Streptokinase, 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. 

Indications for treatment with streptokinase include acute occlusion of arteries, deep vein thrombosis, and pulmonary embolism. Streptokinase therapy in coronary thrombosis, which is the usual cause of myocardial infarction (54,71,72), has proved to be valuable. In this frequently fatal condition, the enzyme is adrninistered intravenously at a dose of 1.5 million units over 60 min, or given by intracoronary infusion at a 20,000- to 50,000-unit bolus dose followed by 2000 to 4000 units/min for 60 min therapy must be instituted as soon as practicable after the diagnosis of heart attack is made. For deep vein thrombosis, pulmonary embolism, or arterial occlusion, streptokinase is infused at a loading dose of 250,000 units given over 30 min, followed by a maintenance dose of 100,000 units over a 60-min period. 

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

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). 

Tissue plasminogen activator has been used successfully to treat acute myocardial infarction, and the benefits of this treatment are well documented.102,116 This drug, however, does not seem to be superior to other thrombolytics when treating coronary artery thrombosis, and streptokinase may be a more cost-effective method of treating myocardial infarction. Alternatively, t-PA may be more effective than other thrombolytics in its ability to initially reopen cerebral vessels this drug is often used preferentially during ischemic stroke.4,44 Hence, the added cost of t-PA may be justified in this situation. 

Anderson JL, Marshall HW, Bray BE, et al. A randomized trial of intracoronary streptokinase in the treatment of acute myocardial infarction. N Engl J Med. 1983 308 1312-1318. 

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. 

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. 

Pharmacokinetics Streptokinase therapy is instituted within 4 hours of a myocardial infarction and is infused for 1 hour. Its ti/2 is less than a half-hour. Thromboplastin time is monitored and maintained at two to five times control value. On discontinuation of treatment, either heparin or oral anticoagulants may be administered. 

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. 

Maclennan AC, Ahmad N, Lawrence JR. Activities of aminotransferases after treatment with streptokinase for acute myocardial infarction. BMJ 1990 301(6747) 321-2. 

Bucknall C, Darley C, Flax J, Vincent R, Chamberlain D. Vasculitis complicating treatment with intravenous anisoy-lated plasminogen streptokinase activator complex in acute myocardial infarction. Br Heart J 1988 59(1) 9-11. 

Streptokinase is administered by intravenous or intra-arterial infusion in the treatment of thromboembolic disorders, e.g. pulmonary embolism, deep vein thrombosis and arterial occlusions. It is also used in acute myocardial infarction. 

Streptokinase (1,500,000 lU within 60 minutes by fV infusion) is indicated in lysis of coronary artery thrombosis after acute myocardial infarction streptokinase (250,000 lU by IV infusion pump into each occluded limb of the cannula over 25 to 35 minutes) is indicated in arteriovenous cannula occlusion and streptokinase (250,000 lU IV infusion over 30 minutes) is indicated in the treatment of venous thrombosis, pulmonary embolism, and arterial thrombosis and embolism. 

Both streptokinase and t-PA have been approved for the treatment of myocardial infarction. Both reduce mortality. Although there are more side effects associated with the use of streptokinase, it is substantially cheaper than t-PA. 

Streptokinase is a drug of choice for thrombolytic therapy based on its cost-effectiveness consideration, and it is the only thrombolytic drug approved by the U.S. Food and Drug Administration (FDA) for peripheral vascular disease (126). The drug is approved for treatment of myocardial infarction but rarely is used for this condition today, having been replaced with the fibrin-specific agents discussed below (127). 

Fletcher AP, AUcjaersig N, Smymiotis FE, Sherry S. The treatment of patients suffering from early myocardial infarction with massive and prolonged streptokinase therapy. Trans Assoc Am Phys 1958 71 287-296. 

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