TAVI benefits outweigh risks in patients with severe AS, says FDA panel

The Circulatory System Devices Advisory Panel voted 9-0-1 today that the benefits of Edwards Lifesciences’ Sapien transcatheter heart valve system outweigh the risk in patients with severe aortic stenosis who meet the criteria specified in the company’s proposed indication of use.

The indication, which was revised by panel members, states that the transcatheter heart valve — model 9000TFX, sizes 23 mm and 26 mm, and RetroFlex 3 Delivery System — is intended for “transfemoral delivery in symptomatic patients with severe symptomatic native valve aortic stenosis [AS] who have been determined by a cardiac surgeon to be inoperable for open aortic valve replacement and in whom existing co-morbidities would not preclude the expected benefit from correction of the aortic stenosis.”

The Circulatory System Devices Advisory Panel discussed several questions from the FDA that addressed among other items recommendations for post-approval study and the quality of data from the Cohort B arm of the PARTNER trial, which compared the transcatheter aortic valve implantation (TAVI) with “standard” medical therapy among inoperable patients with severe AS.

Following the FDA questions, the panel was asked three voting questions that assessed whether there is reasonable assurance that the heart valve is safe (7 Yes, 3 No), effective (9 Yes, 1 No) and whether the benefits outweigh the risks (9 Yes, 0 No, 1 abstain) in patients with severe AS.

“I think that this is an innovative technology that is going to meet unmet needs for a population that is clearly going to be helped with the appreciation of challenges in terms of the technology and the skill sets,” said Ralph Brindis, MD, with the Oakland Kaiser Medical Center, Oakland, Calif., regarding his three affirmative votes. “I am incredibly encouraged by the endorsement of the advisory panel to the concept of a national registry so that we will not have missed opportunities in understanding how we can assure safety related to the utilization and roll out of this device but also new clinical information for its proper application and potential off-label use.”

John C. Somberg, MD, with Rush University Medical Center, Lake Bluff, Ill., on the other hand, was more cautious and as a result voted no to the question on whether there was reasonable assurance that the device was effective.

“I found aspects today very troubling,” he said. “I didn’t think we had an adequate compilation of the data with the continued assess cohort and that concerned me. Therefore, I felt there was some assurance that the device in this situation with a single, non-blinded trial might work. I would have been more assured and might have been able to vote, as I thought I was going to when I came here today, in favor of all three aspects if that data had all been presented more coherently.” – by Brian Ellis

Disclosures: Drs. Brindis and Somberg report no relevant financial disclosures.

The Society [for Cardiac Angiography and Interventions (SCAI)] believes the recent advent of transcatheter treatment of aortic stenosis (TAVI) is a viable alternative to standard open valve replacement in select patient populations at specialized heart centers with expert physicians. Inoperable patients with severe aortic disease are currently treated with medication only since they may be too sick or too old to undergo surgery, despite the extensive historical information that medical therapy alone has no effect on the natural history of the disease. The Edwards SAPIEN device clinical trial demonstrated that TAVI is a superior alternative to medical management in select inoperable patients and is “non-inferior” in patients at high risk for open heart surgery.

While there are significant concerns about the risk of stroke, SCAI believes that the overall survival benefit for this therapy is significant. An absolute survival advantage of this therapy of 20% far exceeds the penalties of adverse events such as stroke and vascular complications. The Society believes that appropriate physician expertise will lead to a reduction in the number of complications as observed in PARTNER Trial Cohort B vs. the later PARTNER Trial Cohort A. Stroke decreased from 5.0% to 3.8%, respectively. Vascular complications decreased from 16.2% to 11.0%, respectively. Therefore, the SCAI hopes that patients with severe aortic stenosis will have access to this treatment option.

– Augusto D. Pichard, MD, FSCAI
Professor of Medicine (Cardiology), Georgetown University Medical School, Washington DC
Director, Catheterization Laboratory, Washington Hospital Center, Washington DC

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