Renin-Angiotensin-Aldosterone System Modulators in Adults with Hypertension: A Network Meta-Analysis of Randomized Controlled Trials.

IF 13 1区医学 Q1 PHARMACOLOGY & PHARMACY

Drugs Pub Date : 2024-09-23 DOI:10.1007/s40265-024-02092-7

Xiaoyan Yi, Shumin Yang, Jun Yang, Xiangjun Chen, Aipin Zhang, Qinglian Zeng, Wenjin Luo, Qifu Li, Jinbo Hu

{"title":"Renin-Angiotensin-Aldosterone System Modulators in Adults with Hypertension: A Network Meta-Analysis of Randomized Controlled Trials.","authors":"Xiaoyan Yi, Shumin Yang, Jun Yang, Xiangjun Chen, Aipin Zhang, Qinglian Zeng, Wenjin Luo, Qifu Li, Jinbo Hu","doi":"10.1007/s40265-024-02092-7","DOIUrl":null,"url":null,"abstract":"Background: Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population.Methods: A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework.Results: We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74-0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68-0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61-13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06-1.91), hypotension (OR 2.10; 95% CI 1.02-4.34), and hyperkalemia (OR 1.99; 95% CI 1.17-3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99-3.62) when compared to placebo.Conclusions: MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely.Registration: PROSPERO identifier number CRD42023405714.","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40265-024-02092-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population.

Methods: A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework.

Results: We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74-0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68-0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61-13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06-1.91), hypotension (OR 2.10; 95% CI 1.02-4.34), and hyperkalemia (OR 1.99; 95% CI 1.17-3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99-3.62) when compared to placebo.

Conclusions: MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely.

Registration: PROSPERO identifier number CRD42023405714.

查看原文本刊更多论文

成人高血压患者的肾素-血管紧张素-醛固酮系统调节剂：随机对照试验的网络 Meta 分析》。

背景：尽管有一系列肾素-血管紧张素-醛固酮系统（RAAS）调节剂可用于降低血压，但该类药物的最佳选择仍不明确。我们旨在比较 RAAS 调节剂在成人高血压人群中的疗效和安全性：在 PubMed、CENTRAL 和 Embase 中进行了系统性文献检索。主要疗效结果为全因死亡率，次要疗效结果为心血管死亡率。耐受性结果为因不良事件而停药。安全性结果包括咳嗽、头晕、水肿、高钾血症和低血压。我们在频数主义框架内利用随机效应模型进行了网络荟萃分析：我们最终从 49 项随机对照试验中确定了 51 篇文章。与安慰剂相比，矿皮质激素受体拮抗剂（MRA）可显著降低全因死亡风险（比值比（OR）0.83；95% 置信区间（CI）0.74-0.92）和心血管死亡风险（比值比（OR）0.79；95% 置信区间（CI）0.68-0.93），而其他 RAAS 调节剂均不能显著降低全因或心血管死亡风险。单项比较显示，MRA 的全因死亡风险明显低于其他 RAAS 调节剂（与血管紧张素相比，降低 16%）：与血管紧张素转换酶抑制剂（ACEIs）相比降低 16%，与血管紧张素受体阻滞剂（ARBs）相比降低 14%，与直接肾素抑制剂（DRIs）相比降低 22%）。在 RAAS 调节剂与安慰剂的比较中，没有发现因不良事件而停药的差异。关于安全性结果，ACEIs 的咳嗽风险较高（OR 4.68；95% CI 1.61-13.60），ARBs 的头晕风险较高（OR 1.42；95% CI 1.06-1.91），低血压风险较高（OR 2.10；95% CI 1.02-4.34）和高钾血症（OR 1.99；95% CI 1.17-3.41），与安慰剂相比，MRAs发生高钾血症的风险更高（OR 2.68；95% CI 1.99-3.62）.结论：结论：MRAs是唯一对成人高血压患者的生存有益处的RAAS调节剂，但其发生高钾血症的风险较高。我们的数据对目前的高血压指南提出了挑战，该指南建议将MRAs作为四线疗法，并建议应更早和更广泛地处方MRAs：注册：PROSPERO 识别号 CRD42023405714。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Drugs 医学-毒理学

CiteScore

22.70

自引率

0.90%

发文量

134

审稿时长

3-8 weeks

期刊介绍： Drugs is a journal that aims to enhance pharmacotherapy by publishing review and original research articles on key aspects of clinical pharmacology and therapeutics. The journal includes: Leading/current opinion articles providing an overview of contentious or emerging issues. Definitive reviews of drugs and drug classes, and their place in disease management. Therapy in Practice articles including recommendations for specific clinical situations. High-quality, well designed, original clinical research. Adis Drug Evaluations reviewing the properties and place in therapy of both newer and established drugs. AdisInsight Reports summarising development at first global approval. Moreover, the journal offers additional digital features such as animated abstracts, video abstracts, instructional videos, and podcasts to increase visibility and educational value. Plain language summaries accompany articles to assist readers with some knowledge of the field in understanding important medical advances.