Comparison of Two Single-Pill Dual Combination Antihypertensive Therapies in Chinese Patients

Objective: Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP) lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. Design and method: In a multi-center, randomized, actively-controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. Results: In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was -13.8±1.2 mmHg in the amlodipine/benazepril group and -12.3±1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of -1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were -1.47 (p = 0.18) in 24-h diastolic BP, -2.86 (p = 0.13) and -2.74 (p = 0.03) in daytime systolic and diastolic BP and 0.45 (p = 0.82) and -0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril than benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). Conclusions: The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP lowering effect in the daytime and a lower incidence rate of dry cough.