3052Non-vitamin K antagonist oral anticoagulants are safe and effective alternatives to warfarin across subgroups by renal function: results from Danish registries
Authors: Bonde A N , Lee C Y , Lip G Y H , Kamper A L , Staerk L S , Torp-Pedersen C , Gislason G , Olesen J B 
Published: October 2019

Abstract

Background
All non-vitamin K antagonist oral anticoagulants (NOACs) have some degree of renal excretion, and patients with severely reduced renal function have been excluded from randomized controlled clinical trials of stroke prevention in atrial fibrillation (AF). Influence of renal function on outcomes has not been assessed in previous real-world studies of NOACs in AF.

Purpose
To assess influence of renal function on efficacy and safety of dabigatran, rivaroxaban or apixaban vs. warfarin.

Methods
Using nationwide registries, we identified all Danish AF patients who initiated warfarin, dabigatran, rivaroxaban or apixaban between 2012 and 2016. We included patients with a plasma creatinine measurement within 14 days from drug initiation and calculated estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Hazard ratio (HR) of stroke/thromboembolism (TE) or major bleeding according to oral anticoagulation was calculated using multivariable-adjusted Cox regression analyses with warfarin as reference.

Results
We included 14,673 AF patients who started first-time oral anticoagulation within 14 days from AF diagnosis, and our study population comprised 2482 (16.9%) initiators of dabigatran (median age 72, 44.5% women), 3806 (25.9%) initiators of rivaroxaban (median age 75, 48.0% women), 5067 (34.5%) initiators of apixaban (median age 76, 48.8% women), and 3318 (22.6%) initiators of warfarin (median age 75, 45.4% women). eGFR was >50, 30–50 and 15 to <30 mL/min/1.73m2 in 10,281 (83.1%), 2079 (14.2%) and 404 (2.8%) patients at baseline. After adjustment for age, sex, year of inclusion, income, cohabitation status, eGFR, hemoglobin, medications and comorbidities, the HRs for stroke/TE compared to warfarin were 0.94 (95% confidence interval (CI) 0.74–1.20) for dabigatran, 1.06 (CI 0.84–1.34) for rivaroxaban, and 1.10 (CI 0.88–1.36) for apixaban. There were no significant heterogeneities in HRs of stroke/TE across subgroups by eGFR. Apixaban (HR 0.74, CI 0.62–0.89) was associated with lower risk of major bleeding compared to warfarin, rivaroxaban (HR 1.06, CI 0.88–1.27) with risk of major bleeding comparable to warfarin, and there were no significant heterogeneities in risk of major bleeding with rivaroxaban or apixaban across subgroups by eGFR. Dabigatran was associated with lower risk of bleeding among patients with eGFR >50 mL/min/1.73m2, but not among patients with eGFR 30–50 mL/min/1.73m2 (interaction P=0.03).

Conclusions
In a large real-world cohort, renal function had no significant influence on efficacy or safety of apixaban or rivaroxaban when compared with warfarin. Dabigatran was associated with lower risk of bleeding among patients with normal or mildly decreased renal function, but not among patients with moderately decreased renal function.

Acknowledgement/Funding
This study was funded by an unrestricted grant from the Capital Region of Denmark, Foundation for Health Research.