HEPARIN AS AN ADJUNCTIVE TREATMENT AFTER THROMBOLYTIC THERAPY FOR ACUTE MYOCARDIAL-INFARCTION

The rationale for considering heparin therapy as an adjunct to thrombolytic treatment for patients with acute myocardial infarction is to prevent rethrombosis after successful thrombolysis. The risk of reocclusion is high immediately after thrombolysis because blood flowing through the newly opened coronary artery is exposed to thrombin bound to fibrin in the residual thrombus. Clinical studies of patients with venous thrombosis and acute myocardial infarction indicate that there is a relation between the anticoagulant response to heparin and clinical efficacy and that the concept of a therapeutic heparin level is valid. Subcutaneous doses of approximately 15,000 U twice a day fail to provide an adequate anticoagulant response at 24 hours in the majority of patients, whereas intravenous administration of a bolus of 5,000 U followed by continuous infusion of 30,000 U per 24 hours produces an adequate anticoagulant response at 24 hours in approximately 80% of patients. Studies of patients with myocardial infarction who received streptokinase showed a significant beneficial effect on mortality when 12,500 U of heparin was administered subcutaneously 2 times per day. In contrast, the single largest study evaluating heparin 12,500 U administered subcutaneously 2 times per day as an adjunct to recombinant tissue-type plasminogen activator (rt-PA) treatment did not show a beneficial effect on mortality. However, studies using full-dose intravenous heparin therapy demonstrated that heparin improves patency after coronary thrombolysis with rt-PA. A plausible explanation for these apparently contradictory findings is that the need for heparin administered early in high doses is greater in patients treated with rt-PA than in those treated with streptokinase, because of the lesser systemic anti-coagulant effects induced by rt-PA treatment.