Net clinical bene t analyses also favored the use of warfarin in different weighted models. These ndings suggest that the age-based treatment threshold for stroke prevention may need to be reset in East Adding biomarkers would (statistically) improve prediction, but c-indexes are still approximately 0.65 to 0.70. Recent studies in real-world cohorts do not support the clinical usefulness of biomarker-based scores over clinical risk scores such as the CHA2DS2-VASc score. The use of biomarkers has to balance the assay availability, laboratory variability, costs, and added complexity and lower practicality for everyday use. Also, many biomarker studies are based on anticoagulated 1144 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] highly selected clinical trial cohorts, with all included subjects already in the high risk group (CHA2DS2-VASc or CHADS2 [congestive heart failure, hypertension, age, diabetes, stroke (doubled)] score of 2 or greater). There are few/no studies on non-anticoagulated AF patients, to ascertain the true impact of biomarkers on (non- anticoagulation treated) stroke rates. Current studies do not inform whether the biomarkers will discriminate/ identify low risk in lower/intermediate risk patients who are not anticoagulated. Rather than focus on identifying high risk, the focus should be on initially identifying low risk patients. 