Platelet and fibrin deposition on coronary stents in minipigs: Effect of hirudin versus heparin

Abstract

Objectives. The present study was designed to test the hypothesis that the direct thrombin inhibitor hirudin is more efficient than heparin in reducing thrombus formation after coronary stenting.Background. Despite aggressive anticoagulation, subacute thrombosis of coronary stents is a major complication associated with these new devices.Methods. In 19 minipigs indium-111-labeled thrombocytes and iodine-125-labeled fibrinogen were injected 14 to 19 h before coronary implantation of tantalum balloon-expandable stents. In group 1 (n = 6, seven stents), a bolus of heparin (100 U/kg body weight) was given before stenting. Group 2 (n = 6, 11 stents) received both dextran (500 ml) and heparin (a 100-U/kg bolus followed by a continuous infusion of 50 U/kg per h). In group 3 (n = 7, 13 stents), hirudin (recombinant desulphatohirudin HV 1 [CGP 39393] [1 mg/kg]) was given before stent implantation, followed by an infusion of 1 mg/kg per h. All animais were pretreated with aspirin (250 mg intravenously).Results. Activated partial thromboplastin time was prolonged to >1.8 times control values in groups 2 and 3. Histologic examination after perfusion fixation 12 h after stenting showed a variable extent of thrombus on all stents. Medial tear was observed in three stents in group 1, six stents in group 2 and six stents in group 3. The number of platelets on all stens averaged 116.2 (range 22 to 522) × 106in group 1, 64.3 (range 11 to 169) × 106in group 2 and 19.7 (range 9 to 38) × 106in group 3 (p < 0.05 vs. group 1 and vs. group 2). The increase in platelet deposition. associated with medial tear in all groups, was lowest in the hirudin group. Similarly, fibrin deposition was lowest on stents in hirudintreated animals.Conclusions. Recombinant hirudin significantly reduces platelet and fibrin deposition on coronary stents compared with the reduction achieved with combined heparin, dextran and aspirin.