Zhao Xiexiong, Liu Tao, Yang Qiong, Yang Guoping, Li Xingli, Tang Xiaohong, Li Jingle, Liang Zhongshu, Li Anying, Zeng Lixiong, Wen Juan, Wang Xiaoyan, Peng Liping, Wang Wenjuan, Cai Jingjing, Chen Ye, Huang Miao, Li Ruixuan, Fu Ru, Zhao Lin, Li Xiaogang, Jiang Weihong
Department of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Hypertension Research Center of Hunan Province, Changsha, Hunan, China.
BMC Med. 2025 Jan 29;23(1):56. doi: 10.1186/s12916-025-03892-8.
Guidelines recognized dual combination in initial antihypertensive therapy. Studies found that low-dose quadruple combination were superior to monotherapy. However, whether low-dose quadruple therapy is better than dual combination is unknown.
A randomized blinded crossover trial was conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg), both in a single pill, in the initial treatment of patients with mild to moderate hypertension. Patients were randomly assigned in a 1:1 ratio to two crossover sequences. Each sequence received four-weeks of either half-dose quadruple antihypertensives or standard-dose dual antihypertensives, followed by a two-week washout and crossover for four-weeks. Participants and researchers were blinded. The main outcomes were the reduction of blood pressure and safety outcomes. Analyses were per intention to treat.
A total of 90 eligible participants were randomized between July 13, 2022, and April 20, 2023. The mean age was 43.88 years (SD 10.31), and 25.6% were women. The mean baseline 24-h blood pressure was 145.59/93.84 mm Hg. Compared to the standard-dose dual treatment, the half-dose quadruple treatment resulted in a further reduction in mean 24-h blood pressure by 4.72/4.17 mm Hg (P < 0.001 for both systolic and diastolic blood pressure), mean daytime blood pressure by 5.52/4.73 mm Hg (P < 0.001 for both), mean nighttime blood pressure by 2.37/2.25 mm Hg (P = 0.034 and 0.014, respectively), and mean office blood pressure by 2.91/1.73 mm Hg (P < 0.001 and 0.014, respectively). Apart from significant increases of fasting blood glucose (P = 0.029) and blood uric acid (P < 0.001) in the half-dose quadruple group, no other adverse events or changes in laboratory values differed significantly between the two treatments.
Initiating treatment with half-dose quadruple combination therapy was more effective in lowering blood pressure than standard-dose dual therapy. The safety of half-dose quadruple therapy was comparable.
ClinicalTrials.gov Identifier: NCT05377203.
指南认可初始抗高血压治疗采用联合用药。研究发现低剂量四联疗法优于单药治疗。然而，低剂量四联疗法是否优于双联疗法尚不清楚。
进行了一项随机双盲交叉试验，比较低剂量四联抗高血压药物（厄贝沙坦75毫克+美托洛尔23.75毫克+氨氯地平2.5毫克+吲达帕胺1.25毫克）与标准剂量双联抗高血压药物（厄贝沙坦150毫克+氨氯地平5毫克）单丸剂在轻度至中度高血压患者初始治疗中的疗效和安全性。患者按1:1比例随机分配到两个交叉序列。每个序列接受为期四周的半剂量四联抗高血压药物或标准剂量双联抗高血压药物治疗，随后为期两周的洗脱期并交叉治疗四周。参与者和研究人员均处于盲态。主要结局为血压降低情况和安全性结局。分析采用意向性治疗。
2022年7月13日至2023年4月20日期间，共有90名符合条件的参与者被随机分组。平均年龄为43.88岁（标准差10.31），女性占25.6%。平均基线24小时血压为145.59/93.84毫米汞柱。与标准剂量双联治疗相比，半剂量四联治疗使平均24小时血压进一步降低4.72/（收缩压和舒张压均P<0.001）、平均日间血压降低5.52/4.73毫米汞柱（两者均P<0.001）、平均夜间血压降低2.37/2.25毫米汞柱（分别为P=0.034和0.014）、平均诊室血压降低2.91/1.73毫米汞柱（分别为P<0.001和0.014）。除半剂量四联组空腹血糖（P=0.029）和血尿酸（P<0.001）显著升高外，两种治疗之间的其他不良事件或实验室值变化无显著差异。
起始采用半剂量四联联合疗法治疗在降低血压方面比标准剂量双联疗法更有效。半剂量四联疗法的安全性相当。
ClinicalTrials.gov标识符：NCT05377203
