Relative efficacy of tafamidis, acoramidis, patisiran and vutrisiran in patients with transthyretin cardiac amyloidosis: a network meta-analysis

Background Transthyretin cardiac amyloidosis (ATTR-CA) is an important cause of heart failure (HF). Several therapies demonstrated an efficacy in reducing hard and surrogate endpoints. Purpose We compared for the first time the relative efficacy of therapies evaluated in completed phase III trials. Methods We conducted a network meta-analysis using data from ATTR-ACT, ATTRIBUTE-CM, APOLLO-B, and HELIOS-B. The primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Secondary endpoints were changes in the 6-minute walk distance (6MWD) and Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) scores. Results For the primary endpoint, tafamidis and vutrisiran demonstrated a significant survival benefit over placebo, while acoramidis only approached significance. Indirect comparisons suggested that tafamidis may have a greater effect than patisiran. Tafamidis was associated with the lowest risk for the primary endpoint (surface under the cumulative ranking, SUCRA 82%), followed by vutrisiran monotherapy (70%). Regarding changes in 6MWD, tafamidis had the highest SUCRA curve value (97%), indicating superior efficacy, followed by acoramidis (69%). For KCCQ-OS changes, tafamidis also had the highest SUCRA (87%), followed by acoramidis (79%) and vutrisiran monotherapy (67%). When the ATTR-ACT trial was excluded from the analysis, vutrisiran monotherapy consistently showed the highest probability of being ranked better than other treatments in terms of primary endpoint. Conclusions Tafamidis demonstrated the highest efficacy in improving survival, reducing cardiovascular hospitalizations, and enhancing functional capacity and quality of life in patients with ATTR-CA, qualifying as the primary treatment choice. Vutrisiran and acoramidis emerged as viable alternatives.