Use of A direct antithrombin, hirulog, in place of heparin during coronary angioplasty

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 multice...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 1993-05, Vol.87 (5), p.1622-1629
Main Authors: TOPOL, E. J, BONAN, R, GANZ, P, COHEN, M. D, RAYMOND, R, FOX, I, MARAGANORE, J, ADELMAN, B, JEWITT, D, SIGWART, U, KAKKAR, V. V, ROTHMAN, M, DE BONO, D, FERGUSON, J, WILLERSON, J. T, STRONY, J
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Amino Acid Sequence
Angioplasty, Balloon, Coronary
Antithrombins - administration & dosage
Antithrombins - adverse effects
Antithrombins - therapeutic use
Biological and medical sciences
Blood Coagulation - drug effects
Blood. Blood coagulation. Reticuloendothelial system
Drug Administration Schedule
Feasibility Studies
Female
Hemorrhage - chemically induced
Heparin - therapeutic use
Hirudin Therapy
Hirudins - administration & dosage
Hirudins - adverse effects
Hirudins - analogs & derivatives
Humans
Male
Medical sciences
Middle Aged
Molecular Sequence Data
Partial Thromboplastin Time
Peptide Fragments - administration & dosage
Peptide Fragments - adverse effects
Peptide Fragments - therapeutic use
Pharmacology. Drug treatments
Recombinant Proteins - administration & dosage
Recombinant Proteins - adverse effects
Recombinant Proteins - therapeutic use
Time Factors
Vascular Patency
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Summary: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. 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. 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.
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.87.5.1622