think about another procedure they may need when they are 65 or 70 if they undergo TAVR now rather than SAVR. They don’t want open-heart surgery; I hear that all the time,” Dr. Cleveland said. “If I were a 55-year-old aortic valve patient I’d strongly consider TAVR, too.”
Financial consideration at the site performing the interventions can also be a factor. “Differential costs and payments associated with SAVR and TAVR create different financial incentives for health systems between these two procedures,” noted Dr. Vemulapalli. “There likely needs to be a system that creates equal incentives to do SAVR or TAVR so that the decision between them can come down to just the patient and heart-valve team. We need further data and decision aids to help better define which patients will likely do better with SAVR and which with TAVR.”
What now?
Since the first large TAVR trials started in 2007, their main thrust has been to prove the efficacy and safety of TAVR in patients at sequentially less risk of undergoing SAVR. Now that this series of comparisons has ended, where will TAVR research turn its attention?
In addition to the big outstanding issues of TAVR-valve long-term durability, and the efficacy and safety of TAVR for replacing bicuspid valves, other big questions and issues loom. They include the optimal anticoagulant regimen for preventing leaflet thrombosis, reducing the need for pacemakers, reducing strokes, the applicability of TAVR to patients with less severe aortic stenosis, the impact of treating severe but asymptomatic aortic valve obstruction, optimizing valve-in-valve outcomes, and further improvements to valve design, hemodynamics, and delivery. In short, the question of TAVR’s suitability for patients regardless of their surgical risk may have now been answered, but many questions remain about the best way to use and to optimize this technology.
Dr. Cleveland and Dr. Carroll have participated in TAVR trials but had no personal financial disclosures. Dr. Otto had no disclosures. Dr. Vemulapalli has received personal fees from Janssen, Novella, Premiere, and Zafgen, and research funding from Boston Scientific and Abbott Vascular. Dr. Lindman has been a consultant to Medtronic, has served as an advisor to Roche, and has received research funding from Edwards Lifesciences.
With the Food and Drug Administration’s approval of two different pairs of transcatheter aortic valve replacement systems for patients at low surgical risk, U.S. case volume for the procedure should markedly rise given that patients at low surgical risk form the largest risk subgroup among patients with aortic stenosis severe enough to warrant valve replacement.
But even as transcatheter aortic valve replacement (TAVR) now becomes the predominant approach for fixing severely stenotic aortic valves regardless of a patient’s risk level, the procedure remains less optimal than surgical aortic valve replacement (SAVR) in selected patients, putting an onus on clinicians to identify and alert patients for whom the transcatheter approach is questionable.
The anticipated surge in TAVR cases for low-risk patients after the FDA’s Aug. 16, 2019, decision will also likely lead to more hospitals offering TAVR. That development will test whether recently enacted rules from the Centers for Medicare & Medicaid Services on procedure-volume minimums for TAVR programs – at least 20 cases a year (or 40 within 2 years) at centers that also perform at least 300 percutaneous coronary interventions annually – lead to outcomes at lower-volume centers that come reasonably close to the outcomes at higher-volume programs for low-risk patients.
“The paradigm has definitely shifted from SAVR as the gold standard to TAVR as the primary treatment for aortic stenosis. This opens TAVR to the vast majority of patients with aortic stenosis,” roughly three-quarters of patients with aortic valve stenosis severe enough to need valve replacement, said Joseph C. Cleveland Jr., MD, a cardiothoracic surgeon and professor of surgery at the University of Colorado at Denver, Aurora.
The actual, immediate increase in TAVR patients may not be quite as large as this fraction suggests. That’s in part because many patients in the low-risk category based on their surgical risk score already have been judged to have higher-risk features by heart-valve teams that has allowed such patients to undergo TAVR, said John D. Carroll, MD, professor of medicine and director of interventional cardiology at the University of Colorado.
For several years, U.S. rates of TAVR have exceeded SAVR, he noted, and in 2018 U.S. programs performed roughly 58,000 TAVR procedures and about 25,000 SAVRs, according to data collected by the Transcatheter Valve Therapy (TVT) Registry run by the Society of Thoracic Surgeons and the American College of Cardiology. Dr. Carroll is vice chair of the steering committee for this registry, which was mandated by the FDA in 2011 when the agency first allowed TAVR onto the U.S. market and is designed to capture every TAVR case performed in routine U.S. practice.
Despite this caveat, “there will be substantial growth in TAVR. Going forward, there will be more of a shift from SAVR to TAVR. That is what the results of the low-risk trials did,” Dr. Carroll predicted. In addition, the coming growth in TAVR numbers will stem from more than just low-risk patients whom a month ago would have undergone SAVR but now undergo TAVR instead. The availability of TAVR as an option for a wider range of patients should help boost public awareness that a nonsurgical way exists to treat severe aortic stenosis, plus the aging of baby boomers is on the verge of generating a substantial wave of new patients, a wave so high that Dr. Carroll called it a looming “tsunami” of patients needing TAVR.
How will low-risk TAVR affect lower-volume sites?
More TAVR patients will inevitably mean more U.S. sites offering the procedure, experts agreed. “We anticipate more low-volume programs,” Dr. Carroll said.
“Approval of TAVR for low-risk patients will result in a significant increase in the number of programs offering it. Approximately 1,100 U.S. programs offer SAVR, and as of now about 600 of these programs also offer TAVR. Health systems face the risk of losing patients if they don’t offer TAVR now that low-risk patients can be treated,” observed Sreekanth Vemulapalli, MD, a cardiologist at Duke University, Durham, N.C. who has run several studies using TVT Registry data and serves as liaison between the registry and its analytic center at Duke.
One of these studies, published earlier in 2019, showed that, among more than 96,000 registry patients who underwent transfemoral TAVR during 2015-2017 at 554 U.S. centers, those treated at sites that fell into the bottom quartile for case volume had an adjusted 30-day mortality rate that was 21% higher relative to patients treated at centers in the top quartile, a statistically significant difference (N Engl J Med. 2019 Jun 27;380[26]:2541-50). The absolute difference in adjusted 30-day mortality between the lowest and highest quartiles was 0.54%, roughly 1 additional death for every 200 patients. The TAVR centers in the lowest-volume quartile performed 5-36 cases/year, averaging 27 TAVRs/year; those in the highest quartile performed 86-371 TAVRs annually with an overall quartile average of 143 procedures/year.
Dr. Vemulapalli and others cautioned that TAVR case volume is currently serving as a surrogate, and imperfect, marker for program quality until TAVR programs generate enough data to allow a directly measured, risk-adjusted, outcome-driven assessment of performance. In the study he and his associates published in June, the 140 TAVR programs in the lowest-volume quartile showed a “high” level of variability in their adjusted mortality rates. Despite this limitation, the prospect that new TAVR programs will soon open to meet growing TAVR demand from low-risk patients poses the question of how these programs will perform during their start-up days (and possibly beyond), when case volumes may be light, especially if sites open in more remote sections of the United States.
“Will the real-world results of TAVR in low-risk patients match the fantastic results in the two low-risk TAVR trials?” wondered Dr. Carroll, referring to the PARTNER 3 (N Engl J Med. 2019 May 2;380[18]:1695-1705) and Evolut Low-Risk Patients trial (N Engl J Med. 2019 May 2;380[18]:1706-15). “It’s unknown whether a site just starting to do TAVRs will get the same results. The sites that participated in the low-risk trials were mostly high-volume sites.” On the other hand, TVT Registry data have shown that patients with surgical risk that was judged prohibitive, high, or intermediate all have had overall real-world outcomes that match what was seen in the relevant TAVR trials.
In addition, some experts view a modest drop in 30-day survival among patients treated at lower-volume TAVR sites as a reasonable trade-off for easier access for patients seeking this life-changing treatment.
“We need to ensure that patients have access to this treatment option,” said Catherine M. Otto, MD, professor of medicine and director of the Heart Valve Clinic at the University of Washington, Seattle. The potentially better outcomes produced at larger TAVR programs “need to be balanced against having a greater number of programs to ensure access for more patients and allow patients to be treated closer to home,” she said in an interview. She suggested that the potential exists to use telemedicine to link larger and more experienced TAVR programs with smaller and newer programs to help boost their performance.
“There is no perfect solution or metric to ensure high quality while also allowing for adequate access. As indications for TAVR expand we need to maintain vigilance and accountability as the therapy is dispersed to more patients at more centers,” said Brian R. Lindman, MD, medical director of the Structural Heat and Valve Center at Vanderbilt University, Nashville, Tenn. “We also need to insure that certain groups of patients have adequate access to this therapy. Adequate access to TAVR and high-quality clinical outcomes are both important goals.”
Plus, “the volume relationship may be less important,” in lower-risk patients, suggested Dr. Cleveland in an interview. Low-risk patients are younger and have fewer comorbidities and less vascular disease. “Low-volume centers should be able to treat these patients,” he said. Despite that, he personally supported the higher volume minimum for TAVR of 50 cases/year that the ACC, STS, and other U.S. professional societies recommended to CMS during public comment on the proposed rules. “We’ll see whether the increased access is worth this volume minimum.”
Who still gets SAVR?
Given the inherent attraction TAVR holds over SAVR for patients, heart-valve teams will need to convey the right message to patients who may be better served with surgical replacement despite the added trauma and recovery time it produces.
“The decision to perform TAVR or SAVR should now be based on a patient’s expected longevity as well as patient preferences and values, and not on the patient’s estimated surgical risk, except for the highest-risk patients in whom TAVR is recommended,” said Dr. Otto. A patient’s age, comorbidities, and overall life expectancy now move to center stage when deciding the TAVR or SAVR question, along with individual anatomic considerations, the possible need for concurrent procedures, and of course what the patient prefers including their willingness and ability to remain on lifelong anticoagulation if they receive a durable mechanical valve. Dr. Otto outlined this new landscape of the heart-valve team’s decision making process in an editorial she recently published (N Engl J Med. 2019 May 2;380[18]: 1769-70) that accompanied publication of PARTNER 3 and the Evolut Low-Risk Patients trial.
“For some patients there will be clear benefit from one approach, but for many patients, particularly those at low surgical risk, both TAVR and SAVR are technically feasible. For these patients it’s essential that the heart-valve team provide unbiased information to guide patients,” Dr. Otto said. The ideal person to provide this unbiased presentation of the pros and cons would be a cardiologist experienced with valve disease but not actively involved in performing valve-replacement procedures.
A big issue younger patients must confront is what remains unknown about long-term durability of TAVR valves. Dr. Otto called this “the most important missing piece of information. We only have robust data out to about 5 years. If TAVR valve will be durable for 15-20 years, then TAVR will become preferred even in younger patients.”
Even after TAVR became available to intermediate-risk patients in 2016, the median age of U.S. patients undergoing TAVR hardly budged, and has recently stood at about 81 years, Dr. Carroll noted. “With low-risk patients, we expect to see this change,” as more patients now who are in their 70s, 60s, and younger start to routinely undergo TAVR. As more younger patients with life expectancies on the order of 30 years consider TAVR, issues of valve durability “enter the discussion,” he said. “We need data to 10, 15 years,” and in its low-risk approval the FDA mandated manufacturers to follow these patients for at least 10 years. Although valve-in-valve replacement of failed TAVR valves is an option, it’s not always a smooth fix with the potential for prosthesis-patient mismatch (J Am Coll Cardiol. 2018 Dec 4;72[22]:2701-11) and resulting hemodynamic problems, Dr. Carroll said.
Bicuspid-valve replacement with TAVR is another big unknown, largely because these patients were excluded from the TAVR trials. A recently published analysis of the 2,726 patients with a bicuspid aortic valve who underwent TAVR anyway in routine U.S. practice between June 2015 and November 2018 and were in the TVT Registry (about 3% of all TAVR patients during this period) showed that these patients had similar mortality, compared with the tricuspid-valve patients, but a significantly increased stroke rate (JAMA. 2019 Jun 11;321[22]:2193-202). The authors concluded that a prospective, randomized study of TAVR, compared with SAVR, is needed for these patients, and many others in the field agree.
As availability of TAVR grows and public awareness increases, heart-valve teams may find it challenging sometimes to help patients understand the upsides of SAVR for their individual clinical needs when TAVR is superficially so much more attractive.
“The desire to avoid the prolonged hospitalization and recovery from SAVR is a huge driver of patient preference,” noted Dr. Carroll.
“It’s hard to tell a 55 year old to think about another procedure they may need when they are 65 or 70 if they undergo TAVR now rather than SAVR. They don’t want open-heart surgery; I hear that all the time,” Dr. Cleveland said. “If I were a 55-year-old aortic valve patient I’d strongly consider TAVR, too.”
Financial consideration at the site performing the interventions can also be a factor. “Differential costs and payments associated with SAVR and TAVR create different financial incentives for health systems between these two procedures,” noted Dr. Vemulapalli. “There likely needs to be a system that creates equal incentives to do SAVR or TAVR so that the decision between them can come down to just the patient and heart-valve team. We need further data and decision aids to help better define which patients will likely do better with SAVR and which with TAVR.”
What now?
Since the first large TAVR trials started in 2007, their main thrust has been to prove the efficacy and safety of TAVR in patients at sequentially less risk of undergoing SAVR. Now that this series of comparisons has ended, where will TAVR research turn its attention?
In addition to the big outstanding issues of TAVR-valve long-term durability, and the efficacy and safety of TAVR for replacing bicuspid valves, other big questions and issues loom. They include the optimal anticoagulant regimen for preventing leaflet thrombosis, reducing the need for pacemakers, reducing strokes, the applicability of TAVR to patients with less severe aortic stenosis, the impact of treating severe but asymptomatic aortic valve obstruction, optimizing valve-in-valve outcomes, and further improvements to valve design, hemodynamics, and delivery. In short, the question of TAVR’s suitability for patients regardless of their surgical risk may have now been answered, but many questions remain about the best way to use and to optimize this technology.
Dr. Cleveland and Dr. Carroll have participated in TAVR trials but had no personal financial disclosures. Dr. Otto had no disclosures. Dr. Vemulapalli has received personal fees from Janssen, Novella, Premiere, and Zafgen, and research funding from Boston Scientific and Abbott Vascular. Dr. Lindman has been a consultant to Medtronic, has served as an advisor to Roche, and has received research funding from Edwards Lifesciences.
With the Food and Drug Administration’s approval of two different pairs of transcatheter aortic valve replacement systems for patients at low surgical risk, U.S. case volume for the procedure should markedly rise given that patients at low surgical risk form the largest risk subgroup among patients with aortic stenosis severe enough to warrant valve replacement.
But even as transcatheter aortic valve replacement (TAVR) now becomes the predominant approach for fixing severely stenotic aortic valves regardless of a patient’s risk level, the procedure remains less optimal than surgical aortic valve replacement (SAVR) in selected patients, putting an onus on clinicians to identify and alert patients for whom the transcatheter approach is questionable.
The anticipated surge in TAVR cases for low-risk patients after the FDA’s Aug. 16, 2019, decision will also likely lead to more hospitals offering TAVR. That development will test whether recently enacted rules from the Centers for Medicare & Medicaid Services on procedure-volume minimums for TAVR programs – at least 20 cases a year (or 40 within 2 years) at centers that also perform at least 300 percutaneous coronary interventions annually – lead to outcomes at lower-volume centers that come reasonably close to the outcomes at higher-volume programs for low-risk patients.
“The paradigm has definitely shifted from SAVR as the gold standard to TAVR as the primary treatment for aortic stenosis. This opens TAVR to the vast majority of patients with aortic stenosis,” roughly three-quarters of patients with aortic valve stenosis severe enough to need valve replacement, said Joseph C. Cleveland Jr., MD, a cardiothoracic surgeon and professor of surgery at the University of Colorado at Denver, Aurora.
The actual, immediate increase in TAVR patients may not be quite as large as this fraction suggests. That’s in part because many patients in the low-risk category based on their surgical risk score already have been judged to have higher-risk features by heart-valve teams that has allowed such patients to undergo TAVR, said John D. Carroll, MD, professor of medicine and director of interventional cardiology at the University of Colorado.
For several years, U.S. rates of TAVR have exceeded SAVR, he noted, and in 2018 U.S. programs performed roughly 58,000 TAVR procedures and about 25,000 SAVRs, according to data collected by the Transcatheter Valve Therapy (TVT) Registry run by the Society of Thoracic Surgeons and the American College of Cardiology. Dr. Carroll is vice chair of the steering committee for this registry, which was mandated by the FDA in 2011 when the agency first allowed TAVR onto the U.S. market and is designed to capture every TAVR case performed in routine U.S. practice.
Despite this caveat, “there will be substantial growth in TAVR. Going forward, there will be more of a shift from SAVR to TAVR. That is what the results of the low-risk trials did,” Dr. Carroll predicted. In addition, the coming growth in TAVR numbers will stem from more than just low-risk patients whom a month ago would have undergone SAVR but now undergo TAVR instead. The availability of TAVR as an option for a wider range of patients should help boost public awareness that a nonsurgical way exists to treat severe aortic stenosis, plus the aging of baby boomers is on the verge of generating a substantial wave of new patients, a wave so high that Dr. Carroll called it a looming “tsunami” of patients needing TAVR.
How will low-risk TAVR affect lower-volume sites?
More TAVR patients will inevitably mean more U.S. sites offering the procedure, experts agreed. “We anticipate more low-volume programs,” Dr. Carroll said.
“Approval of TAVR for low-risk patients will result in a significant increase in the number of programs offering it. Approximately 1,100 U.S. programs offer SAVR, and as of now about 600 of these programs also offer TAVR. Health systems face the risk of losing patients if they don’t offer TAVR now that low-risk patients can be treated,” observed Sreekanth Vemulapalli, MD, a cardiologist at Duke University, Durham, N.C. who has run several studies using TVT Registry data and serves as liaison between the registry and its analytic center at Duke.
One of these studies, published earlier in 2019, showed that, among more than 96,000 registry patients who underwent transfemoral TAVR during 2015-2017 at 554 U.S. centers, those treated at sites that fell into the bottom quartile for case volume had an adjusted 30-day mortality rate that was 21% higher relative to patients treated at centers in the top quartile, a statistically significant difference (N Engl J Med. 2019 Jun 27;380[26]:2541-50). The absolute difference in adjusted 30-day mortality between the lowest and highest quartiles was 0.54%, roughly 1 additional death for every 200 patients. The TAVR centers in the lowest-volume quartile performed 5-36 cases/year, averaging 27 TAVRs/year; those in the highest quartile performed 86-371 TAVRs annually with an overall quartile average of 143 procedures/year.
Dr. Vemulapalli and others cautioned that TAVR case volume is currently serving as a surrogate, and imperfect, marker for program quality until TAVR programs generate enough data to allow a directly measured, risk-adjusted, outcome-driven assessment of performance. In the study he and his associates published in June, the 140 TAVR programs in the lowest-volume quartile showed a “high” level of variability in their adjusted mortality rates. Despite this limitation, the prospect that new TAVR programs will soon open to meet growing TAVR demand from low-risk patients poses the question of how these programs will perform during their start-up days (and possibly beyond), when case volumes may be light, especially if sites open in more remote sections of the United States.
“Will the real-world results of TAVR in low-risk patients match the fantastic results in the two low-risk TAVR trials?” wondered Dr. Carroll, referring to the PARTNER 3 (N Engl J Med. 2019 May 2;380[18]:1695-1705) and Evolut Low-Risk Patients trial (N Engl J Med. 2019 May 2;380[18]:1706-15). “It’s unknown whether a site just starting to do TAVRs will get the same results. The sites that participated in the low-risk trials were mostly high-volume sites.” On the other hand, TVT Registry data have shown that patients with surgical risk that was judged prohibitive, high, or intermediate all have had overall real-world outcomes that match what was seen in the relevant TAVR trials.
In addition, some experts view a modest drop in 30-day survival among patients treated at lower-volume TAVR sites as a reasonable trade-off for easier access for patients seeking this life-changing treatment.
“We need to ensure that patients have access to this treatment option,” said Catherine M. Otto, MD, professor of medicine and director of the Heart Valve Clinic at the University of Washington, Seattle. The potentially better outcomes produced at larger TAVR programs “need to be balanced against having a greater number of programs to ensure access for more patients and allow patients to be treated closer to home,” she said in an interview. She suggested that the potential exists to use telemedicine to link larger and more experienced TAVR programs with smaller and newer programs to help boost their performance.
“There is no perfect solution or metric to ensure high quality while also allowing for adequate access. As indications for TAVR expand we need to maintain vigilance and accountability as the therapy is dispersed to more patients at more centers,” said Brian R. Lindman, MD, medical director of the Structural Heat and Valve Center at Vanderbilt University, Nashville, Tenn. “We also need to insure that certain groups of patients have adequate access to this therapy. Adequate access to TAVR and high-quality clinical outcomes are both important goals.”
Plus, “the volume relationship may be less important,” in lower-risk patients, suggested Dr. Cleveland in an interview. Low-risk patients are younger and have fewer comorbidities and less vascular disease. “Low-volume centers should be able to treat these patients,” he said. Despite that, he personally supported the higher volume minimum for TAVR of 50 cases/year that the ACC, STS, and other U.S. professional societies recommended to CMS during public comment on the proposed rules. “We’ll see whether the increased access is worth this volume minimum.”
Who still gets SAVR?
Given the inherent attraction TAVR holds over SAVR for patients, heart-valve teams will need to convey the right message to patients who may be better served with surgical replacement despite the added trauma and recovery time it produces.
“The decision to perform TAVR or SAVR should now be based on a patient’s expected longevity as well as patient preferences and values, and not on the patient’s estimated surgical risk, except for the highest-risk patients in whom TAVR is recommended,” said Dr. Otto. A patient’s age, comorbidities, and overall life expectancy now move to center stage when deciding the TAVR or SAVR question, along with individual anatomic considerations, the possible need for concurrent procedures, and of course what the patient prefers including their willingness and ability to remain on lifelong anticoagulation if they receive a durable mechanical valve. Dr. Otto outlined this new landscape of the heart-valve team’s decision making process in an editorial she recently published (N Engl J Med. 2019 May 2;380[18]: 1769-70) that accompanied publication of PARTNER 3 and the Evolut Low-Risk Patients trial.
“For some patients there will be clear benefit from one approach, but for many patients, particularly those at low surgical risk, both TAVR and SAVR are technically feasible. For these patients it’s essential that the heart-valve team provide unbiased information to guide patients,” Dr. Otto said. The ideal person to provide this unbiased presentation of the pros and cons would be a cardiologist experienced with valve disease but not actively involved in performing valve-replacement procedures.
A big issue younger patients must confront is what remains unknown about long-term durability of TAVR valves. Dr. Otto called this “the most important missing piece of information. We only have robust data out to about 5 years. If TAVR valve will be durable for 15-20 years, then TAVR will become preferred even in younger patients.”
Even after TAVR became available to intermediate-risk patients in 2016, the median age of U.S. patients undergoing TAVR hardly budged, and has recently stood at about 81 years, Dr. Carroll noted. “With low-risk patients, we expect to see this change,” as more patients now who are in their 70s, 60s, and younger start to routinely undergo TAVR. As more younger patients with life expectancies on the order of 30 years consider TAVR, issues of valve durability “enter the discussion,” he said. “We need data to 10, 15 years,” and in its low-risk approval the FDA mandated manufacturers to follow these patients for at least 10 years. Although valve-in-valve replacement of failed TAVR valves is an option, it’s not always a smooth fix with the potential for prosthesis-patient mismatch (J Am Coll Cardiol. 2018 Dec 4;72[22]:2701-11) and resulting hemodynamic problems, Dr. Carroll said.
Bicuspid-valve replacement with TAVR is another big unknown, largely because these patients were excluded from the TAVR trials. A recently published analysis of the 2,726 patients with a bicuspid aortic valve who underwent TAVR anyway in routine U.S. practice between June 2015 and November 2018 and were in the TVT Registry (about 3% of all TAVR patients during this period) showed that these patients had similar mortality, compared with the tricuspid-valve patients, but a significantly increased stroke rate (JAMA. 2019 Jun 11;321[22]:2193-202). The authors concluded that a prospective, randomized study of TAVR, compared with SAVR, is needed for these patients, and many others in the field agree.
As availability of TAVR grows and public awareness increases, heart-valve teams may find it challenging sometimes to help patients understand the upsides of SAVR for their individual clinical needs when TAVR is superficially so much more attractive.
“The desire to avoid the prolonged hospitalization and recovery from SAVR is a huge driver of patient preference,” noted Dr. Carroll.
“It’s hard to tell a 55 year old to think about another procedure they may need when they are 65 or 70 if they undergo TAVR now rather than SAVR. They don’t want open-heart surgery; I hear that all the time,” Dr. Cleveland said. “If I were a 55-year-old aortic valve patient I’d strongly consider TAVR, too.”
Financial consideration at the site performing the interventions can also be a factor. “Differential costs and payments associated with SAVR and TAVR create different financial incentives for health systems between these two procedures,” noted Dr. Vemulapalli. “There likely needs to be a system that creates equal incentives to do SAVR or TAVR so that the decision between them can come down to just the patient and heart-valve team. We need further data and decision aids to help better define which patients will likely do better with SAVR and which with TAVR.”
What now?
Since the first large TAVR trials started in 2007, their main thrust has been to prove the efficacy and safety of TAVR in patients at sequentially less risk of undergoing SAVR. Now that this series of comparisons has ended, where will TAVR research turn its attention?
In addition to the big outstanding issues of TAVR-valve long-term durability, and the efficacy and safety of TAVR for replacing bicuspid valves, other big questions and issues loom. They include the optimal anticoagulant regimen for preventing leaflet thrombosis, reducing the need for pacemakers, reducing strokes, the applicability of TAVR to patients with less severe aortic stenosis, the impact of treating severe but asymptomatic aortic valve obstruction, optimizing valve-in-valve outcomes, and further improvements to valve design, hemodynamics, and delivery. In short, the question of TAVR’s suitability for patients regardless of their surgical risk may have now been answered, but many questions remain about the best way to use and to optimize this technology.
Dr. Cleveland and Dr. Carroll have participated in TAVR trials but had no personal financial disclosures. Dr. Otto had no disclosures. Dr. Vemulapalli has received personal fees from Janssen, Novella, Premiere, and Zafgen, and research funding from Boston Scientific and Abbott Vascular. Dr. Lindman has been a consultant to Medtronic, has served as an advisor to Roche, and has received research funding from Edwards Lifesciences.
Class I recall issued for Sapien 3 balloon
The Food and Drug Administration has issued a class I correction recall for Edward Lifescience’s Sapien 3 balloon system, which is used to deploy transcatheter aortic valve replacements, according to a release from the agency. A class I recall is the most serious the agency issues and indicates risk of severe injury or even death.
Rather than indicate removal of the device from market, this recall provides details on how to use the device cautiously and safely and instructs physicians on proper technique to safely retract the delivery system into the sheath in cases of a suspected balloon burst. Failure to observe these recommendations can result in vascular injury, bleeding, or surgical intervention.
These recommendations and instructions reiterate those issued in an Urgent Field Safety Notice that was provided by Edward Lifesciences on July 9, 2019. Edward Lifesciences could not be reached for comment.
The Food and Drug Administration has issued a class I correction recall for Edward Lifescience’s Sapien 3 balloon system, which is used to deploy transcatheter aortic valve replacements, according to a release from the agency. A class I recall is the most serious the agency issues and indicates risk of severe injury or even death.
Rather than indicate removal of the device from market, this recall provides details on how to use the device cautiously and safely and instructs physicians on proper technique to safely retract the delivery system into the sheath in cases of a suspected balloon burst. Failure to observe these recommendations can result in vascular injury, bleeding, or surgical intervention.
These recommendations and instructions reiterate those issued in an Urgent Field Safety Notice that was provided by Edward Lifesciences on July 9, 2019. Edward Lifesciences could not be reached for comment.
The Food and Drug Administration has issued a class I correction recall for Edward Lifescience’s Sapien 3 balloon system, which is used to deploy transcatheter aortic valve replacements, according to a release from the agency. A class I recall is the most serious the agency issues and indicates risk of severe injury or even death.
Rather than indicate removal of the device from market, this recall provides details on how to use the device cautiously and safely and instructs physicians on proper technique to safely retract the delivery system into the sheath in cases of a suspected balloon burst. Failure to observe these recommendations can result in vascular injury, bleeding, or surgical intervention.
These recommendations and instructions reiterate those issued in an Urgent Field Safety Notice that was provided by Edward Lifesciences on July 9, 2019. Edward Lifesciences could not be reached for comment.
Post-TAVR anticoagulation alone fails to cut stroke risk in AFib
In patients with atrial fibrillation (AFib) who have undergone transcatheter aortic valve replacement (TAVR) and had a CHA2DS2-VASc score of at least 2, oral anticoagulant (OAC) therapy alone was not linked to reduced stroke risk.
By contrast, antiplatelet therapy was linked to a reduced risk of stroke in those AFib-TAVR patients, regardless of whether an oral anticoagulant was on board, according to results of a substudy of the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and its associated registries.
“Anticoagulant therapy was associated with a reduced risk of stroke and the composite of death or stroke when used concomitantly with uninterrupted antiplatelet therapy following TAVR,” concluded authors of the analysis, led by Ioanna Kosmidou, MD, PhD, of Columbia University in New York.
Taken together, these findings suggest OAC alone is “not sufficient” to prevent cerebrovascular events after TAVR in patients with AFib, Dr. Kosmidou and colleagues reported in JACC: Cardiovascular Interventions.
The analysis of the PARTNER II substudy included a total of 1,621 patients with aortic stenosis treated with TAVR who had a history of AFib and an absolute indication for anticoagulation as evidenced by a CHA2DS2-VASc score of at least 2.
Despite the absolute indication for anticoagulation, more than 40% of these patients were not prescribed an OAC upon discharge, investigators wrote, though the rate of nonprescribing decreased over the 5-year enrollment period of 2011-2015.
OAC therapy alone was not linked to reduced stroke risk in this cohort, investigators said. After 2 years, the rate of stroke was 6.6% for AFib-TAVR patients on anticoagulant therapy, and 5.6% for those who were not on anticoagulant therapy, a nonsignificant difference at P = 0.53, according to the reported data.
By contrast, uninterrupted antiplatelet therapy reduced both risk of stroke and risk of the composite endpoint of stroke and death at 2 years “irrespective of concomitant anticoagulation,” Dr. Kosmidou and coinvestigators wrote in the report.
The stroke rates were 5.4% for antiplatelet therapy plus OAC, versus 11.1% for those receiving neither antithrombotic treatment (P = 0.03), while the rates of stroke or death were 29.7% and 40.1%, respectively (P = 0.01), according to investigators.
After adjustment, stroke risk was not significantly reduced for OAC when compared with no OAC or antiplatelet therapy (HR, 0.61; P = .16), whereas stroke risk was indeed reduced for antiplatelet therapy alone (HR, 0.32; P = .002) and antiplatelet therapy with oral anticoagulation (HR, 0.44; P = .018).
The PARTNER II study was funded by Edwards Lifesciences. Senior author Martin B. Leon, MD, and several other study coauthors reported disclosures related to Edwards Lifesciences, in addition to Abbott Vascular, Cordis, Medtronic, Boston Scientific, and other companies. Dr. Kosmidou reported no disclosures.
SOURCE: Kosmidou I et al. JACC Cardiovasc Interv. 2019;12:1580-9.
Results of this PARTNER II substudy investigation by Kosmidou and colleagues are timely and thought provoking because they imply that some current recommendations may be insufficient for preventing stroke in patients with atrial fibrillation (AFib) undergoing transcatheter aortic valve replacement (TAVR).
Specifically, the results showed no difference in risk of stroke or the composite of death and stroke at 2 years in oral anticoagulant (OAC) and non-OAC patient groups, whereas by contrast, antiplatelet therapy was linked with reduced stroke risk versus no antithrombotic therapy, whether or not the patients received OAC.
The substudy reinforces the understanding that TAVR itself is a determinant of stroke because of mechanisms that go beyond thrombus formation in the left atrial appendage and are essentially platelet mediated.
How to manage antithrombotic therapy in patients with AFib who undergo TAVR remains a residual field of ambiguity.
However, observational studies cannot be conclusive, they said, so results of relevant prospective, randomized trials are eagerly awaited.
For example, the effects of novel oral anticoagulants versus vitamin K antagonists will be evaluated in the ENVISAGE-TAVI study, as well as the ATLANTIS trial, which will additionally include non-OAC patients.
The relative benefits of OAC alone versus OAC plus antiplatelet therapy will be evaluated in the AVATAR study, which will include AFib-TAVR patients randomized to OAC versus OAC plus aspirin, while the POPular-TAVI and CLOE trials will also include cohorts that help provide a more eloquent answer regarding the benefit-risk ratio of combining antiplatelet therapy and OAC in these patients.
Davide Capodanno, MD, PhD, and Antonio Greco, MD, of the University of Catania (Italy) made these comments in an accompanying editorial (JACC: Cardiovasc Interv. 2019 Aug 19. doi: 10.1016/j.jcin.2019.07.004). Dr. Capodanno reported disclosures related to Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and Sanofi. Dr. Greco reported having no relevant disclosures.
Results of this PARTNER II substudy investigation by Kosmidou and colleagues are timely and thought provoking because they imply that some current recommendations may be insufficient for preventing stroke in patients with atrial fibrillation (AFib) undergoing transcatheter aortic valve replacement (TAVR).
Specifically, the results showed no difference in risk of stroke or the composite of death and stroke at 2 years in oral anticoagulant (OAC) and non-OAC patient groups, whereas by contrast, antiplatelet therapy was linked with reduced stroke risk versus no antithrombotic therapy, whether or not the patients received OAC.
The substudy reinforces the understanding that TAVR itself is a determinant of stroke because of mechanisms that go beyond thrombus formation in the left atrial appendage and are essentially platelet mediated.
How to manage antithrombotic therapy in patients with AFib who undergo TAVR remains a residual field of ambiguity.
However, observational studies cannot be conclusive, they said, so results of relevant prospective, randomized trials are eagerly awaited.
For example, the effects of novel oral anticoagulants versus vitamin K antagonists will be evaluated in the ENVISAGE-TAVI study, as well as the ATLANTIS trial, which will additionally include non-OAC patients.
The relative benefits of OAC alone versus OAC plus antiplatelet therapy will be evaluated in the AVATAR study, which will include AFib-TAVR patients randomized to OAC versus OAC plus aspirin, while the POPular-TAVI and CLOE trials will also include cohorts that help provide a more eloquent answer regarding the benefit-risk ratio of combining antiplatelet therapy and OAC in these patients.
Davide Capodanno, MD, PhD, and Antonio Greco, MD, of the University of Catania (Italy) made these comments in an accompanying editorial (JACC: Cardiovasc Interv. 2019 Aug 19. doi: 10.1016/j.jcin.2019.07.004). Dr. Capodanno reported disclosures related to Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and Sanofi. Dr. Greco reported having no relevant disclosures.
Results of this PARTNER II substudy investigation by Kosmidou and colleagues are timely and thought provoking because they imply that some current recommendations may be insufficient for preventing stroke in patients with atrial fibrillation (AFib) undergoing transcatheter aortic valve replacement (TAVR).
Specifically, the results showed no difference in risk of stroke or the composite of death and stroke at 2 years in oral anticoagulant (OAC) and non-OAC patient groups, whereas by contrast, antiplatelet therapy was linked with reduced stroke risk versus no antithrombotic therapy, whether or not the patients received OAC.
The substudy reinforces the understanding that TAVR itself is a determinant of stroke because of mechanisms that go beyond thrombus formation in the left atrial appendage and are essentially platelet mediated.
How to manage antithrombotic therapy in patients with AFib who undergo TAVR remains a residual field of ambiguity.
However, observational studies cannot be conclusive, they said, so results of relevant prospective, randomized trials are eagerly awaited.
For example, the effects of novel oral anticoagulants versus vitamin K antagonists will be evaluated in the ENVISAGE-TAVI study, as well as the ATLANTIS trial, which will additionally include non-OAC patients.
The relative benefits of OAC alone versus OAC plus antiplatelet therapy will be evaluated in the AVATAR study, which will include AFib-TAVR patients randomized to OAC versus OAC plus aspirin, while the POPular-TAVI and CLOE trials will also include cohorts that help provide a more eloquent answer regarding the benefit-risk ratio of combining antiplatelet therapy and OAC in these patients.
Davide Capodanno, MD, PhD, and Antonio Greco, MD, of the University of Catania (Italy) made these comments in an accompanying editorial (JACC: Cardiovasc Interv. 2019 Aug 19. doi: 10.1016/j.jcin.2019.07.004). Dr. Capodanno reported disclosures related to Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and Sanofi. Dr. Greco reported having no relevant disclosures.
In patients with atrial fibrillation (AFib) who have undergone transcatheter aortic valve replacement (TAVR) and had a CHA2DS2-VASc score of at least 2, oral anticoagulant (OAC) therapy alone was not linked to reduced stroke risk.
By contrast, antiplatelet therapy was linked to a reduced risk of stroke in those AFib-TAVR patients, regardless of whether an oral anticoagulant was on board, according to results of a substudy of the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and its associated registries.
“Anticoagulant therapy was associated with a reduced risk of stroke and the composite of death or stroke when used concomitantly with uninterrupted antiplatelet therapy following TAVR,” concluded authors of the analysis, led by Ioanna Kosmidou, MD, PhD, of Columbia University in New York.
Taken together, these findings suggest OAC alone is “not sufficient” to prevent cerebrovascular events after TAVR in patients with AFib, Dr. Kosmidou and colleagues reported in JACC: Cardiovascular Interventions.
The analysis of the PARTNER II substudy included a total of 1,621 patients with aortic stenosis treated with TAVR who had a history of AFib and an absolute indication for anticoagulation as evidenced by a CHA2DS2-VASc score of at least 2.
Despite the absolute indication for anticoagulation, more than 40% of these patients were not prescribed an OAC upon discharge, investigators wrote, though the rate of nonprescribing decreased over the 5-year enrollment period of 2011-2015.
OAC therapy alone was not linked to reduced stroke risk in this cohort, investigators said. After 2 years, the rate of stroke was 6.6% for AFib-TAVR patients on anticoagulant therapy, and 5.6% for those who were not on anticoagulant therapy, a nonsignificant difference at P = 0.53, according to the reported data.
By contrast, uninterrupted antiplatelet therapy reduced both risk of stroke and risk of the composite endpoint of stroke and death at 2 years “irrespective of concomitant anticoagulation,” Dr. Kosmidou and coinvestigators wrote in the report.
The stroke rates were 5.4% for antiplatelet therapy plus OAC, versus 11.1% for those receiving neither antithrombotic treatment (P = 0.03), while the rates of stroke or death were 29.7% and 40.1%, respectively (P = 0.01), according to investigators.
After adjustment, stroke risk was not significantly reduced for OAC when compared with no OAC or antiplatelet therapy (HR, 0.61; P = .16), whereas stroke risk was indeed reduced for antiplatelet therapy alone (HR, 0.32; P = .002) and antiplatelet therapy with oral anticoagulation (HR, 0.44; P = .018).
The PARTNER II study was funded by Edwards Lifesciences. Senior author Martin B. Leon, MD, and several other study coauthors reported disclosures related to Edwards Lifesciences, in addition to Abbott Vascular, Cordis, Medtronic, Boston Scientific, and other companies. Dr. Kosmidou reported no disclosures.
SOURCE: Kosmidou I et al. JACC Cardiovasc Interv. 2019;12:1580-9.
In patients with atrial fibrillation (AFib) who have undergone transcatheter aortic valve replacement (TAVR) and had a CHA2DS2-VASc score of at least 2, oral anticoagulant (OAC) therapy alone was not linked to reduced stroke risk.
By contrast, antiplatelet therapy was linked to a reduced risk of stroke in those AFib-TAVR patients, regardless of whether an oral anticoagulant was on board, according to results of a substudy of the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and its associated registries.
“Anticoagulant therapy was associated with a reduced risk of stroke and the composite of death or stroke when used concomitantly with uninterrupted antiplatelet therapy following TAVR,” concluded authors of the analysis, led by Ioanna Kosmidou, MD, PhD, of Columbia University in New York.
Taken together, these findings suggest OAC alone is “not sufficient” to prevent cerebrovascular events after TAVR in patients with AFib, Dr. Kosmidou and colleagues reported in JACC: Cardiovascular Interventions.
The analysis of the PARTNER II substudy included a total of 1,621 patients with aortic stenosis treated with TAVR who had a history of AFib and an absolute indication for anticoagulation as evidenced by a CHA2DS2-VASc score of at least 2.
Despite the absolute indication for anticoagulation, more than 40% of these patients were not prescribed an OAC upon discharge, investigators wrote, though the rate of nonprescribing decreased over the 5-year enrollment period of 2011-2015.
OAC therapy alone was not linked to reduced stroke risk in this cohort, investigators said. After 2 years, the rate of stroke was 6.6% for AFib-TAVR patients on anticoagulant therapy, and 5.6% for those who were not on anticoagulant therapy, a nonsignificant difference at P = 0.53, according to the reported data.
By contrast, uninterrupted antiplatelet therapy reduced both risk of stroke and risk of the composite endpoint of stroke and death at 2 years “irrespective of concomitant anticoagulation,” Dr. Kosmidou and coinvestigators wrote in the report.
The stroke rates were 5.4% for antiplatelet therapy plus OAC, versus 11.1% for those receiving neither antithrombotic treatment (P = 0.03), while the rates of stroke or death were 29.7% and 40.1%, respectively (P = 0.01), according to investigators.
After adjustment, stroke risk was not significantly reduced for OAC when compared with no OAC or antiplatelet therapy (HR, 0.61; P = .16), whereas stroke risk was indeed reduced for antiplatelet therapy alone (HR, 0.32; P = .002) and antiplatelet therapy with oral anticoagulation (HR, 0.44; P = .018).
The PARTNER II study was funded by Edwards Lifesciences. Senior author Martin B. Leon, MD, and several other study coauthors reported disclosures related to Edwards Lifesciences, in addition to Abbott Vascular, Cordis, Medtronic, Boston Scientific, and other companies. Dr. Kosmidou reported no disclosures.
SOURCE: Kosmidou I et al. JACC Cardiovasc Interv. 2019;12:1580-9.
FROM JACC: CARDIOVASCULAR INTERVENTIONS
TAVR valves now FDA approved for low-risk patients
The Food and Drug Administration has expanded the indication for the Sapien 3, Sapien 3 Ultra, CoreValve Evolut R, and CoreValve Evolut PRO transcatheter heart valves to include patients with severe aortic valve stenosis at low risk for death or major complications associated with open-heart surgery.
The announcement was based on results of a pair of clinical trials involving patients with severe aortic valve stenosis. In the first, 1,000 patients were randomly sorted to receive either transcatheter aortic valve replacement (TAVR) with the Edwards Lifescience’s Sapien 3 device or open-heart surgery. In the second, 1,468 patients received either Medtronic’s CoreValve Evolut R or CoreValve Evolut PRO or open heart surgery. In both studies, after an average follow-up time of 15-17 months, outcomes such as all-cause mortality and stroke were similar in patients who underwent open heart surgery and who received the transcatheter heart valve.
Serious adverse events associated with transcatheter heart valves include death, stroke, acute kidney injury, heart attack, bleeding, and the need for a permanent pacemaker. Patients who cannot tolerate blood-thinning medication or have an infection in the heart are contraindicated; in addition, the CoreValve devices should not be used in patients sensitive to titanium or nickel. Because the longevity of transcatheter heart valves, compared with open-heart surgery, has not been established, younger patients should discuss options with their health care provider.
“This new approval significantly expands the number of patients that can be treated with this less invasive procedure for aortic valve replacement and follows a thorough review of data demonstrating these devices are safe and effective for this larger population,” Bram Zuckerman, MD, director of the Office of Cardiovascular Devices in the FDA’s Center for Devices and Radiological Health, said in the press release.
Find the full press release on the FDA website.
The Food and Drug Administration has expanded the indication for the Sapien 3, Sapien 3 Ultra, CoreValve Evolut R, and CoreValve Evolut PRO transcatheter heart valves to include patients with severe aortic valve stenosis at low risk for death or major complications associated with open-heart surgery.
The announcement was based on results of a pair of clinical trials involving patients with severe aortic valve stenosis. In the first, 1,000 patients were randomly sorted to receive either transcatheter aortic valve replacement (TAVR) with the Edwards Lifescience’s Sapien 3 device or open-heart surgery. In the second, 1,468 patients received either Medtronic’s CoreValve Evolut R or CoreValve Evolut PRO or open heart surgery. In both studies, after an average follow-up time of 15-17 months, outcomes such as all-cause mortality and stroke were similar in patients who underwent open heart surgery and who received the transcatheter heart valve.
Serious adverse events associated with transcatheter heart valves include death, stroke, acute kidney injury, heart attack, bleeding, and the need for a permanent pacemaker. Patients who cannot tolerate blood-thinning medication or have an infection in the heart are contraindicated; in addition, the CoreValve devices should not be used in patients sensitive to titanium or nickel. Because the longevity of transcatheter heart valves, compared with open-heart surgery, has not been established, younger patients should discuss options with their health care provider.
“This new approval significantly expands the number of patients that can be treated with this less invasive procedure for aortic valve replacement and follows a thorough review of data demonstrating these devices are safe and effective for this larger population,” Bram Zuckerman, MD, director of the Office of Cardiovascular Devices in the FDA’s Center for Devices and Radiological Health, said in the press release.
Find the full press release on the FDA website.
The Food and Drug Administration has expanded the indication for the Sapien 3, Sapien 3 Ultra, CoreValve Evolut R, and CoreValve Evolut PRO transcatheter heart valves to include patients with severe aortic valve stenosis at low risk for death or major complications associated with open-heart surgery.
The announcement was based on results of a pair of clinical trials involving patients with severe aortic valve stenosis. In the first, 1,000 patients were randomly sorted to receive either transcatheter aortic valve replacement (TAVR) with the Edwards Lifescience’s Sapien 3 device or open-heart surgery. In the second, 1,468 patients received either Medtronic’s CoreValve Evolut R or CoreValve Evolut PRO or open heart surgery. In both studies, after an average follow-up time of 15-17 months, outcomes such as all-cause mortality and stroke were similar in patients who underwent open heart surgery and who received the transcatheter heart valve.
Serious adverse events associated with transcatheter heart valves include death, stroke, acute kidney injury, heart attack, bleeding, and the need for a permanent pacemaker. Patients who cannot tolerate blood-thinning medication or have an infection in the heart are contraindicated; in addition, the CoreValve devices should not be used in patients sensitive to titanium or nickel. Because the longevity of transcatheter heart valves, compared with open-heart surgery, has not been established, younger patients should discuss options with their health care provider.
“This new approval significantly expands the number of patients that can be treated with this less invasive procedure for aortic valve replacement and follows a thorough review of data demonstrating these devices are safe and effective for this larger population,” Bram Zuckerman, MD, director of the Office of Cardiovascular Devices in the FDA’s Center for Devices and Radiological Health, said in the press release.
Find the full press release on the FDA website.
Abbott issues recall on Ellipse ICDs
Abbott Laboratories has issued a recall of all Ellipse Implantable Cardioverter Defibrillators manufactured between April 5, 2019, and May 29, 2019, because of exposed aluminum wires within the device, potentially preventing defibrillation.
The Ellipse Implantable Cardioverter Defibrillators, formerly manufactured by St. Jude Medical (now a wholly-owned subsidiary of Abbott), provide pacing for patients with bradycardia and electric shock or pacing for patients with tachycardia. The device is implanted under the skin in the upper chest area with leads running into the heart.
The recall has been issued because electrical failures have occurred; Abbott has determined that these failures are caused by a faulty manufacturing process that left some aluminum wires in the leads partially exposed. Wires without proper insulation are likely to short, leaving the device without the ability to provide high voltage therapy.
Abbott is aware of no related reports of electrical failure in any of the devices that have already been implanted, the Food and Drug Administration announced, and no reports of patient harm, adverse events, or death have occurred. All affected devices that were implanted have either been replaced or are scheduled to be replaced, the agency said.
Abbott Laboratories has issued a recall of all Ellipse Implantable Cardioverter Defibrillators manufactured between April 5, 2019, and May 29, 2019, because of exposed aluminum wires within the device, potentially preventing defibrillation.
The Ellipse Implantable Cardioverter Defibrillators, formerly manufactured by St. Jude Medical (now a wholly-owned subsidiary of Abbott), provide pacing for patients with bradycardia and electric shock or pacing for patients with tachycardia. The device is implanted under the skin in the upper chest area with leads running into the heart.
The recall has been issued because electrical failures have occurred; Abbott has determined that these failures are caused by a faulty manufacturing process that left some aluminum wires in the leads partially exposed. Wires without proper insulation are likely to short, leaving the device without the ability to provide high voltage therapy.
Abbott is aware of no related reports of electrical failure in any of the devices that have already been implanted, the Food and Drug Administration announced, and no reports of patient harm, adverse events, or death have occurred. All affected devices that were implanted have either been replaced or are scheduled to be replaced, the agency said.
Abbott Laboratories has issued a recall of all Ellipse Implantable Cardioverter Defibrillators manufactured between April 5, 2019, and May 29, 2019, because of exposed aluminum wires within the device, potentially preventing defibrillation.
The Ellipse Implantable Cardioverter Defibrillators, formerly manufactured by St. Jude Medical (now a wholly-owned subsidiary of Abbott), provide pacing for patients with bradycardia and electric shock or pacing for patients with tachycardia. The device is implanted under the skin in the upper chest area with leads running into the heart.
The recall has been issued because electrical failures have occurred; Abbott has determined that these failures are caused by a faulty manufacturing process that left some aluminum wires in the leads partially exposed. Wires without proper insulation are likely to short, leaving the device without the ability to provide high voltage therapy.
Abbott is aware of no related reports of electrical failure in any of the devices that have already been implanted, the Food and Drug Administration announced, and no reports of patient harm, adverse events, or death have occurred. All affected devices that were implanted have either been replaced or are scheduled to be replaced, the agency said.
Does endovascular thrombectomy benefit stroke patients with large infarcts?
Endovascular thrombectomy may benefit patients with stroke with large infarcts, an analysis suggests. The intervention may be more likely to benefit patients who “are treated early and have a core volume less than 100 cm3,” researchers reported in JAMA Neurology.
Clinical trials evaluating thrombectomy have largely excluded patients with large ischemic cores. To examine whether thrombectomy produces reasonable functional and safety outcomes in patients with stroke with large infarcts, compared with medical management alone, the investigators conducted a prespecified secondary analysis of data from the Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) study.
A nonrandomized study
Amrou Sarraj, MD, of the University of Texas, Houston, and his coauthors analyzed data from 105 patients in the prospective, multicenter cohort study, which enrolled patients between January 2016 and February 2018. Their analysis included data from patients who had large ischemic cores on CT (Alberta Stroke Program Early CT Score, 0-5) or on CT perfusion images (an ischemic core volume of at least 50 cm3). The SELECT study included patients with moderate to severe stroke and anterior circulation large-vessel occlusion who presented up to 24 hours from the time they last were known to be well. In the SELECT study, local investigators decided whether patients received endovascular thrombectomy or medical management alone in a nonrandomized fashion.
The 105 patients had a median age of 66 years, and 43% were female. Of the patients with large infarcts, 62 (59%) received endovascular thrombectomy plus medical management, and the rest received medical management alone.
At 90 days, 31% of the patients who received endovascular thrombectomy achieved functional independence (modified Rankin Scale score of 0-2), compared with 14% of patients who received medical management alone (odds ratio, 3.27). In addition, endovascular thrombectomy was associated with better functional outcome, less infarct growth (44 vs. 98 mL), and smaller final infarct volume (97 vs. 190 mL).
The rates of neurologic worsening and symptomatic intracerebral hemorrhage were similar in both treatment groups, while mortality was lower among patients who received thrombectomy (29% vs. 42%). The likelihood of functional independence with endovascular thrombectomy decreased by 40% with each 1-hour delay in treatment and by 42% with each 10-cm3 increase in stroke volume.
Of 10 patients with core volumes greater than 100 cm3 who received endovascular thrombectomy, none had a favorable outcome.
“Although the odds of good outcomes for patients with large cores who received [endovascular thrombectomy] markedly decline with increasing core size and time to treatment, these data suggest potential benefits,” Dr. Sarraj and colleagues concluded. “Randomized clinical trials are needed.”
The authors noted that the results “did not reach significance after adjusting for baseline imbalances” and that “the small sample size limits the power of this analysis.”
The study was funded by an unrestricted grant from Stryker Neurovascular to the University of Texas. Dr. Sarraj is a consultant, speaker bureau member, and advisory board member for Stryker and is the principal investigator for a planned randomized, controlled trial (SELECT 2) funded by an unrestricted grant from Stryker to his institution. In addition, he is a site principal investigator for the TREVO Registry and DEFUSE 3 trials. Coauthors reported financial ties with Stryker and various device and pharmaceutical companies.
SOURCE: Sarraj A et al. JAMA Neurol. 2019 Jul 29. doi: 10.1001/jamaneurol.2019.2109.
Patients who had thrombectomies had improved outcomes in an unadjusted statistical analysis, but these differences did not remain significant after adjustment for baseline age, clinical severity, and other key prognostic variables. However, the analysis was underpowered.
A key finding was that favorable outcomes in patients with large core volumes was strongly time dependent, which was consistent with previous data from the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) collaboration.
Faster treatment is the key to maximizing benefit for patients with poor collateral blood flow and a large ischemic core at baseline. As treatment work flow improves and more patients are transported directly to a thrombectomy-capable center, the number who benefit from reperfusion, despite a large ischemic core, is likely to further increase.
Ongoing randomized clinical trials are assessing the practical question of who to treat with thrombectomy when the estimated ischemic core volume is large.
Bruce C. V. Campbell, MBBS, PhD , of the University of Melbourne made these comments in an accompanying editorial. He reported research support from the several Australian research foundations. He also reported unrestricted grant funding for the Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial (EXTEND-IA) trial to the Florey Institute of Neuroscience and Mental Health in Parkville, Australia, from Covidien (Medtronic).
Patients who had thrombectomies had improved outcomes in an unadjusted statistical analysis, but these differences did not remain significant after adjustment for baseline age, clinical severity, and other key prognostic variables. However, the analysis was underpowered.
A key finding was that favorable outcomes in patients with large core volumes was strongly time dependent, which was consistent with previous data from the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) collaboration.
Faster treatment is the key to maximizing benefit for patients with poor collateral blood flow and a large ischemic core at baseline. As treatment work flow improves and more patients are transported directly to a thrombectomy-capable center, the number who benefit from reperfusion, despite a large ischemic core, is likely to further increase.
Ongoing randomized clinical trials are assessing the practical question of who to treat with thrombectomy when the estimated ischemic core volume is large.
Bruce C. V. Campbell, MBBS, PhD , of the University of Melbourne made these comments in an accompanying editorial. He reported research support from the several Australian research foundations. He also reported unrestricted grant funding for the Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial (EXTEND-IA) trial to the Florey Institute of Neuroscience and Mental Health in Parkville, Australia, from Covidien (Medtronic).
Patients who had thrombectomies had improved outcomes in an unadjusted statistical analysis, but these differences did not remain significant after adjustment for baseline age, clinical severity, and other key prognostic variables. However, the analysis was underpowered.
A key finding was that favorable outcomes in patients with large core volumes was strongly time dependent, which was consistent with previous data from the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) collaboration.
Faster treatment is the key to maximizing benefit for patients with poor collateral blood flow and a large ischemic core at baseline. As treatment work flow improves and more patients are transported directly to a thrombectomy-capable center, the number who benefit from reperfusion, despite a large ischemic core, is likely to further increase.
Ongoing randomized clinical trials are assessing the practical question of who to treat with thrombectomy when the estimated ischemic core volume is large.
Bruce C. V. Campbell, MBBS, PhD , of the University of Melbourne made these comments in an accompanying editorial. He reported research support from the several Australian research foundations. He also reported unrestricted grant funding for the Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial (EXTEND-IA) trial to the Florey Institute of Neuroscience and Mental Health in Parkville, Australia, from Covidien (Medtronic).
Endovascular thrombectomy may benefit patients with stroke with large infarcts, an analysis suggests. The intervention may be more likely to benefit patients who “are treated early and have a core volume less than 100 cm3,” researchers reported in JAMA Neurology.
Clinical trials evaluating thrombectomy have largely excluded patients with large ischemic cores. To examine whether thrombectomy produces reasonable functional and safety outcomes in patients with stroke with large infarcts, compared with medical management alone, the investigators conducted a prespecified secondary analysis of data from the Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) study.
A nonrandomized study
Amrou Sarraj, MD, of the University of Texas, Houston, and his coauthors analyzed data from 105 patients in the prospective, multicenter cohort study, which enrolled patients between January 2016 and February 2018. Their analysis included data from patients who had large ischemic cores on CT (Alberta Stroke Program Early CT Score, 0-5) or on CT perfusion images (an ischemic core volume of at least 50 cm3). The SELECT study included patients with moderate to severe stroke and anterior circulation large-vessel occlusion who presented up to 24 hours from the time they last were known to be well. In the SELECT study, local investigators decided whether patients received endovascular thrombectomy or medical management alone in a nonrandomized fashion.
The 105 patients had a median age of 66 years, and 43% were female. Of the patients with large infarcts, 62 (59%) received endovascular thrombectomy plus medical management, and the rest received medical management alone.
At 90 days, 31% of the patients who received endovascular thrombectomy achieved functional independence (modified Rankin Scale score of 0-2), compared with 14% of patients who received medical management alone (odds ratio, 3.27). In addition, endovascular thrombectomy was associated with better functional outcome, less infarct growth (44 vs. 98 mL), and smaller final infarct volume (97 vs. 190 mL).
The rates of neurologic worsening and symptomatic intracerebral hemorrhage were similar in both treatment groups, while mortality was lower among patients who received thrombectomy (29% vs. 42%). The likelihood of functional independence with endovascular thrombectomy decreased by 40% with each 1-hour delay in treatment and by 42% with each 10-cm3 increase in stroke volume.
Of 10 patients with core volumes greater than 100 cm3 who received endovascular thrombectomy, none had a favorable outcome.
“Although the odds of good outcomes for patients with large cores who received [endovascular thrombectomy] markedly decline with increasing core size and time to treatment, these data suggest potential benefits,” Dr. Sarraj and colleagues concluded. “Randomized clinical trials are needed.”
The authors noted that the results “did not reach significance after adjusting for baseline imbalances” and that “the small sample size limits the power of this analysis.”
The study was funded by an unrestricted grant from Stryker Neurovascular to the University of Texas. Dr. Sarraj is a consultant, speaker bureau member, and advisory board member for Stryker and is the principal investigator for a planned randomized, controlled trial (SELECT 2) funded by an unrestricted grant from Stryker to his institution. In addition, he is a site principal investigator for the TREVO Registry and DEFUSE 3 trials. Coauthors reported financial ties with Stryker and various device and pharmaceutical companies.
SOURCE: Sarraj A et al. JAMA Neurol. 2019 Jul 29. doi: 10.1001/jamaneurol.2019.2109.
Endovascular thrombectomy may benefit patients with stroke with large infarcts, an analysis suggests. The intervention may be more likely to benefit patients who “are treated early and have a core volume less than 100 cm3,” researchers reported in JAMA Neurology.
Clinical trials evaluating thrombectomy have largely excluded patients with large ischemic cores. To examine whether thrombectomy produces reasonable functional and safety outcomes in patients with stroke with large infarcts, compared with medical management alone, the investigators conducted a prespecified secondary analysis of data from the Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) study.
A nonrandomized study
Amrou Sarraj, MD, of the University of Texas, Houston, and his coauthors analyzed data from 105 patients in the prospective, multicenter cohort study, which enrolled patients between January 2016 and February 2018. Their analysis included data from patients who had large ischemic cores on CT (Alberta Stroke Program Early CT Score, 0-5) or on CT perfusion images (an ischemic core volume of at least 50 cm3). The SELECT study included patients with moderate to severe stroke and anterior circulation large-vessel occlusion who presented up to 24 hours from the time they last were known to be well. In the SELECT study, local investigators decided whether patients received endovascular thrombectomy or medical management alone in a nonrandomized fashion.
The 105 patients had a median age of 66 years, and 43% were female. Of the patients with large infarcts, 62 (59%) received endovascular thrombectomy plus medical management, and the rest received medical management alone.
At 90 days, 31% of the patients who received endovascular thrombectomy achieved functional independence (modified Rankin Scale score of 0-2), compared with 14% of patients who received medical management alone (odds ratio, 3.27). In addition, endovascular thrombectomy was associated with better functional outcome, less infarct growth (44 vs. 98 mL), and smaller final infarct volume (97 vs. 190 mL).
The rates of neurologic worsening and symptomatic intracerebral hemorrhage were similar in both treatment groups, while mortality was lower among patients who received thrombectomy (29% vs. 42%). The likelihood of functional independence with endovascular thrombectomy decreased by 40% with each 1-hour delay in treatment and by 42% with each 10-cm3 increase in stroke volume.
Of 10 patients with core volumes greater than 100 cm3 who received endovascular thrombectomy, none had a favorable outcome.
“Although the odds of good outcomes for patients with large cores who received [endovascular thrombectomy] markedly decline with increasing core size and time to treatment, these data suggest potential benefits,” Dr. Sarraj and colleagues concluded. “Randomized clinical trials are needed.”
The authors noted that the results “did not reach significance after adjusting for baseline imbalances” and that “the small sample size limits the power of this analysis.”
The study was funded by an unrestricted grant from Stryker Neurovascular to the University of Texas. Dr. Sarraj is a consultant, speaker bureau member, and advisory board member for Stryker and is the principal investigator for a planned randomized, controlled trial (SELECT 2) funded by an unrestricted grant from Stryker to his institution. In addition, he is a site principal investigator for the TREVO Registry and DEFUSE 3 trials. Coauthors reported financial ties with Stryker and various device and pharmaceutical companies.
SOURCE: Sarraj A et al. JAMA Neurol. 2019 Jul 29. doi: 10.1001/jamaneurol.2019.2109.
FROM JAMA NEUROLOGY
Key clinical point: and who have a core volume less than 100 mL.
Major finding: At 90 days, 31% of the patients who received endovascular thrombectomy achieved functional independence (modified Rankin Scale score of 0-2), compared with 14% of patients who received medical management alone (odds ratio, 3.27).
Study details: A prespecified secondary analysis of nonrandomized data from 105 patients in the Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) study.
Disclosures: The study was funded by an unrestricted grant from Stryker Neurovascular. Dr. Sarraj is a consultant, speaker bureau member, and advisory board member for Stryker and is the principal investigator for a planned randomized, controlled trial (SELECT 2) funded by an unrestricted grant from Stryker to his institution. Coauthors reported financial ties with Stryker and various device and pharmaceutical companies.
Source: Sarraj A et al. JAMA Neurol. 2019 Jul 29. doi: 10.1001/jamaneurol.2019.2109.
Two trials support shorter DAPT without aspirin after stent
An entire year of dual-antiplatelet therapy may be no better at limiting ischemic events or death than a shorter course for patients who have undergone percutaneous coronary intervention with a drug-eluting stent.
The two trials, which tested dual-antiplatelet therapy (DAPT) regimens of 3 months and 1 month, are also noteworthy for giving a P2Y12 inhibitor after DAPT instead of aspirin monotherapy, which is a more common approach. Each randomized about 3,000 patients.
According to lead author Joo-Yong Hahn, MD, of Sungkyunkwan University in Seoul, South Korea, and colleagues, who conducted the first trial (SMART-CHOICE), both shorter and longer DAPT regimens with aspirin have been associated with shortcomings.
Specifically, shorter duration DAPT with subsequent aspirin monotherapy carries increased risks of MI and stent thrombosis, the investigators wrote. “Conversely, prolonged DAPT increases the risk of bleeding, which offsets the benefit from reducing recurrent ischemic events. Therefore, neither prolonged DAPT nor short-duration DAPT followed by aspirin monotherapy is fully satisfactory.” Because of these shortcomings, the investigators suggested that developing novel strategies “is of paramount importance.”
SMART-CHOICE
The multicenter trial by Dr. Hahn and colleagues, conducted in South Korea, involved 2,993 patients undergoing percutaneous coronary intervention with drug-eluting stents. Patients were randomized to receive either standard DAPT with aspirin and a P2Y12 inhibitor for 12 months, or aspirin plus a P2Y12 inhibitor for 3 months followed by 9 months of P2Y12 monotherapy. Patients were stratified by enrolling center, clinical presentation, type of stent, and type of P2Y12 therapy. Stents were limited to those eluting cobalt-chromium everolimus (Xience Prime, Xience Expedition, or Xience Alpine; Abbott Vascular), platinum-chromium everolimus (Promus Element, Promus Premier, or SYNERGY; Boston Scientific), or sirolimus (Orsiro; Biotronik). Acceptable P2Y12 therapies were clopidogrel, ticagrelor, and prasugrel. The primary endpoint was a composite of major adverse cerebrovascular and cardiac events, including stroke, MI, or all-cause death, at 12 months after percutaneous coronary intervention. A number of secondary endpoints were also evaluated, such as bleeding rate, stent thrombosis, and the individual components of the primary endpoint.
Almost all patients (95%) in the DAPT group adhered to the study protocol, while a smaller proportion (79%) followed P2Y12 monotherapy as described. Still, for both groups, more than 97% of patients completed 1-year follow-up. Primary endpoint analysis showed that the cumulative rate of major adverse cerebrovascular and cardiac events was similar between both groups, at 2.9% in the P2Y12 group versus 2.5% in the DAPT group, which was statistically significant for noninferiority (P = .007). Per-protocol analysis supported this finding.
Similarly, the components of the primary endpoint – stroke, MI, or all-cause death – did not vary significantly between groups. No significant difference was detected for the risk of stent thrombosis. Although the major bleeding rate was comparable between groups, the overall bleeding rate was significantly lower in the P2Y12 inhibitor group than the DAPT group (2.0% vs. 3.4%; P = .02); this finding also was supported by per-protocol analysis (1.8% vs. 3.1%; P = .04).
The investigators proposed several explanations for the results. “First, aspirin might provide little additional inhibition of platelet aggregation in the presence of a P2Y12 inhibitor. … Second, the risk of bleeding was significantly lower with P2Y12 inhibitor monotherapy than with DAPT in the present study.”
They noted that second-generation drug-eluting stents were used, which have been shown to significantly reduce MI and stent thrombosis, compared with first-generation products.
STOPDAPT-2
This study, led by Hirotoshi Watanabe, MD, of Kyoto University, and colleagues, followed a similar design, but with an even shorter duration of DAPT in the treatment arm, at 1 month, and stricter criteria for the stent, which was limited to one cobalt-chromium everolimus-eluting model (Xience Series; Abbott Vascular). During the first month of the trial, all patients received aspirin plus either clopidogrel or prasugrel; thereafter, patients in the 12-month group received aspirin and clopidogrel while the 1-month group was given clopidogrel alone.
The primary endpoint was a composite of cardiovascular and bleeding events, including MI, stent thrombosis, cardiovascular death, stroke, and major or minor bleeding. Secondary endpoints included these components individually, as well as a list of other cardiovascular and bleeding measures.
Similarly to the first trial, Dr. Watanabe and colleagues found that the shorter DAPT protocol was noninferior to standard DAPT and associated with a lower rate of bleeding events. The primary endpoint occurred in 2.4% of the 1-month DAPT group, compared with 3.7% of the 12-month DAPT group, thereby meeting noninferiority criteria (P less than .001). This finding was confirmed in the per-protocol population. The 1-month DAPT regimen was significantly associated with fewer major bleeding events than the 12-month protocol (0.41% vs. 1.54%), demonstrating superiority (P = .004). In addition, seven other measures of bleeding frequency were lower in the 1-month DAPT group than the standard DAPT group, including Bleeding Academic Research Consortium type 3 or 5 criteria, and Global Use of Strategies to Open Occluded Arteries moderate or severe criteria.
Dr. Watanabe and colleagues provided some insight into these findings and described clinical implications. “The benefit [of the 1-month DAPT regimen] was driven by a significant reduction of bleeding events without an increase in cardiovascular events,” they wrote. “Therefore, the very short DAPT duration of 1 month would be a potential option even in patients without high bleeding risk. Given the very low rates of stent thrombosis in studies using contemporary drug-eluting stents, avoiding bleeding with de-escalation of antiplatelet therapy may be more important than attempting further reduction of stent thrombosis with intensive antiplatelet therapy.”
SMART-CHOICE was funded by the Korean Society of Interventional Cardiology, Biotronik, Abbott Vascular, and Boston Scientific. Dr. Hahn and colleagues reported receiving additional financial relationships with AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, and others. STOPDAPT-2 was funded by Abbott Vascular. Dr. Watanabe and colleagues reported receiving additional funding from Daiichi Sankyo, Otsuka Pharmaceutical, Kowa Pharmaceuticals, and others.
SOURCES: Watanabe H et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8145; Hahn J-Y et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8146.
These two studies evaluated shorter-duration dual-antiplatelet therapy (DAPT) with a novel variation: Instead of discontinuing the P2Y12 inhibitor, which is a more common approach, the regimens discontinued aspirin. Although the studies had slightly different 1-year endpoints, both found that shorter DAPT with continued P2Y12 monotherapy reduced bleeding complications without increasing risk of ischemic events or death.
Based on these findings, and those from other trials, shorter DAPT will likely gain support, particularly when used with atherosclerosis risk factor reduction, newer implantation techniques, and contemporary stents. However, clinicians considering shorter DAPT for their patients should do so in light of baseline ischemic complication risk and clinical presentation. Furthermore, it remains unclear whether P2Y12 or aspirin monotherapy should be given after shorter DAPT. Until more evidence is available, it is too soon to abandon aspirin monotherapy or traditional DAPT.
Khaled M. Ziada, MD, and David J. Moliterno, MD, are with the department of cardiovascular medicine at the University of Kentucky, Lexington. Dr. Moliterno has received grants from AstraZeneca. No other disclosures were reported. Their remarks are adapted from an accompanying editorial (JAMA. 2019 June 25. doi: 10.1001/jama.2019.7025).
These two studies evaluated shorter-duration dual-antiplatelet therapy (DAPT) with a novel variation: Instead of discontinuing the P2Y12 inhibitor, which is a more common approach, the regimens discontinued aspirin. Although the studies had slightly different 1-year endpoints, both found that shorter DAPT with continued P2Y12 monotherapy reduced bleeding complications without increasing risk of ischemic events or death.
Based on these findings, and those from other trials, shorter DAPT will likely gain support, particularly when used with atherosclerosis risk factor reduction, newer implantation techniques, and contemporary stents. However, clinicians considering shorter DAPT for their patients should do so in light of baseline ischemic complication risk and clinical presentation. Furthermore, it remains unclear whether P2Y12 or aspirin monotherapy should be given after shorter DAPT. Until more evidence is available, it is too soon to abandon aspirin monotherapy or traditional DAPT.
Khaled M. Ziada, MD, and David J. Moliterno, MD, are with the department of cardiovascular medicine at the University of Kentucky, Lexington. Dr. Moliterno has received grants from AstraZeneca. No other disclosures were reported. Their remarks are adapted from an accompanying editorial (JAMA. 2019 June 25. doi: 10.1001/jama.2019.7025).
These two studies evaluated shorter-duration dual-antiplatelet therapy (DAPT) with a novel variation: Instead of discontinuing the P2Y12 inhibitor, which is a more common approach, the regimens discontinued aspirin. Although the studies had slightly different 1-year endpoints, both found that shorter DAPT with continued P2Y12 monotherapy reduced bleeding complications without increasing risk of ischemic events or death.
Based on these findings, and those from other trials, shorter DAPT will likely gain support, particularly when used with atherosclerosis risk factor reduction, newer implantation techniques, and contemporary stents. However, clinicians considering shorter DAPT for their patients should do so in light of baseline ischemic complication risk and clinical presentation. Furthermore, it remains unclear whether P2Y12 or aspirin monotherapy should be given after shorter DAPT. Until more evidence is available, it is too soon to abandon aspirin monotherapy or traditional DAPT.
Khaled M. Ziada, MD, and David J. Moliterno, MD, are with the department of cardiovascular medicine at the University of Kentucky, Lexington. Dr. Moliterno has received grants from AstraZeneca. No other disclosures were reported. Their remarks are adapted from an accompanying editorial (JAMA. 2019 June 25. doi: 10.1001/jama.2019.7025).
An entire year of dual-antiplatelet therapy may be no better at limiting ischemic events or death than a shorter course for patients who have undergone percutaneous coronary intervention with a drug-eluting stent.
The two trials, which tested dual-antiplatelet therapy (DAPT) regimens of 3 months and 1 month, are also noteworthy for giving a P2Y12 inhibitor after DAPT instead of aspirin monotherapy, which is a more common approach. Each randomized about 3,000 patients.
According to lead author Joo-Yong Hahn, MD, of Sungkyunkwan University in Seoul, South Korea, and colleagues, who conducted the first trial (SMART-CHOICE), both shorter and longer DAPT regimens with aspirin have been associated with shortcomings.
Specifically, shorter duration DAPT with subsequent aspirin monotherapy carries increased risks of MI and stent thrombosis, the investigators wrote. “Conversely, prolonged DAPT increases the risk of bleeding, which offsets the benefit from reducing recurrent ischemic events. Therefore, neither prolonged DAPT nor short-duration DAPT followed by aspirin monotherapy is fully satisfactory.” Because of these shortcomings, the investigators suggested that developing novel strategies “is of paramount importance.”
SMART-CHOICE
The multicenter trial by Dr. Hahn and colleagues, conducted in South Korea, involved 2,993 patients undergoing percutaneous coronary intervention with drug-eluting stents. Patients were randomized to receive either standard DAPT with aspirin and a P2Y12 inhibitor for 12 months, or aspirin plus a P2Y12 inhibitor for 3 months followed by 9 months of P2Y12 monotherapy. Patients were stratified by enrolling center, clinical presentation, type of stent, and type of P2Y12 therapy. Stents were limited to those eluting cobalt-chromium everolimus (Xience Prime, Xience Expedition, or Xience Alpine; Abbott Vascular), platinum-chromium everolimus (Promus Element, Promus Premier, or SYNERGY; Boston Scientific), or sirolimus (Orsiro; Biotronik). Acceptable P2Y12 therapies were clopidogrel, ticagrelor, and prasugrel. The primary endpoint was a composite of major adverse cerebrovascular and cardiac events, including stroke, MI, or all-cause death, at 12 months after percutaneous coronary intervention. A number of secondary endpoints were also evaluated, such as bleeding rate, stent thrombosis, and the individual components of the primary endpoint.
Almost all patients (95%) in the DAPT group adhered to the study protocol, while a smaller proportion (79%) followed P2Y12 monotherapy as described. Still, for both groups, more than 97% of patients completed 1-year follow-up. Primary endpoint analysis showed that the cumulative rate of major adverse cerebrovascular and cardiac events was similar between both groups, at 2.9% in the P2Y12 group versus 2.5% in the DAPT group, which was statistically significant for noninferiority (P = .007). Per-protocol analysis supported this finding.
Similarly, the components of the primary endpoint – stroke, MI, or all-cause death – did not vary significantly between groups. No significant difference was detected for the risk of stent thrombosis. Although the major bleeding rate was comparable between groups, the overall bleeding rate was significantly lower in the P2Y12 inhibitor group than the DAPT group (2.0% vs. 3.4%; P = .02); this finding also was supported by per-protocol analysis (1.8% vs. 3.1%; P = .04).
The investigators proposed several explanations for the results. “First, aspirin might provide little additional inhibition of platelet aggregation in the presence of a P2Y12 inhibitor. … Second, the risk of bleeding was significantly lower with P2Y12 inhibitor monotherapy than with DAPT in the present study.”
They noted that second-generation drug-eluting stents were used, which have been shown to significantly reduce MI and stent thrombosis, compared with first-generation products.
STOPDAPT-2
This study, led by Hirotoshi Watanabe, MD, of Kyoto University, and colleagues, followed a similar design, but with an even shorter duration of DAPT in the treatment arm, at 1 month, and stricter criteria for the stent, which was limited to one cobalt-chromium everolimus-eluting model (Xience Series; Abbott Vascular). During the first month of the trial, all patients received aspirin plus either clopidogrel or prasugrel; thereafter, patients in the 12-month group received aspirin and clopidogrel while the 1-month group was given clopidogrel alone.
The primary endpoint was a composite of cardiovascular and bleeding events, including MI, stent thrombosis, cardiovascular death, stroke, and major or minor bleeding. Secondary endpoints included these components individually, as well as a list of other cardiovascular and bleeding measures.
Similarly to the first trial, Dr. Watanabe and colleagues found that the shorter DAPT protocol was noninferior to standard DAPT and associated with a lower rate of bleeding events. The primary endpoint occurred in 2.4% of the 1-month DAPT group, compared with 3.7% of the 12-month DAPT group, thereby meeting noninferiority criteria (P less than .001). This finding was confirmed in the per-protocol population. The 1-month DAPT regimen was significantly associated with fewer major bleeding events than the 12-month protocol (0.41% vs. 1.54%), demonstrating superiority (P = .004). In addition, seven other measures of bleeding frequency were lower in the 1-month DAPT group than the standard DAPT group, including Bleeding Academic Research Consortium type 3 or 5 criteria, and Global Use of Strategies to Open Occluded Arteries moderate or severe criteria.
Dr. Watanabe and colleagues provided some insight into these findings and described clinical implications. “The benefit [of the 1-month DAPT regimen] was driven by a significant reduction of bleeding events without an increase in cardiovascular events,” they wrote. “Therefore, the very short DAPT duration of 1 month would be a potential option even in patients without high bleeding risk. Given the very low rates of stent thrombosis in studies using contemporary drug-eluting stents, avoiding bleeding with de-escalation of antiplatelet therapy may be more important than attempting further reduction of stent thrombosis with intensive antiplatelet therapy.”
SMART-CHOICE was funded by the Korean Society of Interventional Cardiology, Biotronik, Abbott Vascular, and Boston Scientific. Dr. Hahn and colleagues reported receiving additional financial relationships with AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, and others. STOPDAPT-2 was funded by Abbott Vascular. Dr. Watanabe and colleagues reported receiving additional funding from Daiichi Sankyo, Otsuka Pharmaceutical, Kowa Pharmaceuticals, and others.
SOURCES: Watanabe H et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8145; Hahn J-Y et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8146.
An entire year of dual-antiplatelet therapy may be no better at limiting ischemic events or death than a shorter course for patients who have undergone percutaneous coronary intervention with a drug-eluting stent.
The two trials, which tested dual-antiplatelet therapy (DAPT) regimens of 3 months and 1 month, are also noteworthy for giving a P2Y12 inhibitor after DAPT instead of aspirin monotherapy, which is a more common approach. Each randomized about 3,000 patients.
According to lead author Joo-Yong Hahn, MD, of Sungkyunkwan University in Seoul, South Korea, and colleagues, who conducted the first trial (SMART-CHOICE), both shorter and longer DAPT regimens with aspirin have been associated with shortcomings.
Specifically, shorter duration DAPT with subsequent aspirin monotherapy carries increased risks of MI and stent thrombosis, the investigators wrote. “Conversely, prolonged DAPT increases the risk of bleeding, which offsets the benefit from reducing recurrent ischemic events. Therefore, neither prolonged DAPT nor short-duration DAPT followed by aspirin monotherapy is fully satisfactory.” Because of these shortcomings, the investigators suggested that developing novel strategies “is of paramount importance.”
SMART-CHOICE
The multicenter trial by Dr. Hahn and colleagues, conducted in South Korea, involved 2,993 patients undergoing percutaneous coronary intervention with drug-eluting stents. Patients were randomized to receive either standard DAPT with aspirin and a P2Y12 inhibitor for 12 months, or aspirin plus a P2Y12 inhibitor for 3 months followed by 9 months of P2Y12 monotherapy. Patients were stratified by enrolling center, clinical presentation, type of stent, and type of P2Y12 therapy. Stents were limited to those eluting cobalt-chromium everolimus (Xience Prime, Xience Expedition, or Xience Alpine; Abbott Vascular), platinum-chromium everolimus (Promus Element, Promus Premier, or SYNERGY; Boston Scientific), or sirolimus (Orsiro; Biotronik). Acceptable P2Y12 therapies were clopidogrel, ticagrelor, and prasugrel. The primary endpoint was a composite of major adverse cerebrovascular and cardiac events, including stroke, MI, or all-cause death, at 12 months after percutaneous coronary intervention. A number of secondary endpoints were also evaluated, such as bleeding rate, stent thrombosis, and the individual components of the primary endpoint.
Almost all patients (95%) in the DAPT group adhered to the study protocol, while a smaller proportion (79%) followed P2Y12 monotherapy as described. Still, for both groups, more than 97% of patients completed 1-year follow-up. Primary endpoint analysis showed that the cumulative rate of major adverse cerebrovascular and cardiac events was similar between both groups, at 2.9% in the P2Y12 group versus 2.5% in the DAPT group, which was statistically significant for noninferiority (P = .007). Per-protocol analysis supported this finding.
Similarly, the components of the primary endpoint – stroke, MI, or all-cause death – did not vary significantly between groups. No significant difference was detected for the risk of stent thrombosis. Although the major bleeding rate was comparable between groups, the overall bleeding rate was significantly lower in the P2Y12 inhibitor group than the DAPT group (2.0% vs. 3.4%; P = .02); this finding also was supported by per-protocol analysis (1.8% vs. 3.1%; P = .04).
The investigators proposed several explanations for the results. “First, aspirin might provide little additional inhibition of platelet aggregation in the presence of a P2Y12 inhibitor. … Second, the risk of bleeding was significantly lower with P2Y12 inhibitor monotherapy than with DAPT in the present study.”
They noted that second-generation drug-eluting stents were used, which have been shown to significantly reduce MI and stent thrombosis, compared with first-generation products.
STOPDAPT-2
This study, led by Hirotoshi Watanabe, MD, of Kyoto University, and colleagues, followed a similar design, but with an even shorter duration of DAPT in the treatment arm, at 1 month, and stricter criteria for the stent, which was limited to one cobalt-chromium everolimus-eluting model (Xience Series; Abbott Vascular). During the first month of the trial, all patients received aspirin plus either clopidogrel or prasugrel; thereafter, patients in the 12-month group received aspirin and clopidogrel while the 1-month group was given clopidogrel alone.
The primary endpoint was a composite of cardiovascular and bleeding events, including MI, stent thrombosis, cardiovascular death, stroke, and major or minor bleeding. Secondary endpoints included these components individually, as well as a list of other cardiovascular and bleeding measures.
Similarly to the first trial, Dr. Watanabe and colleagues found that the shorter DAPT protocol was noninferior to standard DAPT and associated with a lower rate of bleeding events. The primary endpoint occurred in 2.4% of the 1-month DAPT group, compared with 3.7% of the 12-month DAPT group, thereby meeting noninferiority criteria (P less than .001). This finding was confirmed in the per-protocol population. The 1-month DAPT regimen was significantly associated with fewer major bleeding events than the 12-month protocol (0.41% vs. 1.54%), demonstrating superiority (P = .004). In addition, seven other measures of bleeding frequency were lower in the 1-month DAPT group than the standard DAPT group, including Bleeding Academic Research Consortium type 3 or 5 criteria, and Global Use of Strategies to Open Occluded Arteries moderate or severe criteria.
Dr. Watanabe and colleagues provided some insight into these findings and described clinical implications. “The benefit [of the 1-month DAPT regimen] was driven by a significant reduction of bleeding events without an increase in cardiovascular events,” they wrote. “Therefore, the very short DAPT duration of 1 month would be a potential option even in patients without high bleeding risk. Given the very low rates of stent thrombosis in studies using contemporary drug-eluting stents, avoiding bleeding with de-escalation of antiplatelet therapy may be more important than attempting further reduction of stent thrombosis with intensive antiplatelet therapy.”
SMART-CHOICE was funded by the Korean Society of Interventional Cardiology, Biotronik, Abbott Vascular, and Boston Scientific. Dr. Hahn and colleagues reported receiving additional financial relationships with AstraZeneca, Daiichi Sankyo, Sanofi-Aventis, and others. STOPDAPT-2 was funded by Abbott Vascular. Dr. Watanabe and colleagues reported receiving additional funding from Daiichi Sankyo, Otsuka Pharmaceutical, Kowa Pharmaceuticals, and others.
SOURCES: Watanabe H et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8145; Hahn J-Y et al. JAMA. 2019 Jun 25. doi: 10.1001/jama.2019.8146.
FROM JAMA
Revised CMS TAVR rules expected to widen access
The new National Coverage Determination by Medicare for transcatheter aortic valve replacement should produce a bump in the number of U.S. programs offering the procedure, especially with the Food and Drug Administration on the cusp of approving the procedure for low-risk patients.
In the revised National Coverage Determination (NCD) by the Centers for Medicare & Medicaid Services that went into effect on June 21, 2019, the agency allowed for Medicare coverage of transcatheter aortic valve (TAVR) procedures at hospitals that perform at least 20 of these procedures annually or at least 40 every 2 years, the same volume minimums that CMS first applied to TAVR in its prior 2012 NCD. Retention of this minimum ran against the 2018 proposal of the American College of Cardiology, the Society of Thoracic Surgeons, and two other collaborating societies that called for an annual TAVR volume minimum at a hospital program of 50 procedures annually or 100 every 2 years (J Am Coll Cardiol. 2019 Jan 29;73[3]:340-74).
That change, coupled with a cut in the minimum number of annual percutaneous coronary interventions a TAVR program needs to perform – newly revised to a minimum of 300 cases/year – will likely mean more U.S. sites performing TAVR, predicted James Vavricek, director of regulatory affairs for the ACC in Washington. TAVR volume is seen as a reasonable, approximate surrogate for a more rigorous, statistically adjusted assessment of program quality. The ACC and representatives from the other societies that collaborated on the 2018 statement used a 50 case/year minimum for a TAVR program because volume at that level generates enough outcomes data to allow for a meaningful, risk-adjusted measure of performance.
The ACC does not consider the minimum of 20 TAVR cases/year the “right decision,” Mr. Vavricek said in an interview, but the ACC sees it as a compromise that accommodated the interests of multiple TAVR stakeholders. “It will be interesting to see where new TAVR programs locate,” whether they will expand access in underserved regions or mostly cluster in regions already fairly replete with TAVR access, he added. Currently, over 600 U.S. TAVR programs are in operation.
In April 2019, the president of the ACC along with the presidents of three other U.S. societies with an interest in TAVR told the CMS in a comment letter that “we are extremely concerned that the proposed volume requirements will translate into a proliferation of low-volume TAVR programs at increased risk for having suboptimal outcomes.”
Another change to procedure volume requirements in the new NCD was setting a minimum of 100 total TAVR plus surgical aortic valve replacements in a 2-year period or 50 total procedures/year for each TAVR program. Setting a minimum that bundles TAVR plus surgical valve replacements is a “forward-looking” approach as wider application of TAVR gradually erodes the volume of surgical procedures, Mr. Vavricek said.
An additional notable change in the revised NCD was elimination of the “two-surgeon” rule, which the CMS had made mandatory for TAVR decisions until now, stipulating that a patient considered for TAVR needed independent assessment by two cardiac surgeons. The final 2019 NCD calls for the TAVR decision to come from one cardiac surgeon and one interventional cardiologist working together on a care team.
“The ACC is pleased to see CMS issue updated TAVR coverage criteria that emphasizes care by an interdisciplinary heart team for these complex patients, as well as continues to mandate the collection of TAVR patient data. With the new lowered minimum yearly volume criteria set by CMS in their efforts to improve patient access, the value of the STS/ACC TVT Registry, along with ACC’s Transcatheter Valve Certification, will be critical in assuring quality of care for our patients particularly in low-volume centers,” commented Richard J. Kovacs, MD, ACC’s president.
The new National Coverage Determination by Medicare for transcatheter aortic valve replacement should produce a bump in the number of U.S. programs offering the procedure, especially with the Food and Drug Administration on the cusp of approving the procedure for low-risk patients.
In the revised National Coverage Determination (NCD) by the Centers for Medicare & Medicaid Services that went into effect on June 21, 2019, the agency allowed for Medicare coverage of transcatheter aortic valve (TAVR) procedures at hospitals that perform at least 20 of these procedures annually or at least 40 every 2 years, the same volume minimums that CMS first applied to TAVR in its prior 2012 NCD. Retention of this minimum ran against the 2018 proposal of the American College of Cardiology, the Society of Thoracic Surgeons, and two other collaborating societies that called for an annual TAVR volume minimum at a hospital program of 50 procedures annually or 100 every 2 years (J Am Coll Cardiol. 2019 Jan 29;73[3]:340-74).
That change, coupled with a cut in the minimum number of annual percutaneous coronary interventions a TAVR program needs to perform – newly revised to a minimum of 300 cases/year – will likely mean more U.S. sites performing TAVR, predicted James Vavricek, director of regulatory affairs for the ACC in Washington. TAVR volume is seen as a reasonable, approximate surrogate for a more rigorous, statistically adjusted assessment of program quality. The ACC and representatives from the other societies that collaborated on the 2018 statement used a 50 case/year minimum for a TAVR program because volume at that level generates enough outcomes data to allow for a meaningful, risk-adjusted measure of performance.
The ACC does not consider the minimum of 20 TAVR cases/year the “right decision,” Mr. Vavricek said in an interview, but the ACC sees it as a compromise that accommodated the interests of multiple TAVR stakeholders. “It will be interesting to see where new TAVR programs locate,” whether they will expand access in underserved regions or mostly cluster in regions already fairly replete with TAVR access, he added. Currently, over 600 U.S. TAVR programs are in operation.
In April 2019, the president of the ACC along with the presidents of three other U.S. societies with an interest in TAVR told the CMS in a comment letter that “we are extremely concerned that the proposed volume requirements will translate into a proliferation of low-volume TAVR programs at increased risk for having suboptimal outcomes.”
Another change to procedure volume requirements in the new NCD was setting a minimum of 100 total TAVR plus surgical aortic valve replacements in a 2-year period or 50 total procedures/year for each TAVR program. Setting a minimum that bundles TAVR plus surgical valve replacements is a “forward-looking” approach as wider application of TAVR gradually erodes the volume of surgical procedures, Mr. Vavricek said.
An additional notable change in the revised NCD was elimination of the “two-surgeon” rule, which the CMS had made mandatory for TAVR decisions until now, stipulating that a patient considered for TAVR needed independent assessment by two cardiac surgeons. The final 2019 NCD calls for the TAVR decision to come from one cardiac surgeon and one interventional cardiologist working together on a care team.
“The ACC is pleased to see CMS issue updated TAVR coverage criteria that emphasizes care by an interdisciplinary heart team for these complex patients, as well as continues to mandate the collection of TAVR patient data. With the new lowered minimum yearly volume criteria set by CMS in their efforts to improve patient access, the value of the STS/ACC TVT Registry, along with ACC’s Transcatheter Valve Certification, will be critical in assuring quality of care for our patients particularly in low-volume centers,” commented Richard J. Kovacs, MD, ACC’s president.
The new National Coverage Determination by Medicare for transcatheter aortic valve replacement should produce a bump in the number of U.S. programs offering the procedure, especially with the Food and Drug Administration on the cusp of approving the procedure for low-risk patients.
In the revised National Coverage Determination (NCD) by the Centers for Medicare & Medicaid Services that went into effect on June 21, 2019, the agency allowed for Medicare coverage of transcatheter aortic valve (TAVR) procedures at hospitals that perform at least 20 of these procedures annually or at least 40 every 2 years, the same volume minimums that CMS first applied to TAVR in its prior 2012 NCD. Retention of this minimum ran against the 2018 proposal of the American College of Cardiology, the Society of Thoracic Surgeons, and two other collaborating societies that called for an annual TAVR volume minimum at a hospital program of 50 procedures annually or 100 every 2 years (J Am Coll Cardiol. 2019 Jan 29;73[3]:340-74).
That change, coupled with a cut in the minimum number of annual percutaneous coronary interventions a TAVR program needs to perform – newly revised to a minimum of 300 cases/year – will likely mean more U.S. sites performing TAVR, predicted James Vavricek, director of regulatory affairs for the ACC in Washington. TAVR volume is seen as a reasonable, approximate surrogate for a more rigorous, statistically adjusted assessment of program quality. The ACC and representatives from the other societies that collaborated on the 2018 statement used a 50 case/year minimum for a TAVR program because volume at that level generates enough outcomes data to allow for a meaningful, risk-adjusted measure of performance.
The ACC does not consider the minimum of 20 TAVR cases/year the “right decision,” Mr. Vavricek said in an interview, but the ACC sees it as a compromise that accommodated the interests of multiple TAVR stakeholders. “It will be interesting to see where new TAVR programs locate,” whether they will expand access in underserved regions or mostly cluster in regions already fairly replete with TAVR access, he added. Currently, over 600 U.S. TAVR programs are in operation.
In April 2019, the president of the ACC along with the presidents of three other U.S. societies with an interest in TAVR told the CMS in a comment letter that “we are extremely concerned that the proposed volume requirements will translate into a proliferation of low-volume TAVR programs at increased risk for having suboptimal outcomes.”
Another change to procedure volume requirements in the new NCD was setting a minimum of 100 total TAVR plus surgical aortic valve replacements in a 2-year period or 50 total procedures/year for each TAVR program. Setting a minimum that bundles TAVR plus surgical valve replacements is a “forward-looking” approach as wider application of TAVR gradually erodes the volume of surgical procedures, Mr. Vavricek said.
An additional notable change in the revised NCD was elimination of the “two-surgeon” rule, which the CMS had made mandatory for TAVR decisions until now, stipulating that a patient considered for TAVR needed independent assessment by two cardiac surgeons. The final 2019 NCD calls for the TAVR decision to come from one cardiac surgeon and one interventional cardiologist working together on a care team.
“The ACC is pleased to see CMS issue updated TAVR coverage criteria that emphasizes care by an interdisciplinary heart team for these complex patients, as well as continues to mandate the collection of TAVR patient data. With the new lowered minimum yearly volume criteria set by CMS in their efforts to improve patient access, the value of the STS/ACC TVT Registry, along with ACC’s Transcatheter Valve Certification, will be critical in assuring quality of care for our patients particularly in low-volume centers,” commented Richard J. Kovacs, MD, ACC’s president.
MRI-guided revascularization noninferior to FFR
Myocardial perfusion cardiovascular MRI is as good as invasive angiography and measurement of fractional flow reserve to guide revascularization in patients with angina, research suggests.
In the New England Journal of Medicine, researchers present the outcomes of an unblinded, multicenter, clinical effectiveness trial comparing the two revascularization strategies in 918 patients who had typical angina and either two or more cardiovascular risk factors or a positive exercise treadmill test.
In the fractional flow reserve method, revascularization was recommended in all vessels with an FFR of 0.8 or less. In the MRI-guided method, all patients underwent myocardial perfusion cardiovascular MRI, and patients with clinically significant inducible ischemia then underwent invasive angiography, and revascularization if required.
Significantly fewer patients in the cardiovascular MRI group underwent index revascularization, compared with the fractional flow reserve group (36% vs. 45% respectively; P = .005), and only 48% in the cardiovascular MRI group underwent invasive angiography, compared with 97% of patients in the fractional flow reserve arm.
However, there was no significant difference between the two groups in the incidence of major cardiac adverse events after 1 year, signifying that the MRI approach met the criteria for noninferiority.
There was also no significant difference between the two groups in the percentage of patients who were free from angina after 12 months (49.2% in the MRI group and 43.8% in the FFR group).
“Current guidelines on the management of the care of patients with suspected coronary artery disease separate diagnostic strategies from therapeutic strategies owing to a lack of evidence comparing combined diagnostic and therapeutic pathways,” wrote Eike Nagel, MD, of the Goethe University Frankfurt Institute for Experimental and Translational Cardiovascular Imaging and coauthors. “The MR-INFORM trial closes this knowledge gap by comparing two frequently used, well-defined, standardized, and validated clinical management strategies.”
However, they pointed out that one limitation of their study was the lack of a third group of patients who received medical therapy without planned revascularization. They also noted that the incidence of the primary outcome of major adverse cardiac events was lower than expected at 1 year.
The study was supported by the Guy’s and St. Thomas’ Biomedical Research Centre of the National Institute for Health Research. Three authors declared support from study supporters related to the study, three declared grants, personal fees, and other support from the private sector unrelated to the study. No other conflicts of interest were declared.
SOURCE: Nagel E et al. New Engl J Med. 2019;380:2418-28. doi: 10.1056/NEJMoa1716734.
Myocardial perfusion cardiovascular MRI is as good as invasive angiography and measurement of fractional flow reserve to guide revascularization in patients with angina, research suggests.
In the New England Journal of Medicine, researchers present the outcomes of an unblinded, multicenter, clinical effectiveness trial comparing the two revascularization strategies in 918 patients who had typical angina and either two or more cardiovascular risk factors or a positive exercise treadmill test.
In the fractional flow reserve method, revascularization was recommended in all vessels with an FFR of 0.8 or less. In the MRI-guided method, all patients underwent myocardial perfusion cardiovascular MRI, and patients with clinically significant inducible ischemia then underwent invasive angiography, and revascularization if required.
Significantly fewer patients in the cardiovascular MRI group underwent index revascularization, compared with the fractional flow reserve group (36% vs. 45% respectively; P = .005), and only 48% in the cardiovascular MRI group underwent invasive angiography, compared with 97% of patients in the fractional flow reserve arm.
However, there was no significant difference between the two groups in the incidence of major cardiac adverse events after 1 year, signifying that the MRI approach met the criteria for noninferiority.
There was also no significant difference between the two groups in the percentage of patients who were free from angina after 12 months (49.2% in the MRI group and 43.8% in the FFR group).
“Current guidelines on the management of the care of patients with suspected coronary artery disease separate diagnostic strategies from therapeutic strategies owing to a lack of evidence comparing combined diagnostic and therapeutic pathways,” wrote Eike Nagel, MD, of the Goethe University Frankfurt Institute for Experimental and Translational Cardiovascular Imaging and coauthors. “The MR-INFORM trial closes this knowledge gap by comparing two frequently used, well-defined, standardized, and validated clinical management strategies.”
However, they pointed out that one limitation of their study was the lack of a third group of patients who received medical therapy without planned revascularization. They also noted that the incidence of the primary outcome of major adverse cardiac events was lower than expected at 1 year.
The study was supported by the Guy’s and St. Thomas’ Biomedical Research Centre of the National Institute for Health Research. Three authors declared support from study supporters related to the study, three declared grants, personal fees, and other support from the private sector unrelated to the study. No other conflicts of interest were declared.
SOURCE: Nagel E et al. New Engl J Med. 2019;380:2418-28. doi: 10.1056/NEJMoa1716734.
Myocardial perfusion cardiovascular MRI is as good as invasive angiography and measurement of fractional flow reserve to guide revascularization in patients with angina, research suggests.
In the New England Journal of Medicine, researchers present the outcomes of an unblinded, multicenter, clinical effectiveness trial comparing the two revascularization strategies in 918 patients who had typical angina and either two or more cardiovascular risk factors or a positive exercise treadmill test.
In the fractional flow reserve method, revascularization was recommended in all vessels with an FFR of 0.8 or less. In the MRI-guided method, all patients underwent myocardial perfusion cardiovascular MRI, and patients with clinically significant inducible ischemia then underwent invasive angiography, and revascularization if required.
Significantly fewer patients in the cardiovascular MRI group underwent index revascularization, compared with the fractional flow reserve group (36% vs. 45% respectively; P = .005), and only 48% in the cardiovascular MRI group underwent invasive angiography, compared with 97% of patients in the fractional flow reserve arm.
However, there was no significant difference between the two groups in the incidence of major cardiac adverse events after 1 year, signifying that the MRI approach met the criteria for noninferiority.
There was also no significant difference between the two groups in the percentage of patients who were free from angina after 12 months (49.2% in the MRI group and 43.8% in the FFR group).
“Current guidelines on the management of the care of patients with suspected coronary artery disease separate diagnostic strategies from therapeutic strategies owing to a lack of evidence comparing combined diagnostic and therapeutic pathways,” wrote Eike Nagel, MD, of the Goethe University Frankfurt Institute for Experimental and Translational Cardiovascular Imaging and coauthors. “The MR-INFORM trial closes this knowledge gap by comparing two frequently used, well-defined, standardized, and validated clinical management strategies.”
However, they pointed out that one limitation of their study was the lack of a third group of patients who received medical therapy without planned revascularization. They also noted that the incidence of the primary outcome of major adverse cardiac events was lower than expected at 1 year.
The study was supported by the Guy’s and St. Thomas’ Biomedical Research Centre of the National Institute for Health Research. Three authors declared support from study supporters related to the study, three declared grants, personal fees, and other support from the private sector unrelated to the study. No other conflicts of interest were declared.
SOURCE: Nagel E et al. New Engl J Med. 2019;380:2418-28. doi: 10.1056/NEJMoa1716734.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: .
Major finding: The incidence of major cardiac adverse events similar at 1 year with cardiovascular MRI and invasive angiography.
Study details: MR-INFORM, an unblinded, multicenter, clinical effectiveness trial in 918 patients with angina.
Disclosures: The study was supported by the Guy’s and St. Thomas’ Biomedical Research Centre of the National Institute for Health Research. Three authors declared support from study supporters related to the study, three declared grants, personal fees and other support from the private sector unrelated to the study. No other conflicts of interest were declared.
Source: Nagel E et al. New Engl J Med. 2019;380:2418-28. doi: 10.1056/NEJMoa1716734.