ASPIRIN AND FIBRINOLYSIS IN ACUTE MYOCARDIAL-INFARCTION - META-ANALYTIC EVIDENCE FOR SYNERGY

A meta-analysis of randomized clinical trials of fibrinolysis was performed, examining the interaction between aspirin and fibrinolysis in treating patients with acute myocardial infarction. Reductions in the odds of death up to 35 days were assessed for patients receiving tissue plasminogen activator or streptokinase up to 6 hours after the onset of symptoms. No significant difference in effectiveness between tissue plasminogen activator and streptokinase was demonstrated. The overall reduction in odds of death due to fibrinolytic therapy was 28%. However, there was a significant difference between the odds reduction of 24% when fibrinolysis is compared to placebo, and 40% when fibrinolysis and aspirin combined are compared to aspirin alone (p = 0.02). This difference indicates that there exists a synergistic interaction between coronary fibrinolysis and aspirin rather than independence of their beneficial effects, as is generally believed. These results illustrate the perils of assessing drug efficacy, even in an overview of all relevant trials, without consideration of identifiable sources of heterogeneity such as the interaction between the treatment of interest and co-interventions. They also demonstrate the potential application of logistic regression diagnostic techniques to meta-analyses.