Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy

作者：Matthew J. Maurer, Jeffrey H. Schwartz, Balarama Gundapaneni, Perry Elliott, Giampaolo Merlini, Márcia Waddington‐Cruz, Arnt V. Kristen, Martha Grogan, Ronald Witteles, Thibaud Damy, Brian Drachman, Sanjiv J. Shah, Mazen Hanna, Daniel P. Judge, Alexandra I. Barsdorf, Peter M. Huber, Terrell A. Patterson, Steve Riley, Jennifer Schumacher, Michelle Stewart, Marla B. Sultan, Claudio Rapezzi · 发表于：New England Journal of Medicine · 年份：2018 · DOI：10.1056/nejmoa1805689 · 被引用次数：2792 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Parathyroid Disorders and Treatments、Thyroid and Parathyroid Surgery

BACKGROUND: Transthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin amyloid fibrils in the myocardium. The deposition occurs when wild-type or variant transthyretin becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation and amyloidogenesis. METHODS: In a multicenter, international, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 441 patients with transthyretin amyloid cardiomyopathy in a 2:1:2 ratio to receive 80 mg of tafamidis, 20 mg of tafamidis, or placebo for 30 months. In the primary analysis, we hierarchically assessed all-cause mortality, followed by frequency of cardiovascular-related hospitalizations according to the Finkelstein-Schoenfeld method. Key secondary end points were the change from baseline to month 30 for the 6-minute walk test and the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS), in which higher scores indicate better health status. RESULTS: In the primary analysis, all-cause mortality and rates of cardiovascular-related hospitalizations were lower among the 264 patients who received tafamidis than among the 177 patients who received placebo (P<0.001). Tafamidis was associated with lower all-cause mortality than placebo (78 of 264 [29.5%] vs. 76 of 177 [42.9%]; hazard ratio, 0.70; 95% confidence interval [CI], 0.51 to 0.96) and a lower rate of cardiovascular-related hospitalizations, with a relative risk ratio of 0.68 (0.48 per y...