Oral anticoagulation may be associated with decline in renal function in afib patients
Although the findings are most likely not a “game changer,” they may lead physicians to fine-tune their clinical practice.
Oral anticoagulation, especially warfarin, may be associated with a decline in renal function in patients with atrial fibrillation, according to a recent study.
Researchers analyzed data from the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial to examine changes in glomerular filtration rate (GFR) during long-term treatment with warfarin or dabigatran etexilate. In RE-LY, a total of 18,113 patients were randomly assigned to receive 100 mg of dabigatran etexilate twice daily (5,424 patients), 150 mg of dabigatran etexilate twice daily (5,472 patients), or warfarin (5,594 patients, respectively). Creatinine values were measured in 16,490 patients at baseline and at least 1 follow-up visit. The study's primary outcome measure was change in GFR for up to 30 months. The study results were published online June 8 by the Journal of the American College of Cardiology.
At an average of 30 months, the authors found that GFR had decreased in all 3 treatment groups. The mean decrease was significantly higher with warfarin (−3.68 ± 0.24 mL/min) than with either the 110-mg or 150-mg dose of dabigatran etexilate (−2.57 ± 0.24 mL/min and −2.46 ± 0.23 mL/min; P=0.0009 and 0.0002 vs. warfarin, respectively). During an observation period beyond the first 18 months, substantial deterioration in renal function, defined as a decrease of more than 25% in GFR, was less likely with either dose of dabigatran etexilate (hazard ratios, 0.81 and 0.79; P=0.017 and 0.0056, respectively) than with warfarin. GFR appeared to decrease more quickly in patients whose international normalized ratio control was considered poor (time in the therapeutic range <65%), and an association was seen between more pronounced GFR decline and previous warfarin use or diabetes.
The authors noted that the mean treatment duration was relatively short and that comparisons at 24 months and 30 months were based on subsets of patients. In addition, they called for validation of their results in a future prospective study. However, they concluded that elderly patients with atrial fibrillation who were taking oral anticoagulation experienced decreased renal function at 30 months of follow-up and that this effect was greater in those taking warfarin than in those taking dabigatran etexilate.
“The decline in renal function with both treatments indicates the need for monitoring of renal function at regular intervals (e.g., once a year or more frequently in certain clinical situations when it is suspected that the renal function could deteriorate) during oral anticoagulation treatment with warfarin as well as with [dabigatran etexilate],” the study authors wrote. “The more rapid reduction in renal function during warfarin treatment may be relevant in the selection of oral anticoagulants for long-term treatment.”
An accompanying editorial congratulated the authors for addressing a question with important clinical implications in an innovative way and noted that although the findings are most likely not a “game changer,” they may lead physicians to fine-tune their clinical practice. The editorialists also noted that the recent availability of novel anticoagulants besides warfarin has allowed physicians to remove their “self-imposed blinders” and take a closer, more critical look at the drugs' clinical effects.
“Other oral anticoagulant agents also should be evaluated for any association with a similar phenomenon of [estimated] GFR reduction because the results could influence dosing,” they wrote. “For now, warfarin will continue to have an important role in contemporary therapeutic anticoagulation for [nonvalvular atrial fibrillation] for the simple reason that its anticoagulant effect can be easily measured clinically, and this may be especially desirable for select patient populations, including, ironically, patients with fluctuating renal dysfunction.”