Streptokinase, 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. 

European Cooperative Study Group for Streptokinase Treatment in Acute Myocardial Infarction. Streptokinase in acute myocardial infarction. N Engl J Med 1979 301 797-802. 

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. 

In a more extensive international trial, 17,187 patients were treated intravenously with streptokinase alone, aspirin alone, a combination of streptokinase and aspirin, or placebo (78). Streptokinase and aspirin were equally effective in treating acute myocardial infarction, each decreasing mortahty by 25% their combination further reduced mortahty by 42%. A significant reduction in mortahty was seen even in those patients treated up to 24 hours after the onset of symptoms. 

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. 

Streptokinase infusions in patients with myocardial infarction did not influence significantly Lp(a) concentrations (M22). 

M22. MBewu, A. D., Durrington, P. N., Bullied, S., and Mackness, M. I., The immediate effect of streptokinase on serum lipoprotein(a) concentration and the effect of myocardial infarction on serum lipoprotein(a), apolipoprotein A1 and B. lipids and C-reactive protein. Atherosclerosis (Shannon, Irel.) 103, 65-71 (1993). 

ISIS-3. ISIS-3 a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41299 cases of suspected acute myocardial infarction. Lancet 1992 339 753-70. 

ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction ISIS-2. Lancet 1988 2 349-360. 

Zijlstra F, de Boer M, Hoomtje J, et al. Comparison of immediate coronary angioplasty with intravenous streptokinase in myocardial infarction. N Eng J Med 1993 328 680-684. 

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. 

Example 15.4 Meta-Analysis of trials of magnesium and streptokinase in acute myocardial infarction... 

Figure 15.2 Funnel plot for meta-analysis of trials of magnesium (upper diagram) and streptokinase (lower diagram) in acute myocardial infarction. (Smith and Eggar (1997). Reproduced with kind permission from The Lancet.)...

G. Other applications In combination with streptokinase, Integrilin improved coronary patency in patients experiencing an acute myocardial infarction but had no effect on clinical outcome and increased the rate of bleeding. 

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. 

Thrombolytic drugs (streptokinase, t-PA, others) usually do not have a direct impact on physical therapy or occupational therapy. Thrombolytics are typically given in acute situations, immediately following myocardial infarction. Therapists may, however, benefit indirectly from the effects of these drugs because patients may recover faster and more completely from heart attacks. Thrombolytics may also help reopen occluded peripheral vessels, thus improving tissue perfusion and wound healing in rehabilitation patients. 

All patients with acute myocardial infarction should be considered for intravenous thrombolytic therapy with streptokinase, tissue plasminogen activator (TPA), or anistreplase because these agents are effective in both preserving cardiac function and reducing mortality. 

Clinical trials One of the trials (ISIS-3) showed that streptokinase plus aspirin performed as well as recombinant tissue-type plasminogen activator (rt-PA) or complex formulations of streptokinase such as anistreplase (APSAC). The GUSTO trial showed a small advantage for the much more expensive t-PA over streptokinase, but with a significantly higher risk of hemorrhagic stroke. Nine clinical trials—each containing over 1000 patients with suspected acute myocardial infarction—... 

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