Effects of Vutrisiran on Cardiac Function and Outcomes in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Publication Details
Journal of the American College of Cardiology
August 2025
Author(s)
Karola S Jering1, Marianna Fontana2, Hicham Skali1, Bernard E Bulwer1, Narayana Prasad1, Farideh Roshanali1, Olivier Lairez3, Simone Longhi4, Olga Azevedo5, Shaun Bender6, Patrick Y Jay6, John Vest6, Scott D Solomon7
Affiliations
1Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA; 2National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, United Kingdom; 3Department of Cardiology, Toulouse University Hospital, Toulouse, France; 4Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 5Cardiology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal; 6Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA; 7Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA
Abstract
Background:
Transthyretin amyloid cardiomyopathy (ATTR-CM), caused by deposition of transthyretin amyloid fibrils in the heart, is associated with high morbidity and mortality. In HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy), the RNA interference therapeutic agent vutrisiran reduced rates of the primary composite outcome of all-cause death and recurrent cardiovascular events among patients with ATTR-CM and had beneficial effects on cardiac structure and function over 30 months.
Methods:
HELIOS-B randomized 655 patients with ATTR-CM to vutrisiran (25 mg subcutaneously every 12 weeks) or placebo. Echocardiograms were performed at baseline and months 12, 18, 24, and 30. Associations of baseline echocardiographic parameters with the primary outcome were analyzed using modified Andersen-Gill models adjusted for age, sex, ATTR disease type, and National Amyloidosis Centre stage, and stratified by baseline tafamidis use and treatment assignment. Changes in cardiac function from baseline to month 18 were compared between treatment arms and related to outcomes in landmark analyses.
Results:
Among the 654 participants with available echocardiographic data (median age 77 years, 93% male, 88% wild-type transthyretin), baseline left and right ventricular systolic and diastolic function were independently associated with the primary outcome (HR per unit increase, left ventricular ejection fraction, 0.90 per 5% increase, 95% CI: 0.86-0.95; absolute global longitudinal strain, 0.92 per 1% increase, 95% CI: 0.89-0.96; tricuspid annular systolic myocardial velocity, 0.94 per 1-cm/s increase, 95% CI: 0.90-0.98; average E/e’, 1.03 per 1-U increase, 95% CI: 1.01-1.04). At 18 months, vutrisiran attenuated declines in left ventricular and right ventricular systolic function (least squares mean difference: left ventricular ejection fraction, 1.6%, 95% CI: 0.1-3.2; absolute global longitudinal strain, 0.7%, 95% CI: 0.3-1.2; tricuspid annular systolic myocardial velocity, 0.5 cm/s, 95% CI: 0.1-0.9). Worsening in these parameters at 18 months was associated with a heightened risk of the primary outcome.
Conclusions:
Echocardiographic measures of biventricular systolic and diastolic function provide important prognostic information beyond National Amyloidosis Centre stage in patients with ATTR-CM. Vutrisiran improved diastolic function and attenuated declines in left ventricular and right ventricular systolic function over 18 months. The benefits on cardiac function with vutrisiran may partly underlie its beneficial effects on clinical outcomes.
PMID
40769673
DOI
10.1016/j.jacc.2025.06.022
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