Results:

Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3 hours resulted in a good outcome for 259 (32.9%) of 787 patients who received alteplase versus 176 (23.1%) of 762 who received control (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.35-2.27); delay of greater than 3 hours, up to 4.5 hours, resulted in good outcome for 485 (35.3%) of 1,375 versus 432 (30.1%) of 1,437 (OR, 1.26; 95% CI, 1.05-1.51); and delay of more than 4.5 hours resulted in good outcome for 401 (32.6%) of 1,229 versus 357 (30.6%) of 1,166 (OR, 1.15; 95% CI, 0.95-1.40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial hemorrhage (type 2 parenchymal hemorrhage definition, 231 [6.8%] of 3,391 vs. 44 [1.3%] of 3,365; OR, 5.55; 95% CI, 4.01-7.70; p < 0.0001; SITS-MOST definition 124 [3.7%] vs. 19 [0.6%], OR, 6.67; 95% CI, 4.11-10.84; p < 0.0001) and of fatal intracranial hemorrhage within 7 days (91 [2.7%] vs. 13 [0.4%]; OR, 7.14; 95% CI, 3.98-12.79; p < 0.0001). The relative increase in fatal intracranial hemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17.9%) in the alteplase group versus 556 (16.5%) in the control group (hazard ratio, 1.11; 95% CI, 0.99-1.25; p = 0.07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial hemorrhage of about 2%, by 3-6 months, this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3 hours and about 5% for patients treated after 3 hours, up to 4.5 hours.