Thrombolytic Therapy For Acute Coronary Syndromes

Because of the high incidence and detrimental role of intracoronary thrombus in acute coronary syndromes, much attention has been focused on the potential use of thrombolytic agents to improve outcomes. Several randomized trials (12-25) were undertaken in the late 1980s and early 1990s to assess the effect of thrombolytic therapy on angiographic and clinical outcomes in patients with unstable angina and non-ST-elevation MI. These studies involved relatively small numbers of patients and used a variety of thrombolytic agents including tissue-type plasminogen activator, streptoki-nase, or urokinase. The findings of these studies were not consistent, and most, but not all, showed angiographic and clinical benefits (Table 1). Because of their small size and the conflicting results, no definitive conclusions could be reached about the efficacy of thrombolytic therapy in unstable angina and non-ST-elevation MI.

The Thrombolysis in Myocardial Infarction (TIMI) III trial was the first large randomized, placebo-controlled trial that used a 2 X 2 factorial design to compare tissue-type plasminogen activator and placebo, and conservative vs early invasive strategies in unstable angina and non-ST-elevation MI. A total of 1473 patients presenting within 24 h of ischemic chest discomfort were randomized to either tissue-type plasminogen activator or placebo. All patients received aspirin, intravenous heparin, b-blockers, calcium channel blockers, and nitrates. The angiographic results of a subgroup were published in the TIMI IIIA analysis (26); among 306 patients who underwent angiography at baseline and at 18-48 h, treatment with tissue-type plasminogen activator did not influence either improvement in the caliber of the culprit lesion (by >10% reduction) or improve-

Table 1

Small Randomized Trials of Thrombolytic Therapy Compared to Placebo in Acute Coronary Syndromes

Table 1

Small Randomized Trials of Thrombolytic Therapy Compared to Placebo in Acute Coronary Syndromes

Trial

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