Potential Interaction between Clopidogrel and Proton Pump Inhibitors

Patricia A. Howard; James L. Vacek


Am J Cardiovasc Drugs. 2009;9(6):353-359. 

In This Article

Abstract and Introduction


Clopidogrel is widely used in patients with acute coronary syndromes and following percutaneous coronary intervention with stent implantation. The antiplatelet action of clopidogrel is felt to be of critical importance for the reduction of abrupt thrombotic occlusion of stents, particularly with drug-eluting devices. When clopidogrel is used alone or in combination with aspirin (acetylsalicylic acid), the benefits of antiplatelet therapy must be weighed against the potential for serious bleeding, particularly gastrointestinal (GI) bleeds. To minimize the risk of GI injury, proton pump inhibitors (PPIs) are considered the drugs of choice. However, a growing body of evidence suggests that PPIs may adversely interact with clopidogrel, diminishing the antiplatelet effect. Although the current evidence remains controversial, the potential for increased risk of thrombotic complications warrants cautious use of this drug combination until further research can determine the extent of this interaction and whether it is a drug-class effect.


Clopidogrel is a potent antiplatelet drug with actions mediated through irreversible inhibition of the platelet ADP receptor, P2Y12.[1] Clopidogrel is widely used to prevent thrombotic complications in patients with acute coronary syndromes (ACS), with or without percutaneous coronary intervention (PCI), and is particularly effective for patients with drug-eluting devices. Clopidogrel monotherapy has been associated with an increased risk of bleeding.[2] Several clinical trials have shown that the risk of bleeding, especially gastrointestinal (GI) bleeding, is further increased in high-risk coronary patients who often require dual antiplatelet therapy with both clopidogrel and aspirin (acetylsalicylic acid).[3–5] Guidelines for the prevention or treatment of antiplatelet drug-associated GI injury recommend proton pump inhibitors (PPIs) as first-line agents.[6]

Recently, concerns have been raised over a potential drug interaction between clopidogrel and PPIs that may diminish the antiplatelet activity of clopidogrel. Because of the serious clinical implications of a decreased antiplatelet response in high-risk coronary patients, reports of this potential interaction with PPIs must be further explored.


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