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

Ability of a loading dose of ticlopidine to accelerate safely the onset of antiplatelet effect of the drug was not adequately tested in patients with unstable angina. Aim. To compare effects on ADP-induced platelet aggregatio n of aspirin and combination of aspirin and ticlopidine with the use of loa ding dose of the fatter. Material and methods. Thirty seven patients (age 6 7+/-10 years, 49% men) with unstable angina were randomized to ticlopidine (n=19) or no ticlopidine (control group, n=18) within 48 hours after onset of resting pain with ST-T changes on ECC. Patients of both groups received aspirin, heparin infusion, and P-blockers. The following regimen of ticlopi dine dosing was used: 1000 mg/day (500 mg b.d.) for 2 days and 500 mg/day ( 250 mg b.d.) for 5 subsequent days. ADP-induced platelet aggregation was as sessed by light transmission aggregometry before treatment, at the end of f irst 24 hours, on days 3,7 and 14 after randomization. Results. In ticlopid ine treated patients degree and velocity of ADP induced platelet aggregatio n significantly decreased both relative to baseline level and control group just in 1 day after initiation of treatment. Maximal lowering of these par ameters occurred on day 3. Degree of aggregation decreased from 18+/-8 (bas eline) to 8,6+/-6,8 U (day 3, p<0,01) and from 19,6+/-8,1 (baseline) to 16, 4+/-7,5 U (day 3, n.s.) in ticlopidine and control groups, respectively. Ag gregation velocity decreased from 15,3+/-5,5 (baseline) to 11,6+/-5,1 (day 1, p<0,01) and 7,1+/-5,1 U/min (day 3, p<0,01) in ticlopidine treated patie nts and practically did not change in controls. By day 14 aggregation veloc ity in ticlopidine group was significantly lower compared with baseline lev el but not with controls. Conclusion. The use of a loading dose (1000 mg/da y for 2 days) of ticlopidine in aspirin treated patients with unstable angi na led to rapid (detectable in 1 day, maximal in 3 days) inhibition of ADP induced platelet aggregation. Aggregation did not return to baseline level in 7 days after cessation of ticlopidine therapy.