Interaction between clopidogrel and proton-pump inhibitors

Abstract

The American Heart Association/American College of Cardiology guidelines recommend initiating a proton-pump inhibitor (PPI) to prevent gastrointestinal bleeding if patients are receiving concomitant therapy with clopidogrel and aspirin. Recently, concern has been raised regarding the ability of PPIs to decrease the antiplatelet activity of clopidogrel. To date, there are 16 studies that evaluated the outcomes of using clopidogrel with a PPI. One of the studies has shown that adding lansoprazole to clopidogrel has no effect on the concentration of clopidogrel’s inactive metabolite. The eight clinical trials that studied the effect of using PPIs and clopidogrel together on platelet function testing have shown differing effects between PPIs. Concurrent omeprazole and clopidogrel use was shown to decrease the antiplatelet effects of clopidogrel in three studies; whereas pantoprazole, lansoprazole and esomeprazole have been shown to have no significant effect on the antiplatelet response to clopidogrel. Six other studies showed that using PPIs and clopidogrel together led to adverse clinical outcomes; however, one study that did a separate analysis on pantoprazole, showed that using pantoprazole with clopidogrel had no significant impact on clinical outcomes. Post hoc analysis from a large randomized trial comparing prasugrel with clopidogrel indicated no clinically significant effects of PPIs in patients treated with either prasugrel or clopidogrel. Preliminary results from a prospective, randomized trial comparing cardiovascular clinical outcomes between omeprazole and placebo in clopidogrel-treated patients have been reported and suggest no interaction. However, the study was stopped prematurely secondary to loss of funding and follow-up limited to a median of 133 days so no firm conclusions were drawn. The data currently available regarding concurrent clopidogrel and PPI use are limited, so further studies are needed to provide a definite conclusion. Until additional prospective studies are available, the use of clopidogrel with a PPI should be avoided, if possible, and a H₂-receptor antagonist be selected instead. Prasugrel may be administered safely with a PPI as there is currently no evidence of a pharmacokinetic, pharmacodynamic or adverse clinical effects.

Keywords::

• clopidogrel
• drug interaction
• esomeprazole
• lansoprazole
• omeprazole
• pantoprazole
• platelet responsiveness
• proton-pump inhibitor

Financial & competing interests disclosure

Sarah Spinler has received honoraria for speaking with Sanofi Aventis on Lovenox. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.