STREPTOKINASE FOR ACUTE ISCHEMIC STROKE WITH RELATIONSHIP TO TIME OF ADMINISTRATION

Objectives.-To determine whether the administration of 1.5 million uni ts 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 with in 3 h ours of stroke onset compared with those receiving it after 3 hours. D esign.-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 thro ughout Australia from June 1992 to November 1994. Intervention.-Admini stration of 1.5 million units of streptokinase or placebo intravenousl y in 100 mt of normal saline over 1 hour. Main Outcome Measure.-Combin ed death and disability score (Barthel index <60) 3 months after the s troke. Results.-Using an intention-to-treat analysis with a combined d eath and disability score at 3 months after stroke as the primary end point, we found a nonsignificant overall trend toward unfavorable outc omes for streptokinase vs placebo (relative risk [RR] of unfavorable o utcome, 1.08; 95% confidence interval [CI], 0.74-1.58) and an excess o f hematomas (13.2% [12.6% symptomatic] in the treated group, 3% [2.4% symptomatic] for placebo [P<.01]). However, poor outcomes were confine d to patients receiving therapy more than 3 hours after stroke onset ( RR of unfavorable outcome, 1.22; 95% CI, 0.80-1.86). In contrast, amon g the 70 patients who were entered into the trial within 3 hours of st roke onset, there was a trend toward improved outcomes for those who r eceived streptokinase (FIR of unfavorable outcome, 0.66; 95% CI, 0.28- 1.58), and this outcome pattern was significantly better than for thos e receiving therapy after 3 hours (P=.04). Streptokinase administratio n 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 streptok inase within 4 hours of acute ischemic stroke increased morbidity and mortality at 3 months. While treatment within 3 hours of stroke was sa fer and associated with significantly better outcomes than later treat ment, it showed no significant benefit over placebo, The timing of thr ombolytic therapy for acute stroke is critical.