Transcatheter aortic valve replacement (TAVR) expansion into a low-risk population is on the table in 2019, as two pivotal trials and regulatory review for this indication are widely anticipated.
PARTNER 3 and CoreValve Low Risk will have short-term results available in low-risk patients who got the Sapien 3 valve from Edwards Lifesciences and the Evolut R from Medtronic, respectively, for severe aortic stenosis. Patients have been selected such that no one will have surgical mortality risk exceed 2% in PARTNER 3 and 3% in CoreValve.
Both studies are on track to be presented in March at the American College of Cardiology’s annual meeting. If the results are positive for both, the FDA is highly likely to grant commercial approval for a low-risk indication in the latter half of 2019, speculated George Deeb, MD, who is a part of the CoreValve Low Risk trial’s steering and screening committees.
“If the low-risk trials show that TAVR is non-inferior to SAVR [surgical aortic valve replacement], then the future will have TAVR dominating this arena,” said Deeb, a thoracic surgeon at the University of Michigan, Ann Arbor.
At his institution, clinicians take a multidisciplinary heart team approach in presenting all the appropriate options to the patient and taking into consideration the patient’s preference to come to a shared decision for treatment, he said.
Still, “the majority of patients who have three-leaflet aortic stenosis that are moderate-to-greater risk, they’re going to choose TAVR. The majority of our valves are TAVR. Once low-risk is approved, the majority of patients will request TAVR,” Deeb predicted.
Exceptions, he noted, will be the younger patients who want a surgical mechanical valve that will last longer between interventions.
The question of durability has been an Achilles heel of TAVR. While European data seem to suggest similar longevity between transcatheter and surgical tissue valves out to 5 to 7 years, it’s not clear if that is good enough to get TAVR into younger patients.
“Durability getting into younger patients will still be a big question mark. It’s not right to assume it will be as good as the bioprosthetic surgical valves,” said Richard Shemin, MD, chief of cardiac surgery at David Geffen School of Medicine at UCLA and a site investigator for PARTNER 3.
Certain mechanical properties of TAVR valves may make them more prone to tissue deterioration, he suggested in an interview. For one, the tissue is crimped thinner than the tissue in surgical valves, and it is also placed on a wire stent instead of mounted on a frame.
“The trials will answer many questions and pose many questions. These patients are low-risk for surgery, but in general, usually these low-risk trials do not necessarily have young patients,” Shemin said.
He stressed good clinical judgment even if the indication for TAVR in low-risk patients is approved by the FDA as many expect in 2019.
Expansion of the Sapien line has run into a bit of a snag, in the meantime. The next-generation Sapien 3 Ultra was cleared by European regulators for treating severe, symptomatic aortic stenosis this year but had a wrench thrown into its debut in Europe because of a patent dispute between Edwards Lifesciences and Boston Scientific. The Ultra did get FDA approval, which had been expected by the end of 2018.
Beyond device evolution and expansion into low-risk patients, companies are also trying to make TAVR a treatment for patients before symptoms start. The EARLY TAVR trial, for example, is investigating how this approach compares to clinical surveillance in asymptomatic individuals with severe aortic stenosis.
“Whatever’s good for patients is good for the cardiac surgeon and the interventionalist,” according to Shemin. “There’s often extreme enthusiasm if a trial was good to maybe extend [the treatment] to a patient population that was never tested. I think like everything else, people have focused on the big picture, but the devil’s in the details,” he emphasized.