Prescribing Proton Pump Inhibitor and Clopidogrel Together

Current State of Recommendations

Neena S. Abraham


Curr Opin Gastroenterol. 2011;27(6):558-564. 

In This Article

Abstract and Introduction


Purpose of review: Conflicting evidence has contributed to confusion regarding the safety of co-prescribing a proton pump inhibitor (PPI) and clopidogrel. This review will quantify the risk of gastrointestinal bleeding associated with common cardioprophylactic regimens, review the evidence regarding a PPI–clopidogrel interaction and assess its clinical relevance, and reinforce best-practice recommendations for gastrointestinal bleeding prevention among patients prescribed clopidogrel.
Recent findings: The COGENT trial confirmed a substantial reduction in gastrointestinal bleeding risk without apparent increase in cardiovascular events when clopidogrel was co-prescribed with omeprazole. These data are consistent with secondary data analyses of large cardiovascular trials and well adjusted observational studies that also failed to confirm a consistent, clinically relevant increase in cardiovascular endpoints or mortality. Individual genetic variations in drug metabolism may contribute to increased cardiac event rates observed in small subsets of the population when PPI is co-prescribed. In the future, pharmacogenomics and point-of-care testing will likely play an emerging role in individualizing prescription strategy.
Summary: A pragmatic approach dictates an explicit risk–benefit assessment prior to co-prescription to maximize cardiac benefit and minimize the risk of gastrointestinal bleeding.


The prescription of antiplatelet agents, such as clopidogrel, has become a mainstay of atherosclerotic cardiovascular disease therapy. The international prevalence of acetylsalicylic acid (ASA) and antiplatelet prescription is estimated at 60 and 25%, respectively, among patients with coronary artery disease, cerebrovascular disease and peripheral arterial disease.[1] In the United States, 13% of patients with coronary artery disease are prescribed dual-antiplatelet therapy with ASA and clopidogrel.[2] Dual-antiplatelet therapy reduces major cardiovascular events in patients with established ischemic heart disease as well as thrombosis among patients with coronary stents.[3••] However, mono-prescription or dual-prescription strategy is associated with an increased risk of gastrointestinal bleeding – including peptic ulceration with bleeding, perforation and obstruction. Thus, the risk–benefit of antiplatelet therapy must be considered carefully among patients who are at risk of gastrointestinal bleeding and appropriate measures taken to minimize this risk.[3••]


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