Mavacamten and atrial fibrillation: assessing the risk through FAERS and meta-analysis

Abstract Background Mavacamten is a novel selective cardiac myosin inhibitor indicated for patients with obstructive hypertrophic cardiomyopathy (oHCM). Given its negative inotropic properties, which theoretically reduce myocardial contractility and affect left atrial systolic function, concerns have arisen about its potential association with an increased incidence of atrial fibrillation (AF). The study aims to assess this potential association. Methods We employed a dual approach combining real-world data analysis and evidence synthesis. First, disproportionality and time-to-onset analyses were performed using the FDA Adverse Event Reporting System (FAERS) across two models: the general population (Model 1) and an HCM-specific cohort (Model 2). Independent risk factors for AF were identified using logistic regression. Second, a meta-analysis of placebo-controlled trials was conducted to evaluate the safety profile of mavacamten, with pooled risk ratios (RRs) and 95% confidence intervals (CIs) . Results In the disproportionality analysis, Model 1 revealed a signal for AF with mavacamten (adjusted ROR 18.54, 95% CI 11.53–29.80, P < 0.05; EB05 11.55). In contrast, no significant disproportionality signal was observed in Model 2 (aROR 4.28, 95% CI 1.30–14.07, P = 0.017; EB05 0.74). The time-to-onset analysis indicated a random failure type for AF occurrence in mavacamten-treated patients. The meta-analysis included five RCTs and one retrospective cohort study. Compared with placebo, mavacamten was not associated with an increased risk of AF (RR = 0.92, 95% CI 0.80–1.06, P = 0.12). Conclusion Our findings did not identify a significant association between mavacamten and AF in patients with HCM. These results should be interpreted with caution due to the limited number of studies and small sample sizes.