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 < or = 0.0001) and platelet-rich plasma (PRP) (p < or = 0.0001), and in inhibiting collagen-induced aggregation in PRP (p < or = 0.0001). ASA alone and clopidogrel + ASA were significantly more effective than dipyridamole + ASA in inhibiting arachidonic acid-induced platelet aggregation in whole blood (p < or = 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.
Caplain
H
H
ASTER-CEPHAC, Paris, France. henri.caplain@sanofi-aventis.com
D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003094:Collagen / Q000494:pharmacology; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004176:Dipyridamole / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013988:Ticlopidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*
D003692:Delayed-Action Preparations; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D004176:Dipyridamole; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin