Time to Thrombolysis and Long-Term Outcomes in Patients With Acute Ischemic Stroke A Nationwide Study

Background and Purpose: It is well-established that increasing treatment delay reduces the benefits of thrombolysis in patients with acute ischemic stroke. However, most studies focus on short-term outcomes. This study examined long-term outcomes according to time to thrombolysis in patients with first-time ischemic stroke. Methods: In this nationwide cohort study, all Danish patients with first-time ischemic stroke treated with intravenous thrombolysis between 2011 and 2017 and alive at discharge were identified through the Danish Stroke Registry. The association between time from symptom onset to thrombolysis and the long-term rate of the composite of death and recurrent ischemic stroke was examined using multivariable Cox regression and restricted cubic spline analysis. Results: The study population included 6252 patients with first-time ischemic stroke treated with thrombolysis (median age, 69 years [25th-75th percentile 60-78 years], 60% men). The median follow-up was 2.5 years (25th-75th percentile 1.2-4.1 years). The median time to thrombolysis was 138 minutes (25th-75th percentile 101-185 minutes), and the median National Institutes of Health Stroke Scale score at presentation was 5 (25th-75th percentile 3-10). The absolute 3-year risk of the composite outcome was 19.0% (95% CI, 16.4%-21.8%) in the 0 to 90 minute group, 23.3% (21.8%-24.9%) in the 91 to 180 minute group, and 23.8% (21.6%-26.1%) in the 181 to 270 minute group. Compared with thrombolysis within 90 minutes, time to thrombolysis >90 minutes was associated with a higher rate of the composite outcome (91-180 minute: adjusted hazard ratio, 1.25 [95% CI, 1.06-1.48]; 181-270 minutes: adjusted hazard ratio, 1.35 [95% CI, 1.12-1.61]). In restricted cubic spline analysis, the rate of the composite outcome increased with increasing time to thrombolysis and leveled off after 138 minutes. Conclusions: In this nationwide cohort of patients with ischemic stroke, the long-term rate of the composite of death and recurrent ischemic stroke increased with increasing time from symptom onset to initiation of thrombolysis.