Renal function and outcomes in anticoagulated patients with non-valvular atrial fibrillation: the AMADEUS trial

Eur Heart J. 2013 Dec;34(46):3572-9. doi: 10.1093/eurheartj/eht328. Epub 2013 Aug 21.


Aims: Limited data are available on the impact of renal function on the outcome of patients with atrial fibrillation (AF).

Methods and results: AMADEUS was a multicentre, randomized, open-label non-inferiority study that compared fixed-dose idraparinux with conventional anticoagulation by dose-adjusted vitamin K antagonists. We performed a post hoc analysis to assess the impact of renal function on the outcomes of anticoagulated AF patients. The primary efficacy outcome was the composite of stroke/systemic embolism (SE). The principal safety outcome of this analysis was major bleeding. We calculated c-indexes, reflecting the ability for discriminating diseased vs. non-diseased patients, and the net reclassification improvement (NRI, an index of inferior/superior performance of risk estimation scores). Of 4576 patients, 45 strokes and 103 major bleeding events occurred following an average follow-up of 325 ± 164 days. Patients with CrCl >90 mL/min had an annual stroke/SE 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 < 0.001 for linear association). After adjusting for stroke risk factors, patients with CrCl <60 mL/min had more than two-fold higher risk of stroke/SE and almost 60% higher risk of major bleeding compared with those with CrCl ≥60. In patients with the CHA2DS2VASc score 1-2, CrCl <60 mL/min was associated with eight-fold higher stroke risk. When added to the CHA2DS2VASc or CHADS2 scores, CrCl <60 mL/min did not improve the c-indexes for CHADS2 (P = 0.054) or CHA2DS2VASc (P = 0.63) but resulted in significant NRI (0.26, P = 0.02) in this anticoagulated trial cohort.

Conclusion: Renal impairment (CrCl <60 mL/min) doubles the risk of stroke and increased the risk of major bleeding by almost 60% in anticoagulated patients with AF. Renal impairment was additive to stroke risk prediction scores based on a significant NRI, but no significant improvement in discrimination ability (based on c-indexes) for CHA2DS2VASc or CHADS2 was observed.

Keywords: Atrial fibrillation; Bleeding; Chronic kidney disease; Creatinine clearance; Stroke.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / drug therapy
  • Atrial Fibrillation / physiopathology*
  • Hemorrhage / etiology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Oligosaccharides / therapeutic use*
  • ROC Curve
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Assessment
  • Stroke / etiology
  • Vitamin K / antagonists & inhibitors*


  • Anticoagulants
  • Oligosaccharides
  • Vitamin K
  • idraparinux