Major Win for Preemptive TAVR in Symptomless Aortic Stenosis

Transcatheter aortic valve replacement (TAVR) yielded clinical benefit when given early in the disease process while patients still had no symptoms or other indication for aortic valve replacement, according to the EARLY TAVR trial.

In older people with asymptomatic severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF), upfront TAVR resulted in fewer combined deaths, strokes, or unplanned cardiovascular hospitalizations (26.8% vs 45.3% with standard clinical surveillance, HR 0.50, 95% CI 0.40-0.63) over a median 3.8 years of follow-up.

Upfront TAVR was also associated with more favorable outcomes and better left heart parameters at 2 years compared with watchful waiting, Philippe Généreux, MD, of Morristown Medical Center in New Jersey, told the audience at the Transcatheter Cardiovascular Therapeutics (TCT) meeting in Washington, D.C. The full manuscript of EARLY TAVR was simultaneously published in the New England Journal of Medicine.

While TAVR is well established for severe AS patients with symptoms across surgical risk categories, current guidelines recommend routine monitoring every 6 to 12 months for asymptomatic patients. TAVR is reserved for those with symptoms or asymptomatic individuals who have a reduced LVEF, a positive stress test, or other indication for valve surgery.

Importantly, EARLY TAVR tested the waters of preemptive TAVR in a select asymptomatic cohort that was over 65 years of age and predominantly at low surgical risk.

Généreux pointed out that the control arm underwent intense clinical surveillance that may not be replicated in real-world practice. A steady progression of symptoms led to prompt conversion of controls to TAVR.

In just the first 6 months, approximately one in four controls underwent aortic valve replacement; ultimately, 87.0% of patients in the clinical surveillance group underwent aortic valve replacement in follow-up averaging just under 4 years.

Généreux broke down the results for the individual components of the primary endpoint:

• Death: 8.4% with early TAVR vs 9.2% with conservative care
• Stroke: 4.2% vs 6.7%
• Unplanned cardiovascular hospitalizations: 20.9% vs 41.7%

Scott Lim, MD, of the University of Virginia Health System in Charlottesville, told MedPage Today that he was “pleasantly surprised by the overall results.” The surgical studies that had suggested some benefit to early TAVR had been small and underpowered, he noted.

“I am overall impressed that while the primary endpoint was driven mainly by the difference in future unplanned interventions (which mainly was likely due to patients becoming symptomatic, and then having their aortic valve replaced), the secondary measures indicated significant benefit in terms of favorable outcomes at 2 years, and improved measures of [left ventricular] and [left atrial] health,” Lim commented in an email.

He nevertheless warned that a widening of the pool of TAVR candidates would be concerning in terms of the capacity of many institutions to handle more patients with AS. “This will add to the lists of patients pending cardiac structural procedures,” he suggested.

EARLY TAVR was a randomized open-label trial conducted in 75 centers in the U.S. and Canada. Eligible participants were people age 65 or older with asymptomatic severe AS.

The randomized cohort included 901 people assigned either upfront TAVR (with the balloon-expandable Sapien 3 or Sapien 3 Ultra systems) or standard care with clinical surveillance. Investigators confirmed the lack of symptoms with a treadmill stress test in over 90% of cases.

Baseline characteristics were balanced between the two study groups. Participants had a mean age of 75.8 years, were 30.9% women, and around 95% were white. The cohort had a Society of Thoracic Surgeons Predicted Risk of Mortality score averaging 1.8% (83.6% of patients being at low surgical risk). The prevalence of bicuspid anatomy was 8.4%, and the mean Kansas City Cardiomyopathy Questionnaire score was 92.7 in both groups.

There were no apparent differences in procedure-related adverse events between patients in the upfront TAVR group and those in the surveillance group who eventually got aortic valve replacement.

The EARLY TAVR investigators cautioned against extrapolating their results to other types of patients and other TAVR valves.

“Young patients with bicuspid disease and marked asymmetry of their aortic root/annulus still may be better served by a surgical AVR over TAVR, and young patients in general need to have more forethought into the “lifetime management” of their aortic valve disease,” according to Lim.