Activase is an enzyme (serine protease) which has the property of fibrin-enhanced conversion of plasminogen to plasmin. It produces limited conversion of plasminogen in the absence of fibrin. When introduced into the systemic circulation at pharmacologic concentration, Activase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. This initiates local fibrinolysis with limited systemic proteolysis. Following administration of 100 mg Activase, there is a decrease (16%-36%) in circulating fibrinogen.^1,2 In a controlled trial, 8 of 73 patients (11%) receiving Activase (1.25 mg/kg body weight over 3 hours) experienced a decrease in fibrinogen to below 100 mg/dL.2 The clearance of Alteplase in AMI patients has shown that it is rapidly cleared from the plasma with an initial half-life of less than 5 minutes. There is no difference in the dominant initial plasma half-life between the 3-Hour and accelerated regimens for AMI. The plasma clearance of Alteplase is 380-570 mL/min.^3,4 The clearance is mediated primarily by the liver. The initial volume of distribution approximates plasma volume.

Acute Myocardial Infarction (AMI) Patients

Coronary occlusion due to a thrombus is present in the infarct related coronary artery in approximately 80% of patients experiencing a transmural myocardial infarction evaluated within 4 hours of onset of symptoms.^5,6

Two Activase dose regimens have been studied in patients experiencing acute myocardial infarction. (Please See DOSAGE AND ADMINISTRATION.) The comparative efficacy of these two regimens has not been evaluated.

Accelerated Infusion in AMI Patients

Accelerated infusion of Activase was studied in an international, multi center trial (GUSTO) that randomized 41,021 patients with acute myocardial infarction to four thrombolytic regimens. Entry criteria included onset of chest pain within 6 hours of treatment and ST-segment elevation of ECG. The regimens included accelerated infusion of Activase ( ≤ 100 mg over 90 minutes, See DOSAGE AND ADMINISTRATION) plus intravenous (IV) heparin (accelerated infusion of Alteplase, n=10,396), or the Kabikinase brand of Streptokinase (1.5 million units over 60 minutes) plus IV heparin (SK [IV], n=10,410), or Streptokinase (as above) plus subcutaneous (SQ) heparin (SK [SQ], n=9841). A fourth regimen combined Alteplase and Streptokinase. Aspirin and heparin use was directed by the GUSTO study protocol as follows: All patients were to receive 160 mg chewable aspirin administered as soon as possible, followed by 160-325 mg daily. IV heparin was directed to be a 5000 U IV bolus initiated as soon as possible, followed by a 1000 U/hour continuous IV infusion for at least 48 hours; subsequent heparin therapy was at the discretion of the attending physician. SQ heparin was directed to be 12,500 U administered 4 hours after initiation of SK therapy, followed by 12,500 U twice daily for 7 days or until discharge, whichever came first. Many of the patients randomized to receive SQ heparin received some IV heparin, usually in response to recurrent chest pain and/or the need for a medical procedure. Some received IV heparin on arrival to the emergency room prior to enrollment and randomization.

Bookmark this page: