title: Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial analysis.
abstract: BACKGROUND
  Renal impairment increases the risk of stroke and bleeding in patients with atrial fibrillation. In the Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY) trial, dabigatran, with ≈80% renal elimination, displayed superiority over warfarin for prevention of stroke and systemic embolism in the 150-mg dose and significantly less major bleeding in the 110-mg dose in 18 113 patients with nonvalvular atrial fibrillation. This prespecified study investigated these outcomes in relation to renal function.
  
  
  RESULTS
  Glomerular filtration rate was estimated with the Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Modification of Diet in Renal Disease (MDRD) equations in all randomized patients with available creatinine at baseline (n=17 951), and cystatin C-based glomerular filtration rate was estimated in a subpopulation with measurements available (n=6190). A glomerular filtration rate ≥80, 50 to <80, and <50 mL/min was estimated in 32.6%, 47.6%, and 19.8% and in 21.6%, 59.6%, and 18.8% of patients based on Cockcroft-Gault and CKD-EPI, respectively. Rates of stroke or systemic embolism, major bleeding, and all-cause mortality increased as renal function decreased. The rates of stroke or systemic embolism were lower with dabigatran 150 mg and similar with 110 mg twice daily compared with warfarin, without significant heterogeneity in subgroups defined by renal function (interaction P>0.1 for all). For the outcome of major bleeding, there were significant interactions between treatment and renal function according to CKD-EPI and MDRD equations, respectively (P<0.05). The relative reduction in major bleeding with either dabigatran dose compared with warfarin was greater in patients with glomerular filtration rate ≥80 mL/min.
  
  
  CONCLUSIONS
  The efficacy of both dosages of dabigatran was consistent with the overall trial irrespective of renal function. However, with the CKD-EPI and MDRD equations, both dabigatran dosages displayed significantly lower rates of major bleeding in patients with glomerular filtration rate ≥80 mL/min.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
authors: From Uppsala Clinical Research Center (Z.H., J.O., U.A., A.S., L.W.), Department of Medical Sciences, Cardiology (Z.H., J.O., L.W.), and Department of Medical Sciences, Clinical Chemistry (A.S.), Uppsala University, Sweden; Department of Cardiology, J.W. Goethe University, Frankfurt, Germany (S.H.H.); Population Health Research Institute, Hamilton, Ontario, Canada (S.J.C., J.W.E., S.Y.); Thomas Jefferson Medical College and the Heart Center, Wynnewood, PA (M.D.E.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (P.A.R.).
authors: Ziad
authors: Z
authors: Hijazi
authors: Stefan H
authors: SH
authors: Hohnloser
authors: Jonas
authors: J
authors: Oldgren
authors: Ulrika
authors: U
authors: Andersson
authors: Stuart J
authors: SJ
authors: Connolly
authors: John W
authors: JW
authors: Eikelboom
authors: Michael D
authors: MD
authors: Ezekowitz
authors: Paul A
authors: PA
authors: Reilly
authors: Agneta
authors: A
authors: Siegbahn
authors: Salim
authors: S
authors: Yusuf
authors: Lars
authors: L
authors: Wallentin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D001562:Benzimidazoles / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D004617:Embolism / Q000453:epidemiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D038622:Internationality; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D015091:beta-Alanine; D014859:Warfarin; D000069604:Dabigatran
keywords: anticoagulants; atrial fibrillation; dabigatran; hemorrhage; renal insufficiency; stroke; warfarin