CHICAGO – Transcatheter aortic valve replacement (TAVR) using Sapien 3 – the latest-generation valve – is associated with low mortality, stroke, and paravalvular regurgitation rates at 1 year in intermediate-risk patients, and is superior to surgical valve replacement, according to findings from the SAPIEN 3 study.
The mortality rate at 1 year in the 1,077 patients in the observational study was 7.4% overall and 6.5% in a transfemoral access subgroup, the disabling stroke rate was 2.3%, the aortic valve reintervention rate was 0.6%, and the moderate/severe paravalvular regurgitation rate was 1.5%, Dr. Vinod H. Thourani reported on behalf of the PARTNER trial investigators at the annual meeting of the American College of Cardiology. The findings were published simultaneously in The Lancet (2016 Apr 3. doi: 10.1016/So140-6736[19]30073-3).
Sherry Boschert/IMNG Medical Media
Dr. Vinod Thourani
A prespecified propensity score analysis comparing 963 SAPIEN 3 patients with 747 similar intermediate-risk patients from the PARTNER 2A trial who underwent surgical valve replacement showed that not only was Sapien 3 TAVR noninferior to surgery for the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation, it was also superior to surgery (pooled weighted proportion difference, –9.2% for each). The differences were highly statistically significant.
In fact, Sapien 3 TAVR “blew it out of the water” for both noninferiority and superiority vs. surgery, Dr. Thourani of Emory University, Atlanta said.
The propensity score incorporated 22 characteristics, and the analysis was conducted by blinded investigators. Even using the most conservative strategy for the analysis as approved by the Food and Drug Administration, with the heaviest weighting against TAVR, Sapien 3 TAVR was superior to surgery for the primary composite endpoint, he noted.
Of note, while Sapien 3 TAVR was superior for the individual components of mortality and stroke from the composite endpoint, surgery was superior to Sapien 3 TAVR for the component of moderate or greater aortic regurgitation, he said.
However, the findings represent “strong evidence that in intermediate-risk patients with severe aortic stenosis, SAPIEN 3, compared to surgery, improves clinical outcomes and is the preferred therapy,” he concluded.
In a video interview, he said that if approved by the FDA, “this will become the impetus for [use in] a lower-risk population of patients. Currently we have the inoperative and high-risk patients, and this will open up the intermediate-risk patients for having transcatheter valve therapies, and I think it becomes exceedingly powerful.”
Two ongoing industry-sponsored randomized trials in low-risk patients (those with a Society of Thoracic Surgeons score of less than 4) are underway, he noted.
Sapien 3 TAVR was previously shown to improve 30-day outcomes in intermediate-risk patients with severe aortic stenosis (Eur Heart J. 2016 Mar 31. doi: 10.1093/eurheartj/ehw112), but longer-term data were lacking, and no comparisons with surgery in intermediate-risk patients were available.
For the current study, patients with a mean age of 82 years were evaluated at 51 centers in the United States and Canada during February-September 2014. Subjects had a median Society of Thoracic Surgeons score of 5.2% (range, 4-8) and 73% had New York Heart Association class III/IV heart failure. Almost 90% were treated via the transfemoral route, Dr. Thourani said.
The Sapien 3 device is a balloon expandable valve that differs from prior-generation devices in that it has improved geometry of the trileaflet bovine pericardial valve, a longer cobalt alloy frame with more open outlet cells and denser inlet cells, a polyethylene terephthalate fabric skirt that provides an external circumferential seal to reduce paravalvular leak, four valve sizes, and lower-profile delivery catheters with more precise valve positioning inserted through 14 or 16 French sheaths for increased use of transfemoral access.
Discussant Dr. David E. Kandzari, director of interventional cardiology and chief scientific officer at Piedmont Heart Institute, Atlanta, congratulated Dr. Thourani and his colleagues on “a terrific trial and impactful result.”
“There are, with regard to the Sapien 3 technology, many reasons to believe that this could be an advancement above existing predicate technologies,” he said, specifically mentioning the improvements in the device, compared with prior generations, such as the modification to reduce paravalvular leak, which has been associated with worse outcomes for patients.
“In parallel, there were changes in practice, and one of them implemented in the context of SAPIEN 3 was the use of [computed tomography] imaging to help guide and inform the procedure itself,” he said, adding that the results of the trial “really open the door for at least two very broad pathways.”
First, they expand TAVR to intermediate-risk patients.
“Secondly, they lead the way even further with greater reassurance toward two large ongoing clinical trials in patients considered at low risk, as well,” he said.