USE OF A DIRECT ANTITHROMBIN, HIRULOG, IN PLACE OF HEPARIN DURING CORONARY ANGIOPLASTY

Background. Since the inception of coronary angioplasty, heparin with or without aspirin has been routinely given intraprocedurally to avoid coronary thrombotic complications. Recently, the direct thrombin inhi bitor hirulog has been demonstrated to inactivate clot-bound thrombin. The present study was a multicenter dose escalation of hirulog to det ermine its appropriate dose and feasibility as the sole anticoagulant during coronary angioplasty. Methods and Results. At 11 participating centers, 291 patients undergoing elective coronary angioplasty and pre treated with 325 mg aspirin daily were enrolled in sequential groups o f intravenously administered hirulog instead of heparin as follows: gr oup 1: bolus, 0.15 mg/kg; infusion, 0.6 mg . kg-1 . hr-1 (54 patients) ; group 2: bolus, 0.25 mg/kg; infusion, 1.0 mg . kg-1 . hr-1 (53 patie nts); group 3: bolus, 0.35 mg/kg; infusion, 1.4 mg . kg-1 . hr-1 (44 p atients); group 4: bolus, 0.45 mg/ kg; infusion, 1.8 mg . kg-1 . hr-1 (74 patients); and group 5: bolus, 0.55 mg/kg; infusion, 2.2 mg . kg-1 . hr-1 (54 patients). The hirulog infusion was maintained for 4 hours ; the primary end point was abrupt vessel closure within 24 hours of t he initiation of the procedure. Activated clotting times (ACT) and act ivated partial thromboplastin times (aPTT) were serially monitored. Ab rupt vessel closure occurred in 18 patients (6.2%). By intention to tr eat, the abrupt closure event rate for groups 1-3 was 11.3% compared w ith 3.9% in groups 4 and 5 (p=0.052). There were no significant bleedi ng complications except for one patient in group 1, who received a two -unit transfusion. A dose-response curve of both ACTs and aPTTs was no ted; no coronary thrombotic closures occurred in the small number of p atients with ACT > 300 seconds. Conclusions. The present study documen ts for the first time that it is possible to perform coronary angiopla sty with an anticoagulant other than heparin in aspirin-pretreated pat ients. Hirulog was associated with a rapid onset, dose-dependent antic oagulant effect, minimal bleeding complications, and at doses of 1.8-2 .2 mg/kg, a rate of 3.9% for abrupt vessel closure.