Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation: Validation of the R2CHADS2 Index in the ROCKET AF and ATRIA Study Cohorts

Study Questions:

What are the factors associated with increased risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) enrolled in the ROCKET AF study?


The authors examined data from the 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) study, a multicenter, randomized, double-blind, double-dummy, event-driven trial comparing rivaroxaban with warfarin for prevention of stroke or systemic embolism. Cox proportional hazards modeling identified baseline factors that were independently associated with the outcome of interest, after which the authors developed a risk score. This risk score was validated using the ATRIA cohort, a population of adults with nonvalvular AF within the Kaiser Permanente system of Northern California, collected between July 1996 and December 1997.


Among 14,264 patients in the ROCKET AF study, over a median follow-up of 1.94 years, there were 575 (4.0%) primary endpoints. The authors identified reduced creatinine clearance (CrCl) as a strong, independent associate of the primary endpoint, as well as a history of prior stroke or transient ischemic attack, elevated diastolic blood pressure, increased heart rate, and both coronary artery disease as well as peripheral arterial disease (c-index 0.635). Adding renal function in the form of CrCl to the CHADS2 score (R2CHADS2) improved the net reclassification index (NRI) by 6.2% compared with CHADS2VASc (c-statistic = 0.578), and 8.2% when compared with CHADS2 (c-statistic = 0.575). Validation in the ATRIA cohort improved NRI by 17.4% (95% confidence interval, 12.1-22.5%) compared with CHADS2.


The authors concluded that in patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. The authors further opined that stroke risk stratification in patients with AF should include renal function.


This important observational re-analysis study may add significantly to our understanding of stroke risk in AF. The authors identified renal dysfunction as an extremely potent risk factor for stroke, and systemic embolism in AF. This is concordant with many other studies that have identified renal dysfunction as a potent risk factor for multiple cardiovascular endpoints. Although the newly defined risk score (R2CHADS2), which included renal dysfunction, was validated with an entirely separate cohort, one still must exercise caution in that it was derived in a single clinical trial cohort. That minor reservation notwithstanding, this study contributes significantly to our understanding of stroke risk in AF. It makes sense that renal dysfunction should be considered, as we continue to refine our stroke risk assessment in AF. The R2CHADS2 score should be evaluated and validated in other cohorts.

Clinical Topics: Vascular Medicine

Keywords: Coronary Artery Disease, Stroke, Renal Insufficiency, Ischemic Attack, Transient, California, Peripheral Arterial Disease, Risk Factors, Blood Pressure, Embolism, Creatinine

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