Sandercock P, Wardlaw JM, Lindley RI, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within six hours of acute ischaemic stroke(the third international stroke trial IST 3); a randomized control trial. Lancet 2012; 379: 2352-2363.
Study looked at tpa among patients without clear indication or contraindication to tpa, in a European study. Due to approval initially in Europe for age < 79 and use within 3 hours of onset, this study was in effect for those >79, and those outside 3 hours, in Europe. Study looked at tpa + usual care v. usual care. 156 sites enrolled 2025 patients. 53 % were > 79, 72 % were treated after 3 hours after stroke onset but thin six hours. There was no significant difference in the dichotomized outcome, the initial primary measure, but by shift analsysi of the Oxford Handicap scores, TPA improved the odds of a one level improvement in the outcome. sICH occurred in 7 % v. 1 % of the control group.
In the subset treated within 3 hours, the primary dichotomized outcome occurred more with tpa than with the control group (OR 1.64)
Wardlaw JM, Murray V, Berge E. et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updfated systematic review and metanalysis. Lancet 2012; 309: 2480-2488.
An updated metaanalysis of tpa trials that included IST 3 showed that ivv tpa given within 3 hours of stroke improved the odds of a good functional outcome (OR 1.53)
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