近日，印度乔治全球健康研究所Anthony Rodgers团队研究了抗高血压药物及其组合的降压疗效。相关论文发表在2025年8月30日出版的《柳叶刀》杂志上。

该研究旨在量化五大类降压药及其联合用药的降压效果。

研究组对随机、双盲、安慰剂对照试验进行了系统回顾和荟萃分析，成年受试者被随机分配接受血管紧张素转换酶抑制剂、血管紧张素II受体阻滞剂、β受体阻滞剂、钙通道阻滞剂或利尿剂。入选标准包括随访时间在4周至26周之间，在随访血压评估前，所有参与者至少有4周固定的抗高血压药物治疗；并利用临床血压计算各组间收缩压的平均差异。交叉期之间洗脱期少于2周的交叉试验被排除在外。从Cochrane中央对照试验注册库、MEDLINE和Epistemonikos中检索数据库建立至2022年12月31日期间发表的符合条件的研究；搜索结果更新为包括2023年1月1日至2025年2月28日之间发表的研究。

主要终点是经安慰剂校正的收缩压降低。使用固定效应荟萃分析对纳入试验的平均基线血压进行标准化，以估计降压效果。药物方案分为低、中、高强度，分别对应于从基线154毫米汞柱降压10毫米汞柱、10 - 19毫米汞柱和≥20毫米汞柱的降压效果。研究组建立了一个模型来计算任何联合抗高血压药物的疗效，并在双联和三联抗高血压药物的外部试验中进行了验证。该研究方案已在国际系统评价和荟萃分析方案注册平台（INPLASY202410036）上注册。

研究组分析了484项试验，其中104176名参与者(平均年龄54岁[SD 8]， 57422名[55%]男性，46754[45%]名女性，平均基线收缩压154/100 mm Hg)。平均随访时间8.6周（SD 5.2）。平均而言，标准剂量单药治疗可使收缩压降低8.7 mm Hg (95% CI 8.2 - 9.2)，剂量每增加一倍可使收缩压再降低1.5 mm Hg（1.2 - 7）。一个标准剂量的双重联合可使收缩压降低14.9 mm Hg (95% CI 13.1 - 16.8)，两种药物剂量每增加一倍可使收缩压额外降低2.5 mm Hg（1.4 - 3.7）。基线收缩压每降低10毫米汞柱，单药降压效果降低1.3毫米汞柱（1.0 - 1.5），尽管不同药物类别之间存在差异。在57个标准剂量单药治疗中，45个（79%）被归为低强度。在189种不同剂量的双重联合用药中，110例（58%）为中等强度，21例（11%）为高强度。药物类别之间和药物类别内的剂量反应和基线血压反应关系存在相当大的差异。经外部试验验证，疗效模型显示预测和观察到的收缩压高度相关（r= 0.76, p< 0.0001）。

研究结果表明，这些分析为任何联合降压药物的预期降压效果提供了可靠的估计，使其疗效分为低、中、高强度。

附：英文原文

Title: Blood pressure-lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of randomised, double-blind, placebo-controlled trials

Author: Nelson Wang, Abdul Salam, Rashmi Pant, Amit Kumar, Rupasvi Dhurjati, Faraidoon Haghdoost, Kota Vidyasagar, Prachi Kaistha, Hariprasad Esam, Sonali R Gnanenthiran, Raju Kanukula, Paul K Whelton, Brent Egan, Aletta E Schutte, Kazem Rahimi, Otavio Berwanger, Anthony Rodgers

Issue&Volume: 2025/08/30

Abstract:

Background

We aimed to quantify the blood pressure-lowering efficacy of antihypertensive drugs and their combinations from the five major drug classes.

Methods

We conducted a systematic review and meta-analysis of randomised, double-blind, placebo-controlled trials involving adult participants randomly assigned to receive angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β blockers, calcium channel blockers, or diuretics. Eligibility criteria included follow-up duration between 4 weeks and 26 weeks, antihypertensive drug treatment fixed in all participants for at least 4 weeks before follow-up blood pressure assessment; and availability of clinic blood pressure for the calculation of mean difference in systolic blood pressure between treatment groups. Crossover trials with less than 2 weeks’ washout between the crossover periods were excluded. Eligible studies published between database inception and Dec 31, 2022 were identified from searches of the Cochrane Central Register of Controlled Trials, MEDLINE, and Epistemonikos; searches were updated to include studies published between Jan 1, 2023, and Feb 28, 2025. The primary outcome was placebo-corrected reduction in systolic blood pressure. Blood pressure-lowering efficacy was estimated using fixed-effects meta-analyses standardised to mean baseline blood pressure across included trials. Drug regimens were categorised into low, moderate, and high intensity, corresponding to systolic blood pressure-lowering efficacy of <10 mm Hg, 10–19 mm Hg, and ≥20 mm Hg, respectively, from a baseline of 154 mm Hg. A model was developed to calculate efficacy for any combination of antihypertensives and validated on external trials of dual and triple combination antihypertensives. The study protocol was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202410036).

Findings

We analysed 484 trials including 104176 participants (mean age 54 years [SD 8], 57422 [55%] men, 46754 [45%] women, and mean baseline systolic blood pressure 154/100 mm Hg). Mean follow-up duration was 8·6 weeks (SD 5·2). On average, monotherapy at standard dose reduced systolic blood pressure by 8·7 mm Hg (95% CI 8·2–9·2), and each doubling in dose conferred an additional 1·5 mm Hg (1·2–1·7) reduction. Dual combinations at one standard dose conferred a 14·9 mm Hg (95% CI 13·1–16·8) reduction in systolic blood pressure, with each doubling of doses of both drugs conferring an additional reduction of 2·5 mm Hg (1·4–3·7). Each 10 mm Hg decrease in baseline systolic blood pressure reduced pressure-lowering efficacy by 1·3 mm Hg (1·0–1·5) for monotherapies, although differences between drug classes were observed. Among 57 monotherapies at standard dose, 45 (79%) were classified as low intensity. Of 189 different drug–dose dual combinations, 110 (58%) were classified as moderate intensity, and 21 (11%) as high intensity. There were considerable differences in dose–response and baseline blood pressure–response relationships between and within drug classes. The efficacy model showed a high correlation between predicted and observed systolic blood pressures when validated on external trials (r=0·76, p<0·0001).

Interpretation

These analyses provide robust estimates of the expected blood pressure-lowering effect for any combination of antihypertensive drugs, allowing their efficacy to be classified into low, moderate, and high intensity.

DOI: 10.1016/S0140-6736(25)00991-2

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00991-2/abstract