Michael D. Hill, MD, MSc, FRCPC
What is the efficacy and safety of alteplase given 3 to 4.5 hours after onset of acute ischemic stroke?
Randomized placebo-controlled trial (European Cooperative Acute Stroke Study [ECASS] III). ClinicalTrials.gov NCT00153036.
Blinded (patients and clinicians).*
130 sites in 19 countries in Europe.
821 patients (mean age 65 y, 60% men) who had acute ischemic stroke with symptoms lasting ≥ 30 minutes without improvement before treatment and were able to receive the study drug within 3 to 4.5 hours after onset. Exclusion criteria included intracranial hemorrhage (ICH); severe stroke; seizure at stroke onset; major surgery, stroke, or trauma in the past 3 months; previous stroke and diabetes mellitus; heparin within 48 hours before stroke; platelet count < 100 000/mm3; blood pressure > 185/110 mm Hg; and blood glucose level < 50 mg/dL (2.8 mmol/L) or > 400 mg/dL (22.2 mmol/L).
Alteplase, 0.9 mg/kg, 10% bolus, followed by continuous intravenous (IV) infusion over 60 minutes (n = 418) or matching placebo (n = 403).
Favorable outcome for disability (modified Rankin Scale [mRS] score 0 to 1) and global outcome (based on mRS, Barthel Index, National Institutes of Health Stroke Scale [NIHSS], and Glasgow Outcome Scale). Safety outcomes included any ICH, symptomatic ICH (increase in NIHSS score ≥ 4 points from baseline or leading to death), and death.
89% (intention-to-treat analysis).
More patients in the alteplase group than in the placebo group had favorable outcome for disability (Table) and global outcome (odds ratio 1.3, 95% CI 1.0 to 1.6; individual components in Table). The alteplase group had a higher incidence of ICH (Table), but groups did not differ for death.
Alteplase given 3 to 4.5 hours after acute ischemic stroke reduced disability and improved global outcome.
Alteplase vs placebo given 3 to 4.5 hours after acute ischemic stroke†
†NIHSS = National Institutes of Health Stroke Scale; other abbreviations defined in Glossary. RBI, RRI, NNT, NNH, and CI calculated from data in article based on the intention-to-treat population.
‡Score range 0 (no symptoms) to 6 (death). Analysis adjusted for baseline NIHSS score and time to start of treatment.
§Score range 0 (complete dependence) to 100 (independence).
||Score range 0 to 42, higher values = more severe neurologic impairment.
¶Score range 1 (independence) to 5 (death).
**NIHSS score ≥ 4 points from baseline or leading to death.
Hill MD. Alteplase given 3 to 4.5 hours after stroke reduced disability and improved global outcome. Ann Intern Med. 2009;150:JC1–13. doi: 10.7326/0003-4819-150-2-200901200-02013
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Published: Ann Intern Med. 2009;150(2):JC1-13.
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