Two trials evaluating transcatheter aortic valve replacement (TAVR) in low-risk patients didn’t just shift the TAVR vs. surgical AVR discussion. They’ve completely flipped it, said experts at the American College of Cardiology scientific sessions in March.
“It used to be that TAVR was really a therapy that was appropriate for patients who were not good candidates for surgery,” said Martin B. Leon, MD, lead author of the PARTNER 3 low-risk TAVR trial. “We think that’s turned around and that probably TAVR should be the therapy considered and surgery should be used in patients that are not good candidates for TAVR.”
The PARTNER 3 trial tested Edwards Lifesciences’ SAPIEN 3 balloon-expandable valve, while Michael J. Reardon, MD, presented another TAVR vs. SAVR trial in low-risk patients using Medtronic’s Evolut family of self-expanding valves. Reardon arrived at the same overall conclusion. “TAVR is no longer just an alternative therapy, it is the preferred therapy,” he said. “And as a surgeon, when I sit down and talk to my patients, if you are a candidate for a bioprosthetic valve, if I do not bring TAVR into the conversation, I have not given you complete informed consent.”
Leon and colleagues randomized 1,000 patients with severe aortic stenosis considered to be at low surgical risk to either TAVR or SAVR. Low surgical risk was defined as a predicted risk of 30-day mortality below 4 percent based on the Society of Thoracic Surgeons risk score. The mean STS risk score was 1.9 percent in the population, and the average age was 73.
At one year of follow-up, 8.5 percent of patients in the TAVR group and 15.1 percent of those who underwent SAVR met the primary composite endpoint of death, stroke or rehospitalization. The one-year rates of death or disabling stroke were 2.9 percent with SAVR and 1.0 percent with TAVR, and each component of the primary endpoint favored TAVR.
“As an investigator, I never could’ve imagined that even in a low-risk population that we would achieve at one year a 1 percent death and disabling stroke rate, compared to surgery which was 2.9 percent,” Leon said. “And it was excellent surgery, so this was a surprising finding that was highly statistically significant.”
Using the even lower STS risk score threshold of 3 percent to define low risk, Reardon and colleagues studied 1,403 patients who underwent TAVR or SAVR after randomization. At two years of follow-up, the combined rate of all-cause death or disabling stroke was 5.3 percent in the TAVR group and 6.7 percent in the SAVR group, easily meeting the trialists’ criteria for noninferiority.
Notably, TAVR patients in the trial received all three generations of the Evolut valves, with 74.1 percent getting the second-generation Evolut R and 22.3 percent receiving the newest-generation Evolut Pro.
The trial’s follow-up period was a year longer than that in the PARTNER 3 low-risk trial and the primary endpoint was more restrictive—eliminating the softer endpoint of rehospitalizations. But other outcomes were measured as well, and Reardon reported hospital lengths of stay were cut in half with TAVR (2.6 days vs. 6.2 days on average) and quality-of-life measures were higher in those patients.
One outcome that appeared to favor surgery in both trials was a lower need for pacemaker implantation, but Reardon said it’s difficult to suggest the trials are anything but a clear win for TAVR based on the other results.
“When we were discussing our endpoint, I thought that choosing something that was completely objective would help me convince my surgical brethren in case we were close.” Reardon said. “We’re really not close.
“I went back and did a combined endpoint of death, stroke and hospitalizations because I wanted to see those. That’s what my patients tell me; they tell me they want to be alive without a stroke and be out of the hospital with a reasonable quality of life,” he added. “Both these trials show that you obtain that better with TAVR than surgery.”
Where does SAVR fit now?
Both Edwards Lifesciences and Medtronic said they would work with U.S. regulators to gain a low-risk indication for their respective devices, perhaps this year. TAVR started as an alternative to surgery for patients at high or prohibitive surgical risk but has since been approved by the FDA for intermediate-risk patients.
In a press release, Edwards said it expects the low-risk indication to be added later this year for the SAPIEN 3, which begs the question: What role will SAVR have going forward?
Joseph Cleveland, MD, a surgeon with University of Colorado Anschutz Medical Center, said the discussion now turns from surgical risk profiles to anatomical considerations.
“This technology [TAVR] is applicable to all patients with aortic stenosis and I agree … this is not a paradigm shift—this is a complete flip,” said Cleveland, who wasn’t involved in the studies. “When I sit and talk with patients, it certainly now will be a conversation about TAVR first, and if you have certain anatomic exclusions or other things, then we’ll talk about surgery.”
For one, Reardon believes anyone who isn’t a candidate for a biologic valve isn’t a good candidate for TAVR. Also, certain calcification patterns that protrude into the outflow tract and might raise the risk of paravalvular regurgitation could also push the decision toward surgery.
Leon said many of the SAVRs performed as part of combination operations to also address coronary artery disease could maintain a place in routine practice.
“Forty percent of the AVRs that are done are a combination of AVR and CABG so there are some patients with extreme coronary disease that are going to do better with AVR/CABG than what we could do with TAVR perhaps with PCI,” he said, also noting surgery might be a better option than TAVR for the small proportion of patients for whom transfemoral access isn’t feasible.
Other anatomical factors could point toward surgery, although Reardon said SAVR’s role in treating aortic stenosis is shrinking.
“I still see people that have an annulus that is too big for any of the current TAVR valves and, of course, aortic insufficiency is still a problem. … So, there are still people that still go to surgery [but] they’re getting chipped away at,” he said.
Both of the low-risk TAVR trials presented at ACC.19 were published in the New England Journal of Medicine (online March 16, 2019).