• Jonathan P Piccini, Susanna R Stevens, YuChiao Chang, Daniel E Singer, Yuliya Lokhnygina, Alan S Go, Manesh R Patel, Kenneth W Mahaffey, Jonathan L Halperin, Günter Breithardt, Graeme J Hankey, Werner Hacke, Richard C Becker, Christopher C Nessel, Keith A A Fox, Robert M Califf, and ROCKET AF Steering Committee and Investigators.
• Division of Cardiology, Duke University Medical Center, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27710, USA. jonathan.piccini@duke.edu
• Circulation. 2013 Jan 15;127(2):224-32.

BackgroundWe sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial.Methods And ResultsIn ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance ≥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 embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R(2)CHADS(2)) improved net reclassification index by 6.2% compared with CHA(2)DS(2)VASc (C statistic=0.578) and by 8.2% compared with CHADS(2) (C statistic=0.575). The inclusion of creatinine clearance <60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R(2)CHADS(2) in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%-22.5%) relative to CHADS(2).ConclusionsIn patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function.Clinical Trial RegistrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT00403767.

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