Alteplase, myocardial infarction treatment

Plasminogen, an inactive precursor, is activated to plasmin which as a protease is able to break down fibrin clots. The thrombolytic agents in use promote the conversion of plasminogen to plasmin at the site of a thrombus. Indications include post-myocardial infarction treatment. The thrombolytic must be administered within 6 hours for an optimal effect. Other indications are treatment of acute pulmonary thromboembolism, deep-vein thrombosis, acute arterial thrombosis and thromboembolism, as well as in the clearance of arteriovenous catheters and can-nulae. Agents are streptokinase, anistreplase, urokinase, alteplase, reteplase and tenecteplase. 

Alteplase has proven effective in the early treatment of patients with acute myocardial infarction (i.e. those treated within 12 h after the first symptoms occur). Significantly increased rates of patient survival (as measured 1 day and 30 days after the initial event) are noted when tPA is administered in favour of streptokinase, a standard therapy (see later). tPA has thus established itself as a first-line option in the management of acute myocardial infarction. A therapeutic dose of 90-100 mg (often administered by infusion over 90 min) results in a steady-state alteplase concentration of 3-4 mg l 1 during that period. However, the product is cleared rapidly by the liver, displaying a serum half-life of approximately 3 min. As is the case for most thrombolytic agents, the most significant risk associated with tPA administration is the possible induction of severe haemorrhage. 

E Role in therapy Thrombolytic agents currently licensed for the treatment of AMI in the United States include streptokinase, tissue plasminogen activator, anistreplase, reteplase, and tenecteplase. TNKase and alteplase have similar clinical efficacy for thrombolysis after myocardial infarction (i.e., similar mortality and intracranial hemorrhage rates). However, advantages of TNKase include ease and rapidity of administration, longer half-life, greater fibrin specificity, and lower noncerebral bleeding rates. Reteplase shares some characteristics of tenecteplase (e.g., similar half-life, rapid onset, and ease of administration). 

Alteplase was the first commercially available recombinant tissue-type plasminogen activator (rt-PA) (25), It has a plasma half-life of less than five minutes and is metabolized by the liver, This agent was initially hailed as fibrin-specific unlike its precursors (urokinase and streptokinase). It was thought that this would result in a better safety profile, but this has not been born out in either the coronary or the peripheral experience, where actually there may be a higher bleeding risk as infusion time increases. Alteplase is currently indicated for use in the treatment of myocardial infarction, acute ischemic stroke, and pulmonary embolism. 

Alteplase and Tenecteplase ) are used in the treatment of acute myocardial infarction. 

Therapeutic uses Currently alteplase is approved for the treatment of myocardial infarction, massive pulmonary embolism, and acute ischemic stroke. Alteplase seems to be superior to streptokinase and urokinase in dissolving older clots, and may ultimately be approved for other applications. Alteplase administered within 3 hours of the onset of ischemic stroke significantly improves clinical outcome, that is, the patients ability to perform activites of daily living. 

The combination of thrombolytic agents with an anticoagulant and/or aspirin has been said to be life-threatening. An excess of major bleeding episodes with combined subcutaneous heparin and streptokinase or alteplase treatments (1.0% with heparin versus 0.5% without heparin) has been reported in the International Study Group Trial (103) in patients with suspected acute myocardial infarction. 

The InTIME-II Investigators. Intravenous NPA for the treatment of infarcting myocardium early InTIME-II, a double-blind comparison of single-bolus lanoteplase vs. accelerated alteplase for the treatment of patients with acute myocardial infarction. Eur Heart J. 2000 21 ... 

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