Recombinant plasminogen activators: a comparative review of the clinical pharmacology and therapeutic use of alteplase and reteplase.
Thrombolytic therapy has been shown to reduce mortality after acute myocardial infarction. Great efforts have been undertaken in the past decade to develop more efficient thrombolytic regimens. Novel recombinant thrombolytic substances have been engineered. Reteplase, a deletion mutant of wild-type tissue plasminogen activator with a longer half-life, has been evaluated in clinical trials and is now available for clinical use. In the randomised Reteplase Angiographic Phase II International Dose-Finding (RAPID-1) trial, involving 606 patients with acute myocardial infarction, a double-bolus regimen of reteplase (10 + 10U given 30 minutes apart) achieved significantly higher patency rates at 90 minutes after initiation of thrombolytic therapy than a 10 + 5U double-bolus reteplase regimen, a 15U single bolus reteplase regimen, or a conventional alteplase regimen (100mg in 180 minutes). In the Reteplase versus Alteplase Patency Investigation During Acute Myocardial Infarction (RAPID-2) trial, the reteplase 10 + 10U double-bolus regimen was more effective with regard to patency at 60 and 90 minutes than accelerated alteplase (100mg in 90 minutes). The International Joint Efficacy Comparison of Thrombolytics (INJECT) trial showed that a double-bolus regimen of reteplase 10 + 10U was at least equivalent to streptokinase in terms of 35-day mortality rate. The third Global Utilization of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial resulted in similar 30-day mortality after therapy with double-bolus reteplase 10 + 10U (7.47%) or accelerated alteplase (7.24%). Hence, the higher early patency rates achieved with reteplase treatment did not translate into improved survival. Consequently, there is still some uncertainty as to whether or not these drugs are equivalent.
Moser
M
M
Medizinische Klinik III (Kardiologie, Angiologie und Pulmologie), Universität Heidelberg, Heidelberg, Germany.
Kohler
B
B
Schmittner
M
M
Bode
C
C