Interaction between Thienopyridines and Proton Pump Inhibitors

Adenosin diphospat (ADP) plays a crucial role in thrombus formation. Therefore its inhibition can control excess platelet generation to prevent cardiovascular events in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). One of ADP’s target receptors, P2Y12 has a limited tissue distribution and is therefore an attractive pharmacological target. Thienopyridines are class of drugs that specifically and irreversibly inhibit the P2Y12 receptor. Three generations exist and in most patients, they are administered in combination with aspirin. Because of possible gastro-intestinal toxicity, a proton pump inhibitor (PPI) is often concomitantly prescribed. However, several studies suspect an interaction between thienopyridines (in particular with clopidogrel) and PPIs which decreases the inhibition of platelet formation and thus enhances the risk for cardiac events. In this review, a concise overview of pharmacokinetic and pharmacodynamic properties of all thienopyridines is given and a critical discussion of the presumed interaction with PPIs is provided.