Association of the time of day of EVT with clinical outcomes and benefit from successful recanalization after stroke

Abstract

Experimental and neuroimaging studies suggest an influence of the time of day on acute infarct growth, but whether this could inform patient selection for acute treatments is uncertain. In a multicenter cohort of 9357 stroke patients undergoing endovascular treatment, morning treatment (05:00-10:59) was associated with lowest 90-day mRS scores (adjusted odds ratio, 1.27 [95% CI, 1.08-1.47]; p = 0.004). The association between successful recanalization and outcome was stronger in morning compared to evening-treated patients (p_ia = 0.046) with treatment benefit persisting until 24 h for morning-treated compared to 11.5 h for evening-treated patients suggesting that the time of day might inform patient selection for EVT.

Figure 1

Association of the time of day of endovascular treatment with clinical outcome at 90 days after stroke. (A) The time of day of stroke onset peaked at 09:30 and the time of day of endovascular treatment (i.e., flow restoration) peaked at 14:00. (B) Stratifying patients to 6‐h time‐blocks resulted in mildly larger groups for onset in morning and mid‐day, and a substantially larger group for flow restoration during mid‐day and indicated crossflow between groups of symptom onset and flow restoration. (C) In unadjusted analyses, morning EVT was associated with lower mRS scores at 90 days after stroke compared to patients treated at other times of the day. (D) A sinusoidal fit of the relation of the time of flow restoration with mRS scores 90 days after stroke largely overlapped with a fit derived from unbiased local polynomial regression. (E) Sinusoidal regression analyses mapped the time of day of EVT with best outcomes to 07:12. (F–H) The time of day of symptom onset was not associated with mRS scores at 90 days (F and G) and discharge (H). (I and J) In adjusted analyses, morning EVT was associated with lower mRS scores at 90 days after stroke in the primary cohort (I) and in the independent replication cohort (J). aOR, adjusted odds ratio; EVT, endovascular treatment; mRS, modified Rankin Scale; n.s., not significant; T, time of day.

Figure 2

Secondary outcomes and benefit from successful recanalization. (A–D) Morning treatment was associated with higher rates of functional independence at 90 days (A) and discharge (B), lower mRS scores at discharge (C), and lower NIHSS scores at 24 h after onset (D). (E and F) Morning treatment was associated with higher likelihood of functional independence at 90 days (E) and discharge (F) in patients with an mTICI score of 3. (G) Morning treatment was similarly related to the rate of functional independence at 90 days compared to treatment with intravenous alteplase and a 4‐h delay of the time from onset to treatment. (H) The association between time to treatment and mRS scores at 90 days was weaker in morning‐ compared to evening‐treated patients. (I) The association between successful recanalization and functional independence at 90 days was stronger in morning‐ compared to evening‐treated patients. (J) Predictive margins show that the benefit from successful recanalization persisted until 24 h after onset for morning‐treated patients while it was lost after 11.5 h for patients treated in the evening. 95% CI, 95% confidence interval; aOR, adjusted odds ratio; h, hour; mRS, modified Rankin Scale; T, time of day; ΔT, time from onset to treatment.