Fontana, Marianna and Berk, John L. and Gillmore, Julian D. and Witteles, Ronald M. and Grogan, Martha and Drachman, Brian and Damy, Thibaud and Garcia-Pavia, Pablo and Taubel, Jorg and Solomon, Scott D. and Sheikh, Farooq H. and Tahara, Nobuhiro and González-Costello, José and Tsujita, Kenichi and Morbach, Caroline and Pozsonyi, Zoltán and Petrie, Mark C. and Delgado, Diego and Van der Meer, Peter and Jabbour, Andrew and Bondue, Antoine and Kim, Darae and Azevedo, Olga and Hvitfeldt Poulsen, Steen and Yilmaz, Ali and Jankowska, Ewa A. and Algalarrondo, Vincent and Slugg, Andrew and Garg, Pushkal P. and Boyle, Katherine L. and Yureneva, Elena and Silliman, Nancy and Yang, Lilli and Chen, Jihong and Eraly, Satish A. and Vest, John and Maurer, Mathew S. (2025) Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. New England Journal of Medicine, 392 (1). pp.33-44. ISSN 0028-4793
Full text not available from this repository.Abstract
BACKGROUND: Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease. Vutrisiran, a subcutaneously administered RNA interference therapeutic agent, inhibits the production of hepatic transthyretin. METHODS: In this double-blind, randomized trial, we assigned patients with ATTR-CM in a 1:1 ratio to receive vutrisiran (25 mg) or placebo every 12 weeks for up to 36 months. The primary end point was a composite of death from any cause and recurrent cardiovascular events. Secondary end points included death from any cause, the change from baseline in the distance covered on the 6-minute walk test, and the change from baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score. The efficacy end points were assessed in the overall population and in the monotherapy population (the patients who were not receiving tafamidis at baseline) and were tested hierarchically. RESULTS: A total of 655 patients underwent randomization; 326 were assigned to receive vutrisiran and 329 to receive placebo. Vutrisiran treatment led to a lower risk of death from any cause and recurrent cardiovascular events than placebo (hazard ratio in the overall population, 0.72; 95% confidence interval [CI], 0.56 to 0.93; P = 0.01; hazard ratio in the monotherapy population, 0.67; 95% CI, 0.49 to 0.93; P = 0.02) and a lower risk of death from any cause through 42 months (hazard ratio in the overall population, 0.65; 95% CI, 0.46 to 0.90; P = 0.01). Among the patients in the overall population, 125 in the vutrisiran group and 159 in the placebo group had at least one primary end-point event. In the overall population, treatment with vutrisiran resulted in less of a decline in the distance covered on the 6-minute walk test than placebo (least-squares mean difference, 26.5 m; 95% CI, 13.4 to 39.6; P<0.001) and less of a decline in the KCCQ-OS score (least-squares mean difference, 5.8 points; 95% CI, 2.4 to 9.2; P<0.001). Similar benefits were observed in the monotherapy population. The incidence of adverse events was similar in the two groups (99% in the vutrisiran group and 98% in the placebo group); serious adverse events occurred in 62% of the patients in the vutrisiran group and in 67% of those in the placebo group. CONCLUSIONS: Among patients with ATTR-CM, treatment with vutrisiran led to a lower risk of death from any cause and cardiovascular events than placebo and preserved functional capacity and quality of life. (Funded by Alnylam Pharmaceuticals; HELIOS-B ClinicalTrials.gov number, NCT04153149.).
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 May 2025 00:43 |
| Last Modified: | 05 May 2025 00:43 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1656 |
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