Impact of Cancer on Bleeding and Ischemic Stroke in Atrial Fibrillation Patients Taking Rivaroxaban, a Direct Oral Anticoagulant

Introduction: The impact of cancer in atrial fibrillation (AF) patients who are undergoing anticoagulant therapy is not known because patients with cancer have been excluded from recent randomized clinical trials of direct oral anticoagulants (DOACs) for the prevention of stroke in patients with non-valvular AF (NVAF). Therefore, we examined whether cancer is associated with an increased risk of bleeding or ischemic stroke among patients with NVAF taking the DOAC rivaroxaban. Methods: We enrolled 564 patients who were prescribed rivaroxaban to manage NVAF between July 2012 and July 2016 at our institution. We used multivariate Cox proportional hazard models to assess the relationship between cancer and the risk of bleeding or ischemic stroke. Results: Bleeding events occurred in 19 patients (3.4%), including 6 with major bleeding (0.11%). Patients with cancer or cancer history had more bleeding (hazard ratio (HR), 7.23; 95% confidence interval (CI), 2.48-21.09; P < 0.001). A lower albumin level (<3.6 mg/dl) indicated a higher tendency for bleeding (HR, 2.87; 95% CI, 0.96-8.57; P = 0.059). Nine patients (1.6%) experienced ischemic stroke during therapy; one of them had cancer. The CHA2DS2-VASc score was significantly associated with the incidence of ischemic stroke, whereas comorbidity with cancer was not. Conclusions: Bleeding events in patients with NVAF treated with rivaroxaban were associated with comorbidity of cancer and a lower albumin level, whereas cancer was not correlated with an increased risk of ischemic stroke. Therefore, caution should be used when prescribing DOACs to patients with cancer or low albumin levels, and we should follow-up for bleeding events closely.