Document Detail

Proton pump inhibitors and potential interactions with clopidogrel: an update.
MedLine Citation:
PMID:  23695547     Owner:  NLM     Status:  In-Data-Review    
Clopidogrel, an antiplatelet agent, is increasingly prescribed for patients with recent stroke, myocardial infarction, acute coronary syndrome, and/or patients post-coronary stent insertion to prevent recurrent cardiovascular events. Since clopidogrel can increase the risk of gastrointestinal hemorrhage, co-administration of proton pump inhibitors (PPIs) has been recommended, particularly in patients at high risk. In 2009, the FDA issued warnings about potential interactions between clopidogrel and PPIs, given the fact that both drugs are metabolized via the cytochrome P450 pathway. Prior studies have demonstrated significant reduction in platelet inhibition when PPI therapy is administered to subjects on clopidogrel therapy. Two meta-analyses were published in 2010 and 2011, the first suggesting association of PPIs with adverse cardiovascular events when observational studies were examined, but noting that the results were limited by the presence of significant heterogeneity. The second meta-analysis did not find a significant increase in the risk of adverse primary events (which included all cause mortality, cardiovascular death, myocardial infarction, or stroke), and concluded that analysis of the data from two randomized controlled trials yielded a risk difference of zero. An updated literature search was performed to assess clinical studies describing interactions between PPIs and clopidogrel published from 2011-2012. The majority of these studies did not show significant interactions when primary cardiac outcomes were considered. More importantly, the newer data demonstrated that PPI usage independently was a risk factor for adverse CV outcomes, since most PPI users were older patients who were more likely to have concomitant co-morbid conditions. Two updated reviews also concluded that the presence of confounding factors likely explained differences in results between studies, and that there were no significant differences in effects on clopidogrel between individual proton pump inhibitors. Overall, clinicians can assure their patients that combination therapy is safe when indicated in a patient at high risk of GI bleeding, but they should also stop PPI therapy if it is not clinically indicated.
Lauren B Gerson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current gastroenterology reports     Volume:  15     ISSN:  1534-312X     ISO Abbreviation:  Curr Gastroenterol Rep     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888896     Medline TA:  Curr Gastroenterol Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  329     Citation Subset:  IM    
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