Vutrisiran may improve outcomes in transthyretin amyloidosis with cardiomyopathy

In patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), treatment with vutrisiran appears to reduce the risk of death from any cause and cardiovascular events while preserving functional capacity and quality of life, as shown in a study.

A total of 655 patients with ATTR-CM were randomly assigned to receive either vutrisiran at 25 mg (n=326) or placebo (n=329) every 12 weeks for up to 36 months. A composite of death from any cause and recurrent cardiovascular events was the primary endpoint. Death from any cause, distance covered on the 6-minute walk test, and the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score were also assessed as secondary endpoints.

All endpoints were evaluated in the overall population and in the subpopulation of patients who were not receiving tafamidis at baseline (monotherapy cohort).

Compared with placebo, vutrisiran was associated with a significantly reduced risk of death from any cause and recurrent cardiovascular events both in the overall population (hazard ratio [HR], 0.72, 95 percent confidence interval [CI], 0.56–0.93; p=0.01) and in the monotherapy cohort (HR, 0.67, 95 percent CI, 0.49–0.93; p=0.02).

Patients on vutrisiran vs placebo also had a much lower risk of death from any cause through 42 months (HR, 0.65, 95 percent CI, 0.46–0.90; p=0.01), smaller decrease in the distance covered on the 6-minute walk test (least-squares mean difference, 26.5 m, 95 percent CI, 13.4–39.6; p<0.001), and mitigated decline in the KCCQ-OS score (least-squares mean difference, 5.8 points, 95 percent CI, 2.4–9.2; p<0.001). Similar results were obtained in the monotherapy cohort.

The frequency of adverse events (AEs) was similar between the vutrisiran and placebo groups (99 percent vs 98 percent, respectively), as was the rate of serious AEs (62 percent vs 67 percent).