Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial

• Published in: BMC medicine 2024-01, Vol.22 (1), p.28-12, Article 28
• Main Authors: Huang, Qi-Fang, Zhang, Di, Luo, Yihong, Hu, Kun, Wu, Qiong, Qiu, Hailong, Xu, Fei, Wang, Mei-Ling, Chen, Xin, Li, Yan, Wang, Ji-Guang
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Amlodipine; Amlodipine/benazepril; Angiotensin; Angiotensin-converting enzyme inhibitors; Antihypertensive; Antihypertensive Agents; Antihypertensive drugs; Antihypertensives; Benazepril/hydrochlorothiazide; Blood pressure; Calcium channel blockers; Calcium channels; Cardiovascular disease; China; Clinical trials; Cough; Creatinine; Daytime; Diuretics; Dosage and administration; Drug therapy; Edema; Effectiveness; Enzyme inhibitors; Humans; Hydrochlorothiazide; Hypertension; Hypokalemia; Hypotension; Kidney diseases; Patient outcomes; Patients; Peptidyl-dipeptidase A; Pharmacists; Physical examinations; Safety; Single-pill combination; Triglycerides
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-023-03244-4

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. 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 community 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. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. 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 group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). 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. ClinicalTrials.gov, NCT03682692. Registered on 18