Glenn D. Graham, MD, PhD
How does time to treatment with intravenous alteplase affect outcomes in acute stroke?
Included studies compared alteplase with placebo in patients who had acute stroke and started treatment ≤ 360 minutes after symptoms started. Study exclusion criteria included rapid improvement, seizure associated with stroke onset, and serum glucose level < 2.8 mmol/L (50 mg/dL) or > 22.2 mmol/L (400 mg/dL). Other study inclusion and exclusion criteria varied. Favorable outcomes were modified Rankin Scale (mRS) score 0 to 1 and a composite endpoint (mRS score 0 to 1, Barthel Index 95 to 100, and National Institutes of Health Stroke Scale 0 to 1) at 90 days. Other outcomes included mortality and parenchymal hemorrhage type 2.
Individual patient data meta-analysis of 8 randomized, double-blind, placebo-controlled trials (n = 3670, mean age 66 y, 60% men). Intravenous alteplase, 0.9 mg/kg (maximum 90 mg) in 7 trials and 1.1 mg/kg (maximum 100 mg) in 1 trial, was infused over 1 hour, with a 10% bolus given in the first minute. Anticoagulants or antiplatelet drugs could not be used ≤ 24 hours after treatment. Worst outcomes were imputed for 6.7% of patients with missing data at 90 days.
At 90 days, alteplase given within 270 minutes (4.5 hours) of stroke onset improved function more than placebo; groups did not differ when treatment was given between 271 and 360 minutes (4.5 and 6.0 h) (Table). Results were similar for the composite endpoint. Alteplase increased risk for parenchymal hemorrhage type 2 more than placebo when given up to 6 hours after stroke onset (Table). Groups did not differ for overall mortality (Table); alteplase was associated with a borderline significant increase in mortality at 271 to 360 minutes (relative risk increase 42%, 95% CI 0 to 97).
Alteplase improves functional outcomes when given within 4.5 hours of stroke onset.
Alteplase vs placebo in acute stroke*
*OTT = time from stroke onset to treatment; other abbreviations defined in Glossary. Weighted event rates, RBI, RRI, NNT, NNH, and CI calculated from adjusted analyses in article.
†Modified Rankin Scale score 0 to 1.
‡Treatment by OTT interaction: modified Rankin Scale 0 to 1, P = 0.03; mortality, P = 0.04; parenchymal hemorrhage type 2, P = 0.41.
Graham GD. Meta-analysis: Alteplase improves functional outcomes when given within 4.5 hours of stroke onset. Ann Intern Med. ;153:JC3–2. doi: 10.7326/0003-4819-153-6-201009210-02002
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Published: Ann Intern Med. 2010;153(6):JC3-2.
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