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Oral anticoagulation linked to renal function decline in elderly
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Elderly patients with atrial fibrillation who received treatment with warfarin or dabigatran experienced a decline in renal function, according to results of a post-hoc analysis of the RE-LY study.
At 30-month follow-up, the observed decline in renal function was greater among patients treated with warfarin compared with dabigatran (Pradaxa, Boehringer Ingelheim). Further, the change in renal function was most pronounced among patients previously treated with vitamin K antagonists and in those with diabetes.
Researchers analyzed changes in glomerular filtration rate during long-term anticoagulation treatment among 16,490 patients with AF enrolled in the RE-LY trial. Of those, 5,594 had received treatment with warfarin, 5,424 had received dabigatran 110 mg and 5,472 had received dabigatran 150 mg. Each patient had creatinine measurements collected at baseline and during one or more follow-up visits. Observation periods ranged from 12 to 37 months.
Regardless of treatment, all patients experienced a decline in glomerular filtration rate during oral anticoagulation treatment. The mean decline after an average of 30 months of follow-up was greater among those treated with warfarin (–3.68 mL/min) compared with dabigatran 110 mg (–2.57 mL/min; P = .0009 vs. warfarin) and dabigatran 150 mg (–2.46 mL/min; P = .0002 vs. warfarin).
The treatment groups did not differ significantly with regard to glomerular filtration rate during the first 18 months. Later in the observation period, patients treated with dabigatran 110 mg or 150 mg were significantly less likely than those treated with warfarin to exhibit a decrease in glomerular filtration rate of greater than 25% (HR = 0.81; 95% CI, 0.69-0.96 for 110 mg; HR = 0.79; 95% CI, 0.68-0.93 for 150 mg). The researchers also noted that the glomerular filtration rate was further decreased among patients who spent less than 65% of the time in therapeutic range, both at 24 and 30 months (P <.005 for all).
Patients with diabetes had a lower glomerular filtration rate compared with those without diabetes at baseline and experienced a greater decline during treatment with oral anticoagulation. Among those with diabetes, the decline in glomerular filtration rate was significantly greater during treatment with warfarin compared with dabigatran (P < .005).
The researchers also observed a more pronounced decline in glomerular filtration rate among patients who had previously used vitamin K antagonists compared with those who did use vitamin K antagonists.
“The decline in renal function with both treatments indicates the need for monitoring of renal function at regular intervals … during oral anticoagulation treatment with warfarin as well as with [dabigatran],” the researchers wrote. “The more rapid reduction in renal function during warfarin treatment may be relevant in the selection of anticoagulants for long-term treatment.”
In a related editorial published in the Journal of the American College of Cardiology, Richard W. Asinger, MD, and Gautam R. Shroff, MBBS, from the division of cardiology at Hennepin County Medical Center and the University of Minnesota, Minneapolis, noted that this study “raises provocative questions” about the influence of pharmacotherapy for AF on renal function, but also indicates that the decrease in glomerular filtration rate among patients treated with warfarin does not outweigh the benefits of its use.
“The extraordinarily large number of patients from the RE-LY trial needed to demonstrate these findings highlight the fact that any absolute reduction in [estimated glomerular filtration rate] with warfarin is really quite modest compared with both doses of dabigatran,” Asinger and Shroff wrote. “Thus, even though these observations probably are not a ‘game-changer’ for clinicians, fine-tuning of clinical practice would be appropriate with attention to these findings.” – by Adam Taliercio
Disclosure: The researchers report receiving scientific support from Boehringer Ingelheim. Asinger reports serving as a member of the data and safety monitor board for the Watchman trials, Boston Scientific. Shroff reports no relevant financial disclosures.
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