Mavacamten治療肥厚型心肌病之療效與安全性的系統性文獻回顧與統合分析及臨床試驗計畫書

Abstract

背景： 肥厚型心肌病（HCM）是一種以心肌肥厚為特徵的遺傳性心肌疾病，常伴隨運動不耐與心臟衰竭症狀。Mavacamten（MYK-461）為一種新穎的小分子心肌肌球蛋白抑制劑，近期於多項隨機對照試驗中顯示其對有症狀HCM患者具臨床療效與安全性。 方法： 本研究包含兩部分：(1) 一篇針對Mavacamten治療HCM患者的系統性文獻回顧與統合分析（MA&SR），納入截至2025年5月之英語文獻資料庫（PubMed、EMBASE、Cochrane）中具隨機對照設計之臨床試驗，並以主要臨床療效指標（如 pVO₂、NYHA/KCCQ 分級、LAVI、LVOT 梗阻改善等）與安全性指標進行統合統計分析；(2) 一項自擬之亞洲族群中針對有症狀非阻塞型HCM（nHCM）患者之前瞻性、隨機、雙盲、安慰劑對照臨床試驗，設計重點包含樣本數估計、給藥方案、影像與心臟功能指標監測週期，以及次族群分析策略。 結果： 統合分析結果顯示，Mavacamten 可顯著改善患者的 pVO₂（Mean Difference = 1.200, p = 0.017）、KCCQ 得分、左心房體積指數（LAVI），並降低左心室流出道壓差（LVOT gradient），整體安全性良好。根據本研究設計之RCT初步架構，預期將能提供亞洲族群中針對 nHCM 的補充證據。 結論： Mavacamten 為一項對HCM患者具療效與安全性的創新治療選擇，未來針對nHCM及亞洲人群的臨床試驗將為其全球適應症拓展提供重要依據。

Background: Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disorder characterized by myocardial hypertrophy, commonly associated with exercise intolerance and symptoms of heart failure. Mavacamten (MYK-461) is a novel small-molecule inhibitor of cardiac myosin that has recently demonstrated clinical efficacy and safety in multiple randomized controlled trials (RCTs) involving symptomatic HCM patients. Methods: This study comprises two components: (1) a systematic review and meta-analysis (SR&MA) of RCTs evaluating the efficacy and safety of mavacamten in HCM patients. Literature searches were conducted in English-language databases (PubMed, EMBASE, and Cochrane) up to May 2025. Key efficacy outcomes included peak oxygen consumption (pVO₂), NYHA/KCCQ classification, left atrial volume index (LAVI), and improvement in left ventricular outflow tract (LVOT) obstruction. Safety outcomes were also analyzed; (2) the design of a prospective, randomized, double-blind, placebo-controlled clinical trial targeting symptomatic non-obstructive HCM (nHCM) patients in an Asian population. The proposed protocol includes sample size estimation, dosing regimen, monitoring intervals for imaging and cardiac functional markers, and subgroup analysis strategies. Results: Meta-analysis results indicated that mavacamten significantly improved pVO₂ (Mean Difference = 1.200, p = 0.017), KCCQ scores, and LAVI, and reduced the LVOT gradient, with an overall favorable safety profile. The proposed RCT protocol is expected to provide supplementary evidence for the use of mavacamten in nHCM within Asian populations. Conclusion: Mavacamten represents an innovative and effective therapeutic option for patients with HCM. Future clinical trials focusing on nHCM and Asian cohorts will be critical for expanding its global indications.