Streptokinase for Acute Ischemic Stroke With Relationship to Time of Administration

Objectives. —To determine whether the administration of 1.5 million units of streptokinase intravenously within 4 hours of the onset of acute ischemic stroke would reduce morbidity and mortality at 3 months and whether outcomes may be better for those receiving therapy within 3 hours of stroke onset compared with those receiving it after 3 hours. Design. —Randomized, double-blind, placebo-controlled trial with 3-month follow-up. Participants. —A total of 340 patients, aged 18 to 85 years, with moderate to severe strokes were randomized from 40 centers throughout Australia from June 1992 to November 1994. Intervention. —Administration of 1.5 million units of streptokinase or placebo intravenously in 100 mL of normal saline over 1 hour. Main Outcome Measure. —Combined death and disability score (Barthel index Results. —Using an intention-to-treat analysis with a combined death and disability score at 3 months after stroke as the primary end point, we found a nonsignificant overall trend toward unfavorable outcomes for streptokinase vs placebo (relative risk RR of unfavorable outcome, 1.08; 95% confidence interval CI, 0.74-1.58) and an excess of hematomas (13.2% 12.6% symptomatic in the treated group, 3% 2.4% symptomatic for placebo [PP=.04). Streptokinase administration resulted in excess deaths in the group treated after 3 hours (RR, 1.98; 95% CI, 1.18-3.35), but not among those treated within 3 hours (RR, 1.11; 95% CI, 0.38-3.21). Conclusion. —The administration of streptokinase within 4 hours of acute ischemic stroke increased morbidity and mortality at 3 months. While treatment within 3 hours of stroke was safer and associated with significantly better outcomes than later treatment, it showed no significant benefit over placebo. The timing of thrombolytic therapy for acute stroke is critical.