THROMBOLYTIC THERAPY

Occlusive thrombus within a coronary artery plays a central role in acute myocardial infarction. To salvage myocardium which would otherwise be permanently lost, the restoration of the arterial blood supply must occur early. The pharmacological dissolution of blood clots 'thrombolysis' has been possible for 40 years and depends on activation of the fibrinolytic system which comprises a pro-enzyme plasminogen which is converted by tissue plasminogen activators to a proteolytic enzyme plasmin which lyses fresh fibrin clots onto soluble fibrin degradation products (FDPs). Two pivotal studies GISSI-1 and ISIS-2 demonstrated that iv streptokinase given early to patients with acute myocardial infarction reduced mortality by approximately 20% and furthermore ISIS-2 showed an additional benefit if aspirin was given in conjunction with the streptokinase. Two subsequent trials, GISSI 2 and ISIS 3 were designed to determine if there was any difference between the three most commonly used thrombolytic agents streptokinase (SK), tissue plasminogen activator tPA and acylated plasminogen activator complex (APSAC). All three agents produced a similar reduction in mortality (20%) and there was no difference in the 6-month survival rate. Whilst thrombolysis has reduced in-hospital mortality to 10%, it has not been without complication. The overall incidence of major haemorrhage ranged from 0.3 to 1.5% with intracerebral haemorrhage being the most serious problem and more common with tPA. because SK and APSAC are foreign proteins they can induce an acute allergic reaction such as hypotension, rigour and pyrexia. The development of antibodies to SK precludes its use in subsequent myocardial infarctions for up to 18 months. ISIS showed that 162 mg per day of aspirin for 1 month greatly reduced re-infarction, stroke and death. The effect of heparin in acute myocardial infarction is more controversial. Available data suggests that there are probably no benefits from adding heparin to SK and APSAC, whereas adding heparin to tPA increases vessel patency.