School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK.
Drug Saf. 2011 Jan 1;34(1):47-57. doi: 10.2165/11584750-000000000-00000.
There has been recent concern regarding a possible adverse interaction between clopidogrel and proton pump inhibitors (PPIs), coupled with uncertainty as to whether PPIs genuinely help in reducing gastrointestinal (GI) harm.
To perform a meta-analysis of GI outcomes in patients taking clopidogrel, with and without concomitant PPI.
We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to March 2010, and checked conference abstracts for randomized and non-randomized studies that reported on adverse GI events (haemorrhage, ulcer, perforation or obstruction) with PPI exposure in patients taking clopidogrel. Relevant studies were subcategorized according to the degree of aspirin (acetylsalicylic acid) co-administration and nature of GI events, where available. We performed random effects meta-analysis for risk of adverse GI events with PPI exposure in clopidogrel-treated patients, and assessed heterogeneity using the I2 statistic.
Our review evaluated 71,277 participants in nine retrospective studies and one randomized trial. Exposure to PPI for patients receiving dual antiplatelet therapy (aspirin and clopidogrel in seven studies) was associated with a significant reduction in adverse GI events, odds ratio (OR) 0.38 (95% CI 0.21, 0.68; p=0.001; I2=17%). There was significant heterogeneity in the analysis of patients receiving clopidogrel monotherapy (two studies), and no definite benefit was found. Restricting the analysis to studies specifically reporting upper GI bleeds with any clopidogrel exposure yielded an OR of 0.31 (95% CI 0.19, 0.51; p<0.001; I2=27%) with associated PPI exposure.
Use of PPIs is associated with a reduction in adverse GI events (particularly haemorrhages) in patients who are receiving dual antiplatelet therapy. Clinicians should carefully weigh up the evidence for potential GI benefits against the uncertainties surrounding any possible adverse cardiovascular impact of concomitant clopidogrel PPI therapy.
最近人们对氯吡格雷与质子泵抑制剂（PPIs）之间可能存在不良反应的相互作用表示担忧，同时对于 PPI 是否确实有助于减少胃肠道（GI）损害也存在不确定性。
对接受氯吡格雷治疗的患者中，合并使用或不合并使用质子泵抑制剂（PPIs）的胃肠道（GI）结局进行荟萃分析。
我们检索了 MEDLINE、EMBASE 和 Cochrane 对照试验注册库，从建库至 2010 年 3 月，同时查阅了会议摘要中关于接受氯吡格雷治疗的患者中 PPI 暴露与不良 GI 事件（出血、溃疡、穿孔或梗阻）相关的随机和非随机研究。将相关研究根据阿司匹林（乙酰水杨酸）合用程度和 GI 事件的性质进行了亚组分类（如果有的话）。我们对接受氯吡格雷治疗的患者中 PPI 暴露与不良 GI 事件的风险进行了随机效应荟萃分析，并使用 I2 统计量评估了异质性。
我们的综述评估了 9 项回顾性研究和 1 项随机试验中的 71277 名参与者。在接受双联抗血小板治疗（7 项研究中为阿司匹林和氯吡格雷）的患者中，PPI 暴露与不良 GI 事件的显著减少相关，比值比（OR）为 0.38（95%CI 0.21，0.68；p=0.001；I2=17%）；分析氯吡格雷单药治疗（两项研究）的患者时存在显著的异质性，并且没有明确的获益。将分析仅限于明确报告任何氯吡格雷暴露的上胃肠道出血的研究时，OR 为 0.31（95%CI 0.19，0.51；p<0.001；I2=27%），与 PPI 暴露相关。
在接受双联抗血小板治疗的患者中，使用质子泵抑制剂（PPIs）与不良 GI 事件（尤其是出血）的减少相关。临床医生应该仔细权衡潜在的 GI 获益与同时使用氯吡格雷 PPI 治疗可能存在的不良心血管影响之间的证据。
