Impact of Vutrisiran on Functional Capacity and Quality of Life in Transthyretin Amyloidosis with Cardiomyopathy
Publication Details
Journal of the American College of Cardiology
March 2025
Author(s)
Farooq H Sheikh1, Gilbert Habib2, W H Wilson Tang3, Julian D Gillmore4, Ugochukwu O Egolum5, Simone Longhi6, Chongshu Chen7, Emre Aldinc7, Marianna Fontana4
Affiliations
1Advanced Heart Failure Program, MedStar Heart & Vascular Institute, Georgetown University School of Medicine, Washington, DC, USA; 2Service de Cardiologie, Hôpital de La Timone, AP-HM, Marseille, France; 3Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA; 4National Amyloidosis Centre, UCL, Division of Medicine, Royal Free Hospital, London, United Kingdom; 5Georgia Heart Institute, Gainesville, Georgia, USA; 6Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 7Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA
Abstract
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.
PMID
40099774
DOI
10.1016/j.jacc.2025.03.454
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