Trials of thrombolysis in acute ischemic stroke: does the choice of primary outcome measure really matter?

Abstract

Background and purpose: Controversy regarding the risks and benefits of thrombolysis has not been helped by the perception that some trials were "positive" 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 what 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 randomized trials of thrombolysis in acute ischemic stroke, according to good (modified 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 thrombolysis.

Results: Twelve trials (4342 patients, treated up to 6 hours after stroke) contributed to this analysis. Overall, there was no difference in the estimate of treatment effect between the 2 definitions (modified Rankin 0 to 2 versus 3 to 6, and 0 to 1 versus 2 to 6 [ORs 0.83 and 0.79, respectively]). However, 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 difference between "success" and "failure." Overall, by either analysis, there was a significant benefit in patients treated with thrombolysis up to 6 hours after stroke.