Document Detail

Effects of proton pump inhibitors on adverse gastrointestinal events in patients receiving clopidogrel: systematic review and meta-analysis.
MedLine Citation:
PMID:  21047145     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: 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.
OBJECTIVE: To perform a meta-analysis of GI outcomes in patients taking clopidogrel, with and without concomitant PPI.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
Chun Shing Kwok; Ramanpreet Singh Nijjar; Yoon Kong Loke
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Review    
Journal Detail:
Title:  Drug safety     Volume:  34     ISSN:  0114-5916     ISO Abbreviation:  Drug Saf     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-03-16     Revised Date:  2014-11-17    
Medline Journal Info:
Nlm Unique ID:  9002928     Medline TA:  Drug Saf     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  47-57     Citation Subset:  IM    
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MeSH Terms
Aspirin / administration & dosage,  adverse effects,  pharmacology
Drug Interactions
Drug Therapy, Combination
Gastrointestinal Diseases / chemically induced,  physiopathology
Platelet Aggregation Inhibitors / administration & dosage,  adverse effects*,  pharmacology
Proton Pump Inhibitors / adverse effects*,  pharmacology
Ticlopidine / administration & dosage,  adverse effects,  analogs & derivatives*,  pharmacology
Reg. No./Substance:
0/Platelet Aggregation Inhibitors; 0/Proton Pump Inhibitors; A74586SNO7/clopidogrel; OM90ZUW7M1/Ticlopidine; R16CO5Y76E/Aspirin
Comment In:
Drug Saf. 2011 Feb 1;34(2):173; author reply 174   [PMID:  21247223 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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