S-21-5: comparison of third-dose triple versus third-dose dual antihypertensive combination therapies in patients with essential hypertension during 8-week follow-up

Objective: We compared efficacy and safety of low-dose triple versus low-dose dual antihypertensive combination therapies in patients with essential hypertension. Design and method: This trial was a multicenter, randomized, double-blind, parallel, phase II study. After a 4-week placebo run-in period, 243 patients were randomized to the third -dose triple combination (ALC group, amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg), 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), or (AC group, amlodipine 1.67 mg + chlorthalidone 4.17 mg) for 8 weeks. The primary outcome was to compare the mean changes in systolic blood pressure (SBP) from baseline to week 8. Results: Baseline patient characteristics and blood pressure did not show significant differences among 4 groups. The mean SBP reductions of ALC group, AL group, LC group and AC group were -18.30 ± 13.23, -13.03 ± 13.30, -16.29 ± 12.36, and -13.80 ± 13.21 mmHg at week 8 from baseline, respectively. The ALC group showed significant SBP reductions in comparison to the AL and AC groups at week 4 (p = 0.0097 and p = 0.0179, respectively) and week 8 (p = 0.0170 and p = 0.0357, respectively). The mean diastolic blood pressure (DBP) reduction from baseline was significantly greater in the ALC group when compared to the AL group (-7.93 ± 7.05 and -4.95 ± 7.96 mmHg, respectively, p = 0.0307). The proportion of responders for SBP was significantly greater in the ALC group (42.6%) compared to the AL (22.0%), LC (23.3%) and AC (27.1%) groups (p = 0.0126, 0.0210 and 0.0445, respectively) at week 4. Furthermore, the proportion of responders for SBP and DBP was significantly greater in the ALC group (59.7%) compared to the AL (39.3%) and AC (42.4%) groups (p = 0.0222 and 0.0491, respectively) at Week 8. Study drug-related adverse reactions were rare and did not show significant differences among 4 study groups. Conclusions: Low-dose triple antihypertensive combination therapy when compared to the low-dose dual combination therapies demonstrated early effective BP control without increasing adverse drug reactions in patients with essential hypertension during 8-week follow-up.