Abstract
Transthyretin (TTR) amyloidosis is a progressive and fatal disease caused by the deposition of TTR amyloid fibrils in multiple organs and tissues. The HELIOS-B trial (a phase three, randomized, double-blind, placebo-controlled, multicenter study) tested the safety and efficacy of vutrisiran, a subcutaneous gene silencer, in patients with wild-type or inherited TTR cardiomyopathy. The two primary endpoints were a composite of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent heart failure visits) assessed in the overall population and the monotherapy group. Secondary endpoints included all-cause mortality up to 42 months and 30-month change in functional capacity, health status, and quality of life. A total of 655 patients were enrolled in the study (vutrisiran, n = 326; placebo, n = 329). The mean age was 77 years, and 40% received tafamidis at baseline. Treatment with vutrisiran resulted in a reduction in all-cause and CV mortality events, as well as preservation of functional capacity, quality of life, and health status in patients with TTR cardiomyopathy.