The potential interaction between clopidogrel and proton pump inhibitors: a systematic review

BMC Medicine

Research Article

James M Brophy¹  Joao Paulo de Aquino Lima² 

[1] Department of Medicine, McGill University, Montreal, Quebec, Canada;Federal University of Ceará School of Medicine, Fortaleza, Brazil;

关键词: Clopidogrel;    Lansoprazole;    Esomeprazole;    Pantoprazole;    Rabeprazole;   

DOI  :  10.1186/1741-7015-8-81

 received in 2010-09-23, accepted in 2010-12-06,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundRecently, several publications have investigated a possible drug interaction between clopidogrel and proton pump inhibitors (PPIs), and regulatory agencies have issued warnings despite discordant study results. In an attempt to clarify the situation, we performed a systematic review with a critical analysis of study methodologies to determine whether varying study quality (that is, bias) could explain the discordant results.MethodsA systematic review of all studies reporting clinical outcomes was performed using an electronic literature search of the MEDLINE and EMBASE databases, abstracts from the major cardiology conferences and a hand-search of bibliographies from identified articles. Each study was evaluated for its risk of bias according to a prespecified quality measure scale.ResultsA total of 18 studies were identified. Ten of 13 studies judged to be of low scientific quality reported a statistically positive interaction between clopidogrel and the general class of PPIs, and each concluded this was likely a clinically meaningful effect. None of the five studies judged to be of moderate or high quality reported a statistically significant association. Multiple sources of heterogeneity (that is, different populations, outcomes assessed, drug exposure methods and study quality) prevented a formal quantitative analysis of all studies. An increased risk of bias was observed in the positive studies, resulting in an inverse correlation between study quality and a reported statistically positive interaction (10/13 versus 0/5; P = p = 0.007). There was also no clinical evidence for a positive interaction according to specific PPIs.ConclusionThe observed association between clopidogrel and PPIs is found uniquely in studies judged to be of low quality and with an increased risk of bias. High-quality evidence supporting a clinically significant clopidogrel/PPI interaction is presently lacking.

【 授权许可】

CC BY   
© Lima and Brophy; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.