To analyze available evidence on long-term outcomes of door-to-needle (DTN) time ≤60 and ≤90 minutes.

Acute ischemic stroke is the second leading cause of mortality worldwide. DTN time is a critical quality metric as intravenous thrombolysis is most effective when given quickly. While early treatment improves short-term outcomes, its long-term impact on death and recurrence is less clear. Optimizing stroke therapeutic time becomes clinically relevant.

A PRISMA-based systematic review of observational studies in adults (≥18 years) treated with Alteplase or Tenecteplasewas conducted. Eligible studies reported DTN and ≥1-year mortality. A PubMed, Scopus, Embase, and Cochrane Library (2005–2025) search was performed. The reviewers screened in Covidence and extracted data through standardized forms. Risk of bias was assessed with ROBINS-I. A meta-analysis was performed using random-effects (Hartung–Knapp) in RStudio.

Six studies met inclusion criteria (n=124,944), with sample sizes ranging from 2,370 to 61,426. Median follow-up was 1 year (IQR 1.13). Median age was 68.5 years (IQR 12.75), 51.4% were female, all treated with Alteplase. The baseline NIHSS ranged from 3 to 18 points (6.5 [IQR 4.25]). The most common vascular risk factors were hypertension (n=90,921 [72.77%]), diabetes (n=31,657 [25.34%]), and atrial fibrillation/flutter (n=30,981 [24.80%]). The median DTN was 64.5 minutes (IQR 88) ranging from 36 to 194 minutes. DTN ≤60 minutes was associated with lower all-cause mortality in ≥1-year follow-up (OR 0.78, 95% CI 0.66–0.93, I² = 89.1%). DTN ≤90 minutes was associated with lower all-cause mortality in ≥1-year follow-up (OR 0.67, 95% CI 0.51-0.88, I² = 48.3%).

Although heterogeneity among studies was high, the overall trend consistently favored shorter door-to-needle times, supporting the robustness of the association with reduced long-term mortality. This sustained survival benefit highlights the clinical importance of minimizing treatment delays, as even modest reductions in door-to-needle time can translate into meaningful improvements in patient survival and long-term outcomes