Mavacamten significantly improved New York Heart Association functional class (OR 4.94) and Kansas City Cardiomyopathy Questionnaire scores compared to placebo in patients with hypertrophic cardiomyopathy.
Meta-Analysis (n=609)
Does mavacamten improve clinical, biomarker, and imaging outcomes in patients with hypertrophic cardiomyopathy compared to placebo?
Mavacamten significantly improves symptoms, quality of life, cardiac biomarkers, and LVOT gradients in patients with hypertrophic cardiomyopathy, though it did not significantly improve the specific pVO2/NYHA composite score in this meta-analysis.
Odds Ratio: 4.94 (95% CI 3.25–7.49)
p-value: p=<0.00001
BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM. METHOD: We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant. RESULTS: We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant. CONCLUSION: Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug's impact on the heart's structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.
Vyas et al. (Thu,) conducted a meta-analysis in Hypertrophic Cardiomyopathy (HCM) (n=609). Mavacamten vs. Placebo was evaluated on NYHA grade improvement (OR 4.94, 95% CI 3.25 to 7.49, p=<0.00001). Mavacamten significantly improved New York Heart Association functional class (OR 4.94) and Kansas City Cardiomyopathy Questionnaire scores compared to placebo in patients with hypertrophic cardiomyopathy.