Optimal
thrombolytic therapy in acute
myocardial infarction must aim to achieve early and complete reperfusion of the
infarct related coronary artery. Establishment of normal coronary flow (Thrombolysis in
Myocardial Infarction [TIMI] grade 3) is the key correlate of improved survival. Three large-scale clinical trials, the
Reteplase Angiographic Phase II International Dose-finding Study (RAPID 1), the
Reteplase vs
Alteplase Patency Investigation During Acute
Myocardial Infarction Study (RAPID 2), and the International Joint Comparison of Thrombolytics Study (INJECT), have evaluated the comparative efficacy and safety of
reteplase, a new, rapid-acting
thrombolytic agent that offers the practical clinical convenience of bolus dosing. RAPID 1 and 2 demonstrated that
reteplase was associated with superior early coronary artery patency rates compared with
alteplase, whether
alteplase was infused over 3 h or over 90 min. Further, the TIMI 3 flow rates achieved in
reteplase-treated patients at 60 min were comparable to those achieved at 90 min with the accelerated
alteplase dosing regimen. The INJECT trial showed that
reteplase resulted in comparable mortality and clinical benefits to those achieved with
streptokinase. All three studies demonstrated that
reteplase therapy was not associated with an increase in
bleeding complications or other adverse clinical events. The simple double-bolus regimen of
reteplase administration may permit earlier initiation of thrombolysis with fewer dosing errors than with continuous infusion regimens and thus afford a reduction in the morbidity and mortality risks in patients with acute
myocardial infarction.