Future directions in thrombolysis for myocardial infarction

Substantial advances have been made in the application of intravenous thrombolytic agents for acute myocardial infarction since their introduction 10 years ago. Dosage regimens and timing have been refined, criteria for patient selection expanded, early patency rates improved, and the role for antiplatelet and antithrombotic adjuncts recognized. The most recently completed thrombolysis 'mega-trial', Global Utilization of Streptokinase or t-PA for Occluded Coronary Arteries (GUSTO) [1], established the superiority of accelerated tissue-type plasminogen activator (t-PA) plus intravenous heparin over other thrombolytic strategies. It also confirmed for the first time that early, complete, and sustained patency of the infarct-related artery results in a reduction in mortality — a fact intuitively linked with thrombolytic benefit, but never borne out by previous large-scale trials. However, critical analysis of recent data suggests that thrombolytic intervention, as currently practiced, continues to fall short of the ultimate goal of 'optimal reperfusion'. Early, complete, and sustained reperfusion are the paradigms for ideal thrombolysis. This review will focus on the current limitations to these criteria and will provide a critical evaluation of the emerging strategies toward more optimal reperfusion.