ESC Congress 2026 Abstract · Oct 26, 2026

Vutrisiran is associated with preservation of intrinsic capacity and healthy ageing in patients with transthyretin amyloidosis with cardiomyopathy: post hoc analysis of HELIOS-B

By Lairez O, Malerbi H, Maurer MS et al.

Background: The World Health Organization recently developed the Integrated Care for Older PEople (ICOPE) approach, with a focus on maximising intrinsic capacity (IC; a composite of patient internal reserves of physical and mental capacity) and functional status in a rapidly ageing global population. Ageing-associated decline in IC (including vision, hearing, cognition, locomotion, psychological state, and nutritional state impairments) is included in the International Classification of Diseases 11th revision. Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease predominantly occurring in its wild-type form in older people, often contributing to increased frailty and declines in functional status and quality of life (QoL). Vutrisiran, an RNA interference therapeutic, demonstrated significant clinical benefit in patients with ATTR-CM in the HELIOS-B study but its effect on IC, a crucial concept in healthy ageing, has not been assessed. Purpose: To evaluate how vutrisiran affects six domains of IC outlined in the ICOPE approach over up to 36 months of treatment in HELIOS-B. Methods: This post hoc analysis used proxies for six IC domains defined as per the ICOPE Step 1 assessment, with endpoints, medications, or safety reports from HELIOS-B (Table). Impairment was noted if any of the events listed occurred. The proportion of patients experiencing new impairment in these domains during the double-blind treatment period (up to 36 months) was assessed in patients receiving vutrisiran and placebo in the overall and monotherapy populations, and the baseline tafamidis subgroup. Single domain scores and a composite IC score were estimated (for each IC: 0=impaired; 1=not impaired; totalling 0–6). Results: At the end of the double-blind period, vutrisiran significantly reduced the worsening of composite IC score vs placebo across the overall and monotherapy populations and baseline tafamidis subgroup (–1.15 vs –1.53, p<0.0001; –1.12 vs –1.53, p<0.0001; and –1.20 vs –1.53, p=0.008, respectively). Significantly fewer patients experienced impairments in cognition, locomotion, psychological state, and nutritional state with vutrisiran vs placebo in the overall (Figure) and monotherapy populations. In the baseline tafamidis subgroup, a significant benefit was observed for locomotion. A significantly lower proportion of patients experienced worsening in ≥1 or ≥2 IC domains with vutrisiran vs placebo over the double-blind period across all populations (Figure). Conclusion: Vutrisiran was associated with a significant reduction in worsening of composite IC score and the majority of its domains vs placebo, with benefit to locomotion and nutritional status being relevant in ATTR-CM. Despite conclusions being limited by the use of unvalidated proxies for IC domains, these findings suggest that vutrisiran may help preserve functional reserve and support healthy ageing trajectories and IC in patients with ATTR-CM.

doi.org/10.1093/eurheartj/ehag785.1291Open accessInterventions