Worsening of kidney function in patients with atrial fibrillation and chronic kidney disease: evidence from the real-world CALLIPER study

Figures & data

Table 1. Baseline characteristics before applying IPTW and the absolute standardized difference before and after IPTW.

Characteristic	Overall cohort (N = 7368)	Warfarin (n = 5903)	Rivaroxaban 15 mg once daily (n = 1465)	Absolute standardized difference before IPTW	Absolute standardized difference after IPTW
Male, n (%)	4440 (60.3)	3613 (61.2)	827 (56.5)	0.097	0.006
Age, years, median (IQR)	79 (71–84)	78 (71–84)	79 (73–84)	0.120	0.011
CHADS2 score, median (IQR)	2.67 (3.00–3.50)	2.69 (2.00–3.53)	2.57(2.00–3.40)	0.055	0.005
CHA2DS2-VASc score, median (IQR)	4.43 (2.40–5.62)	4.44 (3.40–5.63)	4.41 (3.44–5.55)	0.011	0.006
Modified HAS-BLED score,^a median (IQR)	3.00 (2.40–3.65)	3.00 (2.38–3.63)	3.00 (2.54–3.74)	0.101	0.012
Comorbidities, n (%)
Alcohol abuse	76 (1.0)	67 (1.1)	9 (0.6)	0.052	0.002
Anemia	2999 (40.7)	2498 (42.3)	501 (34.2)	0.165	0.003
Atherosclerosis of aorta	323 (4.4)	268 (4.5)	55 (3.8)	0.038	0.003
Acute ischemic heart disease	165 (2.2)	124 (2.1)	41 (2.8)	0.047	0.009
Angina	2688 (36.2)	2184 (37.0)	484 (33.0)	0.082	0.005
Ischemic heart disease	1088 (14.8)	890 (15.1)	198 (13.5)	0.044	0.003
Acute myocardial infarction	616 (8.4)	513 (8.7)	103 (7.0)	0.060	0.011
Coronary artery bypass graft	828 (11.2)	676 (11.5)	152 (10.4)	0.034	0.000
Percutaneous coronary intervention	517 (7.0)	404 (6.8)	113 (7.7)	0.034	0.004
Chronic gastric or peptic ulcer or gastrointestinal diseases	1730 (23.5)	1368 (23.2)	362 (24.7)	0.036	0.004
Chronic lower respiratory diseases (bronchitis, asthma, emphysema)	2343 (31.8)	1886 (31.9)	457 (31.2)	0.016	0.010
Dementia	508 (6.9)	409 (6.9)	99 (6.8)	0.007	0.002
Depression and mood affective disorders	886 (12.0)	719 (12.2)	167 (11.4)	0.024	0.003
Diabetes	3903 (53.0)	3157 (53.5)	746 (50.9)	0.051	0.007
Drug abuse	343 (4.7)	286 (4.8)	57 (3.9)	0.045	0.008
H. pylori infection	67 (0.90)	51 (0.9)	16 (1.1)	0.024	0.003
Heart failure	4023 (54.6)	3327 (56.4)	696 (47.5)	0.178	0.005
Hypertension	6860 (93.1)	5479 (92.8)	1381 (94.3)	0.057	0.017
Hypothyroidism	1643 (22.3)	1314 (22.3)	329 (22.5)	0.005	0.007
Inflammatory bowel disease	705 (9.6)	576 (9.8)	129 (8.8)	0.032	0.014
Ischemic stroke or transient ischemic attack	1309 (17.8)	1075 (18.2)	234 (16.0)	0.059	0.003
Liver disease	392 (5.3)	321 (5.4)	71 (4.8)	0.026	0.0200
Cancer	1952 (26.5)	1563 (26.5)	389 (26.6)	0.002	0.027
Metabolic disorders	5767 (78.3)	4626 (78.4)	1141 (77.9)	0.012	0.008
Obesity	1459 (19.8)	1153 (19.5)	306 (20.9)	0.034	0.004
Peripheral artery disease	1302 (17.7)	1040 (17.6)	262 (17.9)	0.007	0.004
Pulmonary disease (except pulmonary embolism)	813 (11.0)	669 (11.3)	144 (9.8)	0.048	0.001
Rheumatoid arthritis or collagen vascular disease	624 (8.5)	448 (8.1)	146 (10.0)	0.067	0.004
Tobacco abuse	327 (4.4)	263 (4.5)	64 (4.4)	0.004	0.001
Vascular disease (except peripheral artery disease)	2863 (38.9)	2363 (40.0)	500 (34.1)	0.121	0.011
Comedications
Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers	4717 (64.0)	3731 (63.2)	986 (67.3)	0.085	0.004
Antiarrhythmics	1692 (23.0)	1318 (22.3)	374 (25.5)	0.076	0.007
Antidepressants	1857 (25.2)	1483 (25.1)	374 (25.5)	0.009	0.003
Antiplatelets	1530 (20.8)	1181 (20.0)	349 (23.8)	0.094	0.001
Antiulcer drugs other than proton pump inhibitors	3433 (46.6)	2719 (46.1)	714 (48.7)	0.054	0.004
Beta-blockers	5744 (78.0)	4589 (77.7)	1155 (78.8)	0.027	0.005
Calcium channel blockers	3682 (50.0)	2880 (48.8)	802 (54.7)	0.119	0.001
Diabetes medications	3813 (51.8)	3088 (52.3)	725 (49.5)	0.057	0.005
Diuretics	5433 (73.7)	4355 (73.8)	1078 (73.6)	0.004	0.001
Estrogens	135 (1.8)	106 (1.8)	29 (2.0)	0.014	0.003
Non-steroidal anti- inflammatory drugs	1088 (14.8)	854 (14.5)	234 (16.0)	0.042	0.002
Proton pump inhibitors	2333 (31.7)	1848 (31.3)	485 (33.1)	0.039	0.007
Statins	5285 (71.7)	4226 (71.6)	1059 (72.3)	0.016	0.011

Abbreviations. CHADS₂, Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke or transient ischemic attack (2 points); CHA₂DS₂-VASc, Congestive heart failure, Hypertension, Age ≥75 years (2 points), Diabetes mellitus, Stroke or transient ischemic attack (2 points), Vascular disease, Age 65–74, Sex category (female); HAS-BLED, Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio (not assessed), Elderly (age ≥65 years), Drugs/alcohol abuse, medication usage predisposing to bleeding; INR, international normalized ratio; IPTW, inverse probability of treatment weighting; IQR, interquartile range.

^aDoes not include INR as it was not available in the databases. The other components of the HAS-BLED score that are normally assessed based on laboratory data, including abnormal kidney and liver function, were estimated based on diagnostic codes.

Figure 1. Patient disposition. Abbreviations. AF, atrial fibrillation; CKD, chronic kidney disease; DVT, deep vein thrombosis; ESKD, end-stage kidney disease; NOAC, non-vitamin K antagonist oral anticoagulant; PE, pulmonary embolism; VKA, vitamin K antagonist; VTE, venous thromboembolism

Table 2. Reasons for censoring in the main patient cohort and for each exposure group for the worsening kidney function outcome.

Reason for censoring	Overall cohort (N = 7368)	Warfarin (n = 5903)	Rivaroxaban 15 mg once daily (n = 1465)
Outcome	283 (3.8)	248 (4.2)	35 (2.4)
Disenrollment	1156 (15.7)	946 (16.0)	210 (14.3)
Index anticoagulant discontinuation/switch	5395 (73.2)	4392 (74.4)	1003 (68.5)
End of data availability	486 (6.6)	317 (5.4)	169 (11.5)

Values are the number of patients with an event and (%).

Figure 2. Worsening kidney function (progression to CKD stage 5, kidney failure, or need for dialysis) in the overall cohort and diabetes subgroup using stabilized IPTW methodology to adjust for differences in baseline characteristics. Abbreviations. CI, confidence interval; CKD, chronic kidney disease; HR, hazard ratio; IPTW, inverse probability of treatment weighting

Data availability statement

This study used data from US IBM Watson MarketScan Commercial Claims and Medicare Supplemental databases.