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

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.