Effect of Aficamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy in SEQUOIA-HCM

BACKGROUND: Women with obstructive hypertrophic cardiomyopathy often present with a greater burden of disease and worse prognosis. Whether there are sex-related differences in response to aficamten is unknown. METHODS: We performed a prespecified subgroup analysis of sex differences in the double-blind, randomized-controlled SEQUOIA-HCM trial (Safety, Efficacy and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) of aficamten versus placebo in patients with obstructive hypertrophic cardiomyopathy. Baseline characteristics were compared using the t test for continuous variables and the χ 2 test for categorical variables. Prespecified primary (change in peak oxygen uptake) and secondary end points from baseline to end of treatment (week 24) were analyzed using linear regression models, adjusted for baseline values, β-blocker use, and exercise mode. RESULTS: Of the 282 participants, women (n=115) were older (64 years in women versus 56 years in men) and had lower Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, and lower peak oxygen uptake at baseline. Women had smaller left ventricular chamber sizes, higher E/e’ ratios, and higher left ventricular outflow tract gradients. At 24 weeks, there was a significant treatment-related increase in peak oxygen uptake in women (+1.5 [+0.7 to +2.4]) and men (+2.0 [+0.9 to +3.0]). Both women and men had significant treatment-related decreases in left ventricular outflow tract gradients at rest and with Valsalva, with no sex-by-treatment interaction at week 24 ( P interaction ≥0.13). There was a significant improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score in women (11 [6–15]) and men (6 [2–9]; P interaction =0.08). Women had a greater reduction in lateral E/e’ ratio ( P interaction =0.01). The geometric mean proportional reduction in NT-proBNP was similar in women and men ( P interaction =0.10). CONCLUSIONS: Women enrolled in SEQUOIA-HCM were older with worse baseline health status, higher NT-proBNP, and higher left ventricular outflow tract gradients compared with men. Despite these differences, both men and women derived significant benefits in the primary and secondary end points following treatment with aficamten.