Thrombolysis in Myocardial Ischemia Trial (TIMI III)

Objectives

Investigate the role of a thrombotic agent added to conventional medical therapies and to compare an early invasive management strategy to a more conservative early strategy in patients with unstable angina and non-Q wave myocardial infarction.

Background

The myocardial ischemic syndromes, which account for a large portion of the annual mortality and morbidity from all causes in industrialized countries, encompass a wide clinical-pathologic spectrum. At one end of this spectrum are patients with chronic stable angina. When studied by coronary arteriography, such patients usually have obstructive atherosclerotic disease with no evidence of fresh thrombosis. At the other end of the spectrum are patients with acute MI who present with a discreet episode of prolonged chest pain accompanied by persistent ST segment elevation. Such patients have a high incidence of thrombotic coronary artery occlusion, and the early intravenous administration of thrombolytic agents has been shown to reestablish perfusion, limit the extent of left ventricular dysfunction, and reduce both early (in-hospital) and late (1-year) mortality in this group.

Subjects

1,473 men and women enrolled through 25 participating centers. Ages ranged from 21 to 79 years; however, patients 75 to 79 years old were eligible for only a brief period during enrollment. Patients were required to have chest discomfort at rest suggestive of myocardial ischemia, lasting greater than 5 minutes but less than 6 hours, that occurred within 24 hours of the time of enrollment.

Conclusions

In a large study of unstable angina and non-Q wave myocardial infarction, the incidence of death and non-fatal infarction or reinfarction was low but not trivial after one year. An early invasive management strategy was associated with slightly more coronary angioplast procedures but equivalent numbers of bypass surgery procedures than a more conservative early strategy of catherization and revascularization only for signs of recurrent ischemia. The incidence of death or non-fatal infarction, or both, did not differ after one year by strategy assignment, but fewer patients in the early invasive strategy group underwent later repeat hospital admission. Either strategy is appropriate for patient management; differences in hospital admissions and revascularization procedures, with their attendant costs, are likely to be minimal.

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