TAVR Beats Surveillance for Asymptomatic Aortic Stenosis

WASHINGTON, DC — Transcatheter aortic valve replacement (TAVR) is superior to surveillance in patients with severe but asymptomatic aortic stenosis with no apparent cost in adverse events, according to the EARLY TAVR study, which was immediately characterized as a landmark by several experts.

The study results challenge current guidelines that call for aortic valve replacement only when severe aortic stenosis produces symptoms. In the study, patients with severe aortic stenosis but no symptoms were randomized to TAVR or surveillance.

The composite primary endpoint of death, stroke, and unplanned hospitalization was 50% lower in the TAVR group than in the surveillance group (hazard ratio [HR], 0.50; P

When the slide showing the primary endpoint results was displayed by Philippe Généreux, MD, medical director of the Structural Heart Program at the Atlantic Medical Group in Morristown, New Jersey, during his presentation at the late-breaker session here at Transcatheter Cardiovascular Therapeutics 2024, the audience broke into a sustained round of applause.

50% Risk Reduction After TAVR

“The world has been waiting for the results of this trial,” said Bernard Prendergast, DM, chair of cardiology at Cleveland Clinic London and consultant cardiologist at St. Thomas’ Hospital, London. He was one of several who described EARLY TAVR as a landmark study, and called the results “a major reset in our approach to severe aortic stenosis.”

In EARLY TAVR, conducted at 75 sites in the United States and Canada, 901 patients with severe aortic stenosis, a left ventricular ejection fraction of at least 50%, and no symptoms of aortic stenosis were randomized. An emphasis was placed on early intervention, and the median time to TAVR after study enrollment was only 14 days. During the follow-up period, those in the surveillance group were followed closely and referred for TAVR as soon as symptoms developed.

At 2 years, fewer patients in the TAVR group than in the surveillance group experienced a primary event (35.1% vs 51.2%), according to the data, which were published simultaneously in the New England Journal of Medicine.

The primary benefit of being randomized to TAVR was driven by a 57% reduction in unplanned hospitalization (HR, 0.43; 95% CI, 0.33-0.55). The 38% reduction in the risk for stroke (HR, 0.62; 95% CI, 0.35-1.10) fell short of significance. There was no significant difference in the risk for death (13.4% vs 13.6%).

Even without a mortality advantage, the favorable effect of TAVR on hospitalization corresponded to a clinically meaningful improvement in quality of life, Généreux reported. On the 12-point Kansas City Cardiomyopathy Questionnaire, the sustained advantage was described as substantial and clinically meaningful.

Majority of Surveillance Patients Developed Symptoms

Importantly, there was a steady increase in conversion to symptomatic aortic stenosis among patients in the surveillance group. As a result, nearly 90% of those patients crossed over to aortic valve replacement during the follow-up period.

By 6 months, 26.2% of patients in the surveillance group had been directed to TAVR to relieve symptoms. By 2 years, that rate had reached 71.4%, and at the median follow-up of 3.8 years, it had reached 87%. The median time of conversion to aortic valve replacement in the surveillance group was only 11.1 months.

TAVR was not associated with any periprocedural risks, although there was a nominal 4.5% increase in the rate of atrial fibrillation in the TAVR group, according to Prendergast. However, the overall safety of TAVR, as reflected in this study, is one of the things that makes the results of this trial so practice changing, he explained.

After agreeing that “there should be some penalty to pay for being more aggressive,” invited expert Jeffrey W. Moses, MD, professor of cardiology at the Columbia University Medical Center, New York City, said he is impressed that there appears to be no downside.

The impressive safety of TAVR, which is consistent with current practice at many centers, makes a major contribution to the message of this trial, which is that preemptive TAVR in patients with severe but asymptomatic aortic stenosis appears to be justified by better outcomes, according to Moses and others.

The fact that only 9.1% of patients in the surveillance group remained symptom free at 36 months underlines the progressive nature of aortic stenosis. Although this is not a new observation, the EARLY TAVR data are the first to provide support for treatment before symptoms develop.

“We have been looking for these data for so long,” said Robert O. Bonow, MD, professor of cardiology at the Feinberg School of Medicine, Northwestern University, Chicago. They reconfirm that most aortic stenosis patients with severe disease but no symptoms will be candidates for TAVR — 90% in this study — within a few years. The EARLY TAVR study provides the proof that preemptive TAVR reduces symptoms and hospitalizations while improving quality of life.

“We don’t get any gain in waiting,” Bonow said.