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tafamidis治疗甲状腺素运载蛋白淀粉样变心肌病患者
Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy


Mathew S. Maurer ... 心脑血管疾病 • 2018.09.13

tafamidis改善甲状腺素运载蛋白淀粉样变心肌病患者生存

 

曹云山

甘肃省人民医院心内科

 

甲状腺素运载蛋白淀粉样变心肌病是一种因错误折叠的甲状腺素运载蛋白形成的淀粉样物质沉积于心脏的导致的致命性疾病。这类淀粉样物质非常坚硬,且不溶于水、不易被蛋白酶降解,而且可以像聚合物一样无限延长。它们充填于心肌纤维之间引起心脏舒张功能受限,最后引起一系列症状,包括气短、疲乏、直立性低血压、晕厥等,此类物质还可以累及心脏传导系统,引起束支阻滞、房室阻滞、窦房疾病和房颤。

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摘要


背景

甲状腺素运载蛋白淀粉样变心肌病是由甲状腺素运载蛋白淀粉样蛋白原纤维在心肌内沉积引起。当野生型或变异型甲状腺素运载蛋白变得不稳定并错误折叠时发生沉积。tafamidis与甲状腺素运载蛋白结合,防止四聚体解离和淀粉样蛋白生成。

 

方法

在一项多中心、国际性、双盲、安慰剂对照、3期试验中,我们以2∶1∶2的比例将441例甲状腺素运载蛋白淀粉样变心肌病患者随机分组,给予80 mg tafamidis、20 mg tafamidis或安慰剂治疗30个月。在主要分析中,我们按照Finkelstein-Schoenfeld方法对全因死亡率和其次的心血管相关住院率进行了分级评估。关键次要终点为6分钟步行试验和堪萨斯城心肌病问卷-全面汇总(Kansas City Cardiomyopathy Questionnaire-Overall Summary,KCCQ-OS)评分(较高的评分表示较好的健康状况)从基线至第30个月的变化。

 

结果

在主要分析中,tafamidis组264例患者的全因死亡率和心血管相关住院率低于安慰剂组177例患者(P<0.001)。与安慰剂相比,tafamidis与较低的全因死亡率(78/264 [29.5%] vs. 76/177 [42.9%];风险比,0.70;95%置信区间[CI],0.51~0.96)和较低的心血管相关住院率(每年0.48 vs.每年0.70;相对危险比,0.68;95% CI,0.56~0.81)相关。30个月时,tafamidis组6分钟步行距离的减少比例(P<0.001)和KCCQ-OS评分的降低比例(P<0.001)均较小。两组的不良事件发生率和类型相似。

 

结论

在甲状腺素运载蛋白淀粉样变心肌病患者中,与安慰剂相比,tafamidis与全因死亡率和心血管相关住院率降低相关,并且减少了功能能力和生活质量的下降(由辉瑞资助;ATTR-ACT在ClinicalTrials.gov注册号为NCT01994889)。





作者信息

Mathew S. Maurer, M.D., Jeffrey H. Schwartz, Ph.D., Balarama Gundapaneni, M.S., Perry M. Elliott, M.D., Giampaolo Merlini, M.D., Ph.D., Marcia Waddington-Cruz, M.D., Arnt V. Kristen, M.D., Martha Grogan, M.D., Ronald Witteles, M.D., Thibaud Damy, M.D., Ph.D., Brian M. Drachman, M.D., Sanjiv J. Shah, M.D., Mazen Hanna, M.D., Daniel P. Judge, M.D., Alexandra I. Barsdorf, Ph.D., Peter Huber, R.Ph., Terrell A. Patterson, Ph.D., Steven Riley, Pharm.D., Ph.D., Jennifer Schumacher, Ph.D., Michelle Stewart, Ph.D., Marla B. Sultan, M.D., M.B.A., and Claudio Rapezzi, M.D. for the ATTR-ACT Study Investigators*
From the Columbia University Vagelos College of Physicians and Surgeons (M.S.M.) and Pfizer (J.H.S., A.I.B., P.H., J.S., M.B.S.), New York; Syneos Health, Raleigh, NC (B.G.); University College London and St. Bartholomew’s Hospital, London (P.M.E.); the Amyloidosis Center, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, and the University of Pavia, Pavia (G.M.), and the Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna (C.R.) — both in Italy; the Amyloidosis Center (CEPARM), Federal University of Rio de Janeiro, Rio de Janeiro (M.W-C.); the Amyloidosis Center, Medical University of Heidelberg, Heidelberg, Germany (A.V.K.); the Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (M.G.); Stanford University School of Medicine, Stanford, CA (R.W.); the French Referral Center for Cardiac Amyloidosis, Amyloidosis Mondor Network, GRC Amyloid Research Institute and Department of Cardiology, Assistance Publique–Hôpitaux de Paris, CHU Henri Mondor, and INSERM Unité 955, Clinical Investigation Center 006, and DHU ATVB, Creteil, France (T.D.); Penn Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia (B.M.D.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); Cleveland Clinic, Cleveland (M.H.); the Medical University of South Carolina, Charleston (D.P.J.); and Pfizer, Groton, CT (T.A.P., S.R., M.S.). Address reprint requests to Dr. Maurer at Columbia University Irving Medical Center, 622 W. 168th St., PH 12 Stem Rm. 134, New York, NY 10032, or at msm10@cumc.columbia.edu. *The complete list of the ATTR-ACT Study Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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