Residual stroke risk despite oral anticoagulation in patients with atrial fibrillation

Background: Oral anticoagulation (OAC) reduces the risk of thromboembolic events in patients with atrial fibrillation (AF); however, thromboembolism (TE) still can occur despite OAC. Factors associated with residual risk for stroke, systemic embolism, or transient ischemic attack events despite OAC have not been well described. Objective: The purpose of this study was to evaluate the residual risk of thromboembolic events in patients with AF despite OAC. Methods: A total of 18,955 patients were analyzed in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF I and II) using multivariable Cox proportional hazard modeling. Mean age was 72 ± 10.7, and 42% were women. There were 451 outcome events. Results: The risk of TE despite OAC increased with CHA₂DS₂-VASc score: 0.76 (95% confidence interval [CI] 0.63–0.92) events per 100 patient-years for CHA₂DS₂-VASc score <4 vs 2.01 (95% CI 1.81–2.24) events per 100-patient years for CHA₂DS₂-VASc score >4. Factors associated with increased risk were previous stroke or transient ischemic attack (hazard ratio [HR] 2.87; 95% CI 2.30–3.59; P <.001), female sex (HR 1.52; 95% CI 1.24–1.86; P <.001), hypertension (HR 1.50; 95% CI 1.09–2.06; P = .01), and permanent AF (HR 1.47; 95% CI 1.12–1.94; P = .001). When transient ischemic attack was excluded, the results were similar, but permanent AF was no longer significantly associated with thromboembolic events. Conclusion: Patients with AF have a residual risk of TE with increasing CHA₂DS₂-VASc score despite OAC. Key risk markers include previous stroke/transient ischemic attack, female sex, hypertension, and permanent AF.