Safety, Efficacy, and Effectiveness of Coronary Sinus Reducer Implantation in Refractory Angina: A Meta-Analysis.

Background: Previous coronary sinus reducer (CSR) meta-analyses in refractory angina (RA) focused on single-arm studies, capturing observed effectiveness-comprising the physical effect of CSR, contextual effects (eg, placebo), and non-treatment-related phenomena (eg, confounding). Efficacy evaluation requires comparative estimates from randomized controlled trials (RCTs), ideally double blind and placebo controlled, to isolate the physical effect.

Objectives: The aims of this study were to evaluate the safety and efficacy of CSR in RA and to compare its efficacy with observed effectiveness.

Methods: The study was preregistered with the International Prospective Register of Systematic Reviews (CRD42023399099). Electronic databases were searched until April 2024. Random-effects models separately pooled single-arm, isolated RCT intervention-arm, and RCT placebo-controlled estimates. Therapeutic outcomes included improvements in Canadian Cardiovascular Society classification, Seattle Angina Questionnaire scores, and treadmill exercise time. Safety outcomes, summarized descriptively, comprised procedural success and adverse events.

Results: Three double-blind, placebo-controlled RCTs (n = 180) and 13 single-arm studies (n = 668) were analyzed. The overall unweighted procedural success rate was 98.3% (95% CI: 97.0%-99.1%). Single-arm studies and RCT intervention arms demonstrated statistically significant improvements across therapeutic outcomes. For Canadian Cardiovascular Society classification, placebo-controlled rates were 26% (95% CI: 11%-38%; P < 0.001) for ≥1-class improvement and 17% (95% CI: 2%-37%; P = 0.02) for ≥2-class improvement, representing approximately one-third of single-arm improvement rates. Seattle Angina Questionnaire domain analyses demonstrated insufficient placebo-controlled evidence of benefit. Placebo-controlled exercise time change was 49.62 seconds (95% CI: 1.84-97.40 seconds; P = 0.04).

Conclusions: CSR implantation is safe and feasible and demonstrates promising antianginal efficacy in patients with RA. However, uncertainty in current efficacy findings and susceptibility of effectiveness data to nonphysical influences preclude definitive conclusions about clinical utility, warranting larger placebo-controlled trials.