Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans.
BACKGROUND
We conducted a double-blind, randomized, crossover study to assess the antithrombotic effects of the combination of aspirin (acetylsalicylic acid, ASA) and clopidogrel, with or without a loading dose, versus ASA alone in a model of arterial thrombosis in humans.


RESULTS
Eighteen male volunteers received the following 3 regimens for 10 days separated by a 1-month period: (1) 325 mg ASA daily, (2) 325 mg ASA+75 mg clopidogrel daily, (3) 325 mg ASA daily+300-mg clopidogrel loading dose on day 1 and +75 mg clopidogrel per day on days 2 to 10. The antithrombotic effect was measured 1.5, 6, and 24 hours after drug intake on day 1 and 6 hours after drug intake on day 10. Arterial thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel-plate perfusion chamber to native blood for 3 minutes at an arterial wall shear rate. Without a loading dose, clopidogrel+ASA developed an antithrombotic effect within 6 hours after the first intake. It was superior to that produced by ASA, but it was moderate (P</=0.03). However, with the loading dose, the antithrombotic effect of clopidogrel+ASA appeared within 90 minutes, and after 6 hours it was comparable to that on day 10. On day 10, clopidogrel+ASA decreased platelet thrombus formation by approximately 70%, and the effect was significantly more potent than that produced by ASA alone (P<0.001).


CONCLUSIONS
This study confirms the synergistic antithrombotic effects of a combined ASA and clopidogrel therapy and shows the early benefit obtained with a loading dose of clopidogrel.
Cadroy
Y
Y
Laboratoire de Recherche sur l'Hémostase et la Thrombose, Pavillon Lefèbvre, CHU Purpan, 31059 Toulouse CEDEX, France. cadroy.y@chu-toulouse.fr
Bossavy
J P
JP
Thalamas
C
C
Sagnard
L
L
Sakariassen
K
K
Boneu
B
B
D000328:Adult; D001158:Arteries / Q000187:drug effects; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D013927:Thrombosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin