SAN FRANCISCO—In severe aortic stenosis (AS) patients who are not candidates for surgery, an updated transcatheter aortic valve replacement (TAVR) system (Sapien XT, Edwards Lifesciences) showed a non-significantly lower rate of death and strokes at 30 days than in the original Sapien model, and both valves demonstrated notably better short-term outcomes than seen in PARTNER I, according to the first results from the PARTNER II trial presented March 10 at the American College of Cardiology (ACC) scientific session.
“This is a non-inferior trial, both at 30 days and one year, so it did not show any statistical significance differences in the major three endpoints of all-cause mortality, disabling stroke and rehospitalization. There was a trend toward reduction of early all-cause mortality at 30 days [5.1 vs. 3.1 percent], but that was not statistically significant,” summed co-principal investigator of the PARTNER studies, Martin B. Leon, MD, director of the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center in New York City.
PARTNER II is the first randomized clinical trial involving the Sapien XT valve and the only one that compares the updated iteration of the original Sapien design. Sapien XT is available in Europe and elsewhere globally, but not in the U.S.
The new valve is part of a three-component system—a metal stent frame, a valve leaflet and a catheter—and each piece has been materially changed to make the device smaller and thinner. The frame, formerly stainless steel, is now a thinner cobalt chromium alloy and uses less metal overall.
For PARTNER II, 28 U.S centers enrolled 560 patients with severe AS who were deemed by a heart team to be unsuitable candidates for surgery. Patients were randomly assigned to TAVR using either the first-generation Sapien (276 patients) or the new Sapien XT (284 patients) TAVR system. All patients were followed for a minimum of one year and the researchers performed analyses (non-inferiority and superiority) on both intent-to-treat and as-treated cohorts. They also performed detailed assessments of frailty status and pre/post-treatment neurologic evaluations in all patients.
The primary endpoint was the composite of mortality, stroke and rehospitalization at one year.
The baseline patient demographics were “interesting,” according to Leon, with a mean age of 84.4 years, a mean STS score of 10.7 percent, 49.5 percent were female, 20.4 percent had a prior MI, 26.5 percent had a prior CABG, 11.6 percent had a prior stroke, 38.4 percent had atrial fibrillation and 18.6 percent had a previous pacemaker.
More than 96 percent were classified with New York Heart Association Class III (moderate) or Class IV (severe) heart failure, and 59 percent were assessed as clinically frail. All patients were deemed unsuitable for standard open-heart surgery.
This non-inferiority study was designed to show that the new Sapien XT is at least as safe and effective as the old device. At 30 days, all-cause deaths were 3.5 percent for Sapien XT and 5.1 percent for the original device.
“These are the lowest 30-day mortality results for transcatheter aortic valve replacement in any study using rigorous clinical trial methodology,” Leon said. “They’re surprisingly good.”
Stroke rates at 30 days also were low in both groups, at 3.2 percent for Sapien XT and 3 percent for Sapien, and much lower than in PARTNER I.
One caveat was the trend toward an increase in paravalvular and total aortic regurgitation with the new device versus the old device, which had not previously been observed. “This is a core laboratory assessment, and we’re still trying to understand a little bit more about the importance of that trend,” said Leon. “It’s confounded a little bit by the fact that the older device—the Sapien valve—required more second or third valves to treat paravalvular regurgitation.”
“I’m not at all surprised by the data because this is a better, easier device to use, but it is still fundamentally correcting the problem of severe aortic stenosis, said study discussant Gary S. Mintz, MD, chief medical officer of the Cardiovascular Research Foundation in New York City. “If you look at the history of surgical valves, very few actually change mortality, so these results are superb.”
“This trial justifies the use of this device over the currently FDA-approved Sapien device,” said Leon.
In further research, PARTNER II Cohort A will compare the new Sapien XT with open-heart surgery in intermediate-risk rather than high-risk patients.
Edwards funded PARTNER II.