No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: Meta-analysis
No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: Meta-analysis
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DOI：
10.1016/j.ijcard.2012.03.085
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发表时间：
2013-08-10
影响因子：
3.5
通讯作者：
Loke, Yoon Kong
中科院分区：
文献类型：
--
作者：
Kwok, Chun Shing;Jeevanantham, Vinodh;Loke, Yoon Kong
背景：来自药代动力学和药效学研究的数据表明，氯吡格雷-质子泵抑制剂(PPI)的不良相互作用在不同的PPI之间可能不同，潘托拉唑被认为是相对较小的问题。我们的目标是系统地评估在与氯吡格雷联合应用时，单个PPI是否在心血管事件风险方面存在差异。方法：我们检索了截至2011年12月的MEDLINE、EMBASE和Cochrane Trials Register，以获得随机和非随机研究，这些研究报告了在接受氯吡格雷的患者中暴露于特定PPI的不良心血管事件。我们进行随机效应荟萃分析，并使用I-2统计量评估异质性。结果：共纳入23项研究，222311名参与者。主要不良心血管事件的荟萃分析主要受到中度-实质性异质性的限制。当与氯吡格雷一起使用时，单独的PPI，如奥美拉唑、埃索美拉唑、兰索拉唑和潘托拉唑的心血管风险的合并估计显著增加。然而，在报告了单独使用PPI治疗(没有伴随的氯吡格雷)的七项观察性研究中，对不良心血管风险的荟萃分析也发现，与不使用氯吡格雷/不使用PPI相比，优势比增加了1.28(95%可信区间1.14-1.44)。两个随机对照试验的Meta分析没有显示奥美拉唑或埃索美拉唑对心血管的显著不良影响。结论：缺乏一致的证据表明PPI之间存在不同的心血管风险(特别是潘托拉唑的安全性)，这与血小板功能和药代动力学数据直接相反。我们的研究发现，在没有氯吡格雷的情况下，PPI增加了心血管风险，这表明混淆和偏见是很有可能的。假想的PPI-氯吡格雷相互作用的临床有效性或相关性仍然值得怀疑。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
Background: Data from pharmacokinetic and pharmacodynamic studies indicate that the adverse clopidogrel - proton pump inhibitor (PPI) interaction may vary between PPIs, with pantoprazole considered relatively less problematic. We aimed to evaluate systematically whether individual PPIs differ in their risk for cardiovascular events when concomitantly administered with clopidogrel.Methods: We searched MEDLINE, EMBASE and Cochrane Trials Register up to December 2011 for randomized and non-randomized studies that reported adverse cardiovascular events with exposure to specific PPIs in patients receiving clopidogrel. We performed random effects meta-analysis, and assessed heterogeneity using the I-2 statistic.Results: A total of 23 studies with 222,311 participants were included. Meta-analysis of major adverse cardiovascular events was mostly limited by moderate-substantial heterogeneity. Pooled estimates of cardiovascular risk were significantly elevated for individual PPIs such as omeprazole, esomeprazole, lansoprazole, and pantoprazole when used with clopidogrel. However, meta-analysis of adverse cardiovascular risk in seven observational studies reporting on PPI therapy alone (without concomitant clopidogrel) also found an elevated odds ratio of 1.28 (95% CI 1.14-1.44) compared with no clopidogrel/no PPI exposure. Meta-analysis of two randomized controlled trials did not show significant adverse cardiovascular effect from omeprazole or esomeprazole.Conclusions: The absence of consistent evidence on differential cardiovascular risk amongst PPIs (particularly regarding safety of pantoprazole) is in direct opposition to the platelet function and pharmacokinetic data. Our findings of increased cardiovascular risk with PPIs in the absence of clopidogrel suggest that confounding and bias are strong possibilities. The clinical validity or relevance of the hypothesized PPI-clopidogrel interaction remains questionable. (C) 2012 Elsevier Ireland Ltd. All rights reserved.