FDA advisory committee supports expanded indication for Sapien Transcatheter Heart Valve

Issue: July 2012

The FDA’s Circulatory System Devices Panel of the Medical Devices Advisory Committee today voted 11-0 with one abstention that the Edwards Sapien Transcatheter Heart Valve is safe and effective for patients with severe aortic stenosis who are eligible, but at high risk, for surgical aortic valve replacement.

The vote encompassed transfemoral and transapical procedures.

For the transfemoral procedure, the currently approved indication is for patients with severe symptomatic native aortic valve stenosis who have been examined by a heart team including a cardiac surgeon and found to be inoperable and in whom existing comorbidities would not preclude the expected benefit from correction of the aortic stenosis. The new proposed indication includes operative candidates for aortic valve replacement but who are at a greater than or equal to 15% (high) risk for mortality for surgical aortic valve replacement, according to FDA materials.

The RetroFlex Balloon Catheter is indicated for valvuloplasty of a stenotic cardiac valve before implantation of the valve, and the RetroFlex 3 Delivery System is indicated for the transfemoral delivery valve. There is also a Crimper that is indicated for use in preparing the valve for implantation.

The transapical delivery is for patients included in the proposed expanded indication.

The Ascendra Balloon Aortic Valvuloplasty Catheter is indicated for valvuloplasty of a stenotic native aortic valve prior to implantation of the valve.

Vote results

The results of the three questions at hand were as follows:

Is there reasonable assurance that the Edwards SAPIEN Transcatheter Heart Valve is safe for use in patients who meet the criteria specified in the proposed indication? 10 yes, 2 no.
Is there reasonable assurance that the Edwards SAPIEN Transcatheter Heart Valve is effective for use in patients who meet the criteria specified in the proposed indication? 12 yes, 0 no.
Do the benefits of the Edwards SAPIEN Transcatheter Heart Valve for use in patients who meet the criteria specified in the proposed indication outweigh the risks for use in patients who meet the criteria specified in the proposed indication? 11 yes, 0 no, 1 abstain.

The discussion came in the wake of results of the PARTNER trial, which indicated that the 1-year all-cause mortality rate for patients in the TAVR (treatment) group was 24.27%, compared with a rate of 26.8% in the AVR (control) group. The survival difference was 0.0253, and the 95% one-sided lower confidence limit for the difference was –0.0299. This was greater than the pre-defined noninferiority margin of –0.075.

For full coverage of the PARTNER Trial on Healio.com, please visit here. Background information on the trial provided by the FDA may be viewed here and here.

Patients treated with the heart valve system had an increase in strokes perioperatively compared to the controls. This stroke risk was a topic of discussion among panel members.

Discussion questions

The FDA had posed nearly two dozen questions for the panel on topics including stroke risk, trial conduct issues, gender differences in outcomes, potential changes to labeling or indication, valve-in-valve risk, long-term durability and informed consent.

“Certainly microemboli are not a good thing, and, presumably that’s happening in this trial, as well,” said David C. Good, MD, of the Penn State Hershey Neurology department. “It is encouraging in the continuing study that strokes are going down, but it’s hard to draw any conclusions on whether or if the strokes are actually going down. One of the problems here is that they didn’t look at other important measures such as the modified Rankin scale. It is quite likely that strokes were missed. Large symptomatic ones may not have been missed, but small strokes probably were. Overall, though, given the population, they have done a reasonable job.”

Temporary panel chair Warren Laskey, MD, of the New Mexico School of Medicine in Albuquerque, added, “We need to get a better handle on aortic regurgitation and its prognostic significance.”

David C. Naftel, PhD, University of Alabama at Birmingham, commented on both the study design and the topic of informed consent. “Some of the subgroups of the trial were not sufficiently addressed,” he said. “Patients need to know that the procedure is not necessarily a winner. This was a noninferiority trial. We can’t tell patients, ‘look, we have a winner.’ This should be part of informed consent. We have this neat little technique that will shorten your hospital stay without opening your chest, but it comes with risk.”

The topic of informed consent generated spirited debate from several members of the panel, including George W. Vetrovec, MD, of Medical College of Virginia in Richmond. “The FDA’s role is safety and efficacy,” he said. “An informed consent form is moving into the practice of medicine.”

Valluvan Jeevanandam, MD, of the University of Chicago, disagreed. “There will be a good number of benefits from this technology, but patients need to know that there is a good chance of stroke,” he said.

Laskey noted the disagreement on the issue and moved the panel to a discussion of the uncertain data regarding differing outcomes among men and women.

“Surgery is more challenging in women,” Jeevanandam said. “They are more fragile, they have more fragile hearts and sternum,” he said. “This device may be good in patients who are really high risk, and this is why it may be better for females.”

Laskey also highlighted issues with long-term durability data and valve-in-valve risk mitigation measures. “Simply put, we don’t have long-term data, if we define long-term as beyond 24 months,” he said. Regarding valve-in-valve risk, he added, “We have not heard enough about this, so it is difficult to hold forth on it. There is so little information, so it may be best to say least on this topic.”

In the end, though, Laskey noted that the FDA asked the panel to review the data as a whole. “We believe that the totality of data demonstrates a reasonable assurance of safety and efficacy, with a number of caveats, including stroke, complications for stroke in the transapical group, women and the aortic regurgitation question. These questions give us concern but don’t impede our acceptance of the totality of the data.”

Although the FDA is not required to follow the recommendations of the advisory committee, it usually does. – by Rob Volansky