Sex differences in response to triple single-pill combinations for hypertension: a secondary analysis of the OPTION TREAT Trial

Background Further research is needed to better understand sex differences in antihypertensive response to triple single-pill combinations, particularly given the increasing use of these regimens in contemporary clinical practice Purpose To assess whether sex modifies treatment effects on systolic blood pressure reduction at 12 weeks. Methods The OPTION TREAT trial was a randomised, double-blind, multicenter study conducted in Brazil, comparing a novel triple single-pill combination (candesartan cilexetil 16 mg, amlodipine 5 mg, and chlorthalidone 12.5 mg) with an active control (valsartan 160 mg, hydrochlorothiazide 12.5 mg, and amlodipine 5 mg) for patients with uncontrolled hypertension. This secondary analysis evaluated changes in systolic blood pressure (SBP) from baseline to week 12 according to sex, using mixed-effects models with random center effects, fixed effects for treatment and sex, a sex-by-treatment interaction term, and baseline SBP as a covariate. Results Of the 703 participants included, 441 (62.7%) were women. Baseline SBP was similar between sexes (152.2 ± 10.7 mmHg in women and 153.7 ± 10.5 mmHg in men). At week 12, mean changes in SBP in the experimental arm were −25.8 ± 15.9 mmHg in women and −21.3 ± 15.0 mmHg in men. In the active control arm, SBP changes were −21.9 ± 15.0 mmHg and −16.4 ± 15.7 mmHg in women and men, respectively. Pooling data according to sex, changes in SBP were −23.9 ± 15.6 mmHg in women and −18.7 ± 15.5 mmHg in men. Across both treatment arms, women appeared to be associated with greater SBP reduction than men (−5.47 mmHg; 95% CI −7.7 to −3.2). The experimental treatment seemed to result in greater SBP reduction compared with the active control in both women (least-squares mean difference −4.4 mmHg; 95% CI −7.1 to −1.6) and men (−4.8 mmHg; CI −8.3 to −1.2), with no meaningful sex-by-treatment interaction. Conclusion Women appear to achieve greater response to antihypertensive single-pill combination therapy than men. No difference was observed regarding the treatment effect of the novel triple single-pill combination compared to the active control according to sex. These findings suggests that sex may influence blood pressure control and may be considered when tailoring treatment approaches.