Early Intervention in Asymptomatic Patients with Severe Aortic Stenosis

To Editor,

Initially, the RECOVERY and AVATAR trials supported early surgical aortic valve replacement (SAVR) in asymptomatic patients with severe aortic stenosis (AS) by showing improved clinical outcomes, not mortality, in comparison with conservative management.[1,2] In the recently published EARLY TAVR trial, early transcatheter aortic valve replacement (TAVR) was superior to conservative management in reducing adverse cardiovascular (CV) events driven by reducing hospitalization from CV causes.[3] The EVOLVED trial, another recently published trial, that randomized patients to early intervention (SAVR or TAVR) or conservative management, did not demonstrate improved composite of all-cause death and AS-related hospitalization in asymptomatic patients with severe AS and myocardial fibrosis. There was no benefit in terms of secondary endpoints (i.e., all-cause death, CV death, and stroke) except in decreasing AS-related hospitalization.[4] EVOLVED trial was well-designed and probably more pragmatic than other trials by considering both SAVR and TAVR. However, it was underpowered by not meeting its planned sample size and including only patients with myocardial fibrosis. We undertook a meta-analysis of randomized trials, using random-effects model, to test the consistency of effects of early invasive intervention (SAVR or TAVR) compared with conservative strategy. By considering both SAVR and TAVR, it would be possible to pool EVOLVED trial’s data with those of others to increase power and include wider patient characteristics (e.g. with or without myocardial fibrosis, or critical stenosis as in the RECOVERY trial). A PubMed literature search was conducted on October 28, 2024, by combining broad appropriate MeSH terms. Of the 843 records, four randomized trials were included (i.e., RECOVERY, AVATAR, EARLY TAVR, and EVOLVED).[1,2,3,4] The trials recruited 1427 patients (intervention = 719, conservative = 708) with a follow up of 3–4 years[2,3,4] except in one trial (6 years).[1] The mean age was 65–76 years with males’ majority (50%–70%). The mean AV area was 0.65 cm–0.90 cm squared. All-cause (odds ratio [OR] 0.65, 95% confidence interval [CI]: 0.35–1.18, P = 0.1573; I² = 56%) and CV (OR 0.80, 95 CI: 0.50–1.27, P = 0.3424; I² = 49%) death rates did not differ between groups. Whereas, rates of heart failure or AS-related hospitalization (OR 0.35, 95% CI: 0.27–0.46, P < 0.0001; I² = 0%) and stroke (OR 0.59, 95% CI: 0.37–0.95, P = 0.0315; I² = 0%) were significantly lower in the intervention group [Figure 1]. These findings are consistent with The EVOLVED trial results by demonstrating the absence of mortality benefit and a reduction in hospitalization with early intervention. The ADANVAR (NCT03972644) and EASY-AS (NCT04204915) trials randomize patients to either intervention (SAVR or TAVR) compared with conservative management, and their results are awaited to resolve the current uncertainty.

Figure 1.

Forest and funnel plots for clincal outcomes. (a) All-cause mortality; (b) Cardiovascular mortality; (c) Heart failure or AS-related hospitalization; (d) Stroke. OR: Odds ratio, CI: Confidence interval

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.