Implications of Clinical Risk Phenotypes on the Management and Natural History of Atrial Fibrillation: A Report From the GLORIA‐AF

Background: Clinical risk factors are common among patients with atrial fibrillation (AF), but there are still limited data on their association with oral anticoagulant (OAC) treatment patterns and major outcomes. We aim to analyze the association between clinical risk phenotypes on AF treatment patterns and the risk of major outcomes. Methods and Results: The GLORIA‐AF (Global Registry on Long‐Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation) phase 2 and 3 registries enrolled patients with a recent diagnosis of AF between 2011 and 2016. We defined 4 features of clinical risk among patients with CHA2DS2‐VASc ≥2: elderly individuals (aged ≥80 years), chronic kidney disease (estimated glomerular filtration rate <45 mL/min), history of stroke, and history of bleeding. We analyzed the odds of receiving OAC and the risk of OAC discontinuation and adverse events at follow‐up according to specific combinations and cumulative burden of these features. Primary outcome was the composite of all‐cause death, thromboembolism, and major bleeding. Among 28 891 (mean±SD age, 70.1±10.5 years; 45.5% women) patients included, 10 797 (37.3%) had at least 1 clinical risk feature. OAC use was lower among patients in the elderly group (odds ratio [OR], 0.85 [95% CI, 0.75–0.96]), those with history of both stroke and bleeding (OR, 0.45 [95% CI, 0.35–0.56]), and those with multiple features (OR, 0.71 [95% CI, 0.62–0.82]). Increasing burden of clinical risk features was associated with OAC discontinuation, with highest magnitude in those with ≥3 features (hazard ratio [HR], 1.68 [95% CI, 1.31–2.15]). Groups with increasingly complex clinical risk phenotypes were associated with the occurrence of the primary composite outcome, with the highest figures observed for groups with a history of both stroke and bleeding (adjusted HR, 2.36 [95% CI, 1.83–3.04]) and multiple features (adjusted HR, 2.86 [95% CI, 2.52–3.25]). Conclusions: In patients with AF, clinical risk phenotypes are multifaceted and heterogenous, and they are associated with differences in stroke prevention and worse prognosis.