Effect of aficamten compared with metoprolol in women versus men: analysis of MAPLE-HCM
X Wang, M Pabon, B Claggett, P Garcia-Pavia, M A Fifer, O Bilen, E C De Barros, A Mann, M S Maron, A Wang, D R Zwas, R Sohn, S B Heitner, S D Solomon, S HegdeAbstract
Background
Aficamten monotherapy was superior to metoprolol monotherapy among patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Whether there are sex differences in the effect of aficamten compared with metoprolol is unknown.
Purpose
To evaluate sex differences in baseline characteristics and the efficacy of aficamten compared with metoprolol in MAPLE-HCM.
Methods
A secondary analysis of sex differences in the double-blind, randomized-controlled MAPLE-HCM trial of aficamten versus metoprolol in patients with oHCM was performed. Baseline clinical and echocardiographic characteristics were compared using t-test for continuous variables and chi-square test for categorical variables. Primary (change in peak oxygen uptake, pVO2) and secondary end points from baseline to end of treatment (Week 24) were analyzed using linear regression models, adjusted for baseline values, exercise mode, and diagnosis group (chronic versus treatment-naïve).
Results
Among 175 participants in MAPLE-HCM, 73 (42%) were women. Women were older, more likely to have New York Heart Association (NYHA) Class III symptoms, had lower Kansas City Cardiomyopathy Questionnaire clinical summary scores (KCCQ-CSS), and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at enrollment (Table 1). Women had smaller left ventricle (LV) size, higher LV ejection fractions, and higher E/e’ ratios. Compared with those receiving metoprolol, both women and men in the aficamten group had significant improvements in pVO2 at 24 weeks (women: +2.2 [+1.2 to +3.3] mL/kg/min; men: +2.2 [+1.2 to +3.3] mL/kg/min, sex-by-treatment P-interaction=1.00). Both women and men receiving aficamten had improvements in KCCQ-CSS (+6.3 in women and +6.9 in men) and reductions in NT-proBNP levels (-84% in women and -78% in men), LV outflow tract (LVOT) gradients (-43 mmHg in women and -30 mmHg in men), left atrial volume indices (-6.1 mL/m² in women and -7.6 mL/m² in men), and lateral E/e’ ratios (sex-by-treatment p-interaction > 0.10 for all, Figure 1). Both women and men receiving aficamten demonstrated a modest and similar decline in LV ejection fraction (Figure 1).
Conclusions
Aficamten monotherapy was superior to metoprolol monotherapy in both women and men. Despite more severe baseline HCM disease characteristics in women, aficamten resulted in similar improvements by sex in exercise capacity and health status, reductions in LVOT obstruction, and improvements in measures of diastolic function.Table 1.Baseline CharacteristicsFor image description, please refer to the figure legend and surrounding text.Figure 1.Treatment EffectFor image description, please refer to the figure legend and surrounding text.