Use of A Direct Antithrombin, Hirulog, in Place of Heparin During Coronary Angioplasty

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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 inhibitor hirulog has been demonstrated to inactivate clot-bound thrombin. The present study was a multicenter dose escalation of hirulog to determine 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 pretreated with 325 mg aspirin daily were enrolled in sequential groups of intravenously administered hirulog instead of heparin as follows: group 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 patients); group 3: bolus, 0.35 mg/kg; infusion, 1.4 mg · kg-1 · hr-1 (44 patients); 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 the initiation of the procedure. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) were serially monitored. Abrupt vessel closure occurred in 18 patients (6.2%). By intention to treat, the abrupt closure event rate for groups 1-3 was 113% compared with 3.9% in groups 4 and 5 (p=0.052). There were no significant bleeding complications except for one patient in group 1, who received a two-unit transfusion. A dose-response curve of both ACTs and aPTTs was noted; no coronary thrombotic closures occurred in the small number of patients with ACT >300 seconds.Conclusions.The present study documents for the first time that it is possible to perform coronary angioplasty with an anticoagulant other than heparin in aspirin-pretreated patients. Hirulog was associated with a rapid onset, dose-dependent anticoagulant effect, minimal bleeding complications, and at doses of 1.8-2.2 mg/kg, a rate of 3.9% for abrupt vessel closure.(Circulation1993;87:1622-1629)

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