After a drawn out eight-plus hours, the FDA’s Circulatory Systems Devices Panel gave a nod of approval to Edwards Lifesciences’ Sapien heart valve system for the indication to treat patients with severe, systematic aortic stenosis who are at a high risk for surgery. Now, Edwards’ transcatheter aortic heart valve may soon have two indications: for aortic stenosis patients who are both inoperable and at high risk for surgery.

The panel members voted 10-2 that the Edwards transcatheter heart valve is overall safe for the current indication in high-risk aortic stenosis patients. Panel members also agreed that the heart valve is effective for use for patients who fall under the current indications (12-0 vote).  As a means to persuade panel members, Craig R. Smith, MD, principal investigator of the PARTNER trial, said, “Procedures all have a common objective.” He went on to say that the “frequency of complications … is relatively well-defined and must be taken seriously and hopefully will improve over time.”

While he noted that there are pros and cons he said, “Your course is clear. We will see what you decide.”

Panel members agreed with Smith, voting that the Edwards Lifesciences’ transcatheter heart valve benefits outweigh the risk when used in aortic stenosis patients who fit the bill in the proposed indication; 11 panel members voted yes and one voting member abstained.

Earlier, Smith called aortic stenosis "one of the conditions we understand best in cardiovascular disease.” He called transcatheter aortic valve replacement (TAVR) a “miracle therapy,” and said that outcomes for the procedure will only continue to improve.

And while most of the day’s conversation gave kudos to the PARTNER trial and its findings, concerns did focus on gender differences and neurological events.

All about stroke

Smith, PARTNER trial’s principal investigator of Cohort A during the sponsor presentation, urged that the higher frequency of neurological events that occurred within the TAVR group should not be “trivialized” in either treatment group.

Martin B. Leon, MD, reported all-cause mortality and major stroke to be 26.5 percent for TAVR and 28 percent for AVR at 12 months. Additionally, Leon said that peri-procedural strokes occurred in 15 TAVR patients and eight AVR patients, a two-fold difference.

However, one panelist, David C. Naftel, PhD, director of clinical research, cardiac surgery, at the University of Alabama at Birmingham, said that he felt reassured by what was reported in terms of stroke.

Piggybacking off Naftel’s comment, another panelist urged the others to “get past the risk of stroke,” because the risk will never be zero. He added that patients will need to be told that they may have a risk of stroke with TAVR, but said that these types of issues can’t be solved during the panel discussion.

During the comment period, panelists commented on the problems of ascertainment of stroke within the PARTNER trial. FDA Panel Chairperson Warren Laskey, MD, said, “I think we are all happy saying pretty good, not perfect.”

Subpopulation discussions

There also was much ado about the differences in outcomes between males and females throughout the meeting, as well as understanding the long-term data. During the afternoon session, Leon brought forth three-year PARTNER data that had not been reviewed by the FDA that reported all-cause mortality to be 46.5 percent for TAVR patients and 46.2 percent for AVR patients.

Earlier in the day, one panelist asked the sponsors to elaborate on long-term gender data from the PARTNER trial. Leon noted, “Looking at gender, we don’t see very much of a difference out to three years for male patients.”  However, he went on to say that the researchers saw curves that were constant with the same differences that were observed at one and two years—that women performed better with TAVR.

One panelist asked with these gender data whether TAVR is a procedure for women and not for men. Another said that these differences could be due to the fact that women have more fragile hearts and sternums. “Men have better results after open heart surgery and that may be why TAVR may be better for females.”

The panelists questioned whether something should be placed on the label in terms of the outcomes of gender differences. “If you are talking to a man and you are talking to women and you are looking at these PARTNER data, who would you give a Sapian valve to?”

When the panelists questioned gender data in the study, Laskey said, “We’re intrigued but don’t understand the results. We need to understand many, many differences between males and females.” They panelists agreed that a large registry trial will be necessary to confirm these findings.

The FDA is not required to take the recommendations of the panel, but it most often does.