Safety and efficacy of rivaroxaban compared to warfarin in patients with atrial fibrillation and advanced stages of chronic kidney disease
Authors: Chashkina M , Andreev D.A , Kozlovskaya N.L , Salpagarova Z.K , Bykova A.A , Suvorov A.Y , Baturina O.A , Osipova A.I , Syrkin A.L 
Published: November 2020

Abstract

Background
Atrial fibrillation (AF) is a common comorbidity in around 10–15% of patients (pts) with CKD, while 30% of those with AF have CKD. In pts with advanced stages of CKD, safety and efficacy profiles of novel oral anticoagulants, in particular rivaroxaban, have been understudied.

Purpose
To evaluate safety and efficacy of rivaroxaban in pts with stage 4 CKD or a transient reduction in glomerular filtration rate (GFR) to 15–29 ml/min/1.73 m2.

Materials and methods
Data of 3,500 pts with nonvalvular AF in cardiovascular units for the period from 2017 to 2019 were analyzed. Of these, 507 (15%) showed a decrease in GFR to 29–15 ml/min/1.73 m2. 109 (3.1%) pts enrolled in the study (in accordance with inclusion criteria) and were randomized in a 2: 1 fashion to either the 15 mg rivaroxaban (n=74) or warfarin (n=36) group. The pts had either not previously been taking anticoagulants, or TTR was &lt;65% in the case of taking warfarin. The average follow-up period was 18 months. Visits took place every 3 months, when compliance, haemoglobin were checked and GFR calculation was carried out. Primary endpoint: development of major and minor bleeding on the BARC scale. Secondary endpoints: thromboembolic events, cardiovascular mortality and all-cause mortality.

Results
The pts were of similar clinical and demographic profile. The median age was 77 years with 32 men in the rivaroxaban group and 14 in the warfarin group. The average CHA2DS2-VASc score was 4.6 and 4.7 (n/s) in the rivaroxaban and warfarin group, respectively, while the average HAS-BLED score was 3 (n/s) in both. Pts taking warfarin were significantly more likely to develop minor bleedings: 26 (72%) vs 27 (37%) in the rivaroxaban group, p=0.001. There were not detected significant differences in the ratio of major bleedings (warfarin 3 (8.3%) versus rivaroxaban 2 (2.7%) cases, p=0.3). No significant differences at secondary endpoints were observed. In the warfarin group, 1 (2.8%) ischemic stroke and 1 fatal haemorrhagic stroke occurred. In the rivaroxaban group, 1 (1.4%) ischemic stroke occurred during a 5-day break in taking the anticoagulant. 5 (6.9%) pts in the rivaroxaban group developed ACS, vs 1 (2.8%) in the warfarin group (n/s). 2 (2.7%) pts died from myocardial infarction in the rivaroxaban group and 1 (2.8%) - in the warfarin group (n/s). Mortality from all causes was 5 (6.6%) in the rivaroxaban group and 3 (8.3%) in the warfarin group (n/s). In the rivaroxaban group, GFR (CG formula) improved significantly more since the 3rd month of observation (in the 18th month of observation, the median value was 35.0 [29.0; 39.5] ml/min/1.73 m2 vs 27.0 [21.5; 31.5] ml/min/1.73 m2 in the warfarin group, p&lt;0.001).

Conclusion
Significantly more pts within the warfarin group had minor bleedings. Pts during warfarin and rivaroxaban therapy showed an improvement in glomerular filtration, which was more pronounced in the rivaroxaban group.

Funding Acknowledgement
Type of funding source: None