Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM

作者：Ahmad Masri, Daniel P. Judge, Frederick L. Ruberg, Julian D. Gillmore, Justin L. Grodin, Laura Obici, Matthew J. Maurer, Marianna Fontana, Steen Hvitfeldt Poulsen, Peter van der Meer, Richard K. Cheng, Sarah Cuddy, Amrut V. Ambardekar, Kuangnan Xiong, Xiaofan Cao, Gillian Murtagh, Suresh Siddhanti, Adam Castaño, Jean‐François Tamby, Jonathan C. Fox, Kevin Alexander, Ronald Witteles · 发表于：Journal of the American College of Cardiology · 年份：2025 · DOI：10.1016/j.jacc.2025.09.013 · 被引用次数：9 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Parathyroid Disorders and Treatments、Coagulation, Bradykinin, Polyphosphates, and Angioedema

BACKGROUND: Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a progressive disease with a significant burden of recurrent cardiovascular (CV) events. Acoramidis, an approved oral therapy for ATTR-CM, achieves early, near-complete (≥90%) TTR stabilization. In the phase 3 ATTRibute-CM (Efficacy and Safety of Acoramidis in Participants with Transthyretin Amyloid Cardiomyopathy) study, acoramidis significantly reduced the composite of all-cause mortality or first CV-related hospitalization (CVH), with an effect observed at month 3. Its efficacy on the burden of cumulative CV outcome events has not been reported. OBJECTIVES: This study was a post hoc exploratory recurrent-event analysis of the efficacy of acoramidis on the cumulative incidence of CV outcomes from ATTRibute-CM and its open-label extension. METHODS: Cumulative incidences of centrally adjudicated CV-related mortality (CVM) or recurrent CVH (first and, if applicable, subsequent CVH), recurrent CVH alone (month 30), and CVM (month 42) were measured in the modified intention-to-treat population (acoramidis, n = 409; placebo, n = 202). Mean cumulative events by treatment, and the difference between treatment groups were estimated by using a modified Andersen-Gill model. RESULTS: Acoramidis significantly reduced the cumulative risk of CVM or recurrent CVH through month 30 vs placebo (HR: 0.51; 95% CI: 0.43-0.62; P < 0.0001). A notable proportion of CV outcome events (19% of CVM or recurrent CVH events, 22% of CVH) ...