The Antiplatelet Effects of Ticlopidine and Clopidogrel

Abstract

Ticlopidine and clopidogrel achieve antiplatelet effects by inhibiting the binding of adenosine 5'-disphosphate to its platelet receptor. Ticlopidine was first shown to decrease major events compared with placebo or aspirin in patients with stroke or recent transient ischemic attack. Randomized studies in patients undergoing coronary artery stenting have shown that ticlopidine reduces the risk for subacute stent thrombosis compared with warfarin-based regimens. Smaller studies have also shown this drug to have benefit during follow-up in patients with unstable angina, peripheral arterial disease, saphenous vein coronary bypass grafts, and diabetic retinopathy. Clopidogrel was recently approved by the U.S. Food and Drug Administration for the reduction of ischemic events in patients with recent myocardial infarction, stroke, or peripheral arterial disease (incidence, 5.32% per year compared with 5.83% per year for aspirin; P = 0.043) with no added risk for neutropenia. The combination of clopidogrel and aspirin, as well as the utility of clopidogrel in other patient populations and in stenting, requires further study. Ticlopidine and clopidogrel seem to have beneficial effects compared with aspirin (the current standard) in a broad range of patients. These observations highlight the importance of antiplatelet therapy in cardiovascular disease.

A multiple dose study of prasugrel (CS‐747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy humans

“…Clopidogrel is a prodrug which, following oral administration, is metabolized to an active metabolite that binds to and irreversibly antagonizes the platelet G i -linked P2Y 12 class of ADP receptors [14]. Clopidogrel is currently the thienopyridine of choice due to its more favourable safety profile compared with the first approved thienopyridine, ticlopidine.…”

Contribution of Hepatic Cytochrome P450 3A4 Metabolic Activity to the Phenomenon of Clopidogrel Resistance

“…1 Clopidogrel was approved by the United States Food and Drug Administration (FDA) in 1997 for the reduction of myocardial infarction, stroke, and vascular death in patients with recent stroke, recent myocardial infarction, or established peripheral arterial disease after the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial 2 showed superior reduction of these events with clopidogrel compared with aspirin (annual risk, 5.3% versus 5.8%; Pϭ0.04). Dual antiplatelet therapy (aspirin plus clopidogrel) for acute coronary syndromes was approved by the FDA in 2002 on the basis of the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) trial 3 results, which showed a significant reduction in the 9-month composite end point of cardiovascular death, nonfatal myocardial infarction, or stroke versus aspirin monotherapy (9.3% versus 11.4%, PϽ0.001).…”

The Effect of Tirofiban and Clopidogrel Pretreatment on Outcome of Old Saphenous Vein Graft Stenting in Patients with Acute Coronary Syndromes

“…Although aspirin is an effective antiplatelet agent, coronary stenting is associated with a high incidence of stent thrombosis despite aspirin therapy. Ticlopidine or clopidogrel is structurally related thienopyridine derivates and they exert their antiplatelet effects by inhibiting the adenosine diphosphate dependent pathway of platelet activation (Sharis et al 1998). Trials have shown the superiority of the combination antiplatelet regimen of aspirin and thienopyridines over aspirin alone, or aspirin plus oral anticoagulation with warfarin in preventing stent thrombosis, not only in patients with optimal stent deployment but also in patients who are at high risk of stent thrombosis (Schomig et al 1996;Schuhlen et al 1997;Bertrand et al 1998;Leon et al 1998;Urban et al 1998).…”