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Background and Purpose— TNK (tenecteplase), a newer fibrinolytic agent, has practical delivery advantages over ALT (alteplase) that would make it a useful agent if noninferior in acute ischemic stroke treatment outcome. Accordingly, the most recent US American Heart Association/American Stroke Association acute ischemic stroke guideline recognized TNK as an alternative to ALT, but only based on informal consideration, rather than formal meta-analysis, of completed randomized control trials. Methods— Systematic literature search and formal meta-analysis were conducted per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses), adapted to noninferiority analysis. The primary outcome of freedom from disability (modified Rankin Scale score, 0–1) outcome at 3 m, and additional efficacy and safety outcomes, were analyzed. Results— Systematic search identified 5 trials enrolling 1585 patients (828 TNK, 757 ALT). Across all trials, mean age was 70.8, 58.5% male, baseline National Institutes of Health Stroke Scale mean 7.0, and time from last known well to treatment start mean 148 minutes. All ALT patients received standard 0.9 mg/kg dosing, while TNK dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6%. For the primary end point, crude cumulative rates of disability-free (modified Rankin Scale score, 0–1) 3 m outcome were TNK 57.9% versus ALT 55.4%. Informal, random-effects meta-analysis, the risk difference was 4% (95% CI, −1% to 8%). The lower 95% CI bound fell well within the prespecified noninferiority margin. Similar results were seen for the additional efficacy end points: functional independence (modified Rankin Scale score, 0–2): crude TNK 71.9% versus ALT 70.5%, risk difference 2% (95% CI, −3% to 6%); and modified Rankin Scale shift analysis, common odds ratio 1.21 (95% CI, 0.93–1.57). For safety end points, lower event rates reduced power, but point estimates were also consistent with noninferiority Conclusions— Accumulated clinical trial data provides strong evidence that TNK is noninferior to ALT in the treatment of acute ischemic stroke. These findings provide formal support for the recent guideline recommendation to consider TNK an alternative to ALT.

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Background: Tenecteplase (TNK), a newer lytic easier to administer than alteplase (ALT), was recognized in the 2018 US AHA/ASA Guideline Update as an alternative to ALT in patients with acute ischemic stroke (AIS). But this recommendation was advanced based on informal consideration, rather than formal meta-analysis, of completed RCTs. Methods: Systematic literature search identified all RCTs comparing TNK vs ALT; formal non-inferiority meta-analysis was conducted per PRISMA guidelines. Based on a prior non-inferiority lytic AIS trial (ENCHANTED), the primary meta-analytic endpoint was disability-free (mRS 0-1) outcome at 3m, with a non-inferiority margin of 0.88. Additional efficacy and safety outcomes were also analyzed. Results: The systematic search identified 5 trials enrolling 1585 patients (828 TNK, 757 ALT). Across all trials, mean age was 70.8, 58.5% were male, baseline NIHSS was mean 7.0, and time from last known well to treatment start was mean 148 mins. All ALT patients received standard 0.9 mg/kg dosing, while TNK dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6%. For the primary endpoint, rates of disability-free (mRS 0-1) 3m outcome were: TNK 57.9% vs ALT 55.4%, RR 1.06 (95%CI 0.98-1.16) (Figure). The lower 95%CI bound fell well within the 0.88 non-inferiority margin. Similar results were seen for the additional efficacy endpoints: functional independence (mRS 0-2): TNK 71.9% vs ALT 70.5%, RR 1.02 (95% CI 0.96-1.09); and mRS shift analysis. For safety endpoints, lower event rates reduced power, but point estimates were also consistent with non-inferiority: Symptomatic ICH - TNK 3% vs ALT 3%, RR 0.96 (95% CI 0.56-1.65). Death – TNK 7.6% vs ALT 8.1%, RR 0.86 (95% CI 0.62-1.21). Conclusion: Accumulated clinical trial evidence provides strong evidence indicating that TNK is non-inferior to ALT in the treatment of AIS. These findings provide formal support for the recent guideline recommendation to consider TNK an alternative to ALT.

Background Advances in diagnostic imaging of stroke include multimodal techniques such as noninvasive angiography and perfusion imaging. We aimed to characterize trends in neuroimaging utilization among acute stroke patients. Utilization of multimodal imaging for acute stroke in the community has remained largely uncharacterized despite its increased adoption at academic medical centers. Methods We quantified neuroimaging utilization in the emergency department for 1700 hyperacute stroke patients presenting <2 hours after symptom onset who participated in the National Institutes of Health Field Administration of Stroke Therapy Magnesium (FAST-MAG) study throughout Los Angeles and Orange Counties. FAST-MAG provided no recommendation as to imaging utilization. Results 1700 cases were imaged a median (Interquartile range: IQR) of 92 (74–120) minutes after last known well time and 28 (19–41) minutes after ED arrival. The initial scanner used in the ED was CT in a preponderance of cases (N=1612, 95%), with MRI in 88 cases (5%). CT angiography was obtained in 192 (11%) and perfusion CT in 91 (5.4%) cases. MRI imaging was universally obtained using diffusion-weighted images, 60% with MR angiography and 33% included perfusion imaging. Rates of concomitant CTA or CTP use increased in the later years of the study from 4% in 2005–2006, 2% in 2007–2008, 8% in 2009–2010 and 26% in 2011–2012 (p for trend <0.001). Conclusions Among acute stroke patients, non-contrast CT was the most common initial imaging strategy in clinical practice in the 2005–2012 time period, though use of concomitant CTA grew to one-quarter of cases, suggestive of an upward trend.