DOACs in Nonvalvular Atrial Fibrillation Linked to Lower Risk of CKD, AKI

In patients with nonvalvular AF, direct oral anticoagulant therapy has lower risk for CKD progression compared with vitamin K antagonist therapy.

Among patients with nonvalvular atrial fibrillation (AF), use of direct oral anticoagulants (DOAC) is associated with a lower risk for chronic kidney disease (CKD) progression, acute kidney injury (AKI), and major bleeding compared with vitamin K antagonists (VKA), according to a study in the American Journal of Kidney Diseases.

The findings are based on a cohort of adults (aged ≥18 years) who were diagnosed with AF between 2011 and 2018 and who initiated DOAC or VKA treatment from the Stockholm Creatinine Measurements project. New users were defined as patients who had no previous dispensation of either treatment since at least 2006.

The exposure was treatment with a DOAC (apixaban, dabigatran, rivaroxaban, or edoxaban) or a VKA (warfarin) at the index date. The primary outcomes were CKD progression and AKI.

A total of 32,699 individuals with AF who initiated either therapy were included, of whom 56% used a DOAC and 44% began VKA treatment. The overall median age was 75 years (IQR, 68-83), and 45% were women. The median estimated glomerular filtration rate (eGFR) was 73 (IQR, 59-85) mL/min/1.73 m2, and 27% had an eGFR of less than 60 mL/min/1.73 m2. The median follow-up before censoring or end of follow-up was 3.0 (IQR, 1.4-5.0) years.

In routine clinical practice, compared with VKA, DOAC use was associated with a lower risk of CKD progression, AKI, and major bleeding, but similar risk of stroke/systemic embolism.

CKD progression was observed in 1208 individuals in the DOAC group and in 2244 individuals in the VKA group, with incidence rates of 30.4 and 36.3 per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for CKD progression for DOAC users was 0.87 (95% CI, 0.78-0.98), compared with VKA users. A decrease in CKD progression was associated with reductions in the risks of both components of the composite of kidney failure (HR, 0.43; 95% CI, 0.25-0.73) and sustained 30% eGFR reduction (HR, 0.88; 95% CI, 0.78-0.98).

An AKI event occurred in 1825 patients in the DOAC group and in 3277 patients in the VKA group, with incidence rates of 46.7 and 54.5 per 1000 person-years, respectively. DOAC use was associated with a decreased AKI risk compared with VKA use (aHR, 0.88; 95% CI, 0.80-0.97).

The median follow-up regarding all-cause mortality was 3.8 (IQR, 2.1-5.8) years. In the aHR for the DOAC vs VKA treatment groups, no differences were found for the composite outcome of ischemic stroke or systemic embolism (HR, 0.93; 95% CI, 0.78-1.11). A significantly lower risk for major bleeding (HR, 0.77; 95% CI, 0.67-0.89) also was observed.

In the DOAC group, 3222 participants died, compared with 4842 in the VKA group, for incidence rates of 57.1 and 64.1 per 1000 person-years, respectively. After adjustment, the HR was 1.04 (95% CI, 0.95-1.14) for all-cause death and 0.99 (95% CI, 0.84-1.17) for cardiovascular death for DOAC vs VKA use.

Consistent findings with no signs of heterogeneity were observed for the risk for CKD progression or AKI across prespecified subgroups of age and baseline eGFR strata. A suggestion of heterogeneity was found with a lower risk of the composite of ischemic/systemic embolism and ischemic stroke associated with DOAC use vs VKA therapy in women.

The VKA group had a higher proportion of participants (77%) who discontinued treatment or switched to the other therapy vs the DOAC group (21%), with most attributed to switching. DOAC use was still associated with a lower risk of CKD progression (HR, 0.77; 95% CI, 0.64-0.92) and AKI (HR, 0.79; 95% CI, 0.71-0.89) compared with VKA after accounting for the propensity of discontinuing and switching.

Study limitations include the absence of data for the time in therapeutic range for VKA, too few patients initiated therapy with eGFR of less than 30 mL/min/1.73 m2, and information is lacking for DOAC dosages. Also, the study is observational and residual confounding cannot be excluded.

“In routine clinical practice, compared with VKA, DOAC use was associated with a lower risk of CKD progression, AKI, and major bleeding, but similar risk of stroke/systemic embolism,” the investigators wrote.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Trevisan M, Hjemdahl P, Clase CM, et al. Cardiorenal outcomes among patients with atrial fibrillation treated with oral anticoagulants. Am J Kidney Dis. Published online October 5, 2022. doi: 10.1053/j.ajkd.2022.07.017