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Clinical Trial
. 2025 May 27;85(20):1943-1955.
doi: 10.1016/j.jacc.2025.03.454. Epub 2025 Mar 17.

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

Farooq H Sheikh  1 , Gilbert Habib  2 , W H Wilson Tang  3 , Julian D Gillmore  4 , Ugochukwu O Egolum  5 , Simone Longhi  6 , Chongshu Chen  7 , Emre Aldinc  7 , Marianna Fontana  4
Affiliations
Free article
Clinical Trial

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

Farooq H Sheikh et al. J Am Coll Cardiol. .
Free article

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.

Keywords: cardiac; functional capacity; quality of life; transthyretin amyloidosis.

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Conflict of interest statement

Funding Support and Author Disclosures This study was funded by Alnylam Pharmaceuticals Inc. The funder collaborated with the authors during the study design, data collection, data analysis, data interpretation, and writing of the report. All authors had full access to all the data in the study and took final responsibility for the decision to submit the manuscript for publication. Dr Sheikh has received consulting fees from Abbott, Alnylam Pharmaceuticals Inc, AstraZeneca, BridgeBio, Intellia, Pfizer, Procyrion, and XVIVO; and has received research grants from Abbott, Alnylam Pharmaceuticals Inc, AstraZeneca, BridgeBio, and Intellia. Dr Tang has received consulting fees from Alexion Pharmaceuticals, Alleviant Medical, BioCardia, Boston Scientific, Bristol Myers Squibb, CardiaTec Biosciences, Cardiol Therapeutics, Genomics, Salubris Biotherapeutics, WhiteSwell, and Zehna Therapeutics; and has received honoraria from the American Board of Internal Medicine, Belvoir Media Group, and Springer Nature. Dr Gillmore has received consulting fees from Alnylam Pharmaceuticals Inc, AstraZeneca, Attralus, Eidos, Intellia, Ionis, and Pfizer. Drs Chen and Aldinc are employees of Alnylam Pharmaceuticals Inc and may hold stock and/or stock options. Dr Fontana has received consulting fees from Ackea, Alexion, Alnylam Pharmaceuticals Inc, AstraZeneca, Attralus, BridgeBio, Cardior, Eidos, Intellia, Ionis, Janssen, Lexeo Therapeutics, Novo Nordisk, Pfizer, and Prothena Biosciences; has received research grants and/or speaker fees from Alnylam Pharmaceuticals Inc, the British Heart Foundation, Eidos, and Pfizer; and has share options in Lexeo Therapeutics, and shares in Mycardium. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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Supplementary concepts