title: Renal function and outcomes in anticoagulated patients with non-valvular atrial fibrillation: the AMADEUS trial.
abstract: OBJECTIVE
  Limited data are available on the impact of renal function on the outcome of patients with atrial fibrillation (AF).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, UK.
authors: Stavros
authors: S
authors: Apostolakis
authors: Yuotao
authors: Y
authors: Guo
authors: Deirdre A
authors: DA
authors: Lane
authors: Harry
authors: H
authors: Buller
authors: Gregory Y H
authors: GY
authors: Lip
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000503:physiopathology*; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009844:Oligosaccharides / Q000627:therapeutic use*; D012372:ROC Curve; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology; D018570:Risk Assessment; D020521:Stroke / Q000209:etiology; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D009844:Oligosaccharides; D014812:Vitamin K; C479958:idraparinux
keywords: Atrial fibrillation; Bleeding; Chronic kidney disease; Creatinine clearance; Stroke