EARLY TAVR and EVOLVED Trials Offer Divergent Conclusions but Similar Results for AVR in Patients with Asymptomatic Severe Aortic Stenosis

At TCT 2024, results from two pivotal trials—EARLY TAVR and EVOLVED—were presented, each exploring early intervention in asymptomatic severe aortic stenosis (AS) patients but yielding contrasting findings.

The EARLY TAVR trial, conducted across 75 sites with 901 participants, investigated whether early transcatheter aortic valve replacement (TAVR) could improve outcomes compared to clinical surveillance in asymptomatic severe, high-gradient AS. Patients aged 65 and above with preserved left ventricular ejection fraction (LVEF) were randomized to either TAVR or monitoring. The primary endpoint—a composite of all-cause death, stroke, or unplanned cardiovascular hospitalization—was significantly lower in the TAVR group (26.8%) than in the surveillance group (45.3%), with a hazard ratio (HR) of 0.50 (95% CI, 0.40–0.63; p < 0.001). Median follow-up was 3.8 years. EARLY TAVR’s positive results support early intervention, suggesting a 50% reduction in adverse events compared to surveillance, driven primarily by hospitalization​.

In contrast, the EVOLVED trial, which enrolled 224 patients across 24 centers in the UK and Australia, focused on asymptomatic severe AS patients with myocardial fibrosis detected through cardiac magnetic resonance imaging (CMR). These patients were randomized to early valve replacement (surgical or TAVR) or guideline-directed conservative management. The primary outcome—a composite of all-cause mortality or unplanned AS-related hospitalization—occurred in 18% of the intervention group and 23% of the conservative management group (HR 0.79; 95% CI, 0.44–1.43; p = 0.44), with no statistically significant difference. The median follow-up was 42 months. While early intervention reduced unplanned AS-related hospitalizations (HR 0.37, 95% CI 0.16–0.88), it did not significantly impact mortality.

At face value, the results of the two trials seem to paint divergent conclusions on the value of early intervention for asymptomatic severe AS. There could be some plausibility for this. Perhaps reliance on myocardial fibrosis to guard access to early intervention selects for those in whom the damage is already done, thereby diluting the possible protective impact of early AVR. More likely, however, is that the two trials aren’t that different, but rather, the differences may be explained by implantation. EVOLVED was a smaller trial with COVID-related under-enrollment likely leading to underpowered results. Moreover, the time from randomization to AVR was substantially longer in EVOLVED (5 months) than in EARLY TAVR (14 days), a relative delay that may have washed out much of the possible benefit of early intervention given that over a quarter of conservatively managed patients in EARLY TAVR converted to symptomatic status in the first six months. Despite these shortcomings, the EVOLVED trial still showed a significant 63% lower risk of unplanned hospitalizations with early intervention and improvement in NYHA functional class.

Taken together, the EVOLVED and EARLY TAVR trials are actually quite consistent. Offering AVR for asymptomatic AS patients does not increase longevity, but it probably improves the quality of life with fewer unplanned hospitalizations and health status deterioration. Enthusiasm for widespread adoption of this strategy should be tempered until longer-term follow-up is available for these relatively young and low-risk patients who will likely outlive their first valve.

References

Généreux P, Schwartz A, Oldemeyer JB, et al; for the EARLY TAVR Trial Investigators. Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis. N Engl J Med. 2024; DOI: 10.1056/NEJMoa2405880. Published online October 28, 2024.

Loganath K, Craig NJ, Everett RJ, et al; for the EVOLVED Investigators. Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Myocardial Fibrosis: The EVOLVED Randomized Clinical Trial. JAMA. 2024; DOI: 10.1001/jama.2024.22730. Published online October 28, 2024.