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减肥药物对高血压患者的长期影响。

Long-term effects of weight-reducing drugs in people with hypertension.

机构信息

Institute of General Practice and Evidence-Based Health Services Research, Medical University of Graz, Graz, Austria.

Institute for General Practice, Goethe University, Frankfurt am Main, Germany.

出版信息

Cochrane Database Syst Rev. 2021 Jan 17;1(1):CD007654. doi: 10.1002/14651858.CD007654.pub5.


DOI:10.1002/14651858.CD007654.pub5
PMID:33454957
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8094237/
Abstract

BACKGROUND: This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect. OBJECTIVES: Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction. SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work. SELECTION CRITERIA: Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo.  DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity. MAIN RESULTS: This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension. AUTHORS' CONCLUSIONS: In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.

摘要

背景:这是对 2009 年 7 月首次发表的综述的第三次更新。所有主要的高血压治疗指南都建议减肥;抗肥胖药物可能在这方面有所帮助。

目的:主要目的:评估在成人原发性高血压患者中,药物诱导的体重减轻对全因死亡率、心血管发病率和不良事件(包括所有严重不良事件、因不良事件而停药以及所有非严重不良事件)的长期影响。次要目的:评估在成人原发性高血压患者中,药物诱导的体重减轻对收缩压和舒张压从基线变化以及体重减轻的长期影响。

检索方法:为本次更新综述,Cochrane 高血压信息专家检索了截至 2020 年 3 月的随机对照试验数据库,包括 Cochrane 高血压专业登记库、CENTRAL、MEDLINE(从 1946 年开始)、Embase(从 1974 年开始)、世界卫生组织国际临床试验注册平台和 ClinicalTrials.gov。检索无语言限制。我们联系了相关论文的作者,以获取进一步发表和未发表的研究成果。

选择标准:比较批准的长期减肥药物与安慰剂的持续至少 24 周的成人高血压随机对照试验。

数据收集和分析:两位综述作者独立选择研究、评估偏倚风险并提取数据。在研究之间没有显著异质性(P > 0.1)的情况下,我们使用固定效应荟萃分析对研究进行合并。当存在异质性时,我们使用随机效应方法并调查异质性的原因。

主要结果:本次综述的第三次更新增加了一项新的试验,调查纳曲酮/安非他酮与安慰剂的比较。以前版本的综述中包含的两种药物(利莫那班和西布曲明)不再被认为与本次更新相关,因为它们的市场批准分别于 2010 年和 2009 年被撤回。因此,本次综述更新的纳入研究数量为六项(共 12724 名参与者患有高血压,平均年龄为 46 至 55 岁):四项 RCT 比较奥利司他与安慰剂,涉及 3132 名高血压高血患者,平均年龄为 46 至 55 岁;一项试验比较芬特明/托吡酯与安慰剂,涉及 1305 名高血压患者,平均年龄为 53 岁;一项试验比较纳曲酮/安非他酮与安慰剂,涉及 8283 名高血压患者,平均年龄为 62 岁。我们认为,评估奥利司他或纳曲酮/安非他酮的试验的偏倚风险不明确,评估芬特明/托吡酯的试验的偏倚风险较低。只有纳曲酮/安非他酮的研究将心血管死亡率和发病率作为预设结局。纳曲酮/安非他酮与安慰剂组之间全因死亡率、心血管死亡率或发病率、主要心血管事件或严重不良事件无差异。纳曲酮/安非他酮组的总体不良事件发生率明显较高。与安慰剂相比,奥利司他组胃肠道副作用的发生率始终较高。芬特明/托吡酯组最常见的副作用是口干和感觉异常。在 6 至 12 个月后,奥利司他与安慰剂相比,收缩压降低了 -2.6mmHg(95%置信区间(CI)-3.8 至-1.4mmHg;4 项试验,2058 名参与者),舒张压降低了-2.0mmHg(95%CI-2.7 至-1.2mmHg;4 项试验,2058 名参与者)。在 13 个月的随访后,与安慰剂相比,芬特明/托吡酯降低了收缩压 -2.0 至-4.2mmHg(1 项试验,1030 名参与者)(取决于药物剂量),舒张压 -1.3 至-1.9mmHg(1 项试验,1030 名参与者)(取决于药物剂量)。纳曲酮/安非他酮与安慰剂组之间的收缩压或舒张压变化无差异(1 项试验,8283 名参与者)。我们未发现研究奥利司他或 lorcaserin 在高血压患者中的相关研究。

作者结论:在高血压患者中,奥利司他、芬特明/托吡酯和纳曲酮/安非他酮可减轻体重;效果最大的是芬特明/托吡酯。在相同的试验中,奥利司他和芬特明/托吡酯,但不是纳曲酮/安非他酮,降低了血压。一项纳曲酮/安非他酮与安慰剂的 RCT 显示,两年后全因死亡率或心血管死亡率或发病率无差异。由于安全性问题,欧洲药品管理局拒绝批准芬特明/托吡酯上市,而 lorcaserin 由于总体获益/风险平衡不佳,其在欧洲的上市申请被撤回。2020 年,lorcaserin 也从美国市场撤出。另外两种药物(利莫那班和西布曲明)分别于 2009 年和 2010 年被撤回市场。

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