Why the next TAVR vs. SAVR trial should be in bicuspid AS patients

Physicians are facing a new issue as transcatheter aortic valve replacement (TAVR) expands to younger populations—an increased incidence of bicuspid aortic stenosis (AS). Some experts worry it’s too late for a trial of TAVR vs. surgical AVR (SAVR) in patients with bicuspid AS, but others, like Raj R. Makkar, MD, are working hard to make it a reality.

In a presentation at the Cardiovascular Research Foundation’s TVT symposium in Chicago this month, Makkar, associate director of the Cedars-Sinai Heart Institute and a professor of medicine at the University of California, Los Angeles, argued that while there’s healthy competition for the next TAVR vs. SAVR trial—researchers are considering focuses on aortic regurgitation, failed bioprosthetic valves and mixed valvular heart disease, to name a few—a study of bicuspid AS patients is critical.

“I believe that the technology is ready, the procedure is mature, and in the low-risk trials, one- and two-year death rates, stroke and rehospitalization rates were very low, even lower than surgery,” Makkar said. “And imaging has evolved to the point that we can actually choose the right patients to do the randomized clinical trial.”

Though TAVR isn’t the most popular approach to treatment for patients with bicuspid AS, bicuspid patients have been undergoing SAVR with relative success. Makkar said nearly 50% of SAVRs in younger patients involve bicuspid AS, and outcomes in those patients have been “stellar.”

On the other hand, less than 7% of patients in TAVR registries have bicuspid AS. It’s not the biggest surprise, Makkar said, since many large-scale randomized trials exclude patients with bicuspid valves entirely.

When session moderator Michael Mack, MD, the medical director of cardiovascular surgery at Baylor Health Care System, asked his other seven panelists whether a randomized clinical trial in bicuspid patients is warranted and whether it would be able to enroll enough patients, six were quick to say “yes” to both questions. Co-moderator Hasan Jilaihawi, MD, however, was a little more hesitant.

Jilaihawi, an interventional cardiologist at NYU Langone, said that while he’d like to see a clinical trial, the healthcare industry as a whole is less enthused about the prospect.

“The reason they don’t want to do it is the low-risk label,” he said. “The question is if the low-risk label says ‘approved for tricuspid,’ then they will have to do it. If it doesn’t mention tricuspid or bicuspid then it will never get done unless we, as physicians, organize that. So the answer is yes and I hope so, but can we influence CMS to restrict the label for low-risk to tricuspid so that we can facilitate this?”

Mack said it will largely depend on what the FDA label says, since CMS will reimburse systems according to that label. He said that while he’s not a CMS insider, he’s heard talk that the label might mention bicuspid valves, meaning a trial would be “clearly called for and will be done.” But if the label doesn’t mention bicuspids, the industry doesn’t want to do it and neither do a lot of clinicians.

“We all know about what the gold standard is when it comes to evidence, and I think randomized clinical trials are our way out,” Makkar said. “So I think for this particular question, I think why should we infer when we’re going to treat thousands of patients globally? I think it’s a bonus. It is important that we actually do a randomized clinical trial.”