Comparison of anticoagulants and risk of ischemic stroke in patients with acute cancer-associated venous thromboembolism

Venous thromboembolism (VTE) is a frequent occurrence in patients with cancer. However, it is not known whether treatment with different classes of anticoagulants impacts the risk of subsequent arterial thromboembolism (ATE). We performed a retrospective, population-based cohort study using Surveillance, Epidemiology, and End Results data linked with Medicare claims. Patients were eligible for study inclusion if they had a diagnosis of primary brain, colorectal, gastric, pancreatic, lung, or ovarian cancer between 2007 and 2015, were diagnosed with VTE, and had a prescription claim for a direct oral anticoagulant (DOAC), low-molecular-weight heparin (LWMH), or warfarin. We propensity score matched patients 1:1:1 into anticoagulant treatment groups based on baseline demographic information, cancer-specific characteristics, and cardiovascular comorbidities. The primary aim of the study was to determine and compare the 6-month cumulative incidence of ischemic stroke across anticoagulant classes. The study comprised of 4,875 total patients with 1,625 in each treatment group. At 6-months, the cumulative incidence of ischemic stroke was 5.6% (95% confidence interval [CI] 5.0 - 6.3) overall and 6.8% (95% CI 5.6 - 8.1) in DOAC, 4.9% (95% CI 3.9 - 6.0) in LMWH, and 5.2% (95% CI 4.1 - 6.2) in warfarin treatment groups (p = 0.040). We identified hypertension (odds ratio [OR] 1.75), atrial fibrillation/flutter (OR 1.37), DOAC use (OR 1.36), and prior stroke (OR 3.59) as statistically significant risk factors for ischemic stroke on multivariable modeling. In conclusion, ischemic stroke is a common occurrence after cancer-associated VTE and may occur more frequently in patients treated with DOACs.