AN ANALYSIS OF THE CAUSE OF EARLY MORTALITY AFTER ADMINISTRATION OF THROMBOLYTIC THERAPY

Background: The use of thrombolytic therapy in myocardial infarction has been associated with a considerable improvement in survival rate; however, almost 40% of the deaths during hospitalization occur during the first 24 h. Clinical and angiographic characteristics identified through careful comparison of those patients who die early with those who survive may serve as important targets for the development of new strategies for the management of myocardial infarction. Methods: Medical records and autopsy reports of 810 patients enrolled into four sequential studies evaluating thrombolytic therapy and angioplasty in acute myocardial infarction were reviewed. All patients were enrolled into four similar protocols with administration of thrombolytic therapy (intravenous tissue plasminogen activator in 561 patients, urokinase in 102, and a combination of tissue plasminogen activator and urokinase in 147) and acute cardiac catheterization performed 90 min after starting therapy. Results: The overall in-hospital mortality rate was 6.8% (55 out of 81 0), with 21 of these deaths (38%) occurring within the first day. The median (25th, 75th percentile) time to death was 3 (0, 12) days. Infarct location was more frequently anterior in patients who died within the first day. Patients who died 24 h after admission to hospital had the lowest patency rate (45%) compared with patients who died within 24 h (59%) and those who survived (71%, P = 0.003). The deaths within the first day were more likely to be a result of cardiogenic shock (48%), ventricular arrhythmias (14%), or cardiac rupture (9%), whereas late deaths were more likely to be a result of recurrent ischemia or reinfarction (32%) and non-cardiac causes (1 8%). Two patients had an intracranial hemorrhage within the first 24 h which caused immediate death in one and death on the third day of hospitalization in the other. Conclusion: Mortality within the first 24 h of thrombolytic therapy administration can be defined by inadequate myocardial reperfusion in patients with cardiac failure, possibly associated reperfusion injury leading to cardiac rupture, and an increased risk of intracranial hemorrhage. These factors may serve as targets for the development of new treatment strategies in acute myocardial infarction that may alter prognosis.