FDA Reviewers Raise Questions About Sapien Heart Valve System

FDA reviewers have raised a number of questions about the safety and efficacy of the Sapien heart valve system. The review was published online ahead of Wednesday’s meeting of the Circulatory System Devices Panel meeting to evaluate the Sapien system for use in patients eligible but at high risk for aortic valve surgery. The Sapien system was previously approved in November 2011 for patients not considered surgical candidates for aortic valve replacement.

The FDA briefing document cites numerous examples of possible bias in the pivotal PARTNER A trial. The most serious problem appears to be caused by the high number of patients randomized to surgery who did not undergo surgery, including 7.9% who refused treatment or withdrew from the study. By contrast, only 0.3% of TAVR patients refused treatment or withdrew from the study. Surgical patients were also more likely to receive concomitant operations, another possible source of bias.

Another important topic of discussion will undoubtedly be the differences in outcome between patients receiving the transapical (TA) and transfemoral (TF) approaches. Unlike the TF stratum, where mortality was lower in the Sapien group, in the TA stratum mortality was higher in the Sapien group. Because there were only a relatively small number of patients in the TA group in the PARTNER trial, the panel will also consider TA patients treated outside the context of randomized trials.

The FDA reviewers were also concerned about stroke and aortic regurgitation. In the first 30 days the stroke rate was doubled in the Sapien group, and there were more strokes overall in the Sapien group in the TA stratum. Concern was also raised about the 53% of Sapien-treated patients who had mild or greater aortic insuficiency.

One interesting point raised by the FDA is that transcatheter aortic valve replacement (TAVR) is not nearly as noninvasive as many have been led to believe:

The results of this study show that the comparison was not between “open” AVR and percutaneous AVR. For patients having open AVR who had not had a previous operation, about one half of the patients had a minimally invasive approach. For TAVR patients, about three quarters required either an open surgical procedure for direct arterial access, or an open surgical procedure for vascular repair after a percutaneous approach. Therefore, this trial compared open AVR with transcatheter AVR that frequently required surgery for vascular access or repair.

The outcomes of FDA panels are notoriously difficult to predict. Wells Fargo analyst Larry Biegelsen wrote that he continued “to anticipate a challenging panel on Wednesday” but that ultimately he expected a positive vote, leading to FDA approval later this year.

Related reading: Politics and Transcatheter Aortic Valve Replacement


  1. […] Valve for use in patients with symptomatic severe aortic stenosis who have high operative risk. As reported here earlier this week, FDA reviewers have raised a number of questions about the safety and efficacy of the Sapien heart […]

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