A DOUBLE-BLIND RANDOMIZED COMPARISON OF COMBINED ASPIRIN AND TICLOPIDINE THERAPY VERSUS ASPIRIN OR TICLOPIDINE ALONE ON EXPERIMENTAL ARTERIAL THROMBOGENESIS IN HUMANS

No randomized study comparing the effect of combined ticlopidine and a spirin therapy versus each drug alone in reducing poststenting thrombo tic complications has been performed. To compare these three antiplate let regimens versus placebo, we conducted a double-blind randomized st udy using an ex vivo model of thrombosis. Sixteen healthy male volunte ers were assigned to receive for 8 days the following four regimens se parated by a 1-month period: aspirin 325 mg/d, ticlopidine 500 mg/d, a spirin 325 mg/d + ticlopidine 500 mg/d, and placebo. At the end of eac h treatment period, native nonanticoagulated blood was drawn directly from an antecubital vein over collagen- or tissue factor (TF)-coated c overslips positioned in a parallel-plate perfusion chamber at an arter ial wall shear rate (2,600 s(-1)) for 3 minutes. Thrombus, which forme d on collagen in volunteers treated by placebo, were rich in platelets and poor in fibrin. As compared with placebo, aspirin and ticlopidine alone reduced platelet thrombus formation by only 29% and 15%, respec tively (P > .2). In contrast, platelet thrombus formation was blocked by more than 90% in volunteers treated by aspirin + ticlopidine (P < . 01 v placebo or each treatment alone). Furthermore, the effect of the drug combination therapy was significantly larger than the sum of the two active treatments (P < .05). Thrombus, which formed on TF-coated c overslips in volunteers treated by placebo, were rich in fibrin and pl atelets. Neither of the three antiplatelet treatments significantly in hibited fibrin deposition and platelet thrombus formation on this surf ace (P > .2). Thus, the present study shows that combined aspirin and ticlopidine therapy dramatically potentiates the antithrombotic effect of each drug alone, but that the antithrombotic effect of the combine d treatment depends on the nature of the thrombogenic surface. (C) 199 8 by The American Society of Hematology.