Optimal use of thienopyridines in non-ST-elevation acute coronary syndrome following CURRENT-OASIS 7

Over the past decades, antiplatelet therapy has evolved from the relatively weak oral agent aspirin to additional oral and parenteral agents with greater antiplatelet activity. One example of a successful agent is the second-generation thienopyridine clopidogrel. Clopidogrel inhibits platelet P2Y12 receptors and given with aspirin, which inhibits cyclooxygenase-1 enzyme, composes the actual standard of care of dual antiplatelet therapy.1–3 Dual antiplatelet therapy is recommended by the American College of Cardiology/American Heart Association, American College of Chest Physicians, and the European Society of Cardiology (ESC) for patients undergoing percutaneous coronary intervention (PCI) and patients with ST-elevated myocardial infarction (STEMI) or unstable angina (UA)/non-STEMI (NSTEMI).4–10 A common point of emphasis in these guidelines is the recommendation to provide a clopidogrel loading dose (LD) before PCI, although uncertainty remains in these recommendations on the optimal dose and optimal timing of administration. Whereas the American College of Cardiology/American Heart Association UA/NSTEMI guidelines recommend a 300-mg clopidogrel LD, they acknowledge that although the supporting evidence is much weaker than that for a 300-mg LD, a higher dose of 600 or 900 mg may be more beneficial in some circumstances.8 The PCI guidelines recommend a 600-mg clopidogrel LD before or during the procedure.10 The ESC guidelines suggest that a 600-mg LD may be initiated immediately after the first medical contact for invasively managed patients with NSTEMI.5,6 Unfortunately, there are no clinical data and, therefore, no recommendation on the maintenance dose (MD) during the acute phase or chronic phase. The Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events/Optimal Antiplatelet Strategy for Interventions (CURRENT-OASIS 7) trial is the first large-scale, randomized trial to compare 2 strategies: high-dose clopidogrel (600-mg LD/150-mg MD) versus standard-dose clopidogrel (300-mg LD/75-mg MD) to assess the added benefit of a higher platelet …