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

Background: The use of thrombolytic therapy in myocardial infarction h as been associated with a considerable improvement in survival rate; h owever, almost 40% of the deaths during hospitalization occur during t he first 24 h. Clinical and angiographic characteristics identified th rough careful comparison of those patients who die early with those wh o survive may serve as important targets for the development of new st rategies for the management of myocardial infarction. Methods: Medical records and autopsy reports of 810 patients enrolled into four sequen tial studies evaluating thrombolytic therapy and angioplasty in acute myocardial infarction were reviewed. All patients were enrolled into f our similar protocols with administration of thrombolytic therapy (int ravenous tissue plasminogen activator in 561 patients, urokinase in 10 2, 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 firs t day. The median (25th, 75th percentile) time to death was 3 (0, 12) days. Infarct location was more frequently anterior in patients who di ed within the first day. Patients who died 24 h after admission to hos pital had the lowest patency rate (45%) compared with patients who die d within 24 h (59%) and those who survived (71%, P = 0.003). The death s within the first day were more likely to be a result of cardiogenic shock (48%), ventricular arrhythmias (14%), or cardiac rupture (9%), w hereas late deaths were more likely to be a result of recurrent ischem ia or reinfarction (32%) and non-cardiac causes (1 8%). Two patients h ad an intracranial hemorrhage within the first 24 h which caused immed iate death in one and death on the third day of hospitalization in the other. Conclusion: Mortality within the first 24 h of thrombolytic th erapy administration can be defined by inadequate myocardial reperfusi on in patients with cardiac failure, possibly associated reperfusion i njury leading to cardiac rupture, and an increased risk of intracrania l hemorrhage. These factors may serve as targets for the development o f new treatment strategies in acute myocardial infarction that may alt er prognosis.