ONE-YEAR RESULTS OF THE THROMBOLYSIS IN MYOCARDIAL-INFARCTION (TIMI) IIIB CLINICAL-TRIAL - A RANDOMIZED COMPARISON OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR VERSUS PLACEBO AND EARLY INVASIVE VERSUS EARLY CONSERVATIVE STRATEGIES IN UNSTABLE ANGINA AND NON-Q-WAVE MYOCARDIAL-INFARCTION

Objectives. We report mortality, infarction, revascularization and rep eat hospital admission events for 1 gear after enrollment and randomiz ation in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB clinical trial. Background. The purpose of this trial was to investigate the ro le of a thrombolytic agent added to conventional medical therapies and to compare an early invasive management strategy to a more conservati ve early strategy in patients with unstable angina and non-Q wave myoc ardial infarction. Methods. There were 1,473 patients enrolled, and th ey received conventional anti-ischemic medical therapies. They were ra ndomized to therapy with either tissue-type plasminogen activator (t-P A) or placebo and also to an early invasive management strategy with c oronary arteriography at 18 to 48 h, followed by revascularization as soon as possible if appropriate, or, alternatively, to an early conser vative strategy with arteriography and revascularization reserved for failure of initial therapy to prevent recurrent ischemia. The primary end point was a composite outcome variable and was assessed at 42 days . Patients were then managed entirely at the discretion of their treat ing physician. Follow-up contacts were made at 1 gear. Results. The in cidence of death or nonfatal infarction for the t-PA- and placebo-trea ted groups was similar after 1 year (12.4% vs. 10.6%, p = 0.24). The i ncidence of death or nonfatal infarction was also similar after 1 year for the early invasive and early conservative strategies (10.8% vs. 1 2.2%, p = 0.42). A trial of this size should be able to detect differe nces in relative risk for death or infarction greater than or equal to 1.81 with a power of 80% at a significance level (alpha) of 0.01. Rev ascularization by I year was common, but was slightly more common with the early invasive than the early conservative strategy (64% vs. 58%, p < 0.001). This result was related entirely to a small difference in angioplasty rates (39% vs. 32%, p < 0.001) inasmuch as rates of bypas s grafting by 1 year were equivalent (30% in each group, p = 0.50). Th e high rate of revascularization in both strategies was accompanied by comparable clinical status at the I-year follow-up contact. Conclusio ns. In this large study of unstable angina and non-Q wave myocardial i nfarction, the incidence of death and nonfatal infarction or reinfarct ion was low but not trivial after 1 year (4.3% mortality, 8.8% nonfata l infarction). An early invasive management strategy was associated wi th slightly more coronary angioplasty procedures but equivalent number s of bypass surgery procedures than a more conservative early strategy of catheterization and revascularization only for signs of recurrent ischemia. The incidence of death or nonfatal infarction, or both, did not differ after 1 year by strategy assignment, but fewer patients in the early invasive strategy group underwent later repeat hospital admi ssion (26% vs. 33%, p < 0.001), Either strategy is appropriate for pat ient management; differences in hospital admissions and revascularizat ion procedures, with their attendant costs, are likely to be minimal. (J Am Coll Cardiol 1995;26:1643-50)