Mavacamten and Systolic Dysfunction in the FDA Adverse Event Reporting System: A Disproportionality Analysis With an Indication-Restricted Comparator

Introduction: Mavacamten, a cardiac myosin inhibitor for obstructive hypertrophic cardiomyopathy (HCM), is dispensed under a Risk Evaluation and Mitigation Strategy requiring serial echocardiography for reduced ejection fraction.Because HCM itself causes systolic dysfunction and heart failure, a disproportionality estimate drawn from the whole database confounds the drug with its indication.We examined whether the reporting signal persists when the comparator is restricted to the same indication.Methods: We analysed the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA interface, using the snapshot dated July 30, 2026.The composite outcome comprised 12 Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms covering systolic dysfunction and heart failure.Disproportionality was measured by reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) against two pre-specified comparators: the whole database, which yields the crude, indication-unadjusted estimate, and reports carrying an explicit HCM indication, which is the comparison that addresses the study question.The interval from treatment start to report receipt was described with a Weibull model.Results: Of 5,083 reports naming mavacamten, 379 (7.5%) met the composite outcome.Against the whole database, the signal was strong (ROR 8.29, 95% confidence interval (CI) 7.47-9.21;PRR 7.75; IC025 2.78).Against the 527 reports sharing an HCM indication, it was absent (ROR 0.80, 95% CI 0.58-1.09;PRR 0.81; IC025 -0.22), with the outcome appearing in 7.7% of mavacamten reports versus 9.5% of comparator reports.The interval to report showed an approximately constant hazard (Weibull shape 1.00; median 161 days).Conclusions: The crude signal does not survive restriction of the comparator to the same indication, indicating substantial confounding by indication.The restricted estimate is not evidence of safety: the comparator is small, composed largely of negative inotropes that may carry the same outcome, and subject to ascertainment and reporting biases acting in opposite directions.The magnitude of a crude disproportionality signal is therefore a poor guide to the drug's own contribution to this outcome.