Thrombolysis in Myocardial Ischemia Trial (TIMI III)

BACKGROUND:

TIMI IIIA and TIMI IIIB follow the contract-supported clinical trial, Thrombolysis in Myocardial Infarction (TIMI I, TIMI IIA, and TIMI II).

Myocardial ischemic syndromes account for a large portion of the annual mortality and morbidity from all causes in industrialized countries and 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 myocardial infarction who present with a discrete 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 re-establish perfusion, limit the extent of left ventricular dysfunction, and reduce both early or in-hospital and late or one year mortality in this group.

Patients with non-Q-wave myocardial infarction and unstable angina fall between these two extremes. In the days and weeks following the onset of their disorder, their prognosis for survival is better than that of patients with Q-wave myocardial infarction but worse than that of patients with stable angina. Some patients with unstable angina progress to acute myocardial infarction, and some of those with non-Q-wave infarction experience an unstable course with reinfarction. Although others recover from the acute episode without subsequent infarction or reinfarction, they frequently have severe obstructive coronary artery disease and may be left with severe chronic stable angina. National summaries of hospital records indicate that 750,000 patients are hospitalized yearly with unstable angina and 250,000 with non-Q-wave myocardial infarction.

Once the results of creatine kinase measurements and serial electrocardiograms are available, the identification of patients experiencing non-Q-wave myocardial infarction is relatively simple. Identification of patients experiencing unstable angina is more difficult, since numerous definitions of the condition have been offered. There is agreement, however, on two important features of unstable angina. First, ischemia usually develops at rest or is precipitated by minimal exertion; this differs from chronic stable angina, in which most ischemic episodes are precipitated by physical exertion or strong emotion and the resultant increase in myocardial oxygen demand. Second, ischemia is often associated with transient ST-segment depression or elevation, in contrast to the persistent ST-segment elevation characteristic of patients who develop Q-wave infarction.