Reteplase (
BM 06.022; r-PA) is a recombinant
peptide which consists of the kringle 2 and
protease domains of human
tissue-type plasminogen activator. It has been developed as a thrombolytic treatment for acute
myocardial infarction (AMI). The half-life of
reteplase allows administration as a double-bolus injection (second injection given 30 minutes after the first) rather than by the prolonged and, in some cases, more complex
intravenous infusion regimens that are required for most other
thrombolytic agents.
Reteplase produced rapid and effective coronary artery thrombolysis in a number of dose-finding and comparative studies. Double-bolus administration of
reteplase 10U + 10U produced significantly higher coronary artery patency rates than accelerated
alteplase (100mg as a 1.5-hour infusion) in patients with AMI in the RAPID-II study. The 10U + 10U
reteplase regimen produced a 35-day survival rate at least equivalent to that seen with a 1-hour infusion of
streptokinase 1.5 million units in 5986 patients in the INJECT study, which was designed to demonstrate equivalence between treatments. As with other thrombolytics,
bleeding was the most common adverse event seen in
reteplase recipients. No significant differences in the overall risk of haemorrhage were observed between
reteplase and either accelerated
alteplase or standard
streptokinase treatment in clinical trials. The risk of
stroke in
reteplase recipients appears to be similar to that for other
thrombolytic agents [1.2% incidence in 3288 patients treated with
reteplase 10U + 10U in clinical trials (0.76% for haemorrhagic
stroke)], although accurate statistical assessment of the relative risk is not possible for the data available to date. Thus,
reteplase is an effective
thrombolytic agent which can be administered as a double-bolus injection regimen rather than as a prolonged infusion. Together with acquisition cost and general pharmacoeconomic data (which are not yet available), the results of GUSTO-III (a trial comparing double-bolus
reteplase with accelerated
alteplase in 15 000 patients) will have a major influence on the pattern of use of
reteplase. In the meantime, data from the available clinical trials suggest that
reteplase is a fast-acting and effective thrombolytic treatment for patients with AMI.