Hypertrophic cardiomyopathy (HCM) is a genetic disorder, characterized primarily by left ventricular outflow tract obstruction and asymmetric myocardial hypertrophy, which predisposes to sudden cardiac death and malignant arrhythmias. Although current pharmacological treatments can alleviate symptoms, they are not specific therapeutic approaches. With the increase in clinical studies on the novel targeted therapy of cardiac myosin inhibitors for HCM, there is currently a lack of systematic reviews evaluating the efficacy of these drugs.

To assess the efficacy and safety of cardiac myosin inhibitors in the treatment of HCM.

Systematic searches were conducted in PubMed, EmBase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Database, and the China Biology Medicine disc, up to November 9, 2023, for randomized controlled trials (RCTs) of cardiac myosin inhibitors, including Mavacamten and Aficamten in HCM. Review Manager 5.4.1 software was utilized to conduct the statistical analysis.

A total of 6 RCTs were included[5 related to Mavacamten (4 original studies and 1 sub-study) and 1 related to Aficamten], involving 544 patients. The meta-analysis showed that, compared to placebo, the cardiac myosin inhibitors group exhibited significant reductions in peak gradient pressure under resting conditions in the left ventricular outflow tract (LVOT) (SMD=-1.24, 95%CI=-1.44 to -1.04, P<0.000 01), and under Valsalva maneuver (SMD=-1.37, 95%CI=-1.57 to -1.17, P<0.000 01), alongside at least a≥1 level improvement in the NYHA functional classification (NYHA-FC) (RR=2.22, 95%CI=1.77 to 2.78, P<0.000 01). Secondary endpoints showed reductions in the myocardial markers NT-proBNP (SMD=-1.28, 95%CI=-2.25 to -0.30), P=0.01] and cardiac troponin (SMD=-0.68, 95%CI=-1.32 to -0.04, P=0.04), improvement in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical score (SMD=0.42, 95%CI=0.07 to 0.78, P=0.02), an increase in the rate of patients reaching the composite endpoint events (RR=1.92, 95%CI=1.28 to 2.88, P=0.002), and a reduction in the number of patients needing or eligible for septal reduction therapy (SRT)(RR=0.29, 95%CI=0.22 to 0.39, P<0.000 01). Echocardiographic parameters indicated that cardiac myosin inhibitors could improve the left ventricular mass index (LVMI)(SMD=-0.82, 95%CI =-1.45 to -0.18, P=0.01), decrease the left atrial volume index (LAVI)(SMD=-0.58, 95%CI=-0.90 to -0.27, P=0.000 3), but could also lead to a reduction in the left ventricular ejection fraction (LVEF)(SMD=-0.46, 95%CI =-0.65 to -0.27, P<0.000 01). In terms of safety, the incidence of at least one adverse event in the cardiac myosin inhibitor group was higher than in the placebo group (RR=1.12, 95%CI=1.02 to 1.22, P=0.02), but there was no statistically significant difference in other safety outcomes, including serious adverse events (RR=1.14, 95%CI=0.62 to 2.07, P=0.67), atrial fibrillation (RR=1.27, 95%CI=0.45 to 3.58, P=0.65), nausea (RR=1.77, 95%CI=0.52 to 6.04, P=0.36), dizziness (RR=1.88, 95%CI=0.75 to 4.71, P=0.18), and fatigue (RR=1.35, 95%CI=0.51 to 3.63, P=0.55) compared to the placebo group.

Cardiac myosin inhibitors can improve the peak gradient pressure in the LVOT, enhance NYHA functional classification, reduce myocardial markers, alter cardiac structure, and improve patients' quality of life in HCM, with relatively high safety. They offer clinical benefits to patients with HCM but may reduce LVEF.

肥厚型心肌病（HCM）为遗传性疾病，主要表现为左心室流出道梗阻和心肌非对称性肥厚，易引起心源性猝死和恶性心律失常，目前临床药物治疗虽然可以不同程度地缓解症状，但并非特异性治疗方法。随着新型靶向药物心肌肌球蛋白抑制剂治疗HCM的临床研究增加，目前暂缺乏该药物疗效的系统评价。

评价心肌肌球蛋白抑制剂治疗HCM的疗效和安全性。

计算机检索PubMed、EmBase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、维普网和中国生物医学文献服务系统，从建库至2023-11-09有关心肌肌球蛋白抑制剂（包括Mavacamten和Aficamten）治疗HCM患者的随机对照试验（RCT）。使用RevMan 5.4.1软件进行数据处理。

共纳入6篇RCT[5篇Mavacamten相关（4篇原始研究、1篇亚研究），1篇Aficamten相关]，共544例患者。Meta分析结果显示，相比于安慰剂，心肌肌球蛋白抑制剂组主要终点事件显示：静息状态下左心室流出道（LVOT）峰值梯度压差（SMD=-1.24，95%CI=-1.44~-1.04，P<0.000 01）、Valsalva动作下LVOT峰值梯度压差（SMD=-1.37，95%CI=-1.57~-1.17，P<0.000 01）较基线降低，同时美国纽约心脏病学会（NYHA）心功能分级改善≥1级（RR=2.22，95%CI=1.77~2.78，P<0.000 01）；次要终点心肌标志物N-末端脑钠肽前体（NT-proBNP）（SMD=-1.28，95%CI=-2.25~-0.30，P=0.01）、心肌肌钙蛋白（SMD=-0.68，95%CI=-1.32~-0.04，P=0.04）均降低，堪萨斯城调查表临床评分（SMD=0.42，95%CI=0.07~0.78，P=0.02）改善，达到复合终点事件人数比例上升（RR=1.92，95%CI=1.28~2.88，P=0.002），进一步行室间隔减容治疗（SRT）或符合SRT的指南人数减少（RR=0.29，95%CI=0.22~0.39，P<0.000 01）；超声心动图参数：心肌肌球蛋白抑制剂能改善左心室质量指数（LVMI）（SMD=-0.82，95%CI=-1.45~-0.18，P=0.01），使左心房容积指数下降（LAVI）（SMD=-0.58，95%CI=-0.90~0.27，P=0.000 3），同时会降低左心室射血分数（LVEF）（SMD=-0.46，95%CI=-0.65~-0.27，P<0.000 01）。在安全性指标方面，心肌肌球蛋白抑制剂组至少1例不良事件的发生率高于安慰剂组（RR=1.12，95%CI=1.02~1.22，P=0.02），其余指标严重不良事件（RR=1.14，95%CI=0.62~2.07，P=0.67）、心房颤动（RR=1.27，95%CI=0.45~3.58，P=0.65）、恶心（RR=1.77，95%CI=0.52~6.04，P=0.36）、头晕（RR=1.88，95%CI=0.75~4.71，P=0.18）、疲乏（RR=1.35，95%CI=0.51~3.63，P=0.55）等安全性结局与安慰剂组比较，差异无统计学意义。

心肌肌球蛋白抑制剂可以改善HCM患者的LVOT峰值梯度压差、提高NYHA心功能分级、降低心肌标志物、改变患者心脏结构、提高患者生活质量，且安全性相对较高，对于HCM患者提供临床益处，但可能会降低LVEF。