The Efficacy and Safety of Cardiac Myosin Inhibitors Versus Placebo in Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

IF 2.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS American Journal of Cardiology Pub Date : 2025-04-15 Epub Date: 2025-01-23 DOI:10.1016/j.amjcard.2025.01.016

Chidubem Ezenna MD, BS , Mrinal Murali Krishna MBBS , Meghna Joseph MBBS , Vinicius Pereira , Samia Nadeem MD , Gregory Valania DO , Andrew M. Goldsweig MD, MS

{"title":"The Efficacy and Safety of Cardiac Myosin Inhibitors Versus Placebo in Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials","authors":"Chidubem Ezenna MD, BS , Mrinal Murali Krishna MBBS , Meghna Joseph MBBS , Vinicius Pereira , Samia Nadeem MD , Gregory Valania DO , Andrew M. Goldsweig MD, MS","doi":"10.1016/j.amjcard.2025.01.016","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disorder characterized by myocardial hypertrophy, which can obstruct left ventricular outflow. Cardiac myosin inhibitors (CMIs) have emerged as a novel therapeutic agent targeting cardiac muscle hypercontractility.</div></div><div><h3>Objective</h3><div>To compare the efficacy and safety of CMIs mavacamten and aficamten vs. placebo in patients with oHCM.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed, Scopus, and Cochrane Central databases for randomized controlled trials (RCTs) comparing mavacamten or aficamten to placebo in patients with symptomatic oHCM. Efficacy outcomes included improvement in peak oxygen consumption (pVO2), New York Heart Association functional class (NYHA-FC) improvement of ≥1 class, change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), peak left ventricular outflow tract gradient at rest (rLVOT) and with Valsalva maneuver (vLVOT). Safety outcomes included treatment-emergent adverse events (TEAE), serious adverse events (SAE), and atrial fibrillation (AF). Random effects models generated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I<sup>2</sup> statistics.</div></div><div><h3>Results</h3><div>The systematic search identified 5 RCTs including 767 patients (mavacamten 30.4%, aficamten 22.2%, placebo 47.4%) with a median follow-up of 24 weeks. Compared to placebo, CMIs were associated with improvement of ≥1 NYHA-FC (RR 2.33; 95% CI, 1.92-2.82), rLVOT (MD -38.70; 95% CI, [-46.30]-[-31.10]), vLVOT (MD -47.29; 95% CI, [-57.99]-[-36.58]), pVO2 (MD 1.66; 95% CI, 1.14-2.18), and KCCQ-CSS (MD 7.76; 95% CI, 5.63-9.90). Safety outcomes were similar between CMIs and placebo.</div></div><div><h3>Conclusion</h3><div>CMIs are an effective and safe short-term treatment for symptomatic oHCM. Long-term outcomes require further investigation.</div></div>","PeriodicalId":7705,"journal":{"name":"American Journal of Cardiology","volume":"241 ","pages":"Pages 52-60"},"PeriodicalIF":2.1000,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Cardiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0002914925000463","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disorder characterized by myocardial hypertrophy, which can obstruct left ventricular outflow. Cardiac myosin inhibitors (CMIs) have emerged as a novel therapeutic agent targeting cardiac muscle hypercontractility.

Objective

To compare the efficacy and safety of CMIs mavacamten and aficamten vs. placebo in patients with oHCM.

Methods

We systematically searched PubMed, Scopus, and Cochrane Central databases for randomized controlled trials (RCTs) comparing mavacamten or aficamten to placebo in patients with symptomatic oHCM. Efficacy outcomes included improvement in peak oxygen consumption (pVO2), New York Heart Association functional class (NYHA-FC) improvement of ≥1 class, change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), peak left ventricular outflow tract gradient at rest (rLVOT) and with Valsalva maneuver (vLVOT). Safety outcomes included treatment-emergent adverse events (TEAE), serious adverse events (SAE), and atrial fibrillation (AF). Random effects models generated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I² statistics.

Results

The systematic search identified 5 RCTs including 767 patients (mavacamten 30.4%, aficamten 22.2%, placebo 47.4%) with a median follow-up of 24 weeks. Compared to placebo, CMIs were associated with improvement of ≥1 NYHA-FC (RR 2.33; 95% CI, 1.92-2.82), rLVOT (MD -38.70; 95% CI, [-46.30]-[-31.10]), vLVOT (MD -47.29; 95% CI, [-57.99]-[-36.58]), pVO2 (MD 1.66; 95% CI, 1.14-2.18), and KCCQ-CSS (MD 7.76; 95% CI, 5.63-9.90). Safety outcomes were similar between CMIs and placebo.

Conclusion

CMIs are an effective and safe short-term treatment for symptomatic oHCM. Long-term outcomes require further investigation.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

心肌肌球蛋白抑制剂与安慰剂对症状性梗阻性肥厚性心肌病患者的疗效和安全性：随机对照试验的荟萃分析

梗阻性肥厚性心肌病（oHCM）是一种以心肌肥厚为特征的遗传性疾病，可阻断左心室流出。心肌肌球蛋白抑制剂（CMIs）已成为一种新的治疗心肌过度收缩的药物。目的：比较CMIs马伐卡坦和阿非卡坦与安慰剂对oHCM患者的疗效和安全性。方法：我们系统地检索PubMed、Scopus和Cochrane Central数据库，以比较马伐卡坦或阿非卡坦与安慰剂在症状性oHCM患者中的疗效的随机对照试验（rct）。疗效结果包括峰值耗氧量（pVO2）改善，纽约心脏协会功能分级（NYHA-FC）改善≥1级，堪萨斯城心肌病问卷临床总结评分（KCCQ-CSS）的变化，静息时左室流出道梯度（rLVOT）峰值和Valsalva操作（vLVOT）。安全性结局包括治疗中出现的不良事件（TEAE）、严重不良事件（SAE）和心房颤动（AF）。随机效应模型产生95%置信区间（ci）的风险比（rr）和平均差异（md）。采用I2统计量评估异质性。结果：系统检索确定了5项随机对照试验，包括767例患者（马伐卡坦30.4%，阿非卡坦22.2%，安慰剂47.4%），中位随访时间为24周。与安慰剂相比，CMIs与≥1 NYHA-FC的改善相关(RR 2.33；95%CI 1.92-2.82), rLVOT (MD -38.70；95%CI [-46.30]-[-31.10]), vLVOT (MD -47.29；95%CI [-57.99]-[-36.58]), pVO2 (MD 1.66；95%CI 1.14-2.18), KCCQ-CSS (MD 7.76；95%可信区间5.63 - -9.90)。cmi和安慰剂的安全性结果相似。结论：CMIs是一种有效、安全的治疗症状性oHCM的短期方法。长期结果需要进一步调查。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

American Journal of Cardiology 医学-心血管系统

CiteScore

4.00

自引率

3.60%

发文量

698

审稿时长

33 days

期刊介绍： Published 24 times a year, The American Journal of Cardiology® is an independent journal designed for cardiovascular disease specialists and internists with a subspecialty in cardiology throughout the world. AJC is an independent, scientific, peer-reviewed journal of original articles that focus on the practical, clinical approach to the diagnosis and treatment of cardiovascular disease. AJC has one of the fastest acceptance to publication times in Cardiology. Features report on systemic hypertension, methodology, drugs, pacing, arrhythmia, preventive cardiology, congestive heart failure, valvular heart disease, congenital heart disease, and cardiomyopathy. Also included are editorials, readers'' comments, and symposia.