ESC Congress 2026 Abstract · Oct 26, 2026
Do tafamidis and acoramidis improve survival and cardiovascular outcomes in transthyretin amyloid cardiomyopathy? a systematic review and meta-analysis
By Soomro MU, Khan Z, Munir S et al.
Background: Transthyretin amyloid cardiomyopathy is a progressive and often fatal condition with a five-year survival rate inferior to that of many solid cancers, yet therapeutic strategies that modify disease progression remain scarce. At present, tafamidis is the only approved transthyretin (TTR) stabilizer, whereas acoramidis continues to be evaluated as an investigational alternative. Prior clinical trials have demonstrated signals toward improved survival and reduced cardiovascular events; however, their interpretability has been limited by small cohorts and inconsistent endpoint definitions. Consequently, the overall clinical benefit of TTR stabilization on meaningful outcomes has not been fully established. We therefore conducted a comprehensive synthesis of all randomized and rigorously propensity-matched data to generate a more precise and adequately powered estimate of the impact of TTR stabilization on hard outcomes most relevant to patients and healthcare systems. Methods: Randomized controlled trials (RCTs) and rigorous real-world studies were found through a systematic search of PubMed, Embase, Scopus, and the Cochrane Library to assess the survival benefit of using Tafamidis/Acoramidis with a comparator through May 2025. Data was analyzed using RevMan 5.4. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using Mantel-Haenszel methods. Random- or fixed-effects models were applied based on heterogeneity (Higgins’ I²). Statistical significance was set at p < 0.05. Risk of bias was assessed with RoB 2.0. Results: Tafamidis/Acoramidis decreased all-cause mortality by 34% (163/706 vs 150/412 deaths; RR 0.66, 95% CI 0.55–0.80; P < 0.001; I² = 66%) in 1,118 transthyretin-cardiomyopathy patients who were pooled from ATTRACT, ATTRibute-CM, and a contemporary matched cohort. The prespecified composite of CV death, urgent HF visit, or first CV hospitalization fell by 25% (295/706 vs 231/412; RR 0.75, 95% CI 0.66–0.85; p < 0.001). Effects were directionally consistent across trials and remained robust on leave-one-out analyses, underscoring a class effect in both controlled and real-world settings. Conclusion: TTR-stabilizing therapy delivers clinically meaningful, statistically compelling reductions in death and cardiovascular morbidity for patients with ATTR-CM. These findings support early screening for amyloid cardiomyopathy, routine initiation of tafamidis where available, and rapid completion of ongoing acoramidis trials to expand access and potentially transform the natural history of this once-inexorable disease.Forest Plot