General: Retavase® is a recombinant plasminogen activator which catalyzes the cleavage of endogenous plasminogen to generate plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.^1,2 In a controlled trial, 36 of 56 patients treated for an acute myocardial infarction (AMI) had a decrease in fibrinogen levels to below 100 mg/dL by 2 hours following the administration of Retavase® as a double-bolus intravenous injection (10 + 10 unit) in which 10 units (17.4 mg) was followed 30 minutes later by a second bolus of 10 units (17.4 mg).³ The mean fibrinogen level returned to the baseline value by 48 hours.

Pharmacokinetics: Based on the measurement of thrombolytic activity, Retavase® is cleared from plasma at a rate of 250-450 mL/min, with an effective half-life of 13-16 minutes.Retavase® is cleared primarily by the liver and kidney.

Clinical Studies: The safety and efficacy of Retavase® were evaluated in three controlled clinical trials in which Retavase® was compared to other thrombolytic agents. The INJECT study was designed to assess the relative effects of Retavase® or the Streptase® brand of Streptokinase upon mortality rates at 35 days following an AMI.The other studies (RAPID 1 and RAPID 2) were arteriographic studies which compared the effect on coronary patency of Retavase® to two regimens of Alteplase (a tissue plasminogen activator; Activase® in the USA and Actilyse® in Europe) in patients with an AMI.In all three studies, patients were treated with aspirin (initial doses of 160 mg to 350 mg and subsequent doses of 75 mg to 350 mg) and heparin (a 5,000 unit IV bolus prior to the administration of Retavase®, followed by a 1000 unit/hour continuous IV infusion for at least 24 hours).^3,4,5 The safety and efficacy of Retavase® have not been evaluated using antithrombotic or antiplatelet regimens other than those described above.

Retavase® (10 + 10 unit) was compared to Streptokinase (1.5 million units over 60 minutes) in a double-blind, randomized, European study (INJECT), which studied 6,010 patients treated within 12 hours of the onset of symptoms of AMI.To be eligible for enrollment, patients had to have chest pain consistent with coronary ischemia and ST segment elevation, or a bundle branch block pattern on the EKG. Patients with known cerebrovascular or other bleeding risks or those with a systolic blood pressure >200 mm Hg or a diastolic blood pressure >100 mm Hg were excluded from enrollment. The results of the primary endpoint (mortality at 35 days), six month mortality and selected other 35 day endpoints are shown in Table 1 for patients receiving study medications.

Table 1: INJECT TRIAL Incidence of Selected Outcomes

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