Unstable angina. Short term treatment with clopidogrel with the use of a loading dose: Effect on ADP-induced platelet aggregation

Background. Clopidogrel is an effective inhibitor of platelet aggregation, but its efficacy has not been adequately tested in acute coronary syndromes mostly because of slow onset of antiplatelet action. The use of a loading dose of the drug has been suggested for acceleration of the onset of its an tiaggregatory effect. Aim. To compare effects on ADP-induced platelet aggre gation of aspirin and combination of aspirin and clopidogrel with the use o f loading dose of the latter. Material and methods. Nineteen patients (age 65+9,79 years, 53% men) with unstable angina (Braunwald class IIIb with ST- T changes on ECC) were randomized to clopidogrel (n=10) or no clopidogrel ( control group, n=9). Patients of both groups received aspirin, subcutaneous enoxaparin 1 mg/kg b.d., and beta -blockers. In clopidogrel group the foll owing regimen of dosing was used: 300 mg on first day 1 and 75 mg/day durin g 6 subsequent days. ADP induced platelet aggregation was assessed by light transmission aggregometry before treatment, at the end of first 24 hours, on days 3, 7 and 14 after randomization. Results. In clopidogrel treated pa tients platelet aggregation decreased significantly both relative to baseli ne level and control group from 23,8+/-7,1% to 11,1+/-6,2%, 9,6+/-7,1% and 12,3+/-9,8%, in 1, 3 and 7 days after onset of treatment, respectively. Par ameters of aggregation practically did not change in control group. In most of clopidogrel treated patients decrease of individual values exceed 50% f rom baseline, but 2 of 10 patients did not respond to clopidogrel. By day 1 4 aggregation parameters in clopidogrel group were close to baseline. Concl usion. The use of a single loading dose (300 mg) of clopidogrel followed by conventional dosing for 7 days in most of aspirin treated patients with un stable angina led to rapid (24 hours) inhibition of ADP-induced platelet ag gregation. Aggregation parameters returned to baseline level but did not ex ceed it in 7 days after cessation of clopidogrel therapy.