Renal Function and Outcomes in Anticoagulated Patients With Non-Valvular Atrial Fibrillation: The AMADEUS Trial

Study Questions:

What is the impact of renal function on systemic embolism and bleeding in patients with atrial fibrillation (AF) on anticoagulation, and what is the additive prognostic value of moderate-severe chronic kidney disease (CKD) on CHADS2 and CHA2DS2VASc?


This was a post-hoc analysis of the AMADEUS trial, a multicenter, open-label, noninferiority trial that compared fixed-dose idraparinux with anticoagulation by dose-adjusted vitamin K antagonists in patients with electrocardiogram-documented nonvalvular AF. The primary efficacy outcome was the composite of stroke and systemic embolism; major bleeding was the principal safety outcome. Discriminatory performance was evaluated by receiver operating characteristic analysis.


Patients with creatinine clearance (CrCl) >90 ml/min had an annual stroke/systemic embolism rate of 0.6% compared with 0.8% for those with CrCl 60-90 ml/min and 2.2% for those with CrCl <60 ml/min (p < 0.0001). In adjusted analyses, those with CrCl <60 ml/min had more than two-fold higher risk of stroke/systemic embolism and almost 60% higher risk of major bleeding compared to those with CrCl ≥60 ml/min. When CrCL <60 ml/min was added to CHADS2 or CHA2DS2VASc, there was no improvement in discrimination ability (based on c indices).


In patients with nonvalvular AF on anticoagulation, those with CrCl <60 ml/min had a two-fold higher risk for stroke and systemic embolism, along with a 60% higher risk of major bleeding, when compared to patients with CrCl ≥60 ml/min.


The limitations of this post-hoc analysis aside, the results of this study may suggest the need for more aggressive efforts to prevent systemic embolism in patients with AF and CKD. That said, this population is also at increased risk of bleeding, as also demonstrated in this analysis. The addition of renal impairment to CHADS2 and CHA2DS2VASc did not improve the discrimination ability of these risk scores; this finding may be expected given the overlap of risk factors with patients with CKD and the components of these risk scores. Future studies may help characterize the role of CrCl-adjusted risk scores in non-anticoagulated patients, as suggested by the authors.

Keywords: Vitamin K, Thromboembolism, Oligosaccharides, Blood Coagulation, Stroke, Renal Insufficiency, Risk Factors, Fibrinolytic Agents, Electrocardiography, ROC Curve, Hemorrhage

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