WASHINGTON, D.C.—A randomized trial of patients with a narrowing of their heart’s aortic valve, but who had not yet begun to show the symptoms of cardiovascular disease, demonstrated that replacing their valves early with a minimally invasive implant could help stave off related deaths, strokes and later trips to the hospital, as well as deteriorations in their quality of life.
But at the same time, a separate study of a group of similarly asymptomatic patients with severe aortic stenosis—but who also carried scarring in their cardiac muscle wall unrelated to any previous heart attack—showed that early replacements of the affected heart valve did not produce significant gains against mortality or stroke, however, it did show some reductions in emergency hospitalizations.
Both studies were presented as late-breaking trials at the Cardiovascular Research Foundation’s Transcatheter Cardiovascular Therapeutics conference in Washington, D.C.
The first trial, dubbed EARLY TAVR, examined about 900 people who were able to complete a treadmill exercise test without displaying heightened symptoms such as shortness of breath. About half underwent a transcatheter aortic valve replacement procedure—within a median time of about two weeks after joining the study—to receive a Sapien 3 family implant from Edwards Lifesciences.
The control group, meanwhile, followed the standard schedule of clinical surveillance, with checkups every six to 12 months, and had their heart valves replaced about 32 days after symptoms were caught.
The study met its primary endpoint, with TAVR showing a significant reduction in a combination measurement of death rates, strokes and unplanned cardiovascular hospitalizations after at least two years: About 35.1% of patients were affected in the early intervention group, compared to 51.2% with a watch-and-wait strategy.
“This is the first pivotal trial to generate evidence about the best strategy for disease management of severe aortic stenosis,” Larry Wood, Edwards’ group president of TAVR and surgical structural heart implants, said in a statement.
“EARLY TAVR challenges the current standard of care by definitively showing that patients who don’t have symptoms of severe aortic stenosis have a deadly disease that requires urgent treatment,” Wood added.
While breaking up that measure into its component parts did not show significant differences in all-cause mortality or strokes—which in part meant that pursuing TAVR early did not add to those adverse outcomes, as well—it did reduce subsequent hospitalizations for heart failure.
And within the study’s median follow-up time of 3.8 years, more than 87% of the patients in the surveillance arm eventually did have their aortic valves replaced, with the vast majority through TAVR. The trial’s results were simultaneously published in the New England Journal of Medicine.
“Given the benefits observed and the lack of harm, early TAVR may be preferred to clinical surveillance in patients with asymptomatic severe AS, especially when combined with the challenges of timely symptom recognition and prompt treatment in real-world settings,” said EARLY TAVR lead author Philippe Généreux, director of the structural heart program at Morristown Medical Center. “Not only is early intervention safe and effective, but it also prevents a decline in quality of life for those who later receive TAVR and could prevent the development of cardiac damage.”
The second study presented at TCT, called EVOLVED, also did not show significant gains against rates of death or stroke—missing its primary endpoint—but recorded fewer aortic stenosis-related hospitalizations among patients who had their valves replaced a median of 15 months earlier. More patients in the watch-and-wait group were also classified into more serious categories of heart failure after 12 months.
This trial randomized 224 patients, and focused on those who had myocardial scarring and fibrosis confirmed by an MRI scan—a key driver of decompensation in the left ventricle, and a condition linked with earlier deaths, according to researchers.
Conducted by the University of Edinburgh, the open-label study included both TAVR and open surgical valve replacement approaches. Its results were published in JAMA.
“Although early intervention did not reduce the incidence of the composite primary endpoint of all-cause death or unplanned aortic stenosis hospitalization, our study did find other benefits,” said study presenter Mark Dweck, chair of clinical cardiology at the University of Edinburgh.
“The principal benefit of early intervention appears to be in the reduction of emergency hospitalization and in preventing the development of limiting symptoms,” Dweck said. “This appears to be a consistent finding across all the trials to date and an important outcome for patients with this condition.”