Survival 12 years after randomization to streptokinase: the influence of thrombolysis in myocardial infarction flow at three to four weeks

Abstract

Objectives: The purpose of this study was to determine whether the mortality benefit of intravenous streptokinase administered within 4 h of the onset of acute myocardial infarction is maintained at 12 years, and whether Thrombolysis in Myocardial Infarction (TIMI) flow grades independently influence late survival.

Background: Treatment with reperfusion therapies and achievement of TIMI 3 flow are associated with increased short- and medium-term survival after infarction. Whether infarct artery flow independently influences survival more than five years after infarction is unknown.

Methods: The late survival of patients randomized to receive either streptokinase (1,500,000 IU over 30 to 60 min) or a matching placebo within 4 h of symptom onset in 1984-1986 was determined. Angiography was performed in surviving patients at three to four weeks, and TIMI flow grades were assessed blind to randomization and outcomes. The late vital status was determined in 99% of patients.

Results: Patients randomized to receive streptokinase (n = 107) had improved survival compared with those randomized to placebo (n = 112) at five years (84% vs. 70%; p = 0.023) and 12 years (66% vs. 51%; p = 0.022). At five years 94% of patients with TIMI grade 3 flow, 81% of those with TIMI grade 2 flow and 72% of those with TIMI grade 0-1 flow survived (p = 0.005). At 12 years 72% of patients with TIMI 3, 67% of those with TIMI 2 and 54% of those with TIMI 0-1 flow survived (p = 0.023). Multivariate analysis identified the ejection fraction (p = 0.014), exercise duration (p = 0.013) and TIMI 3 flow (p = 0.04 compared with TIMI 0-2 flow) as important factors for five-year survival. At 12 years multivariate predictors of late survival were the ejection fraction (p = 0.006), exercise duration (p = 0.003) and myocardial score (p = 0.013). The end-systolic volume index was similar to the ejection fraction as a predictor of survival at five and 12 years.

Conclusions: The survival benefits of streptokinase persist for 12 years after infarction. TIMI flow at three to four weeks is an independent predictor of five-year survival.