Renal decline in patients with atrial fibrillation treated with rivaroxaban or warfarin: a population-based cohort study in the United Kingdom

Abstract

Abstract Background A recent observational study (1) has suggested that renal decline among patients with non-valvular atrial fibrillation (NVAF) could be faster in users of warfarin vs. rivaroxaban. Purpose To estimate renal decline in patients with NVAF and preserved renal function who started oral anticoagulant (OAC) therapy with rivaroxaban 20 mg or warfarin. Methods Using primary care electronic health records (EHRs) from the United Kingdom (UK), we identified patients with NVAF who initiated rivaroxaban (20 mg/day, N=5338) or warfarin (N=6314) from January 2014–March 2019. Patients were excluded if they had no estimated glomerular filtration rate (eGFR) or serum creatinine (sCr) values recorded in the year before OAC initiation, a history of end-stage renal disease (ESRD), or baseline eGFR <50 ml/min/1.73m2. We identified three renal decline outcomes during follow-up: a) doubling of sCr levels, b) ≥30% decline in eGFR (confirmed by a subsequent measurement), and c) ESRD (code for ESRD/stage 5 CKD/chronic dialysis, or eGFR <15 ml/min/1.73m2 confirmed by subsequent measurement). To identify incident cases of each outcome, we followed patients from OAC initiation to the earliest of a renal decline event, death, or the end of the study period (September 2019). Cox regression was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome with rivaroxaban vs. warfarin use, overall and among heart failure and diabetes patient subgroups. We estimated the average eGFR slope using a mixed model regression among the subset of individuals with at least two eGFR measurements during follow-up, where the first was recorded within 120 days of the start of follow-up, and the last was recorded >180 days after the first eGFR measurement (rivaroxaban n=2054, warfarin n=2464). Results After a mean follow-up of 2.5 years, the number of incident cases was: doubling sCr (n=322), ≥30% decline in eGFR (n=1179), and ESRD (n=22). As shown in the Table, after adjusting for age, sex, baseline renal function and comorbidity, HRs for the renal outcomes with rivaroxaban vs. warfarin users were: doubling sCr, 0.63 (95% CI: 0.49–0.81); ≥30% decline in eGFR, 0.76 (95% CI: 0.67–0.86); ESRD, 0.77 (95% CI: 0.29–2.04). Similar results were observed among patients with diabetes or heart failure. Estimated mean loss in renal function during the study period was 2.03 ml/min/1.73 m2 per year among warfarin users and 1.65 ml/min/1.73 m2 among rivaroxaban initiators (p=0.03). Conclusion The risk of renal decline events and rate of decline in renal function among patients with baseline eGFR >50 ml/min/1.73m2 was lower in patients using rivaroxaban 20 mg vs. warfarin. As residual confounding could have been present, further research is needed to confirm/refute our findings. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer AG