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


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.
Topol
E J
EJ
Department of Cardiology, Cleveland Clinic Foundation, OH 44195.
Fuster
V
V
Harrington
R A
RA
Califf
R M
RM
Kleiman
N S
NS
Kereiakes
D J
DJ
Cohen
M
M
Chapekis
A
A
Gold
H K
HK
Tannenbaum
M A
MA
D000789:Angina, Unstable / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; C060225:desirudin