Impact of Vutrisiran on Functional Capacity and Quality of Life in Transthyretin Amyloidosis With Cardiomyopathy

BACKGROUND: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) progressively impairs functional capacity, health status, and quality of life (QOL). In HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy), vutrisiran reduced all-cause mortality and recurrent cardiovascular events compared with placebo in patients with ATTR-CM. OBJECTIVES: This study aims to further analyze the efficacy of vutrisiran on functional capacity, health status, and QOL. METHODS: Patients were randomized 1:1 to receive vutrisiran 25 mg or placebo every 12 weeks up to 36 months. The 6-minute walk test (6-MWT) and Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) were completed at baseline and every 6 months. Cutoff values for worsening were a decrease from baseline of >7 m, >15 m, and >35 m (6-MWT), and >5 and >10 points (KCCQ-OS). Additionally, change from baseline was analyzed in prespecified subgroups and KCCQ subdomains. RESULTS: In the overall population at month 30, greater proportions of patients treated with vutrisiran vs placebo had maintained or improved 6-MWT distance according to all cutoffs analyzed (>7 m [49.6% vs 33.2%], >15 m [55.5% vs 38.6%], and >35 m [68.5% vs 51.6%]; all P < 0.001). Similarly, greater proportions of patients experienced maintenance or improvement in KCCQ-OS according to cutoff values (>5 points [63.5% vs 46.6%; P < 0.001], >10 points [74.6% vs 60.7%; P < 0.01]). Additionally, least squares mean difference in change from baseline in KCCQ subdomains, and in 6-MWT and KCCQ-OS across prespecified subgroups, favored vutrisiran vs placebo. Benefits observed with vutrisiran were similar in the monotherapy population. CONCLUSIONS: Vutrisiran maintained or improved functional capacity, health status, and QOL in more patients with ATTR-CM vs placebo over 30 months.