Thrombolytic therapy: a review of its use in acute myocardial infarction

OBJECTIVE: To review the literature on the use of thrombolytic agents in the pharmacotherapeutic management of acute myocardial infarction (AMI). DATA SOURCE: English-language clinical trials, reviews, and editorials derived from MEDLINE (January 1966-September 1997) and/or cross-referencing of selected articles. STUDY SELECTION: Articles that were selected best represent the clinical trials researching the role for thrombolytics in the therapy of AMI to improve morbidity and mortality. DATA SYNTHESIS: AMI is one of the leading causes of mortality in the US. Following supportive data that the most common cause of an AMI is an intracoronary thrombus, clinical investigation has demonstrated that intravenous thrombolytic agents improve survival rates in patients who experience an AMI. Several clinical trials have been conducted to determine whether one thrombolytic agent is superior to others with respect to improving mortality. At present, only the first Global Use of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial has reported any statistically significant difference in mortality rate. In this trial, "front-loaded" alteplase induced a statistically significant (p < 0.001) 1% absolute reduction in 30-day and 1-year mortality compared with streptokinase. This has led to alteplase being the preferred thrombolytic at many US institutions. However, the results of GUSTO-I have been questioned by some on the basis of either study design or clinical significance. CONCLUSIONS: Thrombolytic agents have secured a place in the treatment of AMI due to their well-proven reduction in mortality rates. In general, comparative trials have demonstrated minimal differences in efficacy among these agents. Probably just as important as choosing which thrombolytic agent to use is ensuring that a patient experiencing an AMI is administered thrombolytic therapy unless a contraindication to receive such therapy exists in the patient and/or the patient is a candidate to receive an emergent intracoronary procedure. Trials also indicate that the sooner thrombolytics can be administered, the greater the benefit to the patient.