Clopidogrel – Confounding or Confirming Our Concept of How to Treat Acute Coronary Syndromes?

Clopidogrel, a thienopyridine derivative, selectively and irreversibly inhibits the platelet ADP receptor resulting in platelet inhibition. The utilisation of clopidogrel in the setting of coronary artery disease has been studied in three multicentre trials: CAPRIE, CLASSICS and the CURE study. These clinical trials generally suggest that patients with atherosclerotic vascular disease are more effectively managed with long-term clopidogrel than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction or vascular death, that the combination of clopidogrel and aspirin is safer when compared to ticlopidine and aspirin following percutaneous coronary intervention and that the use of clopidogrel and aspirin is beneficial in patients with acute coronary syndromes without ST segment elevation by reducing major cardiac events when compared with placebo and aspirin. Patients in the CURE study were managed initially ‘conservatively’ with aspirin and clopidogrel. However, recent studies have shown that managing these high-risk patients by pretreatment with antiplatelet and antithrombin agents (aspirin, heparin, clopidogrel and a glycoprotein IIb/IIIa inhibitor) followed by early revascularisation is beneficial. The combination of clopidogrel with aspirin, heparin and a glycoprotein IIb/IIIa inhibitor appears safe, though this requires further study. Furthermore, the risk of bleeding in patients requiring coronary artery bypass graft surgery within 5 days of initiation of clopidogrel is of concern. The length of treatment required with clopidogrel to provide optimum benefit is still not clear.