Two separate late-breaking clinical trials – EARLY TAVR and EVOLVED – presented at TCT 2024 explore whether early aortic valve intervention improves outcomes in patients with asymptomatic aortic stenosis (AS).

In EARLY TAVR, simultaneously published in NEJM, Philippe Généreux, MD, FACC, et al., randomized 901 patients from 75 centers in the U.S. and Canada to either early TAVR with transfemoral placement of a balloon-expandable valve (n=455) or clinical surveillance (n=446). All participants had asymptomatic severe AS, 83.6% were at low surgical risk and the average age was 76 years.

A primary endpoint event – death, stroke, or unplanned hospitalization for cardiovascular causes – occurred in 122 patients (26.8%) of those assigned to the early TAVR group compared with 202 patients (45.3%) in the clinical surveillance group. By event, death occurred in 8.4% of patients who underwent early TAVR and in 9.2% of patients assigned to clinical surveillance, while unplanned hospitalization for cardiovascular causes occurred in 20.9% vs. 41.7%, respectively. Of note, stroke occurred in 4.2% of those assigned to TAVR compared with 6.7% assigned to clinical surveillance – a finding that Généreux and colleagues said was unexpected and needs to be confirmed and explained by further studies.

In other findings, 87% of patients in the clinical surveillance group underwent aortic-valve replacement during the median follow-up period of 3.8 years, with no apparent differences in procedure-related adverse events between this group and those who underwent early TAVR.

"Among patients with asymptomatic severe AS, a strategy of early TAVR was superior to guideline-recommended clinical surveillance in reducing the composite end point of death, stroke, or unplanned hospitalization for cardiovascular causes," said the study authors.

In EVOLVED, Krithika Loganath, MD, et al., investigated whether early valve intervention reduced the incidence of all-cause death or unplanned AS–related hospitalization in asymptomatic patients with severe AS and myocardial fibrosis. The trial, which was simultaneously published in JAMA, randomized 226 patients from 24 centers in the U.K. and Australia to early aortic valve intervention (n=114) or guideline-directed conservative management. The average age of participants was 73 and 28% were women.

Overall finding showed no significant difference in the primary composite end point of all-cause death or unplanned AS–related hospitalization between those assigned to early intervention (18%) and those assigned to conservative management (23%).

"Of nine prespecified secondary endpoints, seven showed no significant difference," according to Loganath and colleagues. The two areas where differences were observed, included unplanned AS hospitalization which occurred in 6% of those assigned to early intervention compared with 17% of those assigned to guideline-directed conservative management. Early intervention was also associated with a lower 12-month rate of New York Heart Association class II-IV symptoms (19.7% vs. 37.9%, respectively).

In a related editorial comment also published in JAMA, Robert O. Bonow, MD, MS, MACC, cautions that "while the results of this small but well-designed mechanistic clinical trial do not support identifying asymptomatic patients with severe AS for preemptive [aortic valve replacement] based on evidence of myocardial fibrosis (and therefore screening them with MRI to detect late gadolinium enhancement), there are several issues to address." He notes the trial results "leave open the opportunity for further investigation of earlier intervention for patients with AS manifesting myocardial structural remodeling."