© 2000 American Heart Association, Inc.
Thrombosis |
Acute Antithrombotic Effect of a Front-Loaded Regimen of Clopidogrel in Patients With Atherosclerosis on Aspirin
From the Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, New York, NY.
Correspondence Dr J.H. Chesebro, Director of Clinical Research, Zena and Michael A. Wiener Cardiovascular Institute, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574. E-mail james.chesebro{at}mssm.edu
Abstract—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<0.05). ADP-induced platelet aggregation (with 5 and 10 µmol/L) was also significantly (P<0.05) reduced with the front-loaded regimen at 2 hours, with the mean platelet aggregation being 82.2±4.4% and 81.8±4.5%, respectively, versus baseline. Similarly, flow cytometry demonstrated a significant decrease (P<0.05) in the ADP-induced fibrinogen binding (with 0.12 and 0.6 µmol/L) at 2 hours in this front-loaded regimen group (36.1±2.0% and 53.2±9.3%). With the standard regimen, platelet activity was not significantly reduced at 2 hours. Our data suggest that a front-loaded regimen of clopidogrel added to aspirin achieves a significant antithrombotic effect at 2 hours in patients with known atherosclerotic disease on chronic aspirin therapy. This provides a rationale for using front-loaded clopidogrel in combination with aspirin in percutaneous coronary interventions.
Key Words: platelet aggregation inhibitors • thrombus • atherosclerosis
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