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 CHA(2)DS(2)-VASc score,4 vs 2.01 (95% CI 1.81-2.24) events per 100-patient years for CHA(2)DS(2)-VASc score.4. Factors associated with increased risk were previous stroke or transient ischemic attack (hazard ratio [HR] 2.87; 95% CI 2.303.59; 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 CHA(2)DS(2)-VASc score despite OAC. Key risk markers include previous stroke/transient ischemic attack, female sex, hypertension, and permanent AF.