Summary Clopidogrel, a thienopyridine, is an antiplatelet drug which currently represents the cornerstone for the treatment of acute coronary events. It is a pro-drug that must be converted at hepatic level into its active form by the CYP2C19 isoenzyme. Recently the interaction between proton pump inhibitors and clopidogrel has been widely brought to attention. The competitive inhibition that these generate on the hepatic enzymatic system probably activates clopidogrel, thus causing a decrease in its effectiveness as an antithrombotic. Nevertheless, evidence is contradictory, and until now no clinical trials have been performed to clear up doubts. If a PPI is to be used on patients who take clopidogrel, the use of Pantoprazole or Esomeprazole is recommended because they exert minimal inhibition on CYP2C19. Key words Proton pump inhibitors, clopidogrel, P450, thrombosis INTRODUCTION Th e proton pump inhibitors (PPIs) are one of the most commonly prescribed medications in the world, with more than 12.4 million prescriptions in 2004 in Canada (1). Clopidogrel (CPDG) has been approved as a fi rst line treatment for reducing major cardiovascular events such as death from cardiovascular origin, stent thrombosis, acute coronary syndrome, and recurrent revascularization (2). It is usually prescribed together with a proton pump inhibitor which reduces the risk of gastrointestinal bleeding (GIB) (3). CPDG is a second gene ration thienopyridine prodrug. Its effi ciency is similar to ticlopidine but it is tolerated bet-ter (2 and 4). In order to turn it into an active metabolite and inhibit platelet aggregation it must be bioactivated by cytochrome P450 at a hepatic level (4). It blocks platelet aggregation by irreversibly inhibiting the P2Y12 adeno-sine diphosphate (ADP) receptor (4).