Changes in Renal Function in Patients With Atrial Fibrillation: An Analysis From the RE-LY Trial

J Am Coll Cardiol. 2015 Jun 16;65(23):2481-93. doi: 10.1016/j.jacc.2015.03.577.

Abstract

Background: Vitamin K-dependent factors protect against vascular and renovascular calcification, and vitamin K antagonists may be associated with a decreased glomerular filtration rate (GFR).

Objectives: This study analyzed changes in GFR during long-term treatment with warfarin or dabigatran etexilate (DE) in patients enrolled in the RE-LY (Randomized Evaluation of Long Term Anticoagulation Therapy) trial.

Methods: Of the 18,113 patients in the RE-LY study randomized to receive DE (110 mg or 150 mg twice daily) or warfarin, 16,490 patients with atrial fibrillation had creatinine values measured at baseline and at least 1 follow-up visit. Changes in GFR for up to 30 months were evaluated.

Results: GFR declined in all treatment groups. After an average of 30 months, the mean ± SE decline in GFR was significantly greater with warfarin (-3.68 ± 0.24 ml/min) compared with DE 110 mg (-2.57 ± 0.24 ml/min; p = 0.0009 vs. warfarin) and DE 150 mg (-2.46 ± 0.23 ml/min; p = 0.0002 vs. warfarin). A decrease in GFR >25% was less likely with DE 110 mg (hazard ratio: 0.81 [95% confidence interval: 0.69 to 0.96]; p = 0.017) or DE 150 mg (hazard ratio: 0.79 [95% confidence interval: 0.68 to 0.93]; p = 0.0056) than with warfarin in the observation period >18 months. Patients with poor international normalized ratio control (i.e., time in therapeutic range <65%) exhibited a faster decline in GFR. A more pronounced decline in GFR was associated with previous warfarin use and with the presence of diabetes.

Conclusions: Patients with atrial fibrillation receiving oral anticoagulation exhibited a decline in renal function that was greater in those taking warfarin versus DE, and it was amplified by diabetes and previous vitamin K antagonist use. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600).

Keywords: anticoagulation; atrial fibrillation; renal function; thrombin inhibition; vitamin K antagonist.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / pharmacology
  • Anticoagulants / therapeutic use
  • Atrial Fibrillation / diagnosis*
  • Atrial Fibrillation / drug therapy
  • Atrial Fibrillation / physiopathology*
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use
  • Dabigatran
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / physiology*
  • Humans
  • Kidney / drug effects
  • Kidney / physiology*
  • Male
  • Middle Aged
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Risk Factors
  • Single-Blind Method
  • Warfarin / pharmacology
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Benzimidazoles
  • Pyridines
  • Warfarin
  • Dabigatran

Associated data

  • ClinicalTrials.gov/NCT00262600