COMPARISON OF A LOW-MOLECULAR-WEIGHT HEPARIN (NADROPARIN CALCIUM) ANDUNFRACTIONATED HEPARIN AS ADJUNCT TO CORONARY THROMBOLYSIS WITH ALTEPLASE AND ASPIRIN IN DOGS

Background: Low-molecular-weight heparins may have a higher benefit to risk ratio than unfractionated heparin in preventing perioperative th rombosis. The antithrombotic effects of low-molecular-weight heparins, given as adjunctive therapy to alteplase and aspirin, have not previo usly been compared with those of unfractionated heparin in experimenta l models of coronary artery thrombosis. Methods: Occlusive coronary th rombosis was induced in 5 groups of 10 dogs by placing a copper coil i nto the left anterior descending coronary artery. After 1 h of occlusi on, intravenous alteplase (0.1 mg/kg bolus followed by 0.01 mg/kg/min for 30 min), and aspirin (bolus of 5 mg/kg) were administered in combi nation with one of the following study treatments given intravenously for 2 h: placebo (group I); unfractionated heparin (200 IU/kg bolus fo llowed by 100 IU/kg/h, group II); the low-molecular weight heparin, na droparin calcium, in three different doses (100 IU/kg bolus followed b y 50 IU/kg/h, group III; 200 IU/kg bolus followed by 100 IU/kg/h, grou p IV; and 300 IU/kg followed by 150 IU/kg/h, group V). Coronary patenc y was assessed with angiography at 10 min intervals and hemostasis par ameters were measured at baseline, after 1 h of occlusion, and 30 and 120 min after commencing drug administration. Results: Optimal reperfu sion [Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 withou t reocclusion] was more frequently observed in groups II (6/10), IV (8 /10) and V (9/10) than in groups I (1/10) and III (3/10) (P<0.05). Gro ups II and IV had similar patency rates (P=NS) and were therefore assu med to represent equivalent antithrombotic doses. Both nadroparin calc ium and unfractionated heparin effectively prevented new thrombin gene ration as shown by repeated measurements of thrombin-antithrombin III complex levels in plasma. At equivalent antithrombotic doses, nadropar in calcium (group IV) was associated with significantly lower steady s tate values than standard heparin (group II) for activated partial thr omboplastin time (41.3+/-48.9 versus 134.7+/-61.6 s); anti-Xa levels ( 2.4+/-0.5 vs 3.4+/-0.9 U/ml) and anti-IIa levels (0.8+/-0.1 versus 2.1 +/-0.7 U/ml). Conclusion: Both nadroparin calcium and unfractionated h eparin significantly enhance alteplase-induced thrombolysis in aspirin -treated dogs. At equivalent antithrombotic doses, nadroparin calcium was associated with less prolongation of the activated partial thrombo plastin time and lower steady-state anti-Xa and anti-IIa activities.