Decline in Renal Function in Patients Receiving Oral Anticoagulants | Journal Scan

Study Questions:

In the RE-LY (Randomized Evaluation of Long Term Anticoagulation Therapy) trial, what are differences in changes in renal function in patients with atrial fibrillation (AF) assigned to receive either dabigatran etexilate (DE) or warfarin?


This was a post hoc analysis of the RE-LY trial. In RE-LY, patients with AF who had at least one additional risk factor for stroke were randomized in a 1:1:1 allocation ratio to receive in a blinded fashion DE in fixed doses of 110 mg twice daily (DE 110) or 150 mg twice daily (DE 150), or adjusted doses of warfarin (target international normalized ratio [INR], 2.0-3.0) for a median of 2 years. Determination of serum creatinine was planned at baseline, at 3, 6, and 12 months, and annually thereafter. Values were available at baseline and at least one post-baseline visit in 16,490 patients. Changes in glomerular filtration rate (GFR) for up to 30 months were evaluated.


While there were similar reductions between the treatment arms after 6 and 12 months, the reductions under DE treatments were smaller after 30 months compared to warfarin (DE 110 = -2.57 ml/min [p = 0.0009 vs. warfarin], DE 150 = -2.46 ml/min [p = 0.0002 vs. warfarin], and warfarin = -3.68 ml/min). Patients on warfarin who were in the therapeutic range (INR, 2.0-3.0) for <65% of the time had a significantly larger decline in GFR at 24 and 30 months compared to both DE doses (p < 0.005 for all). Previous warfarin use and presence of diabetes were associated with a more pronounced decline in GFR.


Patients with AF receiving anticoagulation with warfarin had a greater decline in renal function at 30 months, compared to those taking DE 110 mg or 150 mg twice daily.


This is an interesting post hoc analysis, which demonstrates that in patients with nonvalvular AF in the RE-LY trial, renal function declined less during treatment with either dose of DE (110 mg or 150 mg twice daily), compared to that with warfarin. As the authors posit, this could reflect inhibition by warfarin of vitamin K-dependent matrix gamma-carboxyglutamic acid. The findings from this analysis draw emphasis to the need to monitor renal function at regular intervals in individuals receiving oral anticoagulation. Future studies should clarify whether the modest decline in renal function observed in this analysis translates to changes in clinical outcomes. Prospective validation of these results will be important.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents

Keywords: 1-Carboxyglutamic Acid, Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Benzimidazoles, Creatinine, Diabetes Mellitus, Glomerular Filtration Rate, International Normalized Ratio, Pyridines, Renal Insufficiency, Risk Factors, Stroke, Vitamin K, Warfarin

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