Enhanced antiplatelet effects of clopidogrel plus acetylsalicylic acid compared with acetylsalicylic acid alone or combined with extended-release dipyridamole in healthy volunteers

Background: Previous studies have shown the potential benefit of using antiplatelet agents with complementary modes of action. Methods : Using a crossover design, the ex vivo antiplatelet effects of 10 days ' treatment with clopidogrel 75 mg + acetylsalicylic acid ( ASA) 75 mg daily, ASA 75 mg/ day, or extended- release dipyridamole 200 mg/ low- dose ASA 25 mg twice daily were compared, using various platelet agonists. Results: Clopidogrel + ASA was significantly more effective than dipyridamole + ASA in inhibiting collagen- induced platelet aggregation in whole blood ( mean 44.9 +/- 5.6% inhibition vs. 16.5 +/- 6.7%; p = 0.0009). Clopidogrel + ASA was significantly more effective than ASA or dipyridamole + ASA in inhibiting ADP- induced platelet aggregation in whole blood ( p <= 0.0001) and platelet- rich plasma ( PRP) ( p <= 0.0001), and in inhibiting collagen- induced aggregation in PRP ( p <= 0.0001). ASA alone and clopidogrel + ASA were signifiantly more effective than dipyridamole + ASA in inhibiting arachidonic acid- induced platelet aggregation in whole blood ( p <= 0.0001). Conclusions: Based on ex vivo platelet aggregometry, clopidogrel + ASA is a more potent antiplatelet regimen than either ASA alone or the marketed combination of dipyridamole + ASA. However, the clinical significance of this finding remains to be confirmed.