Long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris: a randomized dose-response trial.
OBJECTIVE
This dose-response study was designed to test two low dose regimens of urokinase administered over a prolonged time period in patients with chronic refractory angina pectoris with respect to effects on clinical symptoms and objective variables of myocardial ischemia.


BACKGROUND
Patients with severe and chronic refractory angina pectoris in end-stage coronary artery disease represent an increasing clinical problem. Favorable therapeutic effects on myocardial ischemia have been reported for long-term application of low dose urokinase.


METHODS
Ninety-eight patients with chronic refractory and end-stage coronary artery disease were randomly assigned to two treatment groups: group A (49 patients) received 50,000 IU and group B (49 patients) 500,000 IU of urokinase as an intravenous bolus infection three times a week over a period of 12 weeks. Variables evaluated were number of weekly anginal events, data from ergometric exercise testing with simultaneous electrocardiographic registration, semiquantitative evaluation of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) scans and rheologic variables.


RESULTS
After 12 weeks of treatment, anginal symptoms (events/week) were reduced significantly in group B by 70% compared with 24% in group A (p < 0.001). Fibrinogen decreased by 3% in group A and by 33% in group B (p < 0.001). Plasma viscosity and red blood cell aggregation were reduced by 6.4% (p < 0.001) and 19.9% (p < 0.001), respectively, in group B. Objective variables of myocardial ischemia were improved significantly in group B only. No cumulation of coronary ischemic events was observed in group B.


CONCLUSIONS
Long-term intermittent urokinase therapy in an applied dose of 3 X 500,000 IU/week represents an effective anti-ischemic and antianginal approach for patients with refractory angina pectoris and end-stage coronary artery disease. Apart from rheologic improvement, antithrombotic properties and plaque regression are likely anti-ischemic mechanisms.
Leschke
M
M
Klinik für Kardiologie, Pneumologie und Angiologie, Heinrich Heine Universität Düsseldorf, Germany.
Schoebel
F C
FC
Mecklenbeck
W
W
Stein
D
D
Jax
T W
TW
Müller-Gärtner
H W
HW
Strauer
B E
BE
D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D002908:Chronic Disease; D003327:Coronary Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010960:Plasminogen Activators / Q000008:administration & dosage*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013727:Terminal Care; D013997:Time Factors; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage*
D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator