Publications

The material below is provided to support scientific exchange. Any content about investigational therapeutics or investigational uses of locally approved products does not establish the safety or efficacy of these therapeutics or uses, and there is no guarantee of local regulatory approval.

For questions beyond a product’s authorized indications or for information not available here, please contact Alnylam Medical Information.

Effects of Vutrisiran on Cardiac Structure and Function in Patients with Transthyretin Amyloidosis with Cardiomyopathy: Secondary Outcomes of the HELIOS-B Trial

Publication Details

Nature Medicine

August 2025

Access Here

Author(s)

Karola S Jering¹, Marianna Fontana², Olivier Lairez³, Simone Longhi⁴, Olga Azevedo⁵, Caroline Morbach^{6 7}, Shaun Bender⁸, Patrick Y Jay⁸, John Vest⁸, Bernard E Bulwer¹, Narayana Prasad¹, Scott D Solomon⁹, Hicham Skali¹

Affiliations

¹Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; ²National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, UK; 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; ⁶Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany; ⁷Department of Medicine I, University Hospital Würzburg, Würzburg, Germany; ⁸Alnylam Pharmaceuticals, Cambridge, MA, USA; ⁹Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA

Abstract

In the HELIOS-B randomized clinical trial, the RNA interference therapeutic agent vutrisiran reduced the risk of all-cause mortality and recurrent cardiovascular events among patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). In this secondary analysis of HELIOS-B, we evaluated vutrisiran’s effects on echocardiographic measures of cardiac structure and function in patients with ATTR-CM receiving vutrisiran or placebo (n = 654, 93% men). At 30 months after treatment, as compared to the placebo group, vutrisiran treatment attenuated increases in mean left ventricular (LV) wall thickness (least squares mean difference: −0.4 mm; 95% confidence interval (CI): −0.8, 0.0; P = 0.03) and LV mass index (−10.6 g m−2; 95% CI: −18.0, −3.3; P < 0.01). Vutrisiran treatment also attenuated declines in LV ejection fraction (2.0%; 95% CI: 0.3, 3.7; P = 0.02), absolute global longitudinal strain (1.2%; 95% CI: 0.7, 1.7; P < 0.01) and LV stroke volume (4.1 ml; 95% CI: 1.7, 6.4; P < 0.01), and decreased both the average ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (−2.0; 95% CI: −2.9, −1.2; P < 0.01) and the early to late diastolic transmitral flow velocities ratio (−0.3; 95% CI: −0.6, −0.0; P = 0.04), as compared to placebo. Consistent with its clinical benefits, these echocardiographic findings indicate favorable effects of vutrisiran on cardiac structure and function in patients with ATTR-CM. ClinicalTrials.gov registration: NCT04153149.