TAVR Low-Risk Studies Get Standing Ovation at ACC

NEW ORLEANS — The success of the two trials of transcatheter aortic valve replacement (TAVR) in low-surgical-risk patients stole the show at the American College of Cardiology 68th Annual Scientific Session 2019 (ACC.19) today, with the presenters receiving a standing ovation after reporting their data showing impressive outcomes compared with surgery.

"This is a historic moment, and of all of us here should remember it as such," proclaimed Eugene Braunwald, MD, Brigham and Women's Hospital, Boston, Massachusetts, during the discussion panel immediately following presentation of the trials. "We will talk to our grandchildren about this — that we were here at the time this incredible advance in the care of patients with aortic stenosis was presented," he added.

And such was the enthusiasm from the audience, the discussion was interrupted several times with spontaneous applause.

Until now, TAVR use has been restricted to patients with severe aortic stenosis at high/intermediate surgical risk, but these new studies open the procedure up to the much larger population of patients at low surgical risk.

At a press conference here, ACC spokesperson, Janet Wyman, DNP, manager, Center for Structural Heart Disease, Henry Ford Hospital, Detroit, Michigan, said, "We have been watching the shift from surgery to TAVR happening over the last few years, but I would say now that this is more than just a shift. We have completely flipped it with these studies, and TAVR will now become the preferred option for most patients."

The PARTNER 3 and Evolut studies of TAVR in patients at low surgical risk were officially presented at this morning's late-breaking clinical trial session at ACC.19, although results were released 1 day early because of an embargo break, and reported by theheart.org | Medscape Cardiology.

The two trials have shown remarkably similar results.

PARTNER 3, using the SAPIEN 3 system (Edwards Lifesciences) showed a significantly lower rate of the primary endpoint, a composite of death, stroke, and rehospitalization at 1 year, compared with surgery.

The second trial, with the self-expanding valve (CoreValve/ Evolut R/Evolut PRO; Medtronic) showed noninferiority compared with surgery in an interim Bayesian analysis of the primary endpoint — death from any cause or disabling stroke at 24 months — as well as significantly lower rates of disabling stroke and hospitalization for heart failure at 1 year.

"Two separate groups using two separate valves have come to very similar conclusions," Braunwald said. "This does not double the acceptability, it quadruples it."

He said the TAVR results were more impressive because the surgery outcome rates were so low.

"What impressed me enormously was how good the surgery was. In doing a trial like this, sometimes the surgery can be downgraded and the TAVR will look terrific, but the surgery outcomes in these studies are as good as I've ever seen."

Co-principal investigator of the Evolut study, Michael Reardon, MD, Houston Methodist DeBakey Heart & Vascular Institute, Texas, said, "What I think we're seeing here is a class effect of TAVR. This technology is evolving at such a rapid rate, it's hard to imagine what we're going to be doing 5 years from now."

Presenting the PARTNER 3 study, Martin Leon, MD, Columbia University Medical Center, New York City, added: "I agree the class effect for these two TAVR systems is very real, but I wouldn't presume to think every TAVR device will perform the same way, so I do think we need more data with some of the newer TAVR devices being introduced."

The devices used in these two trials have evolved "dramatically," he added. "The operators have had the opportunity to get comfortable with them over a period of years. The procedures have also evolved and stabilized. I think it was a combination of all these things that contributed to these excellent outcomes."

Durability of Valves — Key Issue

As part of the panel discussion of the trials, the issue of TAVR valve durability was raised. But both Reardon and Leon challenged the supposition that surgical bioprosthetic valve durability was better than that with TAVR valves.

"As a cardiac surgeon, I can tell you that the number of surgical valves with known durability is somewhat small," Reardon commented. "I can name a number of surgical valves that are used on a daily basis by surgeons who say they're going to last because they're surgical valves, but if you're around long enough they do actually fail."

"There is a myth about surgical bioprosthetic valve immortality," Leon added. "The majority of surgical valves being used today which are touted as being durable is based on 2- to 4-year data. TAVR is not a new procedure any more, and 5-year data is absolutely definitive showing no early structural valve deterioration."

As part of the discussion, the TAVR presenters were asked how the stroke rate had been reduced so much with the procedure compared with earlier trials. "We started off worrying about stroke with TAVR," Reardon responded. "You can't say that any more. In these two trials, the stroke rates are very low in both TAVR and surgery groups. We are almost approaching the background stroke rate in 74-year-olds doing nothing."

Leon added: "We only had six strokes in PARTNER 3, and five of these were nondisabling. I think it is the combination of the low-risk patients, the fact that we have got better with our techniques, and the procedures themselves have stabilized that all contribute to this very low rate."

Study Designs Scrutinized

Other experts raised the issue of including hospitalization in the primary endpoint of PARTNER 3. It was argued that re-hospitalization doesn't have the same weight as stroke or death, and its inclusion in the endpoint could bias against surgery as more surgery patients will be re-hospitalized for complications early on.

Leon replied that hospitalizations were for many reasons including new pleural effusions leading to new thoracotomy, sepsis, endocarditis, and ischemic limbs. "These are significant events for these low-risk patients." He added that if rehospitalizations in the first month are excluded, the results did not change.

Clinical trial guru Sanjay Kaul, MD, Cedars-Sinai Medical Center, Los Angeles, California, told theheart.org | Medscape Cardiology that the Evolut trial design was more robust than PARTNER 3, with the harder primary endpoint of death/disabling stroke. However, he questioned why the trial was published with just an interim Bayesian analysis of the primary endpoint. "The right thing would have been to wait for 2-year data and present the results without statistical juggling to impute 2-year outcomes," he commented

Responding, Reardon pointed out that the same analysis was done for the SURTAVI trial in intermediate-risk patients and "the full 2-year analysis matched the interim Bayesian analysis validating our approach."

"In the Evolut Low Risk Trial, we chose an endpoint of all-cause mortality and disabling stroke as objective and impactful endpoints for a low-risk patient population. We chose 2 years as a meaningful timepoint for this patient population. Bayesian analysis allows an interim analysis and the potential to bring this important therapy to patients sooner."

Kaul also challenged the short follow-up in the PARTNER 3 trial with 1 year as the primary endpoint. "For low-risk patients, the key issue with TAVR is durability of outcomes," he stressed. But Leon pointed out that patients will continue to be followed for at least 10 years.

One downside of TAVR use in the Evolut study was a higher use of pacemakers compared with in the surgery group. On this Reardon commented: "Yes, this has been a problem, but the pacemaker rates are coming down as we get more comfortable with our techniques."

Giving some perspective on the whole aortic stenosis field, ACC spokesperson and cardiac surgeon Joseph Cleveland, MD, University of Colorado Medical Center, Aurora, reported that about 25,000 isolated aortic stenosis surgeries were done in the United States last year. "Of these, I would say 15,000 will now switch to TAVR. By about 2021, I would say there would be less than 5000 aortic valve surgeries being done. No one wants to have an open heart operation if they don't have to."

He explained to theheart.org | Medscape Cardiology that younger patients have a choice between receiving mechanical or bioprosthetic valves. "Mechanical valves, which can only be placed with surgery, give the greatest chance of never having another intervention but require lifelong anticoagulation, and many patients do not want to be beholden to a medication with a significant risk bleeding, so surgeons now use mainly bioprosthetic valves.

"There is very limited data, but the known durability of bioprosthetic surgical valves is about 10 years so far," he added. "In theory, the durability should be the same for surgical and TAVR bioprosthetic valves as they are made from similar material. I say to my patients that they may need another procedure in 15 to 20 years."

After these low-risk trial results, Cleveland said the main reason to choose surgery over TAVR is anatomy. "Younger patients who have aortic stenosis normally have bicuspid valves, and it is not as easy to use TAVR in this population. They are mostly treated with surgery now."

A Hybrid Surgeon-Interventionist Specialty

Regarding how cardiac surgeons are reacting to these results, Cleveland believes most contemporary surgeons will acknowledge that TAVR is the right thing to do for most patients.

"It is important that both the cardiologist and the surgeon remain at the forefront of this treatment, and many surgeons are retraining so they can offer both procedures," he said. "We don't believe this as an 'us or them' technology — it should be more of a partnership between the cardiologist and the surgeon."

"Involvement of both cardiologist and surgeon in the evaluation of the patient and the procedure itself is essential for patient outcomes," he added. "Even though this is a catheter-based procedure, the future will be some sort of hybrid surgeon-interventionist specialty."

He reported that around 1200 centers in the United States have an open-heart center and around half of these also offer TAVR. "But that percentage will now increase."

American College of Cardiology 68th Annual Scientific Session 2019 (ACC.19). Presented March 17, 2019.

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