Optimizing treatment strategies for transthyretin amyloid cardiomyopathy: a comprehensive Bayesian network meta-analysis of disease-specific therapies

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and life-threatening disease associated with high morbidity and mortality. Emerging disease-specific therapies, including tafamidis, patisiran, acoramidis, and vutrisiran, have shown promise in improving clinical outcomes. However, their comparative efficacy remains unclear. Objectives This study conducted a Bayesian network meta-analysis to compare the efficacy of disease-specific therapies in ATTR-CM. Outcomes assessed included all-cause mortality, cardiovascular hospitalizations, 6-minute walk test (6MWT), and Kansas City Cardiomyopathy Questionnaire (KCCQ-OS) scores determine the most effective treatment strategies. Methods A systematic search was conducted to identify randomized controlled trials (RCTs) evaluating the efficacy of tafamidis, patisiran, acoramidis, and vutrisiran in ATTR-CM. Both dichotomous (hazard ratios, HR) and continuous (mean difference, MD) outcomes were analyzed with 95% credible intervals (CrI), using placebo as the reference. A random-effects Bayesian model was employed for network meta-analysis, with Surface Under the Cumulative Ranking Curve (SUCRA) values used to rank treatments. Bayesian inference was performed using Markov Chain Monte Carlo (MCMC) simulations, with model fit assessed via Deviance Information Criterion (DIC). Results We analyzed data from 15 RCTs involving 5,110 patients. Patisiran had the greatest reduction in all-cause mortality (HR: 0.43, 95% CrI: 0.10 to 1.13; SUCRA: 85.97%), followed by tafamidis (HR: 0.60, 95% CrI: 0.52 to 0.68; SUCRA: 70.42%) and acoramidis (HR: 0.67, 95% CrI: 0.51 to 0.86; SUCRA: 50.00%), while vutrisiran ranked lower (HR: 0.73, 95% CrI: 0.48 to 1.06; SUCRA: 41.33%). For cardiovascular hospitalizations, acoramidis ranked highest (HR: 0.50, 95% CrI: 0.28 to 0.82; SUCRA: 93.13%), followed by tafamidis (HR: 0.71, 95% CrI: 0.45 to 0.96; SUCRA: 60.07%) and vutrisiran (HR: 0.79, 95% CrI: 0.34 to 1.58; SUCRA: 53.25%), while patisiran had a modest effect (HR: 0.97, 95% CrI: 0.49 to 2.01; SUCRA: 31.45%). For functional capacity, patisiran showed the greatest improvement in 6MWT (MD: 180.53 m, 95% CrI: -143.37 to 504.74; SUCRA: 82.4%), while acoramidis (MD: 33.90 m; SUCRA: 48.32%), vutrisiran (MD: 25.99 m; SUCRA: 45.83%), and tafamidis (MD: 7.05 m; SUCRA: 38.67%) ranked lower. For quality of life, tafamidis had the greatest improvement in KCCQ-OS (MD: 14.22, 95% CrI: 11.65 to 16.91; SUCRA: 97.83%), followed by acoramidis (MD: 10.19; SUCRA: 65.83%) and vutrisiran (MD: 5.80; SUCRA: 35.85%). Conclusion This study highlights the differential benefits of disease-specific therapies in ATTR-CM. patisiran was most effective for mortality reduction, acoramidis for cardiovascular hospitalizations, patisiran for functional capacity, and tafamidis for quality of life. Treatment selection should be individualized based on mortality risk, functional capacity, and quality of life to optimize ATTR-CM management.