Impact of Dabigatran and Warfarin Treatment on the Risk of Acute Kidney Injury in Patients with Atrial Fibrillation

Impact of Anticoagulants on Renal Function

Previous clinical studies have provided detailed evidence on whether and to what extent individual oral anticoagulants reduce the risk of thromboembolic complications in atrial fibrillation. However, our knowledge of their impact on renal function and kidneys, in general, is rather limited. Warfarin-associated nephropathy has been described only a few years ago, but it is believed that more than one-fifth of patients treated with this vitamin K antagonist may experience at least one episode during therapy. In contrast, post-hoc analysis of the RE-LY clinical trial showed a significant slowing of renal function decline with dabigatran treatment compared to warfarin.

The work by Taiwanese authors therefore focused on the question of what the real-world clinical practice risk of developing AKI in patients with non-valvular atrial fibrillation is, whether this risk differs between those treated with dabigatran and warfarin, and whether the presence of chronic kidney disease (CKD) affects this risk.

Study Methodology

A large retrospective study evaluated data from nearly 20,000 patients with or without a history of CKD who also had non-valvular atrial fibrillation and began anticoagulant therapy, based on the Taiwan National Health Register. Dabigatran and warfarin were used to treat 7,702 and 7,885 patients without CKD history and 2,256 and 2,089 patients with this comorbidity, respectively. The propensity score method was used to balance the differences in other covariating characteristics and achieve comparability between the groups.

Patients were followed for 2 years or until an AKI episode, defined as an absolute increase in serum creatinine of ≥ 26.5 µmol/L within 48 hours, a relative increase of ≥ 50%, or a urine output decline below 0.5 ml/kg/h for at least 6 hours.

Results

AKI incidence in patients in the study was 2.17 and 3.47 per 100 patient-years for those without CKD history treated with dabigatran and warfarin, respectively, and 9.28 and 16.21 in the CKD group. Dabigatran was associated with a lower risk of developing AKI compared to warfarin, both in the group without CKD history (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.49–0.77; p < 0.001) and in patients with this comorbidity (HR 0.56; 95% CI 0.46–0.69; p < 0.001).

Stratification of patients by ischemic risk score CHA₂DS₂-VASc showed that the annual risk of AKI was significantly higher with warfarin treatment than with dabigatran in individuals with higher ischemic risk scores (score ≥ 4 in the group without CKD and ≥ 3 in those with CKD). In patients treated with dabigatran, the incidence of AKI was relatively comparable across the entire spectrum of CHA₂DS₂-VASc scores, while for those on warfarin, the incidence increased significantly with higher CHA₂DS₂-VASc scores – from 2% to 6.16% in patients without CKD history and from 6.82% to 26.03% in those with CKD, as the score increased from 0 or 1 to ≥ 6.

Subgroup analysis further revealed that the lower risk of AKI in patients using dabigatran compared to those on warfarin persisted regardless of the dabigatran dose, prior warfarin use history, presence or absence of diabetes, and even if their HAS-BLED bleeding risk score was ≥ 3.

Conclusion

According to the results of a retrospective study on a large sample of Asian patients with non-valvular atrial fibrillation, anticoagulant therapy with dabigatran is associated with a significantly lower risk of acute kidney injury than warfarin treatment.

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Source: Chan Y. H., Yeh Y. H., See L. C. et al. Acute kidney injury in Asians with atrial fibrillation treated with dabigatran or warfarin. J Am Coll Cardiol 2016; 68 (21): 2272−2283, doi: 10.1016/j.jacc.2016.08.063.