We tested the safety and the usefulness of intravenous urokinase (2 million units administered over 30 min) in 44 patients with refractory unstable angina, defined as persistence of ischemic episodes during 48-h Holter monitoring (Phase 1) despite maximal medical therapy. After thrombolysis, recurrence of ischemia was observed during a week of observation in the CCU, including two 24-h Holter monitorings at the beginning and the end of the week (Phase 2). Seventeen patients completed the observation period without either symptomatic or asymptomatic ischemic episodes (Group A); the remaining 27 continued to manifest ischemia (Group B). No bleeding complications occurred. Within a 6-month follow-up, 2 patients of Group A had recurrence of unstable angina while in Group B, 19 patients had refractory angina or a major cardiac event [10 patients underwent coronary artery bypass surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) for refractory angina (p less than 0.001), 6 other patients with refractory angina continued medical therapy, one patient had a myocardial infarction, and two patients died]. In Phase 1 the duration of total ischemia (min/24 h) was a relevant prognostic marker: higher duration correlated with adverse clinical outcome (p less than 0.01). In comparison to Phase 1, duration of total ischemia in Phase 2 was significantly reduced in both groups (16.9 +/- 19.6 vs. 25.4 +/- 17.7; p less than .001). A percent value expressing this variation was calculated for each patient: the variation thus obtained again gave information on the clinical outcome--the greater the reduction, the lower the risk of cardiac events (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)