Acute Antithrombotic Effect of a Front-Loaded Regimen of Clopidogrel in Patients With Atherosclerosis on Aspirin

There is a need for a rapid antithrombotic effect after the administration of antiplatelet drugs in the setting of acute coronary syndromes and percutaneous interventions. Clopidogrel, a new thienopyridine derivative, is an efficient antiplatelet agent. However, the standard regimen of clopidogrel (75 mg/d) requires 2 to 3 days before significant antithrombotic effects. Patients with stable arterial disease on chronic aspirin therapy (n=20) were treated with clopidogrel either with a front-loaded regimen, 300 mg the first day and 75 mg/d the next 7 days, or with a standard regimen, 75 mg/d for 8 days. Blood thrombogenicity was assessed by quantification of platelet-thrombus formation in an ex vivo perfusion chamber, by ADP-induced platelet aggregation, and by ADP-induced fibrinogen binding. At 2 hours, mean total thrombus area with the standard regimen was not significantly reduced. In contrast, at 2 hours, the mean total thrombus area with the front-loaded regimen was significantly decreased by 23.1±8.5% versus baseline (P