SELECTIVE-INHIBITION OF FACTOR XA IS MORE EFFICIENT THAN FACTOR VIIA-TISSUE FACTOR COMPLEX BLOCKADE AT FACILITATING CORONARY THROMBOLYSIS IN THE CANINE MODEL

Objectives. We determined the effect of adjunctive inhibition of the e xtrinsic coagulation pathway by factor VIIa-tissue factor complex inhi bitors, DEGR VIIa and tissue factor pathway inhibitor (TFPI), and the selective factor Xa inhibitor, tick anticoagulant peptide (TAP), after thrombolytic therapy with tissue-type plasminogen activator (t-PA)) i n a canine model of electrically induced coronary thrombosis, Backgrou nd. Ongoing thrombin generation is considered an important component o f the heightened thrombin activity associated with thrombolytic therap y and may be responsible for reperfusion failure and reocclusion, Meth ods. Forty-two dogs with electrically induced coronary thrombus underg oing thrombolysis with t-PA (1 mg/kg over 20 min) were randomly assign ed to one of the following adjunctive regimens: TAP (30 mu g/kg body w eight per min for 90 min, n = 10); TFPI (100 to 150 mu g/kg per min fo r 90 min, n = 10); DEGR VIIa (1- to 2-mg/kg bolus, n = 10) and saline control (n = 12). The dogs were observed for 120 min after thrombolysi s for reocclusion. Results. All three active study agents accelerated the time to reperfusion by an average of 12 min (all p < 0.05). Durati on of reflow was greatest with TAP (117 +/- 8 min, p < 0.05 compared w ith saline central), whereas DEGR VIIa and TFPI did not prolong the du ration of reflow. Reocclusion rates were similar among control, DEGR V IIa and TFPI groups (70%, 78% and 67%, respectively). Tick anticoagula nt peptide reduced the occurrence of reocclusion (0%, p < 0.05 compare d with saline control), Conclusions. In this experimental model. durin g systematic blockade of various extrinsic coagulation pathway protein s, we demonstrated that whereas acceleration of thrombolysis occurs wi th factor VIIa-tissue factor complex inhibition, optimal enhancement o f thrombolysis was achieved through specific factor Xa blockade. (C) 1 996 by the American College of Cardiology