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.