Anticoagulant versus Antiplatelet Treatment for Secondary Stroke Prevention in Patients with Active Cancer

Moritz C Kielkopf¹Jayan Göcmen¹Selina B Venzin¹Fabienne Steinauer¹Mattia Branca²Anna Boronylo¹Martina B Göldlin¹Johannes Kaesmacher³Adnan Mujanovic³Gianluca Costamagna^4,5Thomas Raphael Meinel¹David J Seiffge¹Philipp Bücke¹Mirjam R Heldner¹Ava Liberman⁶Hooman Kamel⁶Urs Martin Fischer¹Marcel Arnold¹Thomas Pabst⁷Martin D. Berger⁷Simon Jung¹Adrian Scutelnic¹Babak Navi⁶Morin Beyeler^1,6,8*

• ¹Department of Neurology, University Hospital Bern, Bern, Switzerland
• ²CTU Bern, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland, Bern, Switzerland
• ³Institute for Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Bern, Switzerland
• ⁴Stroke Center, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, Lausanne, Switzerland
• ⁵Dino Ferrari Center, University of Milan, Milan, Lombardy, Italy
• ⁶Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York, USA, New York, United States
• ⁷Department of Medical Oncology, Inselspital, Bern University Hospital, and University of Bern, Switzerland, Bern, Switzerland
• ⁸Graduate School for Health Sciences, University of Bern, Bern, Bern, Switzerland

Background Approximately 5-10% of patients with acute ischemic stroke (AIS) have known active cancer. These patients are at high risk for both recurrent AIS and major bleeding. The optimal antithrombotic strategy for cancer-related stroke is uncertain. This study compared clinical outcomes among patients with cancer-related stroke treated with anticoagulant versus antiplatelet therapy for secondary prevention. Methods We identified consecutive patients with AIS and active cancer hospitalized at our comprehensive stroke center from 2015 through 2020. Patients with cardioembolic mechanisms were excluded. We used Cox regression and inverse probability of treatment weighting (IPTW) analyses to evaluate the associations between type of antithrombotic therapy at discharge (anticoagulant versus antiplatelet therapy) and the main outcomes of 1-year mortality and long-term recurrent AIS. Results Among 5012 AIS patients, 306 had active cancer. After applying study eligibility criteria, we analyzed 135 patients (median age 72 years; 44% women), of whom 58 (43%) were treated with anticoagulant and 77 (57%) with antiplatelet therapy. The median follow-up time was 495 days (IQR, 57–1029). Patients treated with anticoagulants, compared to patients treated with antiplatelet therapy, were younger (median 69 versus 75 years), had more metastatic disease (72% versus 41%), and higher median baseline D-dimer levels (median 8536 µg/L versus 1010 µg/L). Anticoagulant versus antiplatelet therapy was associated with similar risks of 1-year mortality (adjusted hazard ratio [aHR], 0.76; 95% confidence interval [CI], 0.36-1.63) and long-term recurrent AIS (aHR 0.49; 95% CI 0.08-2.83). The IPTW analyses for 1-year mortality confirmed the results of the main analyses (HR 0.82; 95% CI 0.39-1.72, P=0.61).