Background: Accumulating evidence from randomized-controlled clinical trials (RCTs) suggest that tenecteplase may represent an effective treatment alternative to alteplase for acute ischemic stroke (AIS). In the present systematic review and meta-analysis we sought to compare the efficacy and safety outcomes of intravenous tenecteplase to intravenous alteplase administration for AIS patients with large vessel occlusions (LVO). Methods: We searched MEDLINE and Scopus for published RCTs providing outcomes of AIS with confirmed LVO receiving intravenous thrombolysis with either tenecteplase at different doses or alteplase at standard dose 0.9mg/kg. The primary outcome was the odds of modified Rankin Scale (mRS) score of 0-2 at 3 months. Results: We included 4 RCTs including a total of 433 patients. Patients with confirmed LVO receiving tenecteplase had higher odds of successful recanalization (OR=3.05, 95%CI: 1.73-5.40; Figure A), mRS scores of 0-2 [odds ratio (OR)=2.06, 95%CI: 1.15-3.69; Figure B], and functional improvement defined as 1-point decrease across all mRS grades (common OR=1.84, 95%CI: 1.18-2.87; Figure C) at 3 months compared to patients with confirmed LVO receiving alteplase. There was little or no heterogeneity between the results provided from included studies regarding the aforementioned outcomes (I 2 ≤20%). No difference in the outcomes of early neurological improvement, symptomatic intracranial hemorrhage (ICH), any ICH and the rates of mRS 0-1 or all-cause mortality at 3 months were detected between patients with LVO receiving intravenous thrombolysis with either tenecteplase or alteplase. Conclusion: AIS patients with LVO receiving intravenous thrombolysis with tenecteplase have significantly better recanalization and clinical outcomes compared to patients receiving intravenous alteplase.

Introduction: The phase 2 PACIFIC-Stroke trial of patients with acute non-cardioembolic ischemic stroke assessed asundexian, the oral small molecule Factor XIa inhibitor, versus placebo administered within 48h of ischemic stroke to prevent recurrent stroke. This trial uniquely included moderate and severe strokes, which were excluded from other early timeframe, secondary prevention trials of escalated antithrombotic therapy. The primary results suggest a reduction in recurrent ischemic stroke and TIA when added to antiplatelet therapy without an overall increase in intracranial hemorrhage (ICH)(in press at the Lancet ). In this post-hoc analysis, we will further characterize the observed ICH. Methods: PACIFIC-Stroke (NCT04304508) was an international, double-blind, placebo-controlled, phase 2 randomized trial enrolling 1808 participants and comparing three dosages (10mg, 20mg, or 50mg daily) of asundexian with placebo. Participants were randomized within 48h of the qualifying ischemic stroke, and all received background antiplatelet therapy chosen by the local investigator. Eligibility for Part A was limited to patients with NIHSS </=7 who did not receive thrombolysis or endovascular thrombectomy, and Part B allowed an NIHSS up to 15 and treatment with reperfusion therapy (if >24 hours prior to randomization). Participants underwent MRIs within 72 hours of randomization and after 6 months. Results: In this presentation, we will further characterize the ICHs observed in the 1808 participants (1334 asundexian, 452 placebo) of the PACIFIC-Stroke trial. Further characterization will include timing, baseline stroke severity, post-thrombolysis/endovascular therapy status, asundexian dosing, and associated symptoms and radiological subtypes will be presented. Conclusions: Early anticoagulation of ischemic stroke patients with asundexian added to antiplatelet therapy was not associated with an increase in ICH compared to placebo, supporting the premise that inhibition of Factor XIa may prevent thrombosis without increasing bleeding. Further characterization of the observed ICHs associated with this novel drug compared to placebo will be presented.

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