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Vutrisiran Improves Survival and Reduces Cardiovascular Events in ATTR Amyloid Cardiomyopathy: HELIOS-B

Publication Details

Journal of the American College of Cardiology

May 2025

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Author(s)

Ronald M Witteles¹, Pablo Garcia-Pavia², Thibaud Damy³, Martha Grogan⁴, Farooq H Sheikh⁵, Caroline Morbach⁶, Shaun Bender⁷, Jason Exter⁷, Satish A Eraly⁷, Marianna Fontana⁸

Affiliations

¹Division of Cardiovascular Medicine and Stanford Amyloid Center, Stanford University School of Medicine, Stanford, California, USA; ²Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; ³Referral Center for Cardiac Amyloidosis and Department of Cardiology, Hôpital Henri Mondor, Créteil, France; ⁴Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; ⁵MedStar Heart and Vascular Institute, MedStar Health/Georgetown University School of Medicine, Washington, DC, USA; ⁶Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Center and Department of Internal Medicine I, Cardiology, University Hospital Würzburg, Würzburg, Germany; ⁷Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA; ⁸National Amyloidosis Centre, University College London, Division of Medicine, Royal Free Hospital, London, United Kingdom

Abstract

Background:

Patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) have high mortality and morbidity. Vutrisiran, a subcutaneous RNA interference therapeutic, reduced the composite of all-cause mortality (ACM) and cardiovascular (CV) events (CV hospitalizations and urgent heart failure [HF] visits) in HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy) in patients with ATTR-CM.

Objectives:

Here we present data from HELIOS-B evaluating the impact of vutrisiran on ACM and CV mortality with additional patient follow-up through 42 months, and CV events such as CV hospitalizations, HF hospitalizations, and urgent HF visits.M.

Methods:

The HELIOS-B trial randomized 655 patients to vutrisiran 25 mg or placebo once every 3 months for up to 33 to 36 months in the double-blind (DB) period, followed by an open-label extension. Prespecified mortality and CV mortality analyses used data through 39 to 42 months of follow-up (DB period and up to 6 months of the open-label extension). CV hospitalizations and HF events were evaluated over the DB period of 33 to 36 months. Differences between vutrisiran and placebo were evaluated in the overall population, and in those stratified by baseline tafamidis use.

Results:

In the overall population, vutrisiran reduced the risk of ACM (HR: 0.64; 95% CI: 0.46-0.88) and CV mortality (HR: 0.67; 95% CI: 0.47-0.96) vs placebo. Vutrisiran also reduced the risk of a composite of CV mortality and CV events (HR: 0.72; 95% CI: 0.55-0.94), and lowered rates of CV hospitalizations (rate ratio [RR]: 0.75; 95% CI: 0.62-0.91), urgent HF visits (RR: 0.54; 95% CI: 0.30-0.98), and HF hospitalizations (RR: 0.67; 95% CI: 0.52-0.86) vs placebo. Consistent trends were seen regardless of baseline tafamidis use.

Conclusions:

Consistent with the primary trial results, vutrisiran reliably reduced the risk of ACM, CV mortality, CV hospitalizations, HF hospitalizations, and urgent HF visits vs placebo in patients with ATTR-CM. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149)