Clinical trials in thrombolytic therapy, Part 1: Outcome markers that go beyond mortality reduction.

Abstract

The use of outcome markers other than mortality reduction alone for evaluating thrombolytic agents in patients with acute myocardial infarction (AMI) is discussed. Mortality has been a primary endpoint in clinical trials evaluating thrombolytic agents for treatment of AMI. However, differences in mortality rates among thrombolytics are 1% or less and require tens of thousands of patients to detect. Broadening the endpoints studied will allow for more extensive data collection and more comprehensive cost-effectiveness analysis, enabling clinicians to make better decisions. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial measured not only mortality but issues related to the patency of the infarct-related artery and complications. Other potentially important outcome markers after AMI are left ventricular function; markers of reperfusion, such as early resolution of ST-segment elevation; and resolution of chest pain. Available long-term data show that the mortality benefit from alteplase is sustained over time and is correlated with enzymatically determined infarct size, left ventricular function, the number of diseased vessels, and Thrombolysis in Myocardial Infarction flow grade at the time of discharge from the hospital. Clinicians must also consider risk factors for stroke. Outcome measures other than mortality alone may help in determining which thrombolytic agent is most effective clinically and in financial decision-making without requiring large, expensive trials.