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Long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina
M Leschke1, F C Schoebel, W Mecklenbeck
1Klinik für Kardiologie, Pneumologie und Angiologie, Heinrich Heine Universität Düsseldorf, Germany.
Insights
A higher dose of urokinase (500,000 IU) significantly reduced angina symptoms and improved myocardial ischemia in patients with refractory coronary artery disease. This low-dose, long-term urokinase therapy offers an effective anti-ischemic and antianginal approach.
Area of Science:
- Cardiology
- Pharmacology
- Ischemia Research
Background:
- Chronic refractory angina pectoris in end-stage coronary artery disease is a growing clinical challenge.
- Long-term low-dose urokinase has shown promise in improving myocardial ischemia.
Purpose of the Study:
- To evaluate the dose-response effects of two low-dose urokinase regimens over 12 weeks.
- To assess impacts on clinical symptoms and objective measures of myocardial ischemia in refractory angina patients.
Main Methods:
- Ninety-eight patients with chronic refractory angina were randomized into two groups.
- Group A received 50,000 IU and Group B received 500,000 IU of urokinase intravenously, three times weekly for 12 weeks.
- Evaluated outcomes included anginal events, exercise testing, MIBI scans, and rheologic variables.
Main Results:
- Group B (500,000 IU) showed a 70% reduction in anginal events versus 24% in Group A (p < 0.001).
- Significant improvements in fibrinogen, plasma viscosity, and red blood cell aggregation were observed in Group B.
- Objective measures of myocardial ischemia improved significantly only in Group B.
Conclusions:
- Long-term intermittent urokinase therapy at 3 x 500,000 IU/week is an effective anti-ischemic and antianginal treatment for refractory angina.
- Potential mechanisms include rheologic improvement, antithrombotic effects, and plaque regression.
- This regimen demonstrated efficacy without accumulating ischemic events.
Objectives:
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.