英国牛津大学James P Sheppard团队分析了心血管疾病一级预防中他汀类药物与不良事件的相关性。2021年7月15日出版的《英国医学杂志》发表了这项成果。
为了评估心血管疾病一级预防中他汀类药物与不良事件之间的相关性，并研究他汀类药物的类型和剂量如何改变这种关系，研究组在Medline、Embase和Cochrane等大型数据库中检索截至2020年8月的文献，筛选出比较无心血管疾病史成人使用他汀类药物与非他汀类药物对照，或比较不同类型或剂量的他汀类药物的随机对照试验，并进行系统回顾和荟萃分析。
主要结局为常见的不良事件：自我报告的肌肉症状、临床证实的肌肉疾病、肝功能障碍、肾功能不全、糖尿病和眼部疾病。次要结局包括心肌梗死、中风和心血管疾病死亡等疗效衡量指标。
对数据进行配对荟萃分析，以计算他汀类药物和非他汀类药物对照物之间各结局的优势比。采用网络荟萃分析比较不同类型他汀类药物的不良反应。采用基于Emax模型的荟萃分析来检验各他汀类药物不良反应的剂量-反应关系。
研究组共纳入62个临床试验，涉及120456名参与者，平均随访3.9年。他汀类药物与自我报告肌肉症状（21项试验，优势比为1.06）、肝功能障碍（21项试验，1.33）、肾功能不全（8项试验，1.14）和眼部疾病（6项试验，1.23）有关，但与临床确诊的肌肉疾病或糖尿病无关。
风险的增加并不超过重大心血管事件风险的减少。阿托伐他汀、洛伐他汀和瑞舒伐他汀分别与一些不良事件相关，但他汀类药物的类型之间没有显著差异。阿托伐他汀对肝功能障碍的影响存在Emax剂量-反应关系，但其他他汀的剂量-反应关系和不良反应尚不确定。
研究结果表明，对于心血管疾病的一级预防，他汀类药物引起的不良事件风险较低，并未超过其预防心血管疾病的疗效，这表明他汀类药物的利弊权衡总体上是有利的。
附：英文原文
Title: Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses
Author: Ting Cai, Lucy Abel, Oliver Langford, Genevieve Monaghan, Jeffrey K Aronson, Richard J Stevens, Sarah Lay-Flurrie, Constantinos Koshiaris, Richard J McManus, F D Richard Hobbs, James P Sheppard
Issue&Volume: 2021/07/15
Abstract:
Objective To assess the associations between statins and adverse events in primary prevention of cardiovascular disease and to examine how the associations vary by type and dosage of statins.
Design Systematic review and meta-analysis.
Data sources Studies were identified from previous systematic reviews and searched in Medline, Embase, and the Cochrane Central Register of Controlled Trials, up to August 2020.
Review methods Randomised controlled trials in adults without a history of cardiovascular disease that compared statins with non-statin controls or compared different types or dosages of statins were included.
Main outcome measures Primary outcomes were common adverse events: self-reported muscle symptoms, clinically confirmed muscle disorders, liver dysfunction, renal insufficiency, diabetes, and eye conditions. Secondary outcomes included myocardial infarction, stroke, and death from cardiovascular disease as measures of efficacy.
Data synthesis A pairwise meta-analysis was conducted to calculate odds ratios and 95% confidence intervals for each outcome between statins and non-statin controls, and the absolute risk difference in the number of events per 10000 patients treated for a year was estimated. A network meta-analysis was performed to compare the adverse effects of different types of statins. An Emax model based meta-analysis was used to examine the dose-response relationships of the adverse effects of each statin.
Results 62 trials were included, with 120456 participants followed up for an average of 3.9 years. Statins were associated with an increased risk of self-reported muscle symptoms (21 trials, odds ratio 1.06 (95% confidence interval 1.01 to 1.13); absolute risk difference 15 (95% confidence interval 1 to 29)), liver dysfunction (21 trials, odds ratio 1.33 (1.12 to 1.58); absolute risk difference 8 (3 to 14)), renal insufficiency (eight trials, odds ratio 1.14 (1.01 to 1.28); absolute risk difference 12 (1 to 24)), and eye conditions (six trials, odds ratio 1.23 (1.04 to 1.47); absolute risk difference 14 (2 to 29)) but were not associated with clinically confirmed muscle disorders or diabetes. The increased risks did not outweigh the reduction in the risk of major cardiovascular events. Atorvastatin, lovastatin, and rosuvastatin were individually associated with some adverse events, but few significant differences were found between types of statins. An Emax dose-response relationship was identified for the effect of atorvastatin on liver dysfunction, but the dose-response relationships for the other statins and adverse effects were inconclusive.
Conclusions For primary prevention of cardiovascular disease, the risk of adverse events attributable to statins was low and did not outweigh their efficacy in preventing cardiovascular disease, suggesting that the benefit-to-harm balance of statins is generally favourable. Evidence to support tailoring the type or dosage of statins to account for safety concerns before starting treatment was limited.
DOI: 10.1136/bmj.n1537
Source: https://www.bmj.com/content/374/bmj.n1537
BMJ-British Medical Journal:《英国医学杂志》，创刊于1840年。隶属于BMJ出版集团，最新IF：93.333
官方网址：http://www.bmj.com/
投稿链接：https://mc.manuscriptcentral.com/bmj
本期文章：《英国医学杂志》：Online/在线发表
