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

Journal Article (Clinical Trial;Journal Article;Multicenter Study)

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 > or = 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 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.

Full Text

Duke Authors

Cited Authors

  • Topol, EJ; Fuster, V; Harrington, RA; Califf, RM; Kleiman, NS; Kereiakes, DJ; Cohen, M; Chapekis, A; Gold, HK; Tannenbaum, MA

Published Date

  • April 1, 1994

Published In

Volume / Issue

  • 89 / 4

Start / End Page

  • 1557 - 1566

PubMed ID

  • 8149521

International Standard Serial Number (ISSN)

  • 0009-7322

Digital Object Identifier (DOI)

  • 10.1161/01.cir.89.4.1557


  • eng

Conference Location

  • United States