4A-05 - Post-marketing Safety Surveillance of Cardiovascular Risk Among Individuals Using Mavacamten for Treatment of Obstructive Hypertrophic Cardiomyopathy: A Retrospective Cohort Study

Background: Mavacamten (mava) is a first-in-class cardiac myosin inhibitor approved by the United States (U.S.) Food and Drug Administration in April 2022 for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).

Objectives: To assess cardiac risk among individuals with oHCM receiving mava with those receiving non-mava pharmacotherapies (non-dihydropyridine calcium channel blockers, disopyramide, and/or non-vasodilating beta blockers, i.e., standard of care).

Methods: This retrospective cohort study utilized PharMetrics® Plus, a large, diverse largely commercial claims database in the U.S. Individuals 18 years or older with a diagnosis of oHCM who received mava or non-mava pharmacotherapies between May 2022 and July 2024 were included. The index date for the mava cohort was defined as the date of the first claim for mava. For every patient in the mava cohort, two patients from the non-mava cohort were randomly selected as contemporaneous controls who received non-mava therapy from the same month and year as the matched mava patient (i.e., claim date). All individuals were followed from index date to censor date, defined as the first instance of reaching an endpoint of interest, death, disenrollment from the data source, end of continuous treatment, or end of the study period. Baseline demographics and clinical characteristics were used to derive propensity scores to further match the treatment cohorts using a nearest neighbor match. Cox proportional hazard models were fitted to estimate the hazard ratio (HR) of major adverse cardiovascular events (MACE) and heart failure (HF).

Results: We identified a total of 587 individuals receiving mava and 1151 receiving non-mava therapies with median follow up of 144 and 120 days, respectively. Mava recipients were younger (mean age 59.9 vs. 63.1), more likely to have history of HF, syncope, arrhythmia and experienced symptoms of breathlessness. After adjustment for potentially confounding covariates, there were no statistically significant differences in the likelihood of outcome of HF (adjusted HR [aHR] 0.87, 95% confidence interval [CI] 0.67 to 1.14), HF with systolic dysfunction (aHR 0.79, CI 0.53 to 1.19), 3-point MACE (aHR 1.03, CI 0.77 to 1.38) or 4-point MACE (aHR 0.94, CI 0.71 to 1.23) between mava users and their counterparts. These findings persisted in sensitivity analyses.

Conclusions: In this post-marketing safety surveillance study of patients with oHCM, there were no significant associations between mavacamten use and cardiovascular events.