Trends in prescribing preferences for anticoagulants among non-valvular atrial fibrillation patients in the UK with and without chronic kidney disease, 2010-2020

Background: Atrial fibrillation (AF) – a frequently occurring condition characterized by substantial morbidity and mortality – disproportionally affects patients with chronic kidney disease (CKD). For decades, warfarin has been the drug of choice for AF, but direct acting oral anticoagulants (DOACs) are now increasingly recommended by clinical guidelines owing to their convenience, safety and effectiveness profiles. However, there is a lack of data on the uptake of these newer therapies among AF patients with and without CKD.

Objectives: To evaluate trends in initiation patterns of anticoagulants among AF patients with and without CKD.

Methods: We used the UK Clinical Practice Research Datalink (2010-2020) to identify a cohort of anticoagulant initiators with diagnosed AF, documented serum creatinine (within 365 days of initiation), and no evidence of valvular disease, end-stage renal disease, or alternative indications for drug use (e.g., hip replacement). The estimated glomerular filtration rate (eGFR) was calculated using chronic kidney disease epidemiology collaboration equations (CKD-EPI), and CKD was defined using an eGFR [mL/min/1.73m2] threshold of < 60. Initiation trends were evaluated overall, for patients with and without CKD, by severity of CKD: Stage 3a [eGFR: 45-59], 3b [30-44], and 4 [15-29], and by individual DOACs.

Results: Among 58,513 AF patients (mean age 77 years, male 52.3%) and over the study period, warfarin initiations declined by 95.6% from 100.0% in 2010 to 4.4% in 2020; these trends were similar among patients with CKD (n=15,472) and without CKD (n=43,041). By 2020, apixaban was the most frequently initiated anticoagulant, regardless of CKD status, comprising of 58.7% and 50.2% of initiations among patients with and without CKD, respectively, and driven by uptake in use in patients with stage 3a (57.1% of initiations in 2020) and stage 3b (64.6%). Patients with stage 4 CKD were over four times more likely to initiated warfarin (18.3%) compared to patients in stage 3a (3.1%), 3b (4.4%), and non-CKD (4.1%) cohorts.

Conclusions: Initiation of DOACs increased regardless of CKD status or severity, albeit by a reduced likelihood in patients with more severe CKD relative to those with milder disease. We attribute this reduced uptake of DOACs in severe CKD to the decades of clinical experience with warfarin and a relative lack of evidence base to support DOAC prescribing in patients with more severe CKD. Further investigation is necessary to overcome barriers to the initiation of DOACs in patients with severe CKD.