Antiplatelet effects of clopidogrel compared with aspirin after myocardialinfarction: Enhanced inhibitory effects of combination therapy

OBJECTIVES We sought to compare the inhibitory effects of the combination o f two doses of aspirin plus clopidogrel with either drug alone on platelet aggregation and activation. BACKGROUND Enhanced platelet inhibitory effects of clopidogrel by aspirin o n platelet aggregation and activation are suggested by experimental studies but have not been shown in humans. METHODS The effects of clopidogrel 75 mg or aspirin 100 (300) mg on platele t aggregation and activation by flow cytometry after stimulation with vario us agonists were determined in 30 patients with a past history of myocardia l infarction. RESULTS Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with mo notherapy with aspirin (24.6 +/- 3.3% or 26.6 +/- 2.7% vs. 44.7 +/- 2.9%; p < 0.001). Combined treatment significantly inhibited collagen-induced aggr egation compared with aspirin and clopidogrel (16.4 +/- 2.4%, 36.5 +/- 4.2% and 59.3 +/- 5.1%, respectively; p < 0.001) and resulted in considerable i nhibition of aggregation induced by thrombin receptor agonist peptide (TRAP , p < 0.03). Clopidogrel with or without aspirin significantly suppressed e xpression of platelet activation markers CD 62p, CD 63 and PAC-1 after stim ulation with ADP or thrombin (p < 0.001). In addition, the combined treatme nt was more effective than either agent alone after activation with low dos e thrombin (p < 0.05). Both doses of aspirin equally potentiated the platel et inhibitory effects of clopidogrel. CONCLUSIONS In this prospective clinical ex vivo platelet study, clopidogre l was more effective than aspirin in inhibiting ADP-mediated platelet aggre gation and activation. Clopidogrel in combination with aspirin showed syner gistic inhibitory effects after stimulation with collagen and thrombin comp ared with monotherapies. Thus, this dual antiplatelet treatment strategy de serves further evaluation in clinical trials for secondary prevention of ac ute myocardial infarction or unstable angina. (C) 2000 by the American Coll ege of Cardiology.