RCT: Vutrisiran Reduces Mortality and Cardiovascular Events in Patients with Transthyretin Amyloidosis Cardiomyopathy

Study Design and Population: This double-blind, randomized clinical trial evaluated the efficacy of vutrisiran in 655 patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Participants were randomly assigned to receive either vutrisiran (25 mg) or placebo every 12 weeks for up to 36 months. The study population included patients both with and without baseline tafamidis treatment.

Main Findings: Vutrisiran treatment significantly reduced the risk of death from any cause and recurrent cardiovascular events compared to placebo (HR: 0.72, 95% CI: 0.56–0.93, p=0.01). In monotherapy patients (no tafamidis), the hazard ratio was 0.67 (95% CI: 0.49–0.93, p=0.02). Vutrisiran also preserved physical function, showing less decline in the 6-minute walk test distance (mean difference: 26.5 meters, p<0.001) and quality of life (mean KCCQ-OS difference: 5.8 points, p<0.001). Adverse events were comparable between groups.

Implications for Practice: Vutrisiran offers a promising treatment option for reducing mortality, cardiovascular events, and functional decline in ATTR-CM patients. Its favorable safety profile supports its potential use in long-term management.

Reference: Fontana M. et al. (2024). Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. New England Journal of Medicine, Published August 30, 2024. http://doi.org/10.1056/NEJMoa2409134