Anne Rasing, Esmée Verburgt, Merel S Ekker, Mijntje M I Schellekens, Maikel H M Immens, Jamie I Verhoeven, Esther M Boot, Mayte E van Alebeek, Paul J A M Brouwers, Renate M Arntz, Gert W van Dijk, Inge W M van Uden, Rob A R Gons, Tom den Heijer, Julia H van Tuijl, Karlijn F de Laat, Anouk G W van Norden, Sarah E Vermeer, Marian S G van Zagten, Robert J van Oostenbrugge, Marieke J H Wermer, Paul J Nederkoorn, Henk Kerkhoff, Fergus A Rooyer, Frank G van Rooij, Ido R van den Wijngaard, Tim J F Ten Cate, Anil M Tuladhar, Edo Richard, Frank-Erik de Leeuw, Nina A Hilkens
In total, 1226 patients were included (median [IQR] age, 44 [38-48] years; 637 male [52.0%]), with a median (IQR) follow-up of 4.2 (2.2-5.9) years. During follow-up, 129 patients experienced at least 1 bleeding event, corresponding to a 5-year cumulative risk of 10.7%. The annual bleeding rate was 2.5 events per 100 person-years. Among patients receiving antiplatelet therapy, the cumulative risk of bleeding at 6 years exceeded that of recurrent vascular events (85 bleeding events [14.7%] vs 105 vascular events [12.9%]). Among patients treated with oral anticoagulants, the cumulative risk of bleeding exceeded the risk of recurrent vascular events at 5 years (22 bleeding events [24.0%] vs 19 vascular events [23.6%]).
IMPORTANCE: Antithrombotic therapy is routinely prescribed to young adults after ischemic stroke to prevent recurrent vascular events. However, the long-term balance between potential benefits and bleeding risks of continued antithrombotic therapy in this population remains uncertain.
OBJECTIVE: To determine the short-term and long-term risk of bleeding associated with antithrombotic therapy in young stroke survivors.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Observational Dutch Young Symptomatic Stroke Study (ODYSSEY), a prospective, multicenter cohort study conducted in 17 hospitals in the Netherlands. Data were collected between 2013 and 2021. Follow-up data were obtained through standardized questionnaires with subsequent verification based on medical records, with data collection continuing until March 2024. Data were analyzed from October to December 2025. Participants included patients aged 18 to 49 years with a first-ever neuroimaging-proven ischemic stroke who survived the first 30 days after the index event.
EXPOSURE: Antithrombotic therapy.
MAIN OUTCOMES AND MEASURES: The primary outcome was the occurrence of a bleeding event requiring medical evaluation. Bleeding complications were stratified by severity according to the Bleeding Academic Research Consortium criteria. Potential factors associated with bleeding risk included sex, age, stroke severity, stroke cause, vascular risk factors, and antithrombotic therapy during follow-up. As a secondary analysis, bleeding risk was compared with the recurrence risk. The estimated bleeding probability during follow-up was calculated using Kaplan-Meier survival analysis with 95% CIs.
RESULTS: In total, 1226 patients were included (median [IQR] age, 44 [38-48] years; 637 male [52.0%]), with a median (IQR) follow-up of 4.2 (2.2-5.9) years. During follow-up, 129 patients experienced at least 1 bleeding event, corresponding to a 5-year cumulative risk of 10.7%. The annual bleeding rate was 2.5 events per 100 person-years. Among patients receiving antiplatelet therapy, the cumulative risk of bleeding at 6 years exceeded that of recurrent vascular events (85 bleeding events [14.7%] vs 105 vascular events [12.9%]). Among patients treated with oral anticoagulants, the cumulative risk of bleeding exceeded the risk of recurrent vascular events at 5 years (22 bleeding events [24.0%] vs 19 vascular events [23.6%]).
CONCLUSION AND RELEVANCE: In this cohort study, young stroke survivors receiving antithrombotic therapy were at substantial long-term risk of bleeding. Although bleeding and recurrent ischemic events may differ in their clinical consequences, these findings highlight that bleeding risk should be carefully considered throughout long-term antithrombotic therapy.