Cardiac myosin inhibitors in obstructive hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT

BACKGROUND: Selective cardiac myosin inhibitors (CMI) are promising therapies for obstructive hypertrophic cardiomyopathy (HCM). Yet, the extent of their benefits remains unclear due to the limited population studied. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing CMI vs. placebo in patients with obstructive HCM. PubMed, Cochrane, and embase were searched. We calculated risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs) with 95% confidence intervals (CI). RESULTS: Four RCTs with 485 patients with obstructive HCM were included, of whom 261 (53.8%) were prescribed CMI (10.7% were aficamten and 89.3% were mavacamten). CMI significantly reduced resting left ventricular outflow tract (LVOT) gradient (SMD -1.4, 95% CI -1.6,-1.2, p<0.001), but also reduced left ventricular ejection fraction (LVEF) (MD -5.1%, 95% CI -7.6,-2.6, p<0,001). Patients receiving CMI had a higher rate of study-defined complete hemodynamic response (RR 16.8, CI 95% 5.5, 51.4, p<0,001; Figure 1A) with a number needed to treat (NNT) of 8; and improvement of at least one point in NYHA functional class (RR 2.29, CI 95% 1.8,2.9, p<0,001; Figure 1B). Conclusion: In this meta-analysis of RCTs including patients with obstructive HCM, CMI led to a significant reduction in LVOT gradient and symptomatic improvement. The NNT to achieve one complete hemodynamic response was 8. There was a significant, albeit modest, decrease in LVEF in the CMI group.