Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy

作者：Marianna Fontana, John L. Berk, Julian D. Gillmore, Ronald Witteles, Martha Grogan, Brian Drachman, Thibaud Damy, Pablo García‐Pavía, Jörg Täubel, Scott D. Solomon, Farooq H. Sheikh, Nobuhiro Tahara, José González‐Costello, Kenichi Tsujita, Caroline Morbach, Zoltán Pozsonyi, Mark C. Petrie, Diego Delgado, Peter van der Meer, Andrew Jabbour, Antoine Bondue, Darae Kim, Olga Azevedo, Steen Hvitfeldt Poulsen, Ali Abbas Yılmaz, Ewa A. Jankowska, Vincent Algalarrondo, Andrew Slugg, Pushkal Garg, Katherine L. Boyle, Elena Yureneva, Nancy Silliman, Lilli Yang, Jihong Chen, Satish A. Eraly, John Vest, Mathew S. Maurer · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2409134 · 被引用次数：403 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Parathyroid Disorders and Treatments、Dermatological and Skeletal Disorders

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 t...