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Thrombolytic therapy reduces mortality and limits infarct size in patients with acute myocardial infarction associated with ST-segment elevation (defined as 01 mV in two inferior or lateral leads or two contiguous precordial leads), or with left bundle branch block The greatest benefit occurs if treatment is initiated within the first 3 hours, when up to a 50% reduction in mortality rate can be achieved The magnitude of benefit declines rapidly thereafter, but a 10% relative mortality reduction can be achieved up to 12 hours after the onset of chest pain The survival benefit is greatest in patients with large usually anterior infarctions Patients without ST-segment elevation (previously labeled non-Q wave infarctions) do not benefit, and may derive harm, from thrombolysis Major bleeding complications occur in 05 5% of patients, the most serious of which is intracranial hemorrhage The major risk factors for intracranial bleeding are age over 65 years, hypertension at presentation, low body weight (< 70 kg), and the use of clot-specific thrombolytic agents (alteplase, reteplase, tenecteplase) Although patients over age 75 years have a much higher mortality rate with

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acute myocardial infarction and therefore may derive greater benefit, the risk of severe bleeding is also higher, particularly among patients with risk factors from bleeding or intracranial hemorrhage, such as severe hypertension or recent stroke Patients presenting more than 12 hours after the onset of chest pain may also derive a small benefit, particularly if pain and ST-segment elevation persist, but rarely does this benefit outweigh the attendant risk Therefore, the current recommendation is to treat patients with ST-segment elevation infarction who seek medical attention within 6 12 hours of the onset of symptoms with reperfusion therapy, either primary percutaneous coronary intervention (PCI) or thrombolytic therapy Contraindications include previous hemorrhagic stroke, other strokes or cerebrovascular events within 1 year, known intracranial neoplasm, active internal bleeding (excluding menstruation), or suspected aortic dissection Relative contraindications are BP > 180/110 mm Hg at presentation, other intracerebral pathology not listed above as a contraindication, known bleeding diathesis, trauma within 2 4 weeks, major surgery within 3 weeks, prolonged (> 10 minutes) or traumatic cardiopulmonary resuscitation, recent (within 2 4 weeks) internal bleeding, noncompressible vascular punctures, active diabetic retinopathy, pregnancy, active peptic ulcer disease, a history of severe hypertension, current use of anticoagulants (INR > 20 30), and prior allergic reaction or exposure to streptokinase or anistreplase within 2 years The following thrombolytic agents are available for acute myocardial infarction and are characterized in Table 10 7

Streptokinase Source Half-life Usual dose Administration Group C streptococcus 20 minutes 15 million units 750,000 units over 20 minutes followed by 750,000 units over 40 minutes Aspirin, 325 mg daily; there is no evidence that adjunctive heparin improves outcome following streptokinase Low +++ + +++ ++ 5 20% $56300 Alteplase; Tissue Plasminogen Activator (t-PA) Recombinant DNA 5 minutes 100 mg Initial bolus of 15 mg, followed by 50 mg infused over the next 30 minutes and 35 mg over the following 60 minutes Aspirin, 325 mg daily; heparin, 5000 units as bolus, followed by 1000 units per hour infusion, subsequently adjusted to maintain PTT 15 2 times control High + + + 0 10 30% $360900 Reteplase Recombinant DNA 15 minutes 20 units 10 units as a bolus over 2 minutes, repeated after 30 minutes Aspirin, 325 mg; heparin as with t-PA Tenecteplase (TNK-t-PA) Recombinant DNA 20 minutes 40 mg Single weightadjusted bolus, 05 mg/kg Aspirin, 325 mg daily

Clot selectivity Fibrinogenolysis Bleeding Hypotension Allergic reactions Reocclusion Approximate cost1

Average wholesale price (AWP, for AB-rated generic when available) for quantity listed Source: Red Book Update, Vol 26, No 3, March 2007 AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions PTT, partial thromboplastin time

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