Vutrisiran Improves Survival, Cardiovascular Outcomes Across Age Groups in ATTR-CM

Vutrisiran reduced mortality and cardiovascular events in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) across all age groups—including those 80 years and older—while maintaining functional capacity and quality of life, according to a prespecified age-based analysis of the phase 3 HELIOS-B trial (NCT04153149) published in the European Journal of Heart Failure.¹

ATTR-CM is a progressive, infiltrative cardiomyopathy caused by misfolded transthyretin protein deposits in the heart and other organs.² It primarily affects older adults, who face high risks of heart failure, hospitalization, and death. Although newer therapies have improved outcomes, clinicians have questioned whether benefits extend to the oldest and most medically complex patients.¹

“Older adults with ATTR‐CM face a disproportionate burden of disease, including higher risk of death and hospitalization, that significantly contribute to health system costs,” the authors explained. “Additionally, the high burden of comorbidities in older patients associated with frailty, polypharmacy, and the limited remaining lifespan, leads to physician concerns about the possibility of attenuated treatment effects and potential safety issues.”

The HELIOS-B trial previously showed that vutrisiran (Amvuttra; Alnylam Pharmaceuticals), a gene-silencing therapy that reduces hepatic production of transthyretin, lowered all-cause mortality and recurrent cardiovascular events compared with placebo. The new analysis evaluated whether age modified those benefits.

Investigators examined outcomes among 654 patients with ATTR-CM, stratified into 3 age groups: younger than 75 years (39%), 75 to under 80 years (31%), and 80 years or older (30%). HELIOS-B included an older population and permitted broader background therapy use than the ATTR‐ACT (NCT01994889) and ATTRibute‐CM (NCT03860935) studies, the authors noted. The mean age of the overall population was 75 years.

Across all age categories, vutrisiran consistently reduced the primary composite outcome of all-cause mortality and recurrent cardiovascular events compared with placebo across age groups (p _interaction = .56), with no significant interaction between treatment effect and age (p _interaction = .50). Benefits were also seen for the individual components of the composite end point, including fewer recurrent cardiovascular events and lower all-cause mortality through 42 months of follow-up.

Importantly, patients 80 years and older—who had more advanced disease at baseline, higher cardiac biomarkers, and lower functional capacity—experienced similar relative risk reductions to younger participants. Continuous age modeling confirmed that treatment efficacy remained stable across the full age spectrum, suggesting no reduction in benefit among older adults.

Older participants were more likely to have wild-type ATTR-CM and advanced disease stage, which reflects real-world epidemiology, the authors noted. They also had higher levels of NT-proBNP and troponin, which are markers associated with worse prognosis, underscoring the clinical significance of achieving consistent benefits in this group.

Beyond clinical events, vutrisiran preserved physical function and health-related quality of life across all age groups. Patients receiving vutrisiran showed improvements in 6-minute walk distance and Kansas City Cardiomyopathy Questionnaire overall summary scores compared with placebo, with no evidence that age influenced these functional outcomes.

Rates of serious adverse events and treatment discontinuation were also comparable between vutrisiran and placebo across age categories, and older patients did not experience higher safety risks.

“There is a historical undertreatment of elderly patients with heart failure, likely due to several factors, including concerns regarding frailty, polypharmacy, limited remaining life expectancy, and perceived marginal benefit,” the authors wrote. “Our findings challenge these assumptions and suggest that age alone should not preclude the initiation of an effective treatment like vutrisiran in elderly patients with ATTR‐CM.”

They noted several limitations of the study, with the main limitation being that the HELIOS-B trial was not powered to definitively compare individual age groups, although the analysis was prespecified. The numbers of patients and events in the stratified age groups were also small. The study’s eligibility criteria also excluded patients with significant frailty or advanced comorbidities, which could limit the generalizability of the findings. Despite limitations, the authors concluded that the analysis shows similar clinical benefits with vutrisiran across age groups.

“Vutrisiran treatment led to a consistent reduction in death and cardiovascular events, preservation of functional status, and maintenance of quality of life, with a favorable safety profile,” the authors wrote. “These findings reinforce that age alone should not be a barrier to offering effective disease‐modifying therapies for ATTR‐CM and support the use of vutrisiran in elderly patients, who represent a substantial and growing proportion of the affected population.”

References

1. Antonopoulos AS, Tsampras T, Terentes-Printzios D, Lazaros G, Tsioufis K, Vlachopoulos C. Real-world effectiveness of targeted therapies in ATTR cardiomyopathy: a meta-analysis integrating population-based data. ESC Heart Fail. 2025;12(6):4475-4485. doi:10.1002/ehf2.70011

2. Transthyretin amyloid cardiomyopathy (ATTR-CM). Heart.org. Updated May 29, 2024. Accessed January 30, 2026. https://www.heart.org/en/health-topics/cardiomyopathy/what-is-cardiomyopathy-in-adults/transthyretin-amyloid-cardiomyopathy-attr-cm