Comparison of efficacy and safety between third-dose triple and third-dose dual antihypertensive combination therapies in patients with hypertension

Abstract

Abstract Purpose We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. Methods This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up after 8 weeks. Results The mean systolic blood pressure (BP) reduction was − 18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and − 13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (p = 0.010 and p = 0.018, respectively) and 8 (p = 0.017 and p = 0.036, respectively). The proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (p = 0.013, p = 0.021 and p = 0.045, respectively) at week 4. The proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (p = 0.022 and p = 0.049, respectively) at week 8. Conclusion Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension. Trial Registration NCT04959305