Circulation, Vol 87, 1622-1629, Copyright © 1993 by American Heart Association
EJ Topol, R Bonan, D Jewitt, U Sigwart, VV Kakkar, M Rothman, D de Bono, J Ferguson, JT Willerson and J Strony
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 11.3%
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.
ARTICLES
Use of a direct antithrombin, hirulog, in place of heparin during coronary angioplasty
Cleveland Clinic Foundation, OH 44195.
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