Efficacy of Acoramidis on All-Cause Mortality and Cardiovascular Hospitalization in Transthyretin Amyloid Cardiomyopathy

作者：Daniel P. Judge, Kevin Alexander, Francesco Cappelli, Marianna Fontana, Pablo García‐Pavía, Simon Gibbs, Martha Grogan, Mazen Hanna, Ahmad Masri, Mathew S. Maurer, Laura Obici, Prem Soman, Xiaofan Cao, Ted Lystig, Jean‐François Tamby, Suresh Siddhanti, Adam Castaño, Leonid Katz, Jonathan C. Fox, Kenneth W. Mahaffey, Julian D. Gillmore · 发表于：Journal of the American College of Cardiology · 年份：2025 · DOI：10.1016/j.jacc.2024.11.042 · 被引用次数：52 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Parathyroid Disorders and Treatments、Dermatological and Skeletal Disorders

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed chronic disease associated with progressive heart failure that results in impaired quality of life, repeated hospitalizations, and premature death. Acoramidis is a selective, oral transthyretin stabilizer recently approved by the U.S. Food and Drug Administration for the treatment of ATTR-CM. In a phase 3, randomized, double-blind study (ATTRibute-CM [Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy]), acoramidis was well tolerated and showed clinical efficacy in improving the primary endpoint, a hierarchical combination of all-cause mortality (ACM), cardiovascular-related hospitalization (CVH), N-terminal pro-B-type natriuretic peptide level, and 6-minute walk distance. OBJECTIVES: The goal of this study was to characterize the efficacy of acoramidis on ACM and CVH. METHODS: ). CVH and the composite of ACM or first CVH were plotted by using Kaplan-Meier curves and summarized with a stratified Cox proportional hazards model. The annualized frequency of CVH was analyzed by using a negative binomial regression model. Subgroup analyses were conducted for the composite of ACM or first CVH. RESULTS: Of the 632 participants randomized to treatment, 611 (97%) were included in efficacy analyses (acoramidis, n = 409; placebo, n = 202). Compared with placebo, acoramidis reduced the occurrence of the composite of ACM or first CVH (acoramidis, 35.9%; placebo, 50.5%; HR: 0.64; ...