COMPARISON OF ENOXAPARIN, HIRULOG, AND HEPARIN AS ADJUNCTIVE ANTITHROMBOTIC THERAPY DURING THROMBOLYSIS WITH RTPA IN THE STENOSED CANINE CORONARY-ARTERY

A canine model of electrolytic injury-induced coronary artery thrombos is and rtPA-induced thrombolysis was used to evaluate the relative ant ithrombotic efficacy of enoxaparin (a low molecular weight heparin), c onventional therapy (heparin or heparin plus aspirin), and hirulog (a direct thrombin inhibitor), when used as adjunctive therapy during thr ombolysis. After 60 min of clot aging, adjunctive therapy was begun at doses which elevated APTT approximately 2-fold over baseline. Fifteen minutes after the start of adjunctive therapy, recombinant tissue pla sminogen activator (rtPA) was administered (100 mu g/kg i.v. bolus + 2 0 mu g/kg/min for 60 min). Adjunctive therapy continued for 1 h after termination of rtPA and blood flow was monitored for two additional ho urs. Enoxaparin (1 mg/kg i.v. bolus + 30 mu g/kg/min, n = 10 for each treatment group) was the only adjunctive treatment that significantly increased the total minutes of flow (143 +/- 25 min out of a possible 240 min, vs 54 +/- 25 min for vehicle, p <0.05) and decreased thrombus mass (6.0 +/- 1.3 mg vs 11.8 +/- 3.2 mg for vehicle). Although hirulo g (2 mg/kg i.v. bolus + 40 mu g/kg/min) did not significantly increase the minutes of flow (120 +/- 27 min, p <0.06) or decrease thrombus ma ss (8.7 +/- 1.7 mg) compared to vehicle, these values were not signifi cantly different than those measured in the enoxaparin group. However, the results with hirulog were achieved at the expense of a significan tly greater increase in template bleeding time than that measured duri ng enoxaparin treatment. Minutes of flow for heparin (50 U/kg i.v. bol us + 0.6 U/kg/min) and heparin plus aspirin (5 mg/kg i.v. bolus) were 69 +/- 20 and 60 +/- 23 min, respectively; thrombus masses were 8.2 +/ - 1.3 and 7.3 +/- 1.0 mg, respectively. In summary, enoxaparin was mor e effective than conventional therapy in this model in terms of vessel patency and thrombus mass, and was as effective as hirulog, at least at a dose of hirulog that only modestly impaired hemostasis. Therefore , enoxaparin may prove to be a safe and effective alternative agent fo r adjunctive therapy during thrombolysis with rtPA.