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.

Efficacy and safety of vutrisiran in transthyretin amyloid cardiomyopathy across the age spectrum: The HELIOS-B trial

Publication Details

European Journal of Heart Failure

October 2025

Access Here

Author(s)

Awais Sheikh¹, Zi Michael Miao², Brian Claggett², Pablo Garcia-Pavia³, Francesco Cappelli⁴, Emre Aldinc⁵, Julian Gillmore¹, Scott D Solomon², Marianna Fontana¹

Affiliations

¹National Amyloidosis Centre, University College London, London, UK; ²Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; ³Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, IDIPHISA, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; ⁴Tuscan Regional Amyloid Center, Careggi University Hospital, Florence, Italy; ⁵Alnylam Pharmaceuticals, Cambridge, MA, USA

Abstract

Aims:

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition primarily affecting older adults, who are at increased risk of morbidity and mortality. In HELIOS-B, vutrisiran reduced all-cause mortality and recurrent cardiovascular events versus placebo in patients with ATTR-CM. This prespecified analysis evaluated efficacy and safety outcomes by age category (<75, 75 to <80, and ≥80 years) and across age as a continuous measure.

Methods and results:

HELIOS-B randomized patients with ATTR-CM in a 1:1 ratio to vutrisiran 25 mg or placebo every 12 weeks for up to 36 months. Eligible patients were aged 18–85 years. We assessed the primary composite of all-cause mortality and recurrent cardiovascular events, changes in 6-min walk test (6MWT) and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS), and safety outcomes across age groups. Among 654 patients (aged 45–85 years; mean 75.3 ± 6.7), 257 (39.3%) were <75, 201 (30.7%) 75 to <80, and 196 (30.0%) ≥80 years. Vutrisiran reduced the risk of the primary composite outcome in all age categories (pinteraction = 0.56) and across the age spectrum as a continuous function (pinteraction = 0.50). Consistent benefits were seen for individual outcome components, with no significant interaction between treatment and age. Functional capacity and quality of life were preserved across age groups (pinteraction = 0.35 and = 1.00 for KCCQ-OSS and 6MWT, respectively). Safety was comparable across groups, with no increase in adverse events in older patients.

Conclusions:

Vutrisiran reduced all-cause mortality and cardiovascular events and maintained function and quality of life in patients with ATTR-CM across the age spectrum, including those ≥80 years.