Abstract WP177: Effects Of The Oral Factor XIa Inhibitor Asundexian On Intracranial Bleeding Among Patients With Acute Non-Cardioembolic Ischemic Stroke: PACIFIC-Stroke Randomized Trial

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 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.