Clopidogrel with proton pump inhibitors: safe or not?

Gastrointestinal (GI) bleeding is a serious complication associated with use of antiplatelet therapy, and proton pump inhibitors (PPIs) are known to be beneficial in decreasing such risk. Several studies in the recent past have suggested concerns regarding interaction between clopidogrel and PPIs, presumably due to inhibition of clopidogrel activity and thus attenuation of its antiplatelet activity. A web-based literature and guidelines search was done using the keywords "clopidogrel," "omeprazole," "proton pump inhibitors" and "interaction." Of the available results, relevant studies (n = 11) were then systematically reviewed and summarized. The studies were categorized based on their retrospective or prospective nature. Most of the retrospective, observational studies suggested a link between the 2; however, recent prospective studies have shown no interaction, as well as a positive influence of PPIs in preventing the GI side effects of antiplatelet therapy. There is currently insufficient clinical evidence to suggest interaction between clopidogrel and PPIs and decision to add PPI therapy to clopidogrel should be guided by its clinical indications rather than as a routine prophylactic measure.