Adverse Effects and Treatment Discontinuation of Blood Pressure-Lowering Drugs and Combinations: A Network Meta-Analysis.

Background

To review adverse effects and discontinuation of BP-lowering drugs and their combinations from the 5 major classes in short-term clinical trials.

回顾短期临床试验中来自五大类的血压降低药物及其组合的不良反应和停药情况。

data_sources_and_study_selection

Cochrane Central Register of Controlled Trials for randomized clinical trials, MEDLINE, and Epistemonikos were searched from the date of inception until December 31, 2024, for double-blindrandomized clinical trials of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers (ARBs), β-blockers, calcium channel blockers (CCBs), thiazide and thiazide-like diuretics, or their combinations, with follow-up durations between 4 and 26 weeks.

检索了Cochrane中央对照试验登记处、MEDLINE和Epistemonikos，从创建日期起至2024年12月31日，寻找双盲随机临床试验，研究对象为血管紧张素转换酶抑制剂、血管紧张素II受体拮抗剂（ARBs）、β受体阻滞剂、钙通道阻滞剂（CCBs）、噻嗪类和类似噻嗪的利尿剂或它们的组合，随访时间在4至26周之间。

data_extraction_and_synthesis

Data extraction was performed by 2 independent reviewers.

数据提取由2名独立的评审员执行。

Synthesis was performed using fixed-effect network meta-analyses according to drug class, summarized using odds ratios (ORs) and 95% credible intervals (CrIs) and surface under the cumulative ranking curves.

合成是根据药物类别使用固定效应网络荟萃分析进行的，结果使用比值比(ORs)和95%可信区间(CrIs)以及累积排名曲线下面积进行总结。

Final statistical analysis was conducted in April 2026.

最终统计分析于2026年4月进行。

main_outcomes_and_measures

Treatment discontinuation due to adverse events (AEs), defined as discontinuation of randomized treatment due to an AE.

因不良事件（AEs）导致的治疗中断，定义为因AE而中断随机治疗。

Secondary outcomes included headache, dizziness, edema, and cough.

次要结果包括头痛、眩晕、水肿和咳嗽。

Results

A total of 716 trials were included, with mean (SD) follow-up of 8.6 (5) weeks, including 159 362 participants (mean [SD] age, 54.6 [7] years; 44% female; mean baseline BP, 158/100 mm Hg).

共有716项试验被纳入，平均（标准差）随访时间为8.6（5）周，包括159 362名参与者（平均[标准差]年龄为54.6[7]岁；44%为女性；平均基线血压为158/100毫米汞柱）。

Compared with placebo, treatment discontinuation due to AEs was significantly increased by CCBs (OR, 1.43 [95% CrI, 1.23-1.67]; risk difference [RD], 1.2% [95% CrI, 0.6%-2.0%]), angiotensin-converting enzyme inhibitors plus CCBs (OR, 1.46 [95% CrI, 1.13-1.87]; RD, 1.1% [95% CrI, 0.2%-2.4%]), and β-blockers plus thiazide diuretics (OR, 1.58 [95% CrI, 1.04-2.47]; RD, 1.7% [95% CrI, 0.1%-4.3%]).

与安慰剂相比，由于不良事件导致的治疗中断显著增加，钙通道阻滞剂（OR，1.43 [95% CrI，1.23-1.67]；风险差异[RD]，1.2% [95% CrI，0.6%-2.0%]），血管紧张素转换酶抑制剂加钙通道阻滞剂（OR，1.46 [95% CrI，1.13-1.87]；RD，1.1% [95% CrI，0.2%-2.4%]），以及β阻滞剂加噻嗪类利尿剂（OR，1.58 [95% CrI，1.04-2.47]；RD，1.7% [95% CrI，0.1%-4.3%]）。

All ARB-containing regimens had fewer treatment discontinuations due to AEs than placebo, and these differences were statistically significant for ARB monotherapy (OR, 0.73 [95% CrI, 0.61-0.86]; RD, -0.8% [95% CrI, -1.3% to -0.4%]) and ARBs plus CCBs (OR, 0.61 [95% CrI, 0.47-0.79]; RD, -1.2% [95% CrI, -1.8% to -0.6%]).

所有含有ARB的治疗方案因不良事件导致的治疗中断次数均少于安慰剂，且ARB单药治疗（比值比，0.73 [95% CrI，0.61-0.86]；风险差，-0.8% [95% CrI，-1.3%至-0.4%]）和ARB联合CCB治疗（比值比，0.61 [95% CrI，0.47-0.79]；风险差，-1.2% [95% CrI，-1.8%至-0.6%]）的这些差异在统计学上具有显著性。

In network meta-analyses, 5 combination and 2 monotherapy regimens had higher surface under the cumulative ranking curve values than placebo for treatment discontinuation due to AEs, suggesting overall symptomatic improvement compared with placebo.

在网状Meta分析中，有5种联合治疗方案和2种单药治疗方案的累积排名曲线下面积值高于安慰剂，这表明与安慰剂相比，总体症状有所改善。

All regimens significantly increased dizziness, and all but CCBs significantly decreased headache compared with placebo.

所有治疗方案显著增加了头晕的发生率，除钙通道阻滞剂（CCBs）外，所有方案与安慰剂相比显著减少了头痛的发生。

conclusions_and_relevance

This meta-analysisof short-term randomized clinical trials found that adverse drug effects that led to discontinuation of BP-lowering therapy varied by drug class and regimen, with several combination therapies being better tolerated than monotherapies.

这项短期随机临床试验的荟萃分析发现，导致降压治疗中断的不良药物反应因药物类别和方案而异，几种联合治疗方案比单一治疗方案更容易被耐受。

Some regimens were associated with fewer drug withdrawals than placebo, suggesting a net symptomatic improvement.

一些治疗方案与安慰剂相比，药物撤回的次数较少，这表明在症状上总体有所改善。

These findings are based on trial-level results and rely on assumptions underlying the network meta-analysis; they may not apply to individual patients.

这些发现基于试验级别的结果，并依赖于网络荟萃分析的假设；它们可能不适用于个别患者。