Vutrisiran Improves Survival and Reduces Cardiovascular Events in ATTR Amyloid Cardiomyopathy: HELIOS-B.

Summary

In HELIOS-B (n=655), subcutaneous vutrisiran significantly reduced all-cause mortality, cardiovascular mortality, and heart failure-related events over up to 39–42 months of follow-up, with consistent benefits irrespective of baseline tafamidis use. These findings reinforce and extend prior efficacy signals, demonstrating durable survival and morbidity benefits in ATTR-CM.

Key Findings

• Reduced all-cause mortality vs placebo (HR 0.64; 95% CI 0.46–0.88).
• Reduced cardiovascular mortality vs placebo (HR 0.67; 95% CI 0.47–0.96).
• Lowered composite of CV mortality and CV events (HR 0.72; 95% CI 0.55–0.94).
• Decreased CV hospitalizations (RR 0.75), HF hospitalizations (RR 0.67), and urgent HF visits (RR 0.54).
• Benefits were consistent regardless of baseline tafamidis use.

Clinical Implications

Vutrisiran can be considered to reduce mortality and heart failure events in ATTR-CM, including in patients already on tafamidis; integration into guideline-directed therapy should be discussed.

Limitations

• Mortality analyses included up to 6 months of open-label extension, introducing potential bias.
• Generalizability may be limited to trial-eligible ATTR-CM populations.

Future Directions

Head-to-head or combination strategies with tafamidis, long-term safety surveillance, and evaluation across genotype and cardiac staging subgroups.