Efficacy and Safety of Dabigatran Compared With Warfarin in Relation to Baseline Renal Function in Patients With Atrial Fibrillation

Abstract

I mpaired renal function is associated with a higher prevalence of atrial fibrillation (AF) [1][2][3] and with an increased risk of thromboembolic events in patients with nonvalvular AF. [4][5][6][7] Current guidelines recommend treatment with oral anticoagulants for AF patients at risk for stroke 8 ; however, impaired renal function also confers a substantially increased risk of major bleeding 9 and often contributes to underutilization of oral anticoagulation therapy in AF populations. 10,11 Clinical Perspective on p 970Background-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. Methods and 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. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Dabigatran etexilate: appropriate use in patients with chronic kidney disease and in the elderly patients

“…In this setting, the rates of major bleeding in patients with eGFR \50 ml/min are nearly identical to those with D110 mg, D150 mg and warfarin (i.e. 5.45, 5.50 and 5.49% per year, respectively) [14].…”

“…The rates of stroke or systemic embolism were lower with DE 150 mg BID and similar with 110 mg BID compared with warfarin, without significant heterogeneity in subgroups defined by renal function (interaction p [ 0.1 for all). These data clearly show that the antithrombotic efficacy of DE versus warfarin in patients with AF is independent of renal function [14].…”

“…The above estimates show some differences when eGFR is measured, post hoc, with equations not pre-specified in the RE-LY protocol (i.e. CKD-EPI and MDRD) [14].…”

“…In patients with no contraindication to its use, the clinical benefit of DE versus warfarin is independent of renal function [14].…”

Novel Anticoagulants in Atrial Fibrillation: A Primer for the Primary Physician

“…Rate of stroke or systemic embolism was lower with dabigatran 150 mg bid and similar with 110 mg bid compared with warfarin, regardless of renal function. 36 In 2010 the FDA approved 2 dosages of dabigatran for reduction of systemic stroke and systemic embolism in patients with nonvalvular AF (class 1B recommendation): 150 mg twice a day for patients with normal renal function and 75 mg twice daily for those with impaired renal function; however, this is not a studied dose but rather a dose based on pharmacokinetic modeling. 37 Although dabigatran has been welcomed with great enthusiasm by many clinicians, there are some areas of concern.…”