The Risk of Acute Kidney Injury with Oral Anticoagulants in Elderly Adults with Atrial Fibrillation

Abstract

Background: Anticoagulation with either with a vitamin K antagonist or a direct oral anticoagulant (DOAC) may be associated with acute kidney injury (AKI). Our objective was to assess the risk of AKI among elderly individuals with atrial fibrillation (AF) newly prescribed a DOAC (dabigatran, rivaroxaban, or apixaban) versus warfarin. Methods: A population-based cohort study of 20,683 outpatients in Ontario, Canada, ≥66 years, with atrial fibrillation who were prescribed warfarin, dabigatran, rivaroxaban or apixaban between 2009- 2017. Inverse probability of treatment weighting based on derived propensity scores for the treatment with each DOAC was used to balance baseline characteristics among patients receiving each of the three DOACs, compared to warfarin. Cox proportional hazards regression was performed in the weighted population to compare the association between the prescribed anticoagulant and the outcomes of interest. The exposure was an outpatient prescription of warfarin, or one of the DOACs. The primary outcome was a hospital encounter with AKI, defined using KDIGO thresholds. Prespecified subgroup analyses were conducted by estimated glomerular filtration rate (eGFR) category, and by the percentage of international normalized ratio measurements in range, a validated marker of anticoagulation control. Results: : Each DOAC was associated with a significantly lower risk of AKI compared to warfarin (weighted HR 0.65; 95% CI 0.53 to 0.80 for dabigatran, weighted HR 0.85; 95% CI 0.73 to 0.98 for rivaroxaban; and weighted HR 0.81; 95% CI 0.72 to 0.93 for apixaban). In subgroup analysis, the lower risk of AKI associated with each DOAC was consistent across each eGFR strata. The risk of AKI was significantly lower among users of each of the DOACs compared to warfarin users who had a percentage of international normalized ratio measurements ≤56.1%. Conclusions: DOACs were associated with a lower risk of AKI compared to warfarin.

Acute kidney injury in patients with non-valvular atrial fibrillation treated with rivaroxaban or warfarin: a population-based study from the United Kingdom

“…warfarin. [23] Consistent with most other studies,[9, 12, 21, 23] our results did not infer any materially different effect between patients with baseline CKD and those without CKD. It is noteworthy that the AKI incidence rates in our study were much lower than those reported by Yao et al in their United Stated claims database study where AKI was based on primary and secondary diagnoses of AKI in linked hospitalisation data.…”

“…Our findings, using the Aberdeen algorithm case ascertainment method, are consistent with several previous studies on this topic, among patients with NVAF using rivaroxaban compared with those using warfarin [9,10,12,21] or phenprocoumon, [11] including among high risk groups such those with CKD [11,12,22], diabetes, [9,12], heart failure [9] or the elderly. [9,10,21] Some have also shown similar effect sizes (15-19% reduced AKI risk), although some have reported a larger, ~30% lower risk with rivaroxaban [9,22] vs. warfarin, including with an even larger ~50% lower risk seen in one study. [22] Furthermore, a recent large meta-analysis of data from randomised controlled trials (RCTs) and observational studies reported a 30% reduced risk of AKI among users of DOACs vs. warfarin.…”

“…However, as IMRD UK does include data communicated back from secondary care, we believe only a small number of cases would potentially not have been captured in the database. Our analysis focused on rivaroxaban vs. warfarin only; however, some other studies,[9, 11] albeit not all,[21-23] which have evaluated different DOACs with VKAs have reported significantly reduced risks of AKI among rivaroxaban or dabigatran users that was not seen for apixaban users. In this present study, we have also demonstrated the importance of an accurate case definition for capturing AKI events shown by the divergent results produced by the two case definitions.…”

IgA Nephropathy Is the Most Common Underlying Disease in Patients With Anticoagulant-Related Nephropathy

“… 48 , 49 In a Canadian population-based cohort study in >20,000 elderly adults with atrial fibrillation, the use of DOACs (dabigatran, rivaroxaban, apixaban) was associated with a significantly lower risk of AKI compared with warfarin, and the risk was consistent across each eGFR strata. 50 The latter suggest that the use of DOACs in patients with multiple risk factors for developing ARN may be an attractive preventive strategy. In addition, it is important to note that approximately 20% of our patients had significant microhematuria several months before the AKI event, advocating that urinary sediment should be closely monitored in those patients with risk factors for ARN in whom anticoagulant therapy is initiated.…”

Atrial Fibrillation and Chronic Kidney Disease—A Risky Combination for Post-Contrast Acute Kidney Injury

“…The risk factors for in-hospital AKI in this population were age (per 10-year increase), the use of diuretics before admission, and baseline hemoglobin (per 20 g/L decrease). Moreover, Harel et al [45] in a very recent population-based cohort study of 20,683 outpatients in Ontario (Canada) assessed the risk of AKI among elderly individuals (more than 66 years old) with atrial fibrillation newly prescribed a DOAC (dabigatran, rivaroxaban, or apixaban) versus warfarin. They postulated several mechanisms for anticoagulant-induced AKI such as: systemic bleeding leading to hypotension, acute interstitial nephritis, and anticoagulant related nephropathy, a condition mediated by glomerular hemorrhage leading to the formation of obstructive red cell casts in distal tubules and free radical injury from lysed red blood cells particularly at supratherapeutic level of anticoagulation [46,47].…”