Graduate Program in Cardiology and Cardiovascular Sciences.
Graduate Program in Epidemiology, School of Medicine, Universidade Federal do Rio Grande do Sul.
J Hypertens. 2023 Jul 1;41(7):1108-1116. doi: 10.1097/HJH.0000000000003436. Epub 2023 Apr 3.
The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension.
A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer.
Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents.
Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.
保钾利尿剂对噻嗪类利尿剂降压效果和不良反应的影响程度仍不确定。本研究旨在比较高（T+）和低剂量（T-）噻嗪类利尿剂单独或联合高（PS+）或低剂量（PS-）保钾利尿剂在原发性高血压患者中的降压疗效和不良反应发生率。
在 PubMed/MEDLINE、Cochrane 对照试验中心注册库、Embase、Web of Science、Scopus 和 LILACS 中进行了系统文献检索。纳入随访 3 周至 1 年的随机双盲安慰剂或阳性对照试验（RCT）。两名独立评审员提取样本量、基线、随访和从基线值变化的均值和标准差。采用配对随机效应模型和贝叶斯网络荟萃分析模型比较治疗效果。使用 Rob 1.0 工具评估个体研究的偏倚风险。主要结局为诊室 SBP 的均数差值。次要结局为生化参数的均数差值和非黑色素瘤皮肤癌的发生率。
纳入 276 项双盲 RCT，共涉及 58807 名参与者（平均年龄：55 岁；45%为女性）。与安慰剂相比，所有治疗组均能更有效地降低血压，从基线变化的平均差值（MD）范围为 T-的-7.66mmHg[95%可信区间（95%CrI）：-8.53 至-6.79]至 T+PS-的-12.77mmHg[95%CrI：-15.22 至-10.31]。T+单独或与保钾剂联合使用比 T-更能有效降低血压。累积排序曲线下面积（SUCRA）估计的排名显示，T+PS-（0.69）、T+PS+（0.65）和 T+（0.54）在降低 SBP 方面效果最好。与安慰剂相比，所有治疗组（T-PS-除外）均导致血钾降低，与所有其他治疗组相比，T+的血钾降低更为明显，与 T-PS-相比，T+的血钾降低更为明显。与安慰剂相比，所有活性治疗组（T+PS+除外）的尿酸升高均升高。保钾剂可减少噻嗪类药物单独引起的血糖升高。
与噻嗪类利尿剂单独使用相比，噻嗪类利尿剂联合保钾利尿剂可增加降压效果，同时将低钾血症和高血糖的风险降至最低。这些发现表明，噻嗪类利尿剂和保钾利尿剂联合治疗高血压优于噻嗪类利尿剂单独治疗。
