Intravenous Thrombolytics in the Treatment of Acute Ischemic Stroke

PURPOSE OF REVIEW: To review the current evidence and ongoing clinical trials evaluating the efficacy and safety of tenecteplase (TNK), an alternative tissue plasminogen activator (tPA), in the acute management of arterial ischemic stroke (AIS). To date, alteplase is the only tPA approved by the United States FDA for use in AIS. RECENT FINDINGS: There have been multiple phase two and three trials investigating the safety and efficacy of TNK in AIS. In patients with AIS due to large vessel occlusion, one randomized controlled trial demonstrated superiority of TNK for vessel recanalization rates and long-term functional outcomes when compared to alteplase. A meta-analysis of all phase two and three trials evaluating TNK in AIS concluded that TNK has a comparable safety and efficacy profile to alteplase. The results of these trials prompted new recommendations in the Acute Stroke Guideline published by the AHA suggesting it may be reasonable to use as an alternative to alteplase. Furthermore, recent real-world data has also reported decreased door-to-needle time with TNK utilization. SUMMARY: In patients with AIS, use of a thrombolytic agent is standard of care and has been shown to reduce neurological disability and improve functional outcome. Randomized controlled trials have demonstrated that TNK is non-inferior to alteplase from a clinical outcome and safety standpoint. The existing data evaluating the efficacy of TNK compared to alteplase in acute AIS within 4.5 h from symptom onset showed no significant difference between these two agents with regard to functional outcome at 90 days but improved median time to treatment and large vessel recanalization in TNK-treated patients. The results from ongoing TNK trials in larger patient cohorts and in wake-up stroke populations will be instrumental to the wide-scale utilization of TNK in acute AIS management.