This antiplatelet agent exerts its effect through direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the lipoprotein GPIIb/IIIa complex.
Anticoagulant approved to reduce CV death, MI, stroke, and refractory ischemia in patients with ACS
This antiplatelet agent exerts its effect through direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the lipoprotein GPIIb/IIIa complex. Clopidogrel was approved on August 17, 2006, for patients with non-ST-segment elevation acute coronary syndrome (ACS) (unstable angina/non-Q-wave myocardial infarction [MI]) to decrease the likelihood of cardiovascular (CV) death, MI, stroke, or refractory ischemia.
Efficacy. The Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial enrolled 12,562 patients with ACS without ST-segment elevation and presenting within 24 hours of onset of the most recent episode of chest pain or symptoms consistent with ischemia. The patients were randomized to receive either clopidogrel (300-mg loading dose followed by 75 mg/d) plus aspirin (75–325 mg once daily) or placebo plus aspirin and were treated for up to 1 year. The patients were also permitted to receive other standard therapies such as heparin; however, the use of GPIIb/IIIa inhibitors was not permitted for 3 days prior to randomization. The use of oral anticoagulants, non-study antiplatelet drugs, and chronic nonsteroidal anti-inflammatory drugs (NSAIDs) was also not permitted in the CURE trial. The primary outcome in the study was a composite end point of CV death, MI, or stroke, while the co-primary outcome was a composite end point of CV death, MI, stroke, or refractory ischemia. Of the patients treated with clopidogrel plus aspirin, 9.30% experienced the primary outcome, compared with 11.41% of patients in the placebo group, representing a 20% relative risk reduction (95% CI, 10%–28%; P=.00009) for the clopidogrel-treated patients. Similarly, patients treated with clopidogrel plus aspirin experienced a 14% relative risk reduction (95% CI, 6%–21%; P=.0005) for the co-primary outcome (16.54% and 18.83% of patients experiencing CV death, MI, stroke, or refractory ischemia in the clopidogrel and placebo groups, respectively). The benefits of clopidogrel in this study were different in populations of patients with different characteristics. These benefits were independent of the use of other acute and long-term cardiovascular therapies, including heparin/low molecular weight heparin (LMWH), IV glycoprotein IIb/IIIa inhibitors, lipid-lowering drugs, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors. Likewise, the benefit derived from clopidogrel therapy was independent of aspirin dose (75–325 mg once daily). The use of clopidogrel in the CURE trial was associated with a decrease in the use of thrombolytic therapy, with only 1.1% of patients in the clopidogrel group receiving thrombolytic therapy compared with 2.0% in the placebo group. Similarly, clopidogrel therapy was associated with a decrease in the use of GPIIb/IIIa inhibitors, with 5.9% of patients in the clopidogrel group and 7.2% in the placebo group receiving GPIIb/IIIa inhibitors.
Dosing. For patients with non-ST-segment ACS, clopidogrel therapy should be initiated with a single 300-mg loading dose followed by 75 mg once daily. Aspirin should be initiated and continued in combination with clopidogrel, at a dose of 75 to 325 mg once daily. Clopidogrel can be administered with or without food.