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The Efficacy of Cardiac Myosin Inhibitors versus Placebo in Patients with Symptomatic Hypertrophic Cardiomyopathy – A Meta-Analysis and Systematic Review

Am J Cardiol. 2023 Oct 24:S0002-9149(23)01209-2. doi: 10.1016/j.amjcard.2023.10.059. Online ahead of print.


We aimed to assess the overall clinical impact of cardiac myosin inhibitors in hypertrophic cardiomyopathy (HCM). We performed a meta-analysis of published trials assessing the effect of cardiac myosin inhibitors (Mavacamten and Aficamten) on resting and Valsalva LVOT gradients and functional capacity in symptomatic HCM. The co-primary outcomes were mean percent change (mean difference, MD) from baseline in resting LVOT gradient and Valsalva LVOT gradient, as well as proportion of patients achieving NYHA Class improvement ≥ 1. Secondary outcomes included mean percent change from baseline NT ProBNP, Troponin I, and left ventricular ejection fraction (LVEF). Four studies (all randomized-control trials, including 3 Mavacamten-focused and 1 Aficamten-focused trials) involving 463 patients were included in the meta-analysis. Compared to placebo, the cardiac myosin inhibitor group demonstrated statistically significant differences in baseline percent change in mean resting LVOT gradient (MD -62.48, CI -65.44, -59.51, p <0.00001) and Valsalva LVOT gradient (MD -54.21, CI -66.05, -42.36, p <0.00001), as well as proportion of patients achieving NYHA Class improvement ≥ 1 (OR 3.43, CI 1.90, 6.20, p <0.0001). Regarding secondary outcomes, the intervention group demonstrated statistically significant reductions in mean percent change from baseline in NT-proBNP (MD -69.41, CI -87.06, -51.75, p < 0.00001), Troponin I (MD, -44.19, CI -50.59, -37.78, p < 0.00001), and LVEF (MD -6.31, CI -10.35, -2.27, p = 0.002). In conclusion, cardiac myosin inhibitors may confer clinical and symptomatic benefits in symptomatic HCM, at the possible expense of LVEF. Further trials with large sample sizes are needed to confirm our findings.

PMID:37884110 | DOI:10.1016/j.amjcard.2023.10.059

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