Sapien 3 Superior to Surgery Among Intermediate-Risk Patients in Observational Trial

(UPDATED) CHICAGO, IL—The latest iteration of the FDA-approved balloon-expandable transcatheter aortic valve has proven itself superior to surgery among intermediate-risk patients in a matched-registry analysis. According to new data released today, patients treated with the third-generation Sapien 3 have low rates of mortality, stroke, and paravalvular leak at 1 year—significantly lower than rates seen among surgery-treated patients in an earlier trial.

Improving on the Sapien XT device, the Sapien 3 valve (Edwards Lifesciences) features a skirt designed to prevent paravalvular leak, improved coaxial alignment, and more accurate positioning. Thirty-day results, reported in 2015, demonstrated the lowest event rates seen with balloon-expandable TAVR at that time.

Presenting 1-year results of the SAPIEN 3 observational study this morning at the American College of Cardiology 2016 Scientific Sessions, Vinod Thourani, MD (Emory University School of Medicine, Atlanta, GA), showed that TAVR with Sapien 3 was both noninferior and superior to surgical valve replacement at 1 year in a propensity score analysis of 1,077 intermediate-risk patients for the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation (pooled weighted proportion difference: -9.2%; P < 0.0001 for both).

The study was simultaneously published in the Lancet.

Few Adverse Events

The study included patients with symptomatic severe aortic stenosis, treated with the Sapien 3 device between February to September 2014, and compared their results to those of 944 patients from PARTNER 2A who underwent surgery between December 2011 and November 2013. In the propensity score analysis, fewer patients who received TAVR versus surgery died or had a stroke within 1 year. By contrast, moderate to severe paravalvular leaks were less common in the surgery-treated patients.

 

Rehospitalization was required for 11.4% of the TAVR arm, primarily for procedure- or valve-related reasons, but rates of endocarditis and aortic valve reintervention were low.

Cardiac symptoms vastly improved within 1 year after TAVR, with 94% of patients in NYHA functional class I or II (compared with 73% of patients in NYHA class III or IV at baseline). Also, the improvements in mean aortic valve area and gradient after TAVR seen at 30 days were maintained at 1 year. Overall, 12.4% of patients in the TAVR arm required new pacemaker implantation, compared with 9.4% in the surgery group from PARTNER 2A.

Commenting on the results for TCTMD, Amar Krishnaswamy, MD (Cleveland Clinic, OH), who was not involved in the trial, predicted that this SAPIEN 3 analysis will be subject to “appropriate criticism” for using the surgical arm from the PARTNER 2A study for their control group, “because it does not have the statistical rigor of a true randomized trial.” But since surgical techniques and outcomes have not changed drastically since PARTNER 2A was conducted, he said, these results “dovetail nicely” with the literature and support use of the Sapien 3 valve in this patient group.

Importantly, Krishnaswamy continued, 88% of all patients received TAVR with transfemoral access. “We don’t know yet exactly what the relevance is of nontransfemoral access to the outcome in comparison to surgery, but at least in PARTNER 2A, there was a suggestion that transfemoral was not only noninferior but remained superior to surgery,” he said.

By contrast, prior studies have suggested that TAVR via transthoracic access and surgery yield similar outcomes, but none have shown the superiority suggested for transfemoral procedures over surgery in PARTNER 2A. Moreover, studies have also raised concern over alternate access routes. “It will be important—especially in an intermediate-risk group and as we move soon to even lower-risk groups—to truly understand whether a nontransfemoral route does enjoy the same benefits of TAVR as the transfemoral group does in comparison to surgery,” Krishnaswamy said.

SAPIEN 3 Plus PARTNER 2A: ‘One-Two Punch’

Speaking with TCTMD, Martin Leon, MD (Columbia University Medical Center, New York, NY), senior author on the study, emphasized the combined impact of PARTNER 2A with the second-generation device and SAPIEN 3 with the newest iteration of the valve. Taken together, he said, “this is kind of a one-two punch. There’s the big randomized controlled trial, with 2-year outcomes done in a very formal, statistically rigorous way, which shows at the very least parity [with surgery]. . . . And then with SAPIEN 3, we look at the surgery arm from that trial compared with the Sapien 3 TAVR results at a year and [what you see is] a massive difference in every parameter.”

Leon acknowledged that the study may take some knocks for being a propensity-matched analysis, but he pointed out that the two studies used the same sites, same operators, same clinical events committee, and same core lab, so the matching was as close as it could possibly be. “It’s not a randomized trial, but it’s probably close, in terms of what its impact will be,” he said. “These are dramatic differences, almost one-half of the one-year outcomes of the primary end point in PARTNER 2A. . . . These results are sufficiently robust that Sapien 3 TAVR was not merely an alternative to surgery, but is clearly the preferred therapy in intermediate-risk patients.”

Discussing the study, panelist Jeffrey Popma, MD (Beth Israel Deaconess Medical Center, Boston), asked for confirmation that the patients in both the TAVR and surgery arms are indeed similar. “I’m going to have to go back home and explain to my surgical colleagues that these populations were really the same,” he said. “We’ve all struggled with using traditional and nontraditional risk factors to [deduce] risk. What do I tell my surgeons with regard to timing of the recruitment for S3 versus the timing of recruitment for PARTNER 2A? . . . How do we know that they really do represent the same risk?”

Thourani replied that the study sites were “almost identical” between PARTNER 2A and SAPIEN 3, as were the study criteria. “You’re looking at same patient population,” he said, adding that he would not want to compare the SAPIEN 3 population to the TVT Registry because the latter is a “free for all,” or at least “not a really well-oiled machine of research enterprise that we have in PARTNER.”

Sapien 3 is “clearly here to stay” for intermediate-risk patients, said panelist and surgeon James McClurken, MD (Doylestown Health, PA), but questions remain in terms of “how much can we move that median age downward,” the role or need for complete revascularization, and the importance of paravalvular leak in terms of survivability, he said.

“We do have to have a little healthy respect for the limitations of any propensity-adjusted analysis, but nonetheless, the results seem to be getting better and better and better for TAVR,” said session chair Gregg Stone, MD (Columbia University Medical Center, NY).

Thourani agreed, saying that the increasing success seen with TAVR over time has to do with not only better patient selection, but also improved operator experience and technological enhancements.

In a press conference, David Kandzari, MD (Piedmont Heart Institute, Atlanta, GA), commented that changes in practice, including the use of CT imaging to guide procedures, have also led to better outcomes. “Aside from the remarkable outcomes with regard to mortality and stroke [in SAPIEN 3]—we can debate propensity score versus the absence of a randomized trial—these are clinically meaningful [and] some of the best observed outcomes we’ve ever witnessed with transcatheter [valve] therapy,” he said.

Are these data alone enough to expand the indication for Sapien 3 to intermediate patients? Both Spencer King III, MD (Emory University School of Medicine, Atlanta, GA), and John Carroll, MD (University of Colorado, Denver), said yes in the press conference. “It’s solid data, and . . . the propensity matching is extremely reasonable,” Carroll said.

King did allude to the differences in need for permanent pacemaker in prior TAVR studies, but Thourani countered that the low rate observed here is “much better than you’ve seen before.”

Note: An earlier version of this story incorrectly cited baseline, not new, pacemaker numbers.

 

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Source:

 

• Thourani VH, Kodali S, Makkar RR, et al. Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Lancet. 2016;Epub ahead of print.

 

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• Thirty-day Outcomes with Sapien 3 Lowest Seen with Balloon-Expandable TAVR
• Low 1-Year Event Rates Seen After TAVR With Sapien 3
• Sapien 3 Experience in Europe, Canada Shows Low Mortality, Paravalvular Leak at 30 Days