Benefit seen with thrombolysis for ischemic stroke beyond the 4.5-hour time window

Reference

Ma H, Campbell BCV, Parsons MW, et al, for the EXTEND Investigators. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med 2019;380(19):1795-1803.

Synopsis

Current guidelines state that intravenous thrombolysis must be initiated within 4.5 hours after onset of ischemic stroke. In this study, investigators enrolled patients with acute ischemic stroke who presented either between 4.5 and 9 hours after stroke onset or upon awakening with stroke symptoms with time of onset of symptoms unknown. Eligible patients were those with excellent functional status prior to stroke who had evidence of hypo-perfused but salvageable areas of brain tissue detected by perfusion imaging. Using concealed allocation, the investigators randomized patients to receive either intravenous alteplase (n = 113) or matching placebo (n = 112). The trial was terminated early (before the target 310 patients were enrolled) because of loss of equipoise after positive results were found in a similar trial. In the current trial, 65% of patients in both groups awoke with stroke symptoms with time of onset unknown, 25% were treated after 6 hours of known symptom onset, and 10% were treated between 4.5 and 6 hours of symptom onset. After adjustment for baseline factors, the patients who received alteplase were more likely to achieve an excellent functional outcome at 90 days, as indicated by a modified Rankin scale score of 0 or 1 (35.4% in alteplase group vs 29.5% in placebo group; P = .04; number needed to treat = 17). The alteplase group was also more likely to have symptomatic intracranial bleeds (6.2% vs 0.9%; P = .05, number needed to treat to harm = 19). No significant mortality difference was detected.