Heart failure reporting signals associated with concomitant mavacamten and CYP inhibitors in obstructive hypertrophic cardiomyopathy: a real-world pharmacovigilance study with propensity score matching

Figures

• 

  FIGURE 1. Study selection flowchart. Flowchart detailing the data extraction, deduplication, and cohort identification process from the FAERS database (Q2 2022 to Q4 2025). A final cohort of 3,570 mavacamten-treated HOCM reports was identified and subsequently stratified into two sub-cohorts: the mavacamten monotherapy group (n = 3,223) and the concomitant CYP inhibitor therapy group (n = 347). Abbreviations: FAERS, FDA Adverse Event Reporting System; HOCM, obstructive hypertrophic cardiomyopathy; CYP, cytochrome P450.

• 

  FIGURE 2. Drug-specific disproportionality signals for heart failure-related reports among prespecified CYP inhibitors. Forest plot showing reporting odds ratios (RORs) and 95% confidence intervals (CIs). Drug-specific counts correspond to Supplementary Table S2. Rows are not mutually exclusive because individual reports may contain more than one CYP inhibitor. Abbreviations: CYP, cytochrome P450; ROR, reporting odds ratio; CI, confidence interval.

• 

  FIGURE 3. Temporal dynamics and reported clinical severity of heart failure-related reports. (A) TTO distribution fitted with a Weibull hazard model. Both the mavacamten monotherapy (β = 0.87) and combination therapy (β = 0.88) groups exhibited an “early failure” hazard profile (β < 1). (B) Comparison of severe reported outcomes between reports involving mavacamten monotherapy and reports involving concomitant CYP inhibitor exposure. Abbreviations: TTO, time-to-onset; CYP, cytochrome P450; β, Weibull shape parameter.

• 

  FIGURE 4. Multivariable logistic regression analysis of factors associated with heart failure-related reporting. The forest plot displays the aORs and 95% CIs on a logarithmic scale. The regression model adjusted for baseline clinical imbalances and potential reporting-related factors, including age (≥65 years), sex, low body weight (<60 kg), history of atrial fibrillation, concomitant diuretic use, and reporting source. Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; HCP, healthcare professional.

• 

  FIGURE 5. Covariate balance before and after PSM. The Love plot displays the SMDs of baseline covariates between the mavacamten monotherapy group and the concomitant CYP inhibitor therapy group. Red circles indicate the unmatched cohort, whereas blue triangles represent the 1:4 propensity score–matched cohort. Vertical dashed lines denote the prespecified balance threshold of SMD = ±0.1. Abbreviations: PSM, propensity score matching; SMD, standardized mean difference; CYP, cytochrome P450.