EFFECTS OF TISSUE-PLASMINOGEN ACTIVATOR AND A COMPARISON OF EARLY INVASIVE AND CONSERVATIVE STRATEGIES IN UNSTABLE ANGINA AND NON-Q-WAVE MYOCARDIAL-INFARCTION - RESULTS OF THE TIMI IIIB TRIAL

Background Although coronary thrombosis plays a critical role in the p athogenesis of unstable angina and non-Q-wave myocardial infarction (N QMI), the effects of thrombolytic therapy in these disorders is not cl ear. Also, the role of routine early coronary arteriography followed b y revascularization has not been established. Methods and Results Pati ents (n=1473) seen within 24 hours of ischemic chest discomfort at res t, considered to represent unstable angina or NQMI, were randomized us ing a 2x2 factorial design to compare (1) TPA versus placebo as initia l therapy and (2) an early invasive strategy (early coronary arteriogr aphy followed by revascularization when the anatomy was suitable) vers us an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients wer e treated with bed rest, anti-ischemic medications, aspirin, and hepar in. The primary end point for the TPA-placebo comparison (death, myoca rdial infarction, or failure of initial therapy at 6 weeks) occurred i n 54.2% of the TPA-treated patients and 55.5% of the placebo-treated p atients (P=NS). Fatal and nonfatal myocardial infarction after randomi zation (reinfarction in NQMI patients) occurred more frequently in TPA -treated patients (7.4%) than in placebo-treated patients (4.9%, P=.04 , Kaplan-Meier estimate). Four intracranial hemorrhages occurred in th e TPA-treated group versus none in the placebo-treated group (P=.06). The end point for the comparison of the two strategies (death, myocard ial infarction, or an unsatisfactory symptom-limited exercise stress t est at 6 weeks) occurred in 18.1% of patients assigned to the early co nservative strategy and 16.2% of patients assigned to the early invasi ve strategy (P=NS). In the latter, the average length of initial hospi talization, incidence of rehospitalization within 6 weeks, and days of rehospitalization all were significantly lower. Conclusions In the ov erall trial, patients with unstable angina and NQMI were managed with low rates of mortality (2.4%) and myocardial infarction or reinfarctio n (6.3%) at the time of the 6-week visit. These results can be achieve d using either an early conservative or early invasive strategy, the l atter resulting in a reduced incidence of days of hospitalization and of rehospitalization and in the use of antianginal drugs. The addition of a thrombolytic agent is not beneficial and may be harmful.