FDA panel backs use of Sapien valve for high-risk surgical patients


The FDA Circulatory System Devices Panel voted unanimously, with one abstention, that transcatheter aortic valve implantation (TAVI) with the Edwards Sapien device should be approved for use in patient considered high-risk for open-heart surgery. Last year, Edwards Lifesciences became the first company in the USA to win FDA approval for using TAVI on inoperable aortic stenosis patients.

The recommendation for expanding TAVI to high-risk surgical patients was based on results of the Cohort A PARTNER trial which showed comparable death and durability rates for TAVI and surgery. In the trial, one-year mortality was similar between TAVI and surgery groups at 24.2% and 26.8%, respectively, meeting the predefined margin for noninferiority for TAVI.

PARTNER trial two-year follow-up data, published in April 2012, also showed that the difference in stroke rates, higher with TAVI at 30 days, diminished over time. The results also suggested that valve regurgitation was associated with late mortality in the TAVI group.

In the Cohort A of PARTNER, 699 high-risk patients (mean age of 84 years) were randomly assigned to surgery (351) or TAVI (348). The TAVI group received the Sapien transcatheter heart valve via the transfemoral or transapical approaches.

At two years, all-cause mortality was 33.9% in the TAVI group, which is statistically equivalent to open-heart surgical aortic valve replacement at 35% (p=0.78). Outcomes were also similar for death from cardiovascular causes: 20.5% for surgery vs. 21.4% for TAVI.

Although the TAVI group had nearly twice as many strokes in the first 30 days (4.6% vs. 2.4%, p=0.12), that early benefit for surgery diminished. Over the course of follow-up, there was no significant difference in the risk of stroke between the TAVI and surgery groups (7.7% vs. 4.9%, p=0.52).

Improvement in valve areas was similar with TAVI and surgical replacement and was maintained for two years. Paravalvular regurgitation was more frequent after TAVI (p<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (p<0.001).

During the follow-up, the investigators observed that significant leakage around the valve was associated with higher subsequent mortality in TAVI patients, possibly related to factors including the ratio of the transcatheter-valve size to the patient’s native valve size. According to the authors, “Recently, the routine use of three-dimensional imaging techniques has improved annulus sizing, resulting in better selection of properly sized valves.”

“I think we are in belief that the totality of the data demonstrates a reasonable assurance of safety and efficacy,” said Warren Laskey, the FDA panel chair and a cardiologist at the University of New Mexico School of Medicine. “There are questions that remain unaddressed, but they do not seem to impede our acceptance of the totality of the data.”

The advisory panel voted 10 to 2 that the device was safe, and 12 to 0 that it was effective.