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 asse ss the antithrombotic effects of the combination of aspirin (acetylsalicyli c acid, ASA) and clopidogrel, with or without a loading dose, versus ASA al one in a model of arterial thrombosis in humans. Methods and Results-Eighteen male volunteers received the following 3 regim ens for 10 days separated by a 1-month period: (1) 325 mg ASA daily, (2) 32 5 mg ASA+75 mg clopidogrel daily, (3) 325 mg ASA daily+300-mg clopidogrel l oading dose on day 1 and +75 mg clopidogrel per day on days 2 to 10, The an tithrombotic 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-p late perfusion chamber to native blood for 3 minutes at an arterial wall sh ear rate. Without a loading dose, clopidogrel+ASA developed an antithrombot ic effect within 6 hours after the first intake. It was superior to that pr oduced by ASA, but it was moderate (P less than or equal to 0.03). However, with the loading dose, the antithrombotic effect of clopidogrel+ASA appear ed 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 appro ximate to 70%, and the effect was significantly more potent than that produ ced 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.