Thrombolysis and angioplasty in unstable angina - TAUSA
Urokinase during PTCA for unstable angina or postinfarct rest angina.
To assess the role of intracoronary urokinase during angioplasty for unstable angina or postinfarct rest angina.
Patients Screened: Not given
Patients Enrolled: 469
Criteria for inclusion were either unstable angina with ischemic rest pain <7 days before angioplasty, non-Q-wave infarction <7 days before angioplasty, or a recent (<30 days) non-Q-wave or Q-wave infarction with recurrent rest pain <7 days before angioplasty. In all patients a "culprit" lesion with ≥70% visual diameter stenosis in a native coronary artery or saphenous vein graft was identifiable and considered suitable for angioplasty. Lesions in degenerated vein grafts were excluded as well as native coronary lesions with abundant (one or more filling defects occupying the entire lumen and ≥5 mm in length) intracoronary thrombi before angioplasty. An additional criterion for enrollment was that the ECGs during an episode of rest pain show transient ST or T changes or, if not available during pain, the baseline ECGs show diagnostic Q waves or resting ST or T changes. Patients with normal baseline ECGs (if none were available during an episode of ischemic rest pain) and those with completely normal ECGs during rest pain were excluded. Additionally, patients >75 years old were initially excluded. However, the age limit was increased to 80 years after the first 200 patients were randomized. Other exclusions included uncontrolled hypertension (>180/110 mm Hg), prior cerebrovascular accident, recent (<10 days) major surgery, bleeding diatheses, active gastrointestinal or genitourinary bleeding, hematocrit <30%, or prior enrollment in the TAUSA pilot study or trial.
Primary endpoints were both angiographic and clinical and consisted of acute closure, the presence of definitive filling defects after angioplasty, recurrent in-hospital ischemia, myocardial infarction, urgent coronary artery bypass graft (CABG), or death.
In-hospital follow-up was performed for evidence of recurrent ischemia, myocardial infarction, the need for urgent (<24 hours after PTCA) CABG, or death.
There were 257 patients in phase I and 212 in phase II. In phase I, 128 patients were assigned to urokinase and 129 to placebo. In phase II, 104 patients received urokinase and 108 received placebo.
Angioplasty was successful in 95% of culprit lesions. Success was higher in the placebo group (97%) versus the urokinase group (94%), although this difference was not significant. In both phases, definite filling defects were less common with urokinase than placebo, although the differences were not significant. On the other hand, acute closure occurred more frequently with urokinase than placebo (23 (10.2%) versus 10 (4.3%), respectively (P<.02)). These differences between urokinase and placebo were more striking in phase II (9 (8.7%) versus 2 (1.9%), respectively (P=.031)) than in phase I (14 (11.5%) versus 8 (6.3%), respectively (P=NS)). Of the 33 lesions with acute closure, the mechanism of acute closure was dissection in 11 and thrombus in 18. In 4 patients the mechanism was unknown. The activated coagulation times were >300 seconds at the end of the procedure in 71% of patients with acute closure compared with 72% of patients without acute closure (P=NS). During the procedure for the entire population of urokinase and placebo patients, there were no significant differences in the median activated clotting time value (1 hour after the start of PTCA: urokinase, 322 seconds versus placebo, 336 seconds; P=NS). The median bolus dose of heparin was also similar between urokinase and placebo (10 000 U in both groups)
No patient died in the hospital.
Seventeen patients (3.6%) underwent emergency CABG (12 (5.2%) in the urokinase group versus 5 (2.1%) in the placebo group (P=.09)). Of these 17 patients, 15 went to surgery from the cardiac catheterization laboratory and 2 patients were sent to surgery within the first 24 hours after the procedure. Eleven patients had (re)infarction after angioplasty, with no difference between urokinase and placebo groups. Ischemia after angioplasty occurred in overall 31 patients (6.6%) (23 (9.9%) on urokinase and 8 (3.4%) on placebo, P=.005). The percentage of urokinase patients who had a clinical end point of either recurrent ischemia, (re)infarction, or CABG (12.9% (30/232)) was significantly greater (P=.018) than the percentage of placebo patients who experienced at least one of these clinical end points (6.3% (15/237)).
The present trial does not indicate a role for prophylactic intracoronary urokinase before angioplasty for ischemic rest angina. Not only was urokinase unable to significantly decrease filling defects, but it also significantly increased both the incidence of acute closure and in-hospital adverse clinical events. These negative results with intracoronary thrombolytic therapy in the present trial are similar to recent studies of intravenous thrombolytic therapy in the acute management of unstable angina, in which the incidence of myocardial infarction was increased after use of these agents. In the manner in which urokinase was administered, prophylactic thrombolytic therapy should not be used routinely before angioplasty in ischemic rest angina.
1. Circulation 1994;90:69-77. Final results
Keywords: Thrombolytic Therapy, Myocardial Infarction, Stroke, Urokinase-Type Plasminogen Activator, Cardiac Catheterization, Heparin, Constriction, Pathologic, Fibrinolytic Agents, Angioplasty, Hematocrit, Thrombosis, Saphenous Vein, Coronary Vessels, Hypertension, Disease Susceptibility
< Back to Listings