Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
Department of Cardiology, Gangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea.
Drug Des Devel Ther. 2020 Dec 31;14:5735-5746. doi: 10.2147/DDDT.S286586. eCollection 2020.
We evaluated the dose-responsiveness, efficacy, and safety of low-dose triple antihypertensive combination therapies in patients with mild-to-moderate hypertension.
After a 1 to 2-week placebo run-in period, 248 patients were randomized to the half-dose triple combination (amlodipine 2.5 mg + losartan 25 mg + chlorthalidone 6.25 mg), third-dose triple combination (amlodipine 1.67 mg + losartan 16.67 mg + chlorthalidone 4.17 mg), quarter-dose triple combination (amlodipine 1.25 mg + losartan 12.5 mg + chlorthalidone 3.13mg), amlodipine 10mg, amlodipine 5mg, losartan 100mg, and placebo groups for 8 weeks. The primary outcome was the mean change in systolic blood pressure (SBP) from baseline to week 8.
The placebo-corrected SBP reductions of the half-dose, third-dose, quarter-dose combination, amlodipine 10 mg, amlodipine 5 mg and losartan 100 mg treatments were -17.2, -19.5, -14.9, -18.5, -11.3 and -9.9 mmHg, respectively. The BP control and response rates were significantly higher in the half-dose, third-dose, and quarter-dose combination groups than in the placebo group (all p < 0.01). Despite no intergroup differences in study drug-related adverse events, ankle circumference increased significantly in the amlodipine group compared to those in the combination treatment groups. The quarter-dose combination, amlodipine 5 mg, and losartan 100 mg groups showed similar SBP reduction and BP response rates. The SBP reduction and BP response rate in the third-dose and half-dose combination groups were not significantly different from those in the amlodipine 10 mg group but superior to those in the losartan 100 mg group.
Low-dose triple combination therapies could be effective as antihypertensive therapies.
ClinicalTrials.gov identifier NCT03897868.
我们评估了低剂量三联抗高血压联合治疗轻度至中度高血压患者的剂量反应、疗效和安全性。
在为期 1 至 2 周的安慰剂导入期后，248 名患者被随机分配至半剂量三联组（氨氯地平 2.5mg+氯沙坦 25mg+氢氯噻嗪 6.25mg）、三剂量三联组（氨氯地平 1.67mg+氯沙坦 16.67mg+氢氯噻嗪 4.17mg）、四分之一剂量三联组（氨氯地平 1.25mg+氯沙坦 12.5mg+氢氯噻嗪 3.13mg）、氨氯地平 10mg、氨氯地平 5mg、氯沙坦 100mg 和安慰剂组，治疗 8 周。主要结局是从基线到第 8 周时收缩压（SBP）的平均变化。
半剂量、三剂量、四分之一剂量联合、氨氯地平 10mg、氨氯地平 5mg 和氯沙坦 100mg 治疗的安慰剂校正 SBP 降低分别为-17.2、-19.5、-14.9、-18.5、-11.3 和-9.9mmHg。半剂量、三剂量和四分之一剂量联合组的血压控制和反应率均显著高于安慰剂组（均 p<0.01）。尽管各组之间研究药物相关不良事件无差异，但与联合治疗组相比，氨氯地平组的踝围明显增加。四分之一剂量联合、氨氯地平 5mg 和氯沙坦 100mg 组的 SBP 降低和血压反应率相似。三剂量和半剂量联合组的 SBP 降低和血压反应率与氨氯地平 10mg 组无显著差异，但优于氯沙坦 100mg 组。
低剂量三联抗高血压联合治疗可能是有效的降压治疗方法。
ClinicalTrials.gov 标识符 NCT03897868。
