Anticoagulation therapy reduces the risk for ischemic stroke in AF but also predisposes to hemorrhagic complications. Patients with GI/GU cancer and AF are at higher risk of hemorrhage with anticoagulation therapy. There is limited knowledge on the risk of first-ever ischemic stroke after extracranial hemorrhage (ECH) in patients with AF and GI/GU cancer.

We conducted a retrospective study using the California State Inpatient Database including all non-federal hospital admissions in California from 2005-2011. The exposure variable was hospitalization with a diagnosis of ECH with a previous diagnosis of AF. The outcome variable was a subsequent hospitalization with acute ischemic stroke. We excluded patients with stroke prior to or at the time of ECH diagnosis. We calculated adjusted hazard ratios (HRs) for ischemic stroke during follow up and at 6-month intervals using Cox regression models adjusted for pertinent demographics and co-morbidities after stratifying patients on the presence/absence of a GI/GU cancer.

We identified 764,257 AF patients (mean age 75yr, 49% women) without a documented history of stroke. Of these, 98,647 (13%) had an ECH-associated hospitalization, and 22,748 patients (3%) developed an ischemic stroke during follow-up. In the setting of GI/GU cancer, patients with ECH had a significantly higher risk of incident ischemic stroke compared to patients without ECH (adjusted HR 1.40, 95% CI 1.20-1.64). However, there was only a modest increase in ischemic stroke risk after ECH in those without GI/GU cancer (adjusted HR 1.14, 95% CI 1.10-1.19).

AF patients with GI/GU cancer hospitalized with ECH have a particularly high risk of ischemic stroke. Particular consideration should be given to the optimal balance between the benefits/risks of anticoagulation therapy and the use of non-anticoagulant alternatives in this population.