Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy
Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy
复制标题
DOI：
10.1056/nejmoa1805689
复制
发表时间：
2018-09-13
影响因子：
158.5
通讯作者：
Rapezzi, Claudio
中科院分区：
文献类型：
--
作者：
Maurer, Mathew S.;Schwartz, Jeffrey H.;Rapezzi, Claudio
转甲状腺素蛋白淀粉样心肌病是由转甲状腺素蛋白淀粉样纤维在心肌中沉积引起的。当野生型或变体甲状腺素运载蛋白变得不稳定和错误折叠时，就会发生沉积。Tafamidis结合到甲状腺素运载蛋白，防止四聚体解离和amyloidogenes. METHODS在一个多中心，国际，双盲，安慰剂对照，3期试验，我们随机分配441例甲状腺素运载蛋白淀粉样心肌病患者在2：1：2的比例接受80毫克的tafamidase，20毫克的tafamidase，或安慰剂30个月。在主要分析中，我们分层评估了全因死亡率，然后根据Finkelstein-Schoenfeld方法评估了心血管相关住院率。关键的次要终点是6分钟步行试验从基线到第30个月的变化和堪萨斯城心肌病量表-总体总结（KCCQ-OS）评分，其中评分越高表明健康状况越好。全因死亡率和心血管疾病发病率，264名接受他法莫司汀治疗的患者的相关住院率低于177名接受安慰剂治疗的患者（P
BACKGROUNDTransthyretin 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.METHODSIn 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.RESULTSIn 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