LONG-TERM INTERMITTENT UROKINASE THERAPY - ANTIISCHEMIC AND HEMODYNAMIC-EFFECTS

Long-term intermittent urokinase therapy has been developed for patien ts with severe coronary artery disease and refractory angina pectoris. This therapeutic approach is predominantly effective at the microcirc ulatory level based on a combination of theologic and fibrinolytic eff ects; furthermore, plaque regression seems to be a possible mechanism. Patients with refractory angina pectoris are characterized by severe coronary artery disease without a therapeutic option for conventional revascularization procedures, only slight impairment of left ventricul ar systolic function and hyperfibrinogenemia, which results in further enhancement of myocardial ischemia due to microcirculatory impairment of blood flow. In this article data on the antiischemic effectiveness as well as first results on the impact of this therapeutic approach o n hemodynamics are described. A dose-response study, which compared 3 x 50 000 IU with 3 x 500 000 IU urokinase three times a week over a tr eatment period of 12 weeks demonstrated subjective as well as objectiv e antiischemic effectiveness. Only patients who were treated with 500 000 IU per injection achieved marked increases in exercise capacity, w hile some patients in the low-dose group presented even with a deterio ration of exercise performance. First hemodynamic studies could not sh ow marked changes of systolic parameters, either at rest or during exe rcise. But a decrease of pulmonary capillary wedge pressure at rest af ter treatment with 500 000 IU per injection indicates an improvement o f diastolic function as a result of enhanced myocardial perfusion. Ech ocardiographic measurements of transmitral Doppler now in 21 patients with end-stage coronary artery disease demonstrated normalization of e arly and late diastolic filling rates in most cases. These changes wer e accompanied by a reduction of clinical signs of heart failure. Long- term intermittent urokinase therapy is a valuable approach as it not o nly improves quality of life during the actual treatment period but by the persistence of therapeutic effects following the cessation ot the rapy.