Everyone looks for some sort of approval, but where we find it is sometimes a different story. In the case of the transcatheter aortic heart valve, Edwards Lifesciences may be one step closer to finding it after FDA’s Circulatory Systems Device Panel voted in favor of expanding device indications to include aortic stenosis patients at a high risk for surgery. While the journey for transcatheter aortic valve replacement (TAVR) has been long, as writer Mark Twain wrote, “We can secure other people's approval, if we do right and try hard.”
Ten hours of discussions, votes and patient accounts later, members of the FDA panel voted almost unanimously to expand the indications for the Edwards device. The new indications would include aortic stenosis (AS) patients who are at a high risk of surgery. If approved, this would be the second indication for the technology, as it already covers inoperable AS patients.
The Edwards transcatheter aortic valve system became a hot commodity in the device community ever since results of the groundbreaking PARTNER trial showed that TAVR may be a good alternative to conventional surgical repair for inoperable AS patients. However, many panelists had a beef with multiple aspects of the trial and its outcomes.
For instance, Craig R. Smith, MD, the trial’s principal investigator, said that the higher risk of stroke seen with TAVR should not be dismissed. However, he went as far as to call TAVR a “miracle therapy” that will only get better in time. Along with Martin B. Leon, MD, Smith was the technology's biggest advocate.
Smith called TAVR a “radical, but completely logical evolutionary simplification of aortic valve replacement,” and told panelists that they “had a clear path” on which way they should vote.
The tone of this meeting seemed rather mellow, especially compared with other hotly debated topics such as those surrounding rivaroxaban (Xarelto, Bayer HealthCare/Janssen Pharmaceuticals) or rosiglitazone (Avandia, GlaxoSmithKlein) that have been discussed by FDA panels. While some panelists had concerns with a higher risk of stroke in TAVR compared with surgical valve replacement, it seemed obvious that this would not dissuade a positive vote.
Another consistent concern throughout the day was linked to the outcomes of the various subsets, including procedure delivery (transapical and transfemoral) and gender. Panelist David C. Naftel, PhD, said, “It does concern me that we are not discussing these subgroups more than we are.”
While the PARTNER trial wasn't specifically powered to look at gender, results did show that women fared better with TAVR, while men fared better with AVR. Naftel referenced the father of modern statistics, Ronald Fisher, saying that “it’s impossible not to look” when talking about the subsets of the PARTNER trial.
He went on to say that if the valve were approved, he would be concerned that it would be portrayed as a winner. "We have to remember this is not a winner," he said. "It’s a non-inferiority trial.”
Many suggested that there may be caveats to the current indications and questioned whether there should be changes to labeling or enhanced patient consent forms due to the complexity of the procedure and the possible risk. Panelist John C. Somberg, MD, said that there should be more discussions of the Centers for Medicare & Medicaid Services' mandate that requires two surgeons be present to evaluate patients prior to a procedure. Panelists questioned whether a cardiologist should be added to this requirement.
Overall, though, the vote was a positive one with a 10-2 vote in favor of TAVR for safety and 11 panelists agreeing that the benefits outweighed the risks. The panelists voted unanimously, agreeing that the device is effective for the indication at hand.
Smith said that the approval was justified and said that clinicians must understand that “decisions to use TAVR after approval must involve an evidence-based balancing of risk and benefit tailored to each patient.”
While FDA doesn't have to take the advice of the panel, it usually does. It will be interesting to see, if approved, what economic and clinical impacts this will have, especially as TAVR comes with a high price tag. However, the fact that elderly patients who didn't have an answer before can now undergo the procedure without major incisions, heart lung machines and perhaps even general anesthesia (in the future) and live may outweigh any