Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy

• Published in: Journal of the American College of Cardiology 2000-09, Vol.36 (3), p.699-705
• Main Authors: Moshfegh, Khatereh, Redondo, Maurice, Julmy, Friedgard, Wuillemin, Walter A, Gebauer, Mathias U, Haeberli, André, Meyer, Beat J
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Adult; Aged; Antigens, CD - metabolism; Aspirin - administration & dosage; Aspirin - therapeutic use; Biological and medical sciences; Blood - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Clopidogrel; Collagen - pharmacology; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dual Specificity Phosphatase 2; Humans; Medical sciences; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - drug therapy; P-Selectin - metabolism; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Platelet Activation - drug effects; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - therapeutic use; Platelet Membrane Glycoproteins - metabolism; Prospective Studies; Protein Phosphatase 2; Protein Tyrosine Phosphatases - metabolism; Tetraspanin 30; Ticlopidine - analogs & derivatives; Ticlopidine - therapeutic use
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(00)00817-2

OBJECTIVES We sought to compare the inhibitory effects of the combination of two doses of aspirin plus clopidogrel with either drug alone on platelet aggregation and activation. BACKGROUND Enhanced platelet inhibitory effects of clopidogrel by aspirin on 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 platelet aggregation and activation by flow cytometry after stimulation with various agonists were determined in 30 patients with a past history of myocardial infarction. RESULTS Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with monotherapy 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 aggregation 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 inhibition of aggregation induced by thrombin receptor agonist peptide (TRAP, p < 0.03). Clopidogrel with or without aspirin significantly suppressed expression of platelet activation markers CD 62p, CD 63 and PAC-1 after stimulation with ADP or thrombin (p < 0.001). In addition, the combined treatment was more effective than either agent alone after activation with low dose thrombin (p < 0.05). Both doses of aspirin equally potentiated the platelet inhibitory effects of clopidogrel. CONCLUSIONS In this prospective clinical ex vivo platelet study, clopidogrel was more effective than aspirin in inhibiting ADP-mediated platelet aggregation and activation. Clopidogrel in combination with aspirin showed synergistic inhibitory effects after stimulation with collagen and thrombin compared with monotherapies. Thus, this dual antiplatelet treatment strategy deserves further evaluation in clinical trials for secondary prevention of acute myocardial infarction or unstable angina.