Proton pump inhibitors and antiplatelet drugs in clinical cardiology.

Dual antiplatelet therapy with clopidogrel and aspirin (acetylsalicylic acid) has been shown to reduce recurrent cardiac events in patients with acute coronary syndromes or those who have undergone coronary artery stent placement. Clopidogrel, a thienopyridine, is a prodrug that is transformed in vivo to an active metabolite by the cytochrome P450 (CYP) enzyme system. Clopidogrel users with decreased CYP2C19 function have less inhibition of platelet aggregation and increased cardiovascular events. Due to the increased risk of bleeding in patients on dual antiplatelet therapy, concomitant gastrointestinal ulcer prophylaxis with a proton pump inhibitor (PPI) is frequently prescribed. PPIs, however, are also extensively metabolized by the cytochrome system, and may decrease the antiplatelet activity of clopidogrel. Recent studies have raised concerns among healthcare providers and patients that an interaction of PPIs and clopidogrel could increase cardiovascular events such as coronary artery stent thrombosis and myocardial infarction. Most of the studies reporting a clinical interaction were case-control and, therefore, particularly prone to bias compared with other analytic design. Current guidelines recommend that patients receiving dual antiplatelet therapy with clopidogrel and aspirin receive a PPI to reduce the risk of gastric ulcers and gastric bleeding. It is important, therefore, to review the clinical need for each drug, as it may be appropriate to either stop the clopidogrel or the PPI. If both drugs are clinically indicated and the clinician or patient is concerned about possible interaction, then it may be appropriate to give one drug in the morning and the other in the evening as both compounds have very short half-lives and this should, in theory, prevent interaction. Nevertheless, well designed, prospective, randomized, controlled trials are urgently needed to better address this important clinical issue.