他汀类药物与贝特类药物单药治疗的疗效和安全性比较：一项头对头随机对照试验的系统评价和荟萃分析。

Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials.

机构信息

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Pfizer Upjohn Hong Kong Limited, Hong Kong SAR, China.

出版信息

PLoS One. 2021 Feb 9;16(2):e0246480. doi: 10.1371/journal.pone.0246480. eCollection 2021.

DOI:10.1371/journal.pone.0246480

PMID:33561179

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7872286/

Abstract

OBJECTIVE

To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates.

METHODS

Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic.

RESULTS

We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty).

CONCLUSIONS

The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.

摘要

目的

评估在患有血脂异常的成年人中，与纤维酸类药物相比，他汀类药物在降低心血管事件、死亡率和不良反应方面的效果。

方法

对他汀类药物和纤维酸类药物单药治疗的头对头随机试验进行系统评价和荟萃分析。通过 MEDLINE、EMBASE、Cochrane、世界卫生组织国际临床试验注册平台和 ClinicalTrials.gov 检索截至 2019 年 10 月 30 日的文献。试验随访时间至少 28 天，并报告死亡率或感兴趣的心血管结局，则符合纳入标准。疗效结局为心血管死亡率和主要心血管事件。安全性结局包括肌痛、严重不良事件、血清肌酐升高和血清丙氨酸氨基转移酶升高。使用 Mantel-Haenszel 固定效应模型估计比值比（OR）和 95%置信区间（CI），并使用 I2 统计量评估异质性。

结果

我们纳入了 19 项直接比较他汀类药物和纤维酸类药物单药治疗并报告死亡率或心血管事件的合格试验。这些研究的随访时间有限（范围为 10 周至 2 年）。我们没有发现他汀类药物和纤维酸类药物在心血管死亡率（OR 2.35，95%CI 0.94-5.86，I2 = 0%；10 项研究，n = 2657；低确定性）、主要心血管事件（OR 1.15，95%CI 0.80-1.65，I2 = 13%；19 项研究，n = 7619；低确定性）和肌痛（OR 1.32，95%CI 0.95-1.83，I2 = 0%；10 项研究，n = 6090；低确定性）方面存在差异。他汀类药物的严重不良事件（OR 0.57，95%CI 0.36-0.91，I2 = 0%；9 项研究，n = 3749；中等确定性）、血清肌酐升高（OR 0.17，95%CI 0.08-0.36，I2 = 0%；6 项研究，n = 2553；高确定性）和丙氨酸氨基转移酶升高（OR 1.43，95%CI 1.03-1.99，I2 = 44%；7 项研究，n = 5225；低确定性）的发生率较低。