The Impact of Circadian Rhythms on Reperfusion Therapy Efficacy in Acute Ischemic Stroke: A retrospective cohort study

Background Ischemic acute stroke displays a well-recognized circadian pattern. However, whether stroke onset time affects the therapeutic efficacy of standard interventions (intravenous thrombolysis) remain uncertain. Methods This retrospective cohort study included 712 patients with acute ischemic stroke receiving reperfusion therapy (intravenous thrombolysis or combined endovascular therapy). Patients were categorized into two groups (day-onset [06:00–18:00] and night-onset [18:00–06:00]) and into 6 groups by 4-hour intervals. The primary outcome was the 3-month functional status, evaluated using the modified Rankin Scale, with scores of 0–2 classified as favorable and scores of 3–6 as unfavorable outcomes. Propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), overlap weighting were used for analyses. Results 148 out of 286 patients (51.7%) in night-onset group and 182 out of 426 patients (42.7%) in day-onset group experienced unfavorable outcome at 3 months. Night-onset stroke was associated with a significantly risk of unfavorable outcome compared to day-onset stroke (OR = 1.44; 95%CI, 1.06–1.94; P  = 0.018). This association remained significant after adjustment using PSM (OR = 1.45; 95% CI, 1.01–2.08; P  = 0.044), and was further confirmed in analyses using IPTW (OR = 1.42; 95% CI,1.02–1.96; P  = 0.036) and overlap weighting (OR = 1.42; 95% CI,1.03–1.96; P  = 0.032). Nighttime strokes during 22:00–02:00 (OR = 2.44; 95% CI, 1.34–4.43; P  = 0.003) was significantly associated with a higher likelihood of unfavorable outcome in adjusted analysis. Conclusions Night-onset strokes are associated with poorer 3-month functional outcomes compared to day-onset strokes. Optimization of stroke treatment workflows is particularly important for patients with nighttime-onset stroke to reduce delays in reperfusion therapy. Further prospective studies are warranted to validate these findings. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2500101844.