Trials of thrombolysis in acute ischemic stroke - Does the choice of primary outcome measure really matter?

Background and Purpose-Controversy regarding the risks and benefits of thro mbolysis has not been helped by the perception that some trials were "posit ive" and others "negative" on their primary outcome measure of either "good " or "poor" functional outcome. We wondered whether the definition of good or poor functional outcome might have contributed to this perception, and w hat effect altering the definition might have on the individual trials and on the systematic review of all the trials combined. Methods-We analyzed data on functional outcome, extracted from the randomiz ed trials of thrombolysis in acute ischemic stroke, according to good (modi fied Rankin scale scores of 0 to 1 versus 2 to 6) and poor (modified Rankin 0 to 2 versus 3 to 6) functional outcome, to determine the effects of thro mbolysis. Results-Twelve trials (4342 patients, treated up to 6 hours after stroke) c ontributed to this analysis. Overall, there was no difference in the estima te of treatment effect between the 2 definitions (modified Rankin 0 to 2 ve rsus 3 to 6, and 0 to 1 versus 2 to 6 [ORs 0.83 and 0.79, respectively]). H owever, the apparent "success" of several individual trials did alter. Conclusions-We should not place undue emphasis on the results of individual trials, when a change of a single point on the Rankin scale can make the d ifference between "success" and "failure." Overall, by either analysis, the re was a significant benefit in patients treated with thrombolysis up to 6 hours after stroke.