Mortality rates in the surgery groups
Dr. Leon also pointed out differences in the mortality rates in the surgery groups in the two trials, which he suggested may contribute to the explanation for the different longer-term results.
“The baseline characteristics for patients in these two trials were almost identical, and results at 1 year were very similar, but for whatever reason, over the course of a few years, the outcomes in the Evolut trial were different to those in PARTNER-3, and in particular the difference was in the surgical arms, with a higher event rate in the surgical arm in Evolut than in the surgery arm in PARTNER-3,” he said. “When the control does not perform well it is a lot easier to show that the experimental arm is better.”
“When you look at the TAVR arms in both studies at each time point they are either similar or PARTNER-3 is actually lower,” he added. “That is why it is so difficult to compare these two trials.”
But Dr. Reardon dismissed this argument.
“What determines long-term survival after a procedure is the intrinsic risk level of the patients,” he said. “Overall mortality rates differ between the two trials because the PARTNER-3 trial enrolled a lower end of a low-risk population while Evolut enrolled an upper end of a low-risk population. You cannot look at absolute numbers between trials. That is intellectually and scientifically invalid.”
“It is the relative difference between surgery and TAVR that we are interested in, and we see in Evolut that the relative difference between the two procedures in terms of benefit with TAVR is widening every year,” he added. “That is because the superior valve performance and hemodynamics of the Evolut valve compared to surgery has translated into excellent clinical outcomes.
“In the PARTNER-3 trial – their curves are coming together. I think that is worrisome, but I don’t want to draw conclusions about their trial,” Dr. Reardon said. “All I know is that in our trial, we have excellent outcomes that are getting better year after year.”
Competition between valves
The different results of the two trials is inevitably producing some competition between the two products.
Dr. Reardon said: “In terms of which valve to use, clinicians will want to choose a valve that has the best durability and shows the best survival vs. surgery and that is clearly the Evolut valve. I think the writing is on the wall. Some clinicians are going to wait for longer term data, but the question is do we have enough long-term data now.”
But Dr. Leon countered: “There’s never been a head-to-head device to suggest that the self- expanding device performs better than the balloon expanding device. We always think about them as being similar in terms of performance. There is an aggressive effort to suggest that by virtue of the current trial results there was a superior outcome with the Medtronic device, but it’s hard to explain why that would be the case, and we should not compare between the two trials.”
Both Dr. Leon and Dr. Reardon stressed that longer-term follow-up is critical because some surgical valves are known to fail between 5-10 years, and it is not known how the TAVR valves will perform over that period.
Both the PARTNER-3 and Evolut trials are planning to keep following patients out to 10 years.
For the time being though, both Dr. Leon and Dr. Reardon agreed that these current results will probably accelerate the already rapid transition from surgery to TAVR in low-risk patients.
“TAVR will be the default therapy,” Dr. Leon commented. “It will be the first choice for patients. Whether TAVR is superior to surgery in terms of outcomes or just the same, there are sufficient benefits from a logistic and patient perspective that most people would prefer to have the less invasive therapy. TAVR is a one-day procedure, there is no need for general anesthetic, a lot of the secondary outcomes that are so problematic with surgery don’t exist, and the ability to be in a symptom-free state is dramatically accelerated.”
“This was the first serious foray into the low-risk population with TAVR,” he added. “We had an age cut of 65 years, but the vast majority of patients in both trials were over 70. We could now start looking at younger patient populations.”
But Dr. Reardon said that these younger patients are already being given TAVR, and future trials randomizing between TAVR and surgery may not be possible.
“Even though US guidelines still recommend surgery for patients under 65 years, patients want TAVR, and they get TAVR,” he said. “Recent data shows that in 2021, use of TAVR rose to 47.5% in patients under 65 needing isolated aortic valve replacement. That doesn’t meet the guidelines but there’s clearly a big shift going on. These results will just keep that momentum going.”
The PARTNER-3 trial was funded by Edwards Lifesciences. The Evolut study was funded by Medtronic. Dr. Leon reports grant support from Edwards Lifesciences and Medtronic. Dr. Reardon receives research grants from Medtronic.
A version of this article first appeared on Medscape.com.