In ROCKET AF, 14,264 patients with nonvalvular AF and creatinine clearance (CrCl) ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system (CNS) embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA, an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 (4.0%) patients experienced primary endpoint events. Reduced CrCl was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack (TIA). Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, and vascular disease of the heart and limbs (C-index 0.635). A model including CrCl (R2CHADS2) improved net reclassification index (NRI) by 6.2% when compared with CHA2DS2VASc (C-statistic=0.578) and 8.2% when compared with CHADS2 (C-statistic=0.575). The inclusion of estimated glomerular filtration rate