Incidence and Risk Factors for Residual Adverse Events Despite Anticoagulation in Atrial Fibrillation: Results From Phase II/III of the GLORIA‐AF Registry

Background Residual risk of ischemic stroke despite anticoagulation in patients with atrial fibrillation (AF) represents a significant clinical issue that remains unaddressed. We aimed to evaluate the incidence and risk factors for residual adverse events in AF. Methods and Results Using data from phase II/III of the prospective GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) registry, we studied anticoagulated patients with newly diagnosed AF and an increased risk of stroke (CHA₂DS₂-VASc ≥1). The primary outcome of interest was ischemic stroke. Secondary outcomes were all-cause death, cardiovascular death and myocardial infarction. A total of 22 410 patients were included; median age 65 (interquartile range 71-78) and 10 044 (44.8%) were female. During a median follow-up period of 3.0 (interquartile range 2.2-3.1) years, the incidence of ischemic stroke was 0.60 (95% CI, 0.54-0.67) per 100-PYs, all-cause death 3.22 (95% CI, 3.08-3.37) per 100-PYs, cardiovascular death 1.08 (95% CI, 1.00-1.16) per 100-PYs and myocardial infarction 0.59 (95% CI, 0.53-0.66) per 100-PYs. Using multivariable Cox proportional hazards analysis, independent predictors of residual ischemic stroke were age (HR 1.05 [95% CI, 1.03-1.07]), diabetes (HR 1.42 [95% CI, 1.08-1.87]), prior thromboembolism (HR 2.27 [95% CI, 1.73-2.98]) and use of antiarrhythmic drugs (HR 0.66 [95% CI, 0.47-0.92]). The incidence of ischemic stroke was comparable among patients treated with nonvitamin K antagonist oral anticoagulants versus vitamin K antagonist; however, there were differences in the independent predictors between both groups. Conclusions Patients with AF remain at significant residual risk of developing complications including ischemic stroke despite anticoagulation therapy. Further efforts among these patients should be directed at the management of modifiable risk factors that contribute to this risk. Registration URL: http://www.clinicaltrials.gov; Unique identifiers: NCT01468701, NCT01671007 and NCT01937377.