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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.

Background: Ischemic stroke (IS) is a leading cause of long-term disability with sex-specific differences in outcomes. Identifying the influential factors that contribute to sex-specific disparities in stroke outcomes, therefore, holds potential to develop individualized interventions for reducing long-term disability. Further, investigating the association between sex and Patient-Reported Outcome Measures (PROMs) provides additional information on the individual impact and heterogeneity of IS. We aimed to identify sex-specific differences in stroke outcomes and relationship with PROMs in IS patients with 3-month follow-up. Methods: Between February 2017 and February 2020, a total of 410 patients admitted with IS to the Massachusetts General Hospital, in Boston, were enrolled in this prospective cohort. At 3-month poststroke, patients were assessed for Barthel Index, modified Rankin Scale, and PROM-10 questionnaires. T scores for physical and mental health were determined from the summing of PROM-10 responses in each domain. Regression analysis was performed to identify sex-specific determinants of functional and patient-reported outcomes. Results: At baseline, 242 participants were male (mean age, 65 years) and 168 were female (mean age, 70 years). Groups had similar rates of cardiovascular risk factors, admission National Institutes of Health Stroke Scale, and discharge modified Rankin Scale. At follow-up, male participants were more likely to have better rates of T Physical and Barthel Index. In regression analysis, PROMs T Physical (odds ratio, 1.06; P =0.01), Barthel Index (odds ratio, 1.06; P =0.01), and modified Rankin Scale score of ≥2 (odds ratio, 2.60; P =0.01) were associated with female sex. Female sex was also associated with lower scores for PROMs Physical subcomponents and with patient-reported general health and emotional problems. Conclusions: Women have worse outcomes after ischemic stroke, including objective measures of functional disability and patient-reported outcomes. Incorporating PROMs into IS outcome measures may offer additional insight into sex-specific differences in stroke recovery and outcomes.

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