Circadian variation in the effect of intravenous thrombolysis after non-lacunar stroke

The onset of non-lacunar stroke symptoms has a circadian variation, with a higher risk in the early morning hours and lower risk during the nighttime period, but this circadian distribution has not been clearly established on the effect of intravenous (IV) thrombolysis. The aim of the present study was to assess whether the time interval based on time of Alteplase IV infusion may influence the effect of treatment in patients with non-lacunar stroke. We conducted an analysis on prospectively collected data of 476 non-lacunar stroke patients treated with IV thrombolysis. To identify a possible circadian variation in the effect of Alteplase IV infusion, we used the following outcome measures: major neurological improvement (NIH stroke scale [NIHSS] score decrease of ≤8 points from baseline or NIHSS score of 0 at 24 h), and hemorrhagic transformation according to European Cooperative Acute Stroke Study trial definition within 24 h. Multivariate analysis showed that ORs for major neurological improvement were lower in patients who started IV thrombolysis in the 6 AM-noon interval (OR 0.35, 95% CI 0.16-0.74, p = 0.006) and noon-6 PM interval (OR 0.40, 95% CI 0.20-0.81, p = 0.010), whereas ORs for hemorrhagic transformation were lower in patients who started IV thrombolysis in the noon-6 PM interval (OR 0.29, 95% CI 0.12-0.67, p = 0.004) and in the 6 PM-midnight interval (OR 0.26, 95% CI 0.11-0.62, p = 0.002), compared with midnight-6 AM interval. The effect of Alteplase IV infusion could show a circadian variation in patients with non-lacunar stroke. After comparison with the midnight-6 AM interval, thrombolysis could be more safe from noon to midnight, and less effective from 6 AM to 6 PM.