Recombinant hirudin for unstable angina pectoris: A multicenter, randomized angiographic trial

E. J. Topol, V. Fuster, R. A. Harrington, R. M. Califf, N. S. Kleiman, D. J. Kereiakes, M. Cohen, A. Chapekis, H. K. Gold, M. A. Tannenbaum, A. K. Rao, D. Debowey, D. Schwartz, M. Henis, J. Chesebro

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

Background: Coronary artery thrombosis plays an important pathophysiological role in unstable angina and non-Q-wave myocardial infarction. To date, heparin and thrombolytic therapy has not provided complete or consistent benefit. We hypothesized that recombinant hirudin, a direct thrombin inhibitor, would prevent accumulation of coronary artery thrombus in a manner superior to heparin. Methods and Results: Patients with rest ischemic pain, abnormal ECG, and baseline angiogram indicating a ≥60% stenosis of a culprit coronary artery or saphenous vein graft with visual appearance of thrombus were randomized to one of two different doses of heparin (either a target activated partial thromboplastin time [aPTT] of 65 to 90 or 90 to 110 seconds) or one of four doses of hirudin (0.05, 0.10, 0.20, or 0.30 mg · kg-1 · h-1 infusion) in a dose-escalating protocol. After 72 to 120 hours of study drug, a repeat coronary angiogram was obtained, and the paired studies underwent quantitative analysis. The primary end point was change in the average cross-sectional area of the culprit lesion. Other efficacy end points also involved changes in culprit lesion dimensions and TIMI flow grade. Recombinant hirudin led to a dose-dependent elevation of aPTT that appeared to plateau at the 0.2-mg/kg dose. A higher proportion of hirudin-treated patients had their aPTT within a 40-second range (16% heparin versus 71% hirudin, P<.001). Overall, the 116 patients treated with hirudin tended to show more improvement than the 50 patients receiving heparin relative to the primary efficacy variable-the average cross-sectional area (P=.08)-as well as minimal cross-sectional area (P=.028), minimal luminal diameter (P=.029), and percent diameter stenosis (P=.07). Conclusions: Recombinant hirudin appears to be a promising antithrombotic intervention compared with heparin for inhibition of coronary artery thrombus. Large-scale comparative trials are warranted.

Original languageEnglish (US)
Pages (from-to)1557-1566
Number of pages10
JournalCirculation
Volume89
Issue number4
DOIs
StatePublished - 1994

Keywords

  • Angina
  • Anticoagulants
  • Hirudin
  • Thrombin
  • Thrombosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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