Key result
Mavacamten and aficamten cut LVOT gradients by ~57 mmHg vs. placebo in HCM patients.
Why the study?
Cardiac myosin inhibitors are novel, disease-modifying therapies for HCM, prompting this meta-analysis to evaluate their efficacy versus placebo.
Do cardiac myosin inhibitors improve hemodynamics, functional status, and biomarkers compared to placebo in adults with hypertrophic cardiomyopathy?
Do cardiac myosin inhibitors improve hemodynamics, functional status, and biomarkers compared to placebo in adults with hypertrophic cardiomyopathy?
Cardiac myosin inhibitors significantly improve hemodynamics, functional status, and biomarkers in patients with hypertrophic cardiomyopathy, though they are associated with a modest decrease in LVEF and an increase in adverse events such as hypertension.
May support CMI use in symptomatic obstructive HCM with LVEF monitoring; confirms class efficacy on gradients and NYHA class in RCT meta-analysis.
Cardiac myosin inhibitors (CMIs) are novel, disease-modifying therapies for hypertrophic cardiomyopathy (HCM). This meta-analysis evaluates the efficacy of CMIs versus placebo in patients with HCM. A systematic review and meta-analysis of randomized controlled trials (RCTs) involving adults with obstructive and non-obstructive HCM was performed following the PRISMA 2020 guidelines and registered on PROSPERO. Database including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched through September 2025. Random-effects models were performed using SMDs for biomarker and WMDs for echocardiographic parameters. RRs were calculated for dichotomous outcomes, with 95% confidence intervals. Seven RCTs, comprising 1,406 patients (732 CMI; 674 placebo) were included. CMIs significantly improved resting (WMD: −57.27 mmHg [−63.05, −51.49]; p < 0.001) and post-Valsalva LVOT gradient (WMD: −55.87 mmHg [−63.05, −51.49]; p < 0.001). LVEF decreased modestly (WMD: −4.74% [−7.22, −2.26]; p = 0.0002). CMIs increased the likelihood of ≥1 NYHA class improvement (RR: 1.94 [1.37, 2.74]; p < 0.001) and KCCQ-CSS (WMD: +6.60 points [3.84, 9.35]; p < 0.001). NT-proBNP (WMD: -13.35 [-18.04, -8.67]; p < 0.001) and cardiac troponin I (WMD: -11.90 [-15.07, -8.73]; p < 0.001) declined. Peak oxygen uptake showed no overall change (WMD: +0.64 mL/kg/min [−0.18, 1.47]; p = 0.12). CMIs increased adverse events (RR: 1.07 [1.02, 1.13]; p = 0.008), particularly hypertension (RR: 2.19 [1.06, 4.53]; p = 0.03). CMIs improve hemodynamics, functional status, and biomarkers in HCM with an acceptable safety profile and hold promise as disease-modifying therapy, though long-term outcomes require confirmation.
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Ibrahim et al. (2026) studied this question. Mavacamten and aficamten significantly reduced LVOT gradients by ~57 mmHg, improved NYHA class (RR 1.94) and biomarkers, with increased adverse events (RR 1.07) in HCM patients.
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