TEER plus medical therapy vs medical therapy alone for symptomatic moderate-to-severe functional mitral regurgitation: a comprehensive, up-to-date meta-analysis of randomized trials

Abstract Background Transcatheter edge-to-edge repair (TEER) has emerged as a promising treatment for patients with symptomatic moderate-to-severe functional mitral regurgitation (FMR) who are unsuitable for surgery. However, the available evidence supporting clinical benefits over guideline-direct medical therapy (GDMT) alone, is discordant. Against this background, we conducted a comprehensive, up-to-date meta-analysis of randomized trials comparing long-term outcomes between TEER plus GDMT and GDMT alone for symptomatic moderate-to-severe FMR. Methods Major electronic databases were searched for randomized trials comparing long-term outcomes between TEER plus GDMT and GDMT alone in patients with symptomatic moderate-to-severe FMR. The prespecified primary outcome was the composite of all-cause death or hospitalization due to heart failure at 24 months. Secondary outcomes included all-cause death, cardiovascular death, and hospitalization due to heart failure. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models with inverse-variance weighting and restricted maximum likelihood-based estimation of between-trial heterogeneity. Results were complemented with analyses of reconstructed time-to-first-event individual patient data by one-stage mixed-effects Cox models and multiple sensitivity analyses to assess between-trial heterogeneity. Results Three randomized clinical trials (MITRA-FR, COAPT, and RESHAPE-HF2) were identified and included in the meta-analysis for a total of 1423 patients assigned to TEER plus GDMT (n=704) or GDMT alone (n=719). The primary analysis revealed a significant reduction in 24-month all-cause death or hospitalization due to heart failure in the TEER plus GDMT group compared with GDMT alone (HR 0.71, 95% CI, 0.50-1.00). Nevertheless, substantial heterogeneity was observed across studies (I² = 81%, p = 0.005). Exclusion of either the COAPT or RESHAPE-HF2 trials produced non-significant summary estimates (HR 0.79, 95% 0.49-1.28 and HR 0.75, 95% 0.43-1.32, respectively). Results by one-stage mixed-effects model were consistent with those by two-stage random-effects models (HR 0.73, 95% CI 0.56-0.94). Hospitalization due to heart failure at 24 months was significantly lower in the TEER plus GDMT group compared with GDMT alone (HR 0.68, 95% CI 0.47-0.97). Heterogeneity remained significant (I² = 81%, p = 0.007). Results by one-stage mixed-effects model were consistent with those by two-stage random-effects models (HR 0.66, 95% CI 0.50-0.89). There was a trend toward reduced all-cause (HR 0.76, 95% CI 0.57-1.01) and cardiovascular death (HR 0.77, 95% CI 0.56-1.06) in the TEER plus GDMT group compared with GDMT alone at 24 months. Conclusion In patients with symptomatic moderate-to-severe FMR, TEER plus GDMT significantly reduces the risk of all-cause death or hospitalization due to heart failure and hospitalization due to heart failure at 24 months compared to GDMT.