Efficacy of Acoramidis in Wild-Type and Variant Transthyretin Amyloid Cardiomyopathy

作者：Kevin Alexander, Margot K. Davis, Olakunle O. Akinboboye, John L. Berk, Kunal Bhatt, Francesco Cappelli, Sarah Cuddy, Marianna Fontana, Pablo García‐Pavía, Julian D. Gillmore, Jan M. Griffin, Justin L. Grodin, Daniel P. Judge, Michel G. Khouri, Kaitlyn Lam, Ahmad Masri, Matthew J. Maurer, Laura Obici, Frederick L. Ruberg, N. Sarswat, Keyur B. Shah, Prem Soman, L. Stern, Richard Wright, Kuangnan Xiong, Xiaofan Cao, Ted Lystig, Jean‐François Tamby, Adam Castaño, Leonid Katz, Uma Sinha, Jonathan C. Fox, Scott D. Solomon, Martha Grogan · 发表于：JAMA Cardiology · 年份：2025 · DOI：10.1001/jamacardio.2025.4477 · 被引用次数：5 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Dermatological and Skeletal Disorders、Parathyroid Disorders and Treatments

Importance: Transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive disease caused by misfolded transthyretin (TTR), occurs as wild-type (ATTRwt-CM) or variant (ATTRv-CM) forms. p.Val142Ile is the most common variant in the US, linked to rapid progression and increased mortality. Acoramidis achieves near-complete (≥90%) TTR stabilization and showed clinical benefit in the 30-month ATTRibute-CM trial and through month 42 in the ongoing open-label extension (OLE). Objective: To evaluate the efficacy of acoramidis in ATTRwt-CM, ATTRv-CM, and variant subgroups (p.Val142Ile and non-p.Val142Ile). Design, Setting, and Participants: This international, multicenter, phase 3, randomized placebo-controlled study took place from April 2019 to May 2023 with ongoing OLE (month 42). ATTRibute-CM enrolled 632 participants with ATTR-CM; 611 of 632 were included in the modified intention-to-treat (mITT) population. There were 380 participants who continued into the OLE. These data were analyzed from January 2025 to July 2025. Interventions: Oral acoramidis, 712 mg, or placebo twice daily for 30 months, followed by 12 months of open-label treatment. Main Outcomes and Measures: All-cause mortality (ACM), cardiovascular-related hospitalizations (CVH), serum TTR, 6-minute walk distance, Kansas City Cardiomyopathy Questionnaire Overall Summary score, and N-terminal pro B-type natriuretic peptide in participants with ATTRwt-CM and ATTRv-CM. Post-hoc analyses were conducted in variant subgroups...