Abstract TP115: Multiple lacunes are associated with higher risks of ischemic and hemorrhagic events during antithrombotic therapy

Background: Lacunes are clinically silent, and the predominant cause is ischemia. The presence of lacune is associated with the increased risk of ischemic stroke, but there is limited evidence regarding their impact on antithrombotic therapy. The objective of this study was to determine the association between lacunes and ischemic and hemorrhagic risks in patients receiving antithrombotic therapy. Methods: This was a prospective, multicenter, observational study, enrolling patients who newly started or continued taking oral antiplatelets or anticoagulants. All participants underwent multimodal MRI at baseline. Multivariable survival analyses were performed to evaluate the relationship between the lacunes and outcomes including major bleeding, intracranial hemorrhage, all ischemic events, ischemic stroke, and mortality. Results: Of the 5,250 participants (1,762 women; median age 73 years), antiplatelets were prescribed to 3,947 (75.2%) and anticoagulants were prescribed to 1,565 (29.8%). On baseline MRI, no lacunes were observed in 2,103 patients (40.1%), one lacune in 1,130 patients (21.9%), 2-4 lacunes in 1,265 patients (24.4%), ≥5 lacunes in 677 patients (13.1%). During the follow-up period (median 721 days [IQR 686-742 days]), 93 major bleeding, 55 intracranial hemorrhages, 278 ischemic events, 197 ischemic strokes, and 217 deaths were observed. Five or more lacunes were associated with a higher risk of major bleeding (aHR 3.51, [95% CI, 1.99-6.19]), intracranial hemorrhages (4.73 [2.25-9.91]), ischemic events (2.55 [1.82-3.58]), and ischemic strokes (3.37 [2.26-5.04]). The association between ≥5 lacunes and intracranial hemorrhage risk was significant even when further adjusted for cerebral microbleeds (aHR 3.27 [1.52-7.05]). Two to four lacunes were associated with higher risk of ischemic events (aHR 1.51 [1.09-2.09]) and ischemic strokes (aHR 1.83 [1.24-2.71]). In contrast, presence of lacunes was not associated with increased risk of mortality. Conclusion: Two or more lacunes conferred an increased ischemic risk, whereas ≥5 lacunes further increased the excess hemorrhagic risk, highlighting their potential utility in informing clinical decision-making.