Acute Kidney Injury in Patients with Non-Valvular Atrial Fibrillation Treated with Rivaroxaban or Warfarin: A Population-Based Study from the United Kingdom

Figures & data

Figure 1 Flowchart illustrating the identification of the study cohorts. ^aA record of VTE or orthopaedic arthroplasty in the 3 months before the first OAC prescription or in the week after.

Abbreviations: AF, atrial fibrillation; eGFR, estimated glomerular filtration rate; IMRD, IQVIA Medical Research Data; NVAF, non-valvular atrial fibrillation, OAC, oral anticoagulant; SCr, serum creatinine.

Table 1 Baseline Characteristics of the Study Cohorts

	Rivaroxaban Cohort N=6436	Warfarin Cohort N=7129	p value
Age (years)			<0.001
18–49	108 (1.7)	101 (1.4)
50–59	458 (7.1)	391 (5.5)
60–69	1349 (21.0)	1574 (22.1)
70–79	2357 (36.6)	2857 (40.1)
80–89	1763 (27.4)	1972 (27.7)
≥90	401 (6.2)	234 (3.3)
Mean (SD)	74.4 (10.6)	74.2 (9.6)
Sex			0.23
Male	3687 (57.3)	4011 (56.3)
Female	2749 (42.7)	3118 (43.7)
Townsend index			<0.001
1st quintile (least deprived)	1288 (20.0)	1395 (19.6)
2nd quintile	1290 (20.0)	1527 (21.4)
3rd quintile	1195 (18.6)	1220 (17.1)
4th quintile	896 (13.9)	1116 (15.7)
5th quintile (most deprived)	510 (7.9)	674 (9.5)
Missing	1257 (19.5)	1197 (16.8)
Polypharmacy			<0.001
0–4	1136 (17.7)	1081 (15.2)
5–9	3493 (54.3)	3979 (55.8)
≥10	1807 (28.1)	2069 (29.0)
Smoking			<0.001
Non-smoker	2693 (41.8)	2818 (39.5)
Smoker	503 (7.8)	592 (8.3)
Ex-smoker	3233 (50.2)	3718 (52.2)
Missing	7 (0.1)	1 (0.0)
BMI			<0.001
<20	202 (3.1)	181 (2.5)
20–24	1358 (21.1)	1426 (20.0)
25–29	2283 (35.5)	2532 (35.5)
≥30	2335 (36.3)	2758 (38.7)
Missing	258 (4.0)	232 (3.3)
Mean (SD)	29.1 (6.2)	29.5 (6.4)
Comorbidities/previous clinical history
IHD	1524 (23.7)	1866 (26.2)	<0.001
Cancer	1018 (15.8)	1131 (15.9)	0.94
Diabetes	1375 (21.4)	1601 (22.5)	0.12
Heart failure	720 (11.2)	901 (12.6)	<0.05
AKI (history)	0 (0.0)	0 (0.0)
eGFR at baseline (mL/min/1.73m^2)			<0.001
>50	5547 (86.2)	6043 (84.8)
30–50	829 (12.9)	961 (13.5)
<30	60 (0.9)	125 (1.8)
Mean (SD)	70.5 (52.5)	70.4 (78.8)
eGFR at baseline (measurements)			<0.001
1	128 (2.0)	149 (2.1)
2–5	918 (14.3)	1039 (14.6)
6–11	1654 (25.7)	1791 (25.1)
12–23	2403 (37.3)	2728 (38.3)
≥24	1333 (20.7)	1422 (19.9)
Mean (SD)	16.6 (14.8)	16.5 (14.6)
eGFR follow-up (measurements)			<0.001
None	762 (11.8)	746 (10.5)
1	711 (11.0)	549 (7.7)
2–5	2470 (38.4)	2295 (32.2)
6–11	1579 (24.5)	1931 (27.1)
12–23	697 (10.8)	1159 (16.3)
≥24	217 (3.4)	449 (6.3)
Mean (SD)	6.1 (7.4)	8.4 (11.1)
CHA2DS2VASc			<0.001
0–1	903 (14.0)	829 (11.6)
2	1229 (19.1)	1358 (19.0)
3	1546 (24.0)	1806 (25.3)
4	1450 (22.5)	1658 (23.3)
5	800 (12.4)	900 (12.6)
≥6	508 (7.9)	578 (8.1)
Mean (SD)	3.2 (1.6)	3.3 (1.6)
Frailty			<0.05
Fit	1095 (17.0)	1136 (15.9)
Mild frailty	2672 (41.5)	3081 (43.2)
Moderate frailty	1871 (29.1)	2138 (30.0)
Severe frailty	798 (12.4)	774 (10.9)
PCP visits			0.31
0–4	50 (0.8)	43 (0.6)
5–9	587 (9.1)	602 (8.4)
10–19	2720 (42.3)	3051 (42.8)
≥20	3079 (47.8)	3433 (48.2)
Referrals			<0.001
0–9	3824 (59.4)	4434 (62.2)
10–19	2064 (32.1)	2174 (30.5)
≥20	548 (8.5)	521 (7.3)
Hospitalisations			<0.001
0	3573 (55.5)	4236 (59.4)
1	1471 (22.9)	1493 (20.9)
≥2	1392 (21.6)	1400 (19.6)

Note: Data are n (%) unless otherwise stated.

Abbreviations: AKI, acute kidney injury; BMI, body mass index; eGFR, estimated glomerular filtration rate; IHD, ischaemic heart disease; PCP, primary care practitioner; SD, standard deviation.

Table 2 Incidence Rate per 10,000 Person-Years of AKI, and HRs (95% CIs) Comparing AKI in the Rivaroxaban vs Warfarin Cohorts (ITT Analysis)

Cohort	Person-Years	Incident AKI Cases (N)	Incidence Rate Per 10,000 Person-Years	HR^a (95% CI)	p value
AKI Method A
Warfarin (N=7129)	20,027.6	136	67.9	1.00 (ref)
Rivaroxaban (N=6436)	13,917.5	113	81.2	1.19 (0.92–1.54)	0.18
AKI Method B
Warfarin (N=7129)	19,492.2	457	234.5	1.00 (ref)
Rivaroxaban (N=6436)	13,686.8	266	194.4	0.80 (0.68–0.93)	<0.01

Notes: Method A was based on Read codes, and Method B was based on the Aberdeen algorithm. ^aAdjusted for age, sex, baseline eGFR (both as categorical and continuous variables), number of previous eGFR measurements at baseline, Townsend index, polymedication, smoking, body mass index, use of health services in the year before baseline (PCP visits, referrals and hospitalizations), comorbidity (ischemic heart disease, cancer, diabetes, heart failure and liver disease), frailty, CHA₂DS₂VASc score, and use of antiplatelets/anti-infectives.

Abbreviations: AKI, acute kidney injury; CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; ITT, intention-to-treat; PCP; primary care practitioner.

Table 3 Incidence Rate per 10,000 Person-Years of AKI and HR (95% CI) Comparing AKI in the Rivaroxaban vs Warfarin Cohorts, Stratified by Baseline Renal Function (ITT Analysis)

Baseline eGFR	Cohort	Person-Years	Incident AKI Cases (N)	Incidence Rate Per 10,000 Person-Years	HR^a (95% CI)	p value
AKI Method A
eGFR >50 mL/min/1.73m^2	Warfarin (N=6043)	17,366.9	93	53.55	1.00 (ref)
	Rivaroxaban (N=5547)	12,155.1	74	60.88	1.12 (0.82–1.53)	0.48
eGFR ≤50 mL/min/1.73m^2	Warfarin (N=1086)	2660.7	43	161.61	1.00 (ref)
	Rivaroxaban (N=889)	1762.4	39	221.29	1.34 (0.85–2.12)	0.21
AKI Method B
eGFR >50 mL/min/1.73m^2	Warfarin (N=6043)	16,946.4	349	205.94	1.00 (ref)
	Rivaroxaban (N=5547)	11,963.1	208	173.87	0.79 (0.66–0.94)	0.01
eGFR ≤50 mL/min/1.73m^2	Warfarin (N=1086)	2545.8	108	424.23	1.00 (ref)
	Rivaroxaban (N=889)	1723.6	58	336.50	0.82 (0.59–1.14)	0.23

Notes: Method A was based on Read codes, and Method B was based on the Aberdeen algorithm. ^aAdjusted for age, sex, baseline eGFR (both as categorical and continuous variables), number of previous eGFR measurements at baseline, Townsend index, polymedication, smoking, body mass index, use of health services in the year before baseline (PCP visits, referrals and hospitalizations), comorbidity (ischemic heart disease, cancer, diabetes, heart failure and liver disease), frailty, CHA₂DS₂VASc score, and use of antiplatelets/anti-infectives.

Abbreviations: AKI, acute kidney injury; CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; ITT, intention-to-treat; PCP; primary care practitioner.