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

^a Department of Cardiology and Thrombosis Research, University Hospital Bern, Bern, Switzerland
^* Department of Hematology, University Hospital Bern, Bern, Switzerland

View larger version (28K): [in a new window]   Figure 1 (A) Dose-dependent ADP-induced platelet aggregation (percentage of light transmission in platelet-rich plasma) in 30 patients treated with aspirin 100 mg/day, clopidogrel 75 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day. Results represent mean ± SEM. *p < 0.05 versus aspirin (Wilcoxon signed rank test). (B) Effects of different aspirin doses on ADP-induced platelet aggregation (percentage of light transmission in platelet-rich plasma) in 12 patients with aspirin 100 mg/day, aspirin 300 mg/day, aspirin 100 mg/day plus clopidogrel 75 mg/day and aspirin 300 mg/day plus clopidogrel 75 mg/day. Results represent mean ± SEM. *p < 0.05 versus aspirin (Wilcoxon signed rank test). ADP = adenosine diphosphate.

View larger version (24K): [in a new window]   Figure 2 Dose-dependent collagen-induced platelet aggregation (percentage of light transmission in platelet-rich plasma) in 30 patients treated with aspirin 100 mg/day, clopidogrel 75 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day. Results represent mean ± SEM. *p < 0.05 versus aspirin; #p < 0.05 versus clopidogrel (Wilcoxon signed rank test).

View larger version (28K): [in a new window]   Figure 3 Dose-dependent TRAP-induced platelet aggregation (percentage of light transmission in platelet-rich plasma) in 30 patients treated with aspirin 100 mg/day, clopidogrel 75 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day. Results represent mean ± SEM. *p < 0.05 versus aspirin; #p < 0.05 versus clopidogrel (Wilcoxon signed rank test). TRAP = thrombin receptor agonist peptide.

View larger version (37K): [in a new window]   Figure 4 Changes in the expression of platelet activation epitopes after administration of aspirin (100 mg/day, black bars), clopidogrel (75 mg/day, white bars) and aspirin (100 mg/day) plus clopidogrel (75 mg/day, hatched bars). In figures A to C, platelets were stimulated with adenosine diphosphate (ADP; 0.01, 0.1, 1, 10, 100 µmol/L) and in D to F with thrombin (0.01, 0.05, 0.1, 0.5 U/mL). After stimulation, activated platelets were detected by flow cytometry with monoclonal antibodies directed against CD62p (P-selectin), which recognizes alpha-granule release, CD63 recognizing lysosome secretion and PAC-1 detecting activated GP IIb-IIIa complex. Results (n = 30) are expressed as the percentage of the total platelet population binding each monoclonal antibody and represent mean ± SEM. *p < 0.05 versus aspirin; #p < 0.05 versus clopidogrel; p = 0.054; ¶p = 0.065 versus clopidogrel (Wilcoxon signed rank test).

View larger version (30K): [in a new window]   Figure 5 CD62p (P-selectin) positive platelets after stimulation with ADP in 12 patients receiving two different doses of aspirin: aspirin 100 mg/day, aspirin 300 mg/day, aspirin 100 mg/day plus clopidogrel 75 mg/day and aspirin 300 mg/day plus clopidogrel 75 mg/day. Results represent mean ± SEM. *p < 0.05 aspirin 100 mg versus 300 mg (Wilcoxon signed rank test). ADP = adenosine diphosphate.