Mortality within 24 hours of thrombolysis for myocardial infarction: The importance of early reperfusion

Background: A paradoxical increased risk of death has been reported during the first 24 hours after thrombolysis for myocardial infarction. The mechanism of this phenomenon is not known, nor is its relation to the success or failure of reperfusion. The present study was a prospectively designed analysis of deaths occurring within the first 24 hours in the GUSTO trial. Methods and Results: There were 41 021 patients enrolled in GUSTO, a randomized comparison of streptokinase with intravenous or subcutaneous heparin, accelerated tissue-type plasminogen activator (TPA), and combination of streptokinase and TPA. An angiographic mechanistic substudy examined reperfusion (using the TIMI flow grading criteria) 90 minutes after the assigned thrombolytic regimen was begun in 1567 patients. There were 1125 deaths (2.8%) within 24 hours ('early deaths') and 1726 additional deaths (4.2%) after 24 hours but within 30 days ('later deaths'). At the time of presentation, the most potent predictors of early death were hypotension and sinus tachycardia. In a multiple logistic regression model, lower systolic blood pressure, shorter height, higher heart rate, and the absence of prior smoking distinguished early death from later death. Reinfarction occurred in 26 patients (2.4%), shock in 572 patients (52%), atrioventricular block in 308 patients (28%), and tamponade in 106 patients (10%) dying early compared with 262 (15%), 788 (46%), 396 (23%), and 74 (4%) respective patients dying later. There were no differences in early mortality among the thrombolytic regimens for the first 6 hours after randomization. By 24 hours, however, mortality was 2.89% for streptokinase recipients, 2.84% for combination therapy recipients, and 2.36% for accelerated TPA recipients (P=.005). There was little difference among patients with differing flow grades in the infarct artery during the first 4 hours, although mortality among patients with grade 2 flow was initially higher. After the fourth hour, there were very few additional deaths during the first day in patients with grade 3 flow. At 24 hours, mortality was 2.35% for patients with flow grade 0 or 1, 2.92% for patients with flow grade 2, and 0.89% for patients with flow grade 3. Conclusions: Even with aggressive management regimens, mortality within the first 24 hours accounted for a large proportion of postthrombolytic deaths. Patients dying early were more likely to present with pump failure than were those dying later and were more likely to die of events related to left ventricular dysfunction, although cardiac tamponade also accounted for a significant minority of these deaths. Thus, the severity of the clinical presentation rather than the underlying risk factors predicts early mortality. Based on the angiographic substudy data, it appears that rather than hastening early mortality, successful restoration of complete antegrade flow in the infarct-related artery protects against early death.