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

Abstract

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. This study aims to further analyze the efficacy of vutrisiran on functional capacity, health status, and QOL. 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. 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. Vutrisiran maintained or improved functional capacity, health status, and QOL in more patients with ATTR-CM vs placebo over 30 months.