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

Circulation. 1994 Apr;89(4):1557-66. doi: 10.1161/01.cir.89.4.1557.

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 > 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 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angina, Unstable / blood
  • Angina, Unstable / diagnostic imaging
  • Angina, Unstable / drug therapy*
  • Coronary Angiography
  • Coronary Thrombosis / blood
  • Coronary Thrombosis / diagnostic imaging
  • Coronary Thrombosis / prevention & control*
  • Dose-Response Relationship, Drug
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / therapeutic use*
  • Heparin / administration & dosage
  • Heparin / therapeutic use
  • Hirudin Therapy
  • Hirudins / administration & dosage
  • Hirudins / analogs & derivatives*
  • Humans
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use

Substances

  • Fibrinolytic Agents
  • Hirudins
  • Recombinant Proteins
  • Heparin
  • desirudin