Healthcare resource utilization and costs of rivaroxaban versus warfarin among non-valvular atrial fibrillation (NVAF) patients with obesity in a US population

Figures & data

Figure 1. Patient disposition – NVAF population. This figure has been reproduced with permission from Taylor and Francis of Berger, et al. Real-world effectiveness and safety of rivaroxaban versus warfarin among NVAF patients with obesity in a US population. Curr Med Res Opin. 2021. DOI:10.1080/03007995.2021.1901223. Data Source: IQVIA PharMetrics Plus data, consisting of AF patients with obesity, from January 1, 2010 to September 30, 2019. Abbreviations. AF, atrial fibrillation; BMI, body mass index; GPI, generic product identifier; ICD, international classification of disease; NVAF, non-valvular atrial fibrillation; VTE, venous thromboembolism. Notes: 1. GPI drug codes were used to identify pharmacy claims for rivaroxaban and warfarin. 2. A total of 326 rivaroxaban patients with >1 oral anticoagulant medications on the index date were excluded. 3. A total of 379 warfarin patients with >1 oral anticoagulant medications on the index date were excluded. 4. Continuous eligibility was defined as continuous health plan enrollment with medical and pharmacy coverage. 5. Baseline period was defined as the 12 months prior to the index date. 6. AF was identified with the following ICD-9-CM codes: 427.31, and ICD-10-CM: I48.0–148.2x, 148.91. 7. BMI-related ICD-9-CM and ICD-10-CM diagnosis codes were used to identify obesity (defined as BMI ≥30 kg/m²).

Table 1. Baseline demographics and clinical characteristics of NVAF patients treated with rivaroxaban or warfarin.

	Unweighted cohorts			Weighted cohorts
	Rivaroxaban	Warfarin	Std. diff.^a,b	Rivaroxaban	Warfarin	Std. diff.^a,b
	N = 10,555	N = 5,080	(%)	N = 10,555	N = 5,080	(%)
Observation period,^c months, mean ± SD [median]	19.9 ± 12.8 [18]	20.2 ± 13.0 [19]		20.3 ± 12.8 [19]	19.6 ± 12.8 [18]
Demographics^d
Age, years, mean ± SD [median]	58.5 ± 8.6 [59]	60.9 ± 8.8 [61]	27.5	59.3 ± 8.6 [60]	59.4 ± 8.9 [60]	0.7
Gender, female, n (%)	3,220 (30.5)	1,644 (32.4)	4.0	3,274 (31.0)	1,620 (31.9)	1.9
Year of index date,^d n (%)
2013	1,433 (13.6)	1,431 (28.2)	35.9	1,938 (18.4)	948 (18.7)	0.8
2014	1,664 (15.8)	1,015 (20.0)	11.0	1,829 (17.3)	904 (17.8)	1.2
2015	1,620 (15.3)	887 (17.5)	5.7	1,687 (16.0)	815 (16.0)	0.2
2016	1,491 (14.1)	598 (11.8)	7.0	1,387 (13.1)	674 (13.3)	0.3
2017	1,706 (16.2)	499 (9.8)	18.9	1,518 (14.4)	708 (13.9)	1.3
2018	1,621 (15.4)	415 (8.2)	22.3	1,369 (13.0)	648 (12.7)	0.7
2019	1,020 (9.7)	235 (4.6)	19.6	828 (7.8)	384 (7.6)	1.1
Region,^d n (%)
South	2,561 (24.3)	1,478 (29.1)	10.9	2,692 (25.5)	1,248 (24.6)	2.2
Midwest	2,870 (27.2)	1,597 (31.4)	9.3	3,022 (28.6)	1,467 (28.9)	0.6
Northeast	4,267 (40.4)	1,423 (28.0)	26.2	3,863 (36.6)	1,906 (37.5)	1.9
West	857 (8.1)	582 (11.5)	11.2	978 (9.3)	459 (9.0)	0.8
Insurance plan type,^d n (%)
PPO	9,021 (85.5)	4,172 (82.1)	9.1	8,843 (83.8)	4,268 (84.0)	0.7
HMO	867 (8.2)	470 (9.3)	3.7	948 (9.0)	429 (8.4)	1.9
POS	396 (3.8)	186 (3.7)	0.5	387 (3.7)	197 (3.9)	1.1
Indemnity/traditional	226 (2.1)	227 (4.5)	13.0	328 (3.1)	160 (3.1)	0.2
Unknown	37 (0.4)	20 (0.4)	0.7	39 (0.4)	21 (0.4)	0.8
CDHC	7 (0.1)	3 (0.1)	0.3	10 (0.1)	4 (0.1)	0.5
Baseline medication use
Number of different prescription drugs used,^e,f  mean ± SD [median]	12.90 ± 9.17 [11]	14.15 ± 10.42 [12]	12.7	13.54 ± 9.65 [12]	13.56 ± 9.95 [12]	0.2
Use of non-oral anticoagulants,^e n (%)	1,628 (15.4)	938 (18.5)	8.1	1,760 (16.7)	834 (16.4)	0.7
Use of cardiovascular-related medications,^e n (%)	8,795 (83.3)	4,271 (84.1)	2.0	8,838 (83.7)	4,256 (83.8)	0.1
Antihypertensive agents	8,109 (76.8)	3,965 (78.1)	2.9	8,192 (77.6)	3,925 (77.3)	0.8
Antihyperlipidemic agents	5,046 (47.8)	2,739 (53.9)	12.2	5,304 (50.2)	2,578 (50.8)	1.0
Antiplatelet agents	812 (7.7)	604 (11.9)	14.1	1,109 (10.5)	460 (9.1)	4.9
Gastric bypass surgery,^e n (%)	65 (0.6)	41 (0.8)	2.3	63 (0.6)	36 (0.7)	1.5
Cardiovascular procedures,^e n (%)	462 (4.4)	684 (13.5)	31.9	868 (8.2)	390 (7.7)	2.0
Percutaneous coronary intervention	298 (2.8)	302 (5.9)	15.2	526 (5.0)	173 (3.4)	7.9
Coronary bypass graft	190 (1.8)	421 (8.3)	29.6	394 (3.7)	238 (4.7)	4.7
Baseline healthcare resource utilization,^e mean ± SD [median]
All-cause
Hospitalizations	0.63 ± 0.76 [1]	0.96 ± 1.02 [1]	36.9	0.77 ± 0.91 [1]	0.75 ± 0.89 [1]	1.6
ER visits	0.71 ± 1.29 [0]	0.76 ± 1.64 [0]	3.1	0.73 ± 1.34 [0]	0.73 ± 1.60 [0]	0.4
OP visits	18.59 ± 18.23 [14]	25.21 ± 31.07 [17]	26.0	21.74 ± 27.31 [15]	21.24 ± 23.24 [15]	2.0
OP hospital visits	4.50 ± 7.27 [2]	7.66 ± 18.88 [3]	22.1	5.60 ± 10.04 [3]	5.64 ± 12.45 [3]	0.4
Office visits	9.47 ± 9.64 [7]	9.49 ± 9.71 [7]	0.2	9.87 ± 10.49 [7]	9.55 ± 10.22 [7]	3.1
Other visits	4.63 ± 10.24 [2]	8.06 ± 19.37 [3]	22.1	6.27 ± 19.44 [3]	6.05 ± 13.14 [3]	1.3
NVAF-related^g
Hospitalizations	0.51 ± 0.61 [0]	0.70 ± 0.69 [1]	29.6	0.61 ± 0.72 [1]	0.57 ± 0.64 [1]	4.8
ER visits	0.26 ± 0.61 [0]	0.19 ± 0.59 [0]	11.6	0.25 ± 0.60 [0]	0.21 ± 0.62 [0]	6.9
OP visits	2.44 ± 3.46 [1]	2.92 ± 5.77 [1]	10.1	2.51 ± 4.07 [1]	2.84 ± 4.99 [1]	7.1
OP hospital visits	0.90 ± 1.66 [0]	1.13 ± 3.12 [0]	9.1	0.94 ± 2.02 [0]	1.04 ± 2.58 [0]	4.4
Office visits	1.13 ± 1.73 [0]	1.01 ± 2.33 [0]	6.0	1.08 ± 1.73 [0]	1.11 ± 2.35 [0]	1.8
Other visits	0.40 ± 1.59 [0]	0.78 ± 3.00 [0]	15.7	0.49 ± 2.12 [0]	0.68 ± 2.42 [0]	8.2
Baseline healthcare costs,^e,h $US 2019, mean ± SD
All-cause
Total healthcare costs	$28,239 ± 41,800	$59,325 ± 109,468	37.5	$41,725 ± 76,079	$39,185 ± 73,591	3.4
Total medical costs	$24,933 ± 39,817	$55,298 ± 107,599	37.4	$38,125 ± 74,191	$35,756 ± 71,829	3.2
Hospitalization costs	$13,594 ± 31,623	$40,074 ± 97,535	36.5	$24,545 ± 62,307	$24,064 ± 63,516	0.8
ER costs	$1,410 ± 3,580	$1,402 ± 3,951	0.2	$1,436 ± 3,761	$1,311 ± 3,734	3.3
OP costs	$9,929 ± 19,308	$13,822 ± 33,517	14.2	$12,144 ± 27,112	$10,380 ± 24,007	6.9
OP hospital costs	$7,159 ± 17,663	$8,785 ± 23,528	7.8	$8,807 ± 25,333	$6,646 ± 17,591	9.9
Office costs	$1,327 ± 2,464	$1,493 ± 3,512	5.5	$1,647 ± 4,357	$1,451 ± 3,526	4.9
Other costs	$1,443 ± 4,604	$3,544 ± 19,710	14.7	$1,691 ± 5,334	$2,283 ± 12,661	6.1
Pharmacy costs	$3,306 ± 9,387	$4,027 ± 10,199	7.4	$3,600 ± 9,770	$3,429 ± 9,430	1.8
NVAF-related^g
Total medical costs	$15,115 ± 29,777	$35,828 ± 87,696	31.6	$24,902 ± 60,443	$22,274 ± 56,550	4.5
Hospitalization costs	$10,906 ± 27,782	$32,893 ± 87,347	33.9	$20,561 ± 59,058	$19,476 ± 56,084	1.9
ER costs	$751 ± 2,551	$517 ± 2,240	9.7	$720 ± 2,720	$542 ± 2,285	7.1
OP costs	$3,458 ± 10,728	$2,418 ± 9,249	10.4	$3,622 ± 11,789	$2,256 ± 7,943	13.6
OP hospital costs	$3,053 ± 10,511	$1,999 ± 8,764	10.9	$3,224 ± 11,560	$1,854 ± 7,468	14.1
Office costs	$199 ± 486	$160 ± 547	7.6	$189 ± 479	$170 ± 531	3.8
Other costs	$205 ± 1,051	$259 ± 2,162	3.2	$209 ± 1,120	$232 ± 1,912	1.5

Abbreviations. HMO, health maintenance organization; NVAF, non-valvular atrial fibrillation; POS, point of service; PPO, preferred provider organization; SD, standard deviation; SE, systemic embolism; Std. diff, standardized difference.

^a For continuous variables, the standardized difference is calculated by dividing the absolute difference in means of the control and the case by the pooled standard deviation of both groups. The pooled standard deviation is the square root of the average of the squared standard deviations.

^b For dichotomous variables, the standardized difference is calculated using the following equation where P is the respective proportion of participants in each group: |(P_case−P_control)|/√[(P_case(1 − P_case)+P_control(1 − P_control))/2].

^c Observation period spans from the index date to the earliest of: 36 months, end of continuous enrollment, or end of data availability.

^d Evaluated at the index date.

^e Evaluated during the 12 months prior to the index date, excluding the index date.

^f Prescription drugs were based on unique National Drug Codes.

^g NVAF-related HRU and costs were identified as any visits with a primary or secondary diagnosis of atrial fibrillation.

^h Costs are inflated to $US 2019 using the U.S. Medical Care consumer price index from the Bureau of Labor Statistics, U.S. Department of Labor.

Table 2. Baseline comorbidities of NVAF patients treated with rivaroxaban or warfarin.

	Unweighted cohorts			Weighted cohorts
	Rivaroxaban	Warfarin	Std. diff.	Rivaroxaban	Warfarin	Std. diff.
	N = 10,555	N = 5,080	(%)	N = 10,555	N = 5,080	(%)
Morbid obesity (BMI ≥ 40),^a n (%)	3,792 (35.9)	2,094 (41.2)	10.9	3,978 (37.7)	1,980 (39.0)	2.7
Quan-CCI,^b mean ± SD [median]	1.43 ± 1.74 [1]	2.21 ± 2.10 [2]	40.4	1.79 ± 2.18 [1]	1.75 ± 1.92 [1]	2.1
CHA2DS2-VASc score,^b mean ± SD [median]	2.34 ± 1.43 [2]	3.20 ± 1.65 [3]	55.4	2.65 ± 1.59 [2]	2.70 ± 1.54 [3]	3.4
HAS-BLED score,^b mean ± SD [median]	1.65 ± 1.01 [2]	1.98 ± 1.15 [2]	30.2	1.80 ± 1.12 [2]	1.79 ± 1.08 [2]	0.8
Baseline stroke/SE and major bleeding,^b n (%)
Stroke/SE^c	328 (3.1)	433 (8.5)	23.1	614 (5.8)	260 (5.1)	3.1
Ischemic stroke	308 (2.9)	392 (7.7)	21.4	547 (5.2)	239 (4.7)	2.2
Hemorrhagic stroke	16 (0.2)	42 (0.8)	9.7	57 (0.5)	23 (0.4)	1.4
SE	17 (0.2)	38 (0.7)	8.7	31 (0.3)	19 (0.4)	1.3
Major bleeding^d	174 (1.6)	254 (5.0)	18.7	398 (3.8)	148 (2.9)	4.7
Baseline comorbidities,^b n (%)
Stroke and bleeding risk factors
Hypertension	8,942 (84.7)	4,536 (89.3)	13.6	9,136 (86.6)	4,425 (87.1)	1.6
Diabetes	3,958 (37.5)	2,604 (51.3)	27.7	4,486 (42.5)	2,190 (43.1)	1.2
Transient ischemic attack	321 (3.0)	246 (4.8)	9.3	467 (4.4)	200 (3.9)	2.4
Other stroke risk factors
Hyperlipidemia	6,963 (66.0)	3,593 (70.7)	10.2	7,165 (67.9)	3,448 (67.9)	0.0
Congestive heart failure	2,940 (27.9)	2,227 (43.8)	33.3	3,593 (34.0)	1,730 (34.0)	0.0
Depression	1,398 (13.2)	821 (16.2)	8.2	1,572 (14.9)	723 (14.2)	1.9
COPD	955 (9.0)	585 (11.5)	8.1	1,065 (10.1)	517 (10.2)	0.3
Family history of CVD	899 (8.5)	341 (6.7)	6.8	859 (8.1)	392 (7.7)	1.6
Other bleeding risk factors
Arrhythmia (excluding AF)	9,316 (88.3)	4,613 (90.8)	8.3	9,404 (89.1)	4,514 (88.9)	0.8
CAD	2,951 (28.0)	2,189 (43.1)	31.6	3,529 (33.4)	1,699 (33.4)	0.0
NSAID use	2,674 (25.3)	1,021 (20.1)	12.5	2,488 (23.6)	1,231 (24.2)	1.5
Excessive fall risk (Parkinson’s disease, etc.)	2,220 (21.0)	1,129 (22.2)	2.9	2,294 (21.7)	1,104 (21.7)	0.0
Renal disease	2,047 (19.4)	1,835 (36.1)	37.4	2,688 (25.5)	1,289 (25.4)	0.2
Chronic kidney disease	1,716 (16.3)	1,479 (29.1)	30.7	2,180 (20.7)	1,038 (20.4)	0.6
Anemia	1,360 (12.9)	1,370 (27.0)	35.3	1,930 (18.3)	912 (17.9)	0.9
Ethanol abuse	1,245 (11.8)	483 (9.5)	7.4	1,172 (11.1)	569 (11.2)	0.3
Previous bleeding	1,090 (10.3)	844 (16.6)	18.4	1,379 (13.1)	637 (12.5)	1.6
Myocardial infarction	980 (9.3)	889 (17.5)	24.1	1,342 (12.7)	627 (12.3)	1.1
Hepatic disease	859 (8.1)	461 (9.1)	3.3	994 (9.4)	435 (8.6)	3.0
PAD	602 (5.7)	564 (11.1)	19.5	853 (8.1)	385 (7.6)	1.9
Left ventricular dysfunction	338 (3.2)	291 (5.7)	12.2	411 (3.9)	207 (4.1)	0.9
Thrombocytopenia (low platelet count)	262 (2.5)	296 (5.8)	16.8	447 (4.2)	186 (3.7)	2.9
Central venous catheter	216 (2.0)	502 (9.9)	33.1	628 (5.9)	250 (4.9)	4.5
Peptic ulcer	148 (1.4)	88 (1.7)	2.7	214 (2.0)	69 (1.4)	5.1
Coagulation defect	75 (0.7)	241 (4.7)	24.8	225 (2.1)	102 (2.0)	0.8
Diathesis	3 (0.0)	3 (0.1)	1.5	7 (0.1)	2 (0.0)	0.9
Prior history of cancer diagnosis and treatment,^b n (%)	1,237 (11.7)	718 (14.1)	7.2	1,401 (13.3)	642 (12.6)	1.9

Abbreviations. CHA₂DS₂-VASc, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category; AF, atrial fibrillation; CAD, coronary artery disease; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; HAS-BLED, hypertension, abnormal renal and liver function, stroke, bleeding; NVAF, non-valvular atrial fibrillation; NSAID, non-steroidal anti-inflammatory drugs; PAD, peripheral artery disease; Quan-CCI, Quan-Charlson comorbidity index; SD, standard deviation; SE, systemic embolism; Std. diff, standardized difference.

^a Evaluated during the 12 months prior to the index date and on the index date.

^b Evaluated during the 12 months prior to the index date, excluding the index date.

^c Defined as a primary diagnosis of ischemic stroke, hemorrhagic stroke, or SE during a hospitalization or emergency room visit.

^d Major bleeding was identified with the Cunningham algorithm, which identifies hospitalizations with diagnoses and procedures indicating an episode of bleeding (excluding bleeding due to major trauma).

Figure 3. Healthcare Costs among Rivaroxaban vs. Warfarin Cohorts¹. (A) Up to 12 Months. (B) Up to 36 Months. *p value <.05. Abbreviations. ER: emergency room; NVAF: non-valvular atrial fibrillation; OP: outpatient; PPY: per person-years; US: United States. Notes: 1. Cost differences were calculated using a multivariable linear regression model controlling for the healthcare costs during baseline. Confidence intervals and p values were calculated using non-parametric bootstrap procedure (B = 499). 2. Healthcare costs were considered NVAF-related if they had been associated with a primary or secondary diagnosis of AF.