Dr. Murat Demirci

Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy (HELIOS -B)

Published in Congress: ESC 2024

Link:
https://www.nejm.org/doi/full/10.1056/NEJMoa2409134

Backround:
Vutrisiran is an RNA interference agent that inhibits the hepatic synthesis of both wild-type and variant TTR messenger RNA. Following the positive results from the HELIOS-A study, it has been approved by the FDA for the treatment of hereditary ATTR amyloidosis with polyneuropathy. Based on the favorable cardiac outcomes observed in this study, the HELIOS-B study was designed to investigate the effects of vutrisiran in patients with Transthyretin amyloid cardiomyopathy (ATTR-CM).

Objective:
The HELIOS-B study evaluated the effects of vutrisiran treatment on all-cause mortality and cardiovascular events in patients with ATTR-CM. Additionally, the impact of this treatment on functional capacity and quality of life was also assessed.

Methods:
This study was designed as a multicenter, double-blind, 1:1 randomized, and placebo-controlled trial. Patients received either 25 mg of vutrisiran or placebo subcutaneously every 12 weeks for 36 months. The primary endpoint was defined as all-cause mortality and recurrent cardiovascular events, including hospitalizations due to cardiovascular causes or emergency department visits due to heart failure.

Results :
A total of 655 patients were enrolled in the study between December 2019 and August 2021. Among the 326 patients in the vutrisiran group, 196 (60%) were not receiving tafamidis at baseline, and among the 329 patients in the placebo group, 199 (60%) were also not on tafamidis at baseline. These patients constituted the monotherapy population. In both the overall population, including those on tafamidis at baseline, and the monotherapy population, patients treated with vutrisiran exhibited a lower risk of all-cause mortality and recurrent cardiovascular events compared to those on placebo (overall population HR: 0.72; 95% CI, 0.56 - 0.93; P=0.01; monotherapy population HR: 0.67; 95% CI, 0.49 - 0.93; P=0.02). The primary endpoint occurred in 163 patients in the vutrisiran group and 202 patients in the placebo group. Kaplan-Meier curves indicated that the separation between the vutrisiran and placebo groups became evident around 6 months. Over a 42-month follow-up, all-cause mortality was observed in 60 patients (18%) in the vutrisiran group and 85 patients (26%) in the placebo group. Furthermore, patients in the vutrisiran group showed superior outcomes compared to those in the placebo group in terms of the 6-minute walk test, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire (KCCQ) score.

Conclusion:
Vutrisiran has been shown to reduce the risk of all-cause mortality and recurrent cardiovascular events in patients with ATTR-CM.

Interpretations:
Vutrisiran is an effective medication for reducing the risk of mortality and cardiovascular events in patients with cardiomyopathy associated with transthyretin amyloidosis. Additionally, this treatment has proven effective in maintaining patients' quality of life and functional capacity. These findings indicate that vutrisiran could be a viable option for the treatment of patients with ATTR-CM.