Abstract
BACKGROUND: Secondary mitral regurgitation (SMR) worsens outcomes in heart failure. Transcatheter mitral valve repair (MitraClip/TMVr) is an established alternative for patients who remain symptomatic on guideline-directed medical therapy (GDMT), but comparative efficacy versus GDMT and surgery has been debated. METHODS: We searched MEDLINE, Embase, and Cochrane through February 2025. To avoid double counting, quantitative syntheses used unique randomized controlled trials (RCTs) only; RCT substudies informed qualitative context. Pairwise random-effects meta-analyses compared MitraClip + GDMT vs GDMT and MitraClip vs surgery. Primary outcomes were all-cause mortality and heart-failure hospitalization (HFH). Secondary outcomes included quality of life (Kansas City Cardiomyopathy Questionnaire (KCCQ), MR ≤ 2+, stroke/MI, and major adverse events (MAE). Heterogeneity was explored with I(2)/τ(2), leave-one-out, and prespecified sensitivity analyses per Cochrane/JBI guidance. RESULTS: Nineteen studies were included, of which 5 unique Randomized Control Trials (RCTs) (n = 1912 randomized) contributed to pooling. Versus GDMT, MitraClip reduced mortality (RR 0.77, 95 % CI 0.63-0.95; I(2) = 73 %) and (Heart Failure Hospitalization) HFH (RR 0.76, 0.65-0.89; I(2) = 90 %), and improved KCCQ (MD + 13.7 points, 6.6-20.7). Including all available comparators across RCTs, mortality remained lower with MitraClip (RR 0.80, 0.65-1.00; p = 0.047; I(2) = 26 %). Versus surgery, MitraClip had fewer 30-day MAE (Major Adverse events) (RR 0.29, 0.21-0.40; I(2) = 0 %), with no difference in 1-year mortality and similar MR ≤ 2+ at ~1 year. Stroke/MI were comparable. Procedural success exceeded 96 %; partial clip detachment occurred in 1-2 %. CONCLUSIONS: In contemporary RCTs, MitraClip on top of GDMT lowers mortality and HF hospitalizations and improves quality of life in SMR. Compared with surgery, TMVr offers a superior early safety profile with similar MR reduction at ~1 year. These results support Heart-Team use of MitraClip after optimized GDMT in anatomically suitable SMR, while reserving surgery for selected scenarios.