Healthcare costs of NVAF patients treated with rivaroxaban and apixaban in the US

Figures & data

Figure 1. Patient disposition. AF, atrial fibrillation; VTE, venous thromboembolism. Note. 1. Patients initiated on treatment with both rivaroxaban and apixaban on the index date were classified as apixaban, and subsequently excluded (n = 16).

Table 1. Baseline demographics and clinical characteristics – unweighted and weighted rivaroxaban and apixaban cohorts.

Characteristics	Unweighted Cohorts			Weighted Cohorts^a
	Rivaroxaban	Apixaban	Std. diff.^b,c	Rivaroxaban	Apixaban	Std. diff.^b,c
	(N = 23,822)	(N = 53,666)	(%)	(N = 23,822)	(N = 53,666)	(%)
Demographics^d
Age, years, mean ± SD [median]	72.3 ± 10.6 [73]	74.5 ± 10.0 [75]	20.8	73.8 ± 10.1 [75]	73.8 ± 10.3 [75]	0.3
Sex, female, n (%)	10,332 (43.4)	25,774 (48.0)	9.3	11,102 (46.6)	25,003 (46.6)	0.0
Year of index date,^d n (%)
2016	5,743 (24.1)	11,104 (20.7)	8.2	5,193 (21.8)	11,673 (21.8)	0.1
2017	9,132 (38.3)	17,603 (32.8)	11.6	8,189 (34.4)	18,507 (34.5)	0.2
2018	8,947 (37.6)	24,959 (46.5)	18.1	10,439 (43.8)	23,486 (43.8)	0.1
Region,^d n (%)
South	9,253 (38.8)	23,703 (44.2)	10.8	10,139 (42.6)	22,850 (42.6)	0.0
West	5,900 (24.8)	12,851 (23.9)	1.9	5,785 (24.3)	12,998 (24.2)	0.2
Midwest	5,902 (24.8)	11,347 (21.1)	8.6	5,276 (22.1)	11,939 (22.2)	0.2
Northeast	2,685 (11.3)	5,626 (10.5)	2.5	2,533 (10.6)	5,746 (10.7)	0.2
Unknown	82 (0.3)	139 (0.3)	1.6	89 (0.4)	133 (0.2)	2.3
Insurance plan type,^d n (%)
Medicare	18,073 (75.9)	43,921 (81.8)	14.6	19,017 (79.8)	42,898 (79.9)	0.3
Commercial insurance	5,749 (24.1)	9,745 (18.2)	14.6	4,805 (20.2)	10,768 (20.1)	0.3
Quan-Charlson comorbidity index,^e mean ± SD [median]	2.50 ± 2.35 [2]	3.02 ± 2.56 [2]	21.3	2.86 ± 2.51 [2]	2.86 ± 2.51 [2]	0.1
CHA2DS2-VASc score,^e mean ± SD [median]	2.43 ± 1.45 [2]	2.75 ± 1.50 [3]	21.2	2.65 ± 1.51 [2]	2.65 ± 1.49 [2]	0.0
HAS-BLED score,^e mean ± SD [median]	1.48 ± 0.90 [1]	1.59 ± 0.92 [1]	12.7	1.55 ± 0.92 [1]	1.55 ± 0.92 [1]	0.0
Baseline use of injectable anticoagulants,^e n (%)
Unfractionated heparins	1,145 (4.8)	3,220 (6.0)	5.3	1,332 (5.6)	3,040 (5.7)	0.3
Low molecular weight heparins	943 (4.0)	2,731 (5.1)	5.4	1,063 (4.5)	2,634 (4.9)	2.1
Fondaparinux	1 (0.0)	6 (0.0)	0.8	1 (0.0)	6 (0.0)	0.8
All-cause healthcare resource utilization,^e mean ± SD [median]
Hospitalizations	0.51 ± 0.82 [0]	0.66 ± 0.95 [0]	17.5	0.62 ± 0.90 [0]	0.61 ± 0.92 [0]	0.1
ER visits	0.95 ± 2.40 [0]	1.05 ± 2.77 [0]	3.9	1.04 ± 2.81 [0]	1.02 ± 2.62 [0]	0.6
Outpatient visits	14.6 ± 16.2 [11]	16.1 ± 19.7 [12]	8.7	15.7 ± 18.0 [11]	15.7 ± 18.8 [11]	0.0
Outpatient hospital visits	4.8 ± 11.7 [2]	6.1 ± 15.9 [2]	8.7	5.7 ± 13.8 [2]	5.7 ± 14.8 [2]	0.2
Office/physician visits	9.7 ± 10.0 [7]	10.1 ± 10.3 [8]	3.5	10.0 ± 10.2 [8]	10.0 ± 10.2 [8]	0.2
Other visits^f	5.1 ± 10.0 [1]	5.8 ± 11.7 [1]	6.6	5.6 ± 10.9 [1]	5.6 ± 11.3 [1]	0.2
All-cause healthcare costs,^e,g $US 2019, mean ± SD
Total costs (medical + pharmacy)	$26,908 ± 46,636	$34,198 ± 58,949	13.7	$32,022 ± 57,214	$31,970 ± 54,463	0.1
Total medical costs	$24,331 ± 44,999	$31,346 ± 57,224	13.6	$29,258 ± 55,537	$29,205 ± 52,748	0.1
Hospitalization costs	$9,895 ± 29,938	$13,811 ± 30,706	12.9	$12,577 ± 34,439	$12,609 ± 29,326	0.1
ER visit costs	$3,661 ± 11,706	$4,514 ± 19,407	5.3	$4,347 ± 15,158	$4,265 ± 17,275	0.5
Outpatient visit costs	$9,124 ± 26,121	$10,869 ± 38,019	5.3	$10,318 ± 32,044	$10,330 ± 34,606	0.0
Outpatient hospital visit costs	$6,691 ± 21,976	$8,402 ± 36,388	5.7	$7,858 ± 29,814	$7,883 ± 32,660	0.1
Office/physician visit costs	$2,433 ± 13,028	$2,467 ± 9,492	0.3	$2,460 ± 10,465	$2,447 ± 10,070	0.1
Other visit costs^f	$1,651 ± 7,686	$2,152 ± 13,283	4.6	$2,017 ± 11,896	$2,000 ± 11,740	0.1
Pharmacy costs	$2,577 ± 8,990	$2,852 ± 9,275	3.0	$2,763 ± 9,540	$2,765 ± 9,035	0.0

ER, emergency room; HAS-BLED, hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol; NVAF, non-valvular atrial fibrillation; SD, standard deviation; Std. diff., standardized difference.

^aRivaroxaban and apixaban patients were weighted using the inverse probability of treatment weighting approach based on the propensity score. Variables used in the propensity score calculation included the following: age, sex, year of index date, US region, type of insurance plan, Quan-Charlson comorbidity index score, CHA₂DS₂-VASc score, HAS-BLED score, selected NVAF-related comorbidities (those with prevalence ≥ 5%), baseline risk factors for stroke/systemic embolism and bleeding events (those with prevalence ≥ 5%), all-cause baseline HRU and costs.

^bFor continuous variables, the standardized difference was 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.

^cFor dichotomous variables, the standardized difference was 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].

^dEvaluated at the index date.

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

^f Includes visits such as home services and hospice.

^gCosts were inflation-adjusted to US$2019 using the US Medical Care consumer price index from the Bureau of Labor Statistics from the US Department of Labor.

Table 2. NVAF-related comorbidities and risk factors for stroke/systemic embolism and major bleeding – unweighted and weighted rivaroxaban and apixaban cohorts.

Characteristics	Unweighted Cohorts			Weighted Cohorts^a
	Rivaroxaban	Apixaban	Std. diff.^b,c	Rivaroxaban	Apixaban	Std. diff.^b,c
	(N = 23,822)	(N = 53,666)	(%)	(N = 23,822)	(N = 53,666)	(%)
Selected NVAF-related comorbidities,^d n (%)
Diabetes	7,851 (33.0)	19,154 (35.7)	5.8	8,317 (34.9)	18,707 (34.9)	0.1
Renal disease	6,941 (29.1)	19,909 (37.1)	16.9	8,242 (34.6)	18,588 (34.6)	0.1
Congestive heart failure	6,769 (28.4)	18,103 (33.7)	11.5	7,661 (32.2)	17,227 (32.1)	0.1
Myocardial infarction	2,666 (11.2)	7,965 (14.8)	10.8	3,269 (13.7)	7,359 (13.7)	0.0
Diverticulosis	1,970 (8.3)	4,763 (8.9)	2.2	2,073 (8.7)	4,664 (8.7)	0.0
Percutaneous coronary intervention	522 (2.2)	1,515 (2.8)	4.0	638 (2.7)	1,416 (2.6)	0.2
History of previous GI bleed
Lower GI bleed	400 (1.7)	1,070 (2.0)	2.3	435 (1.8)	1,038 (1.9)	0.8
Upper GI bleed	37 (0.2)	137 (0.3)	2.2	51 (0.2)	126 (0.2)	0.4
Coronary bypass graft	195 (0.8)	771 (1.4)	5.9	246 (1.0)	714 (1.3)	2.8
Helicobacter pylori infection	78 (0.3)	179 (0.3)	0.1	84 (0.4)	171 (0.3)	0.6
Baseline risk factors for stroke/systemic embolism and bleeding events,^d n (%)
Hypertension	19,991 (83.9)	46,982 (87.5)	10.4	20,551 (86.3)	46,358 (86.4)	0.3
Hyperlipidemia	17,095 (71.8)	40,725 (75.9)	9.4	17,749 (74.5)	40,019 (74.6)	0.1
Chronic kidney disease	6,483 (27.2)	17,965 (33.5)	13.6	7,493 (31.5)	16,924 (31.5)	0.2
Obesity	6,184 (26.0)	13,309 (24.8)	2.7	6,030 (25.3)	13,514 (25.2)	0.3
Heart failure	5,896 (24.8)	16,232 (30.2)	12.3	6,809 (28.6)	15,322 (28.6)	0.1
Excessive fall risk (i.e. Parkinson’s disease, dementia, and other mental disorders)	5,176 (21.7)	12,948 (24.1)	5.7	5,591 (23.5)	12,557 (23.4)	0.2
Anemia	4,897 (20.6)	13,667 (25.5)	11.7	5,714 (24.0)	12,854 (24.0)	0.1
Chronic obstructive pulmonary disease	4,438 (18.6)	11,546 (21.5)	7.2	4,923 (20.7)	11,070 (20.6)	0.1
Depression	3,941 (16.5)	9,870 (18.4)	4.9	4,251 (17.8)	9,564 (17.8)	0.1
Alcohol abuse	3,239 (13.6)	7,665 (14.3)	2.0	3,355 (14.1)	7,558 (14.1)	0.0
Family history of cardiovascular disease	1,856 (7.8)	4,956 (9.2)	5.2	2,114 (8.9)	4,724 (8.8)	0.3
Hepatic disease	1,355 (5.7)	3,337 (6.2)	2.2	1,437 (6.0)	3,249 (6.1)	0.1
Thrombocytopenia (i.e. low platelet count)	866 (3.6)	2,517 (4.7)	5.3	1,023 (4.3)	2,374 (4.4)	0.6
Left ventricular dysfunction	768 (3.2)	2,025 (3.8)	3.0	839 (3.5)	1,947 (3.6)	0.6
Peptic ulcer	379 (1.6)	1,056 (2.0)	2.8	441 (1.9)	994 (1.9)	0.0
Bleeding diathesis	10 (0.0)	47 (0.1)	1.8	11 (0.0)	44 (0.1)	1.5

NVAF, non-valvular atrial fibrillation; Std. diff., standardized difference.

^aRivaroxaban and apixaban patients were weighted using the inverse probability of treatment weighting approach based on the propensity score. Variables used in the propensity score calculation included the following: age, sex, year of index date, US region, type of insurance plan, Quan-Charlson comorbidity index score, CHA₂DS₂-VASc score, HAS-BLED score, selected NVAF-related comorbidities (those with prevalence ≥ 5%), baseline risk factors for stroke/systemic embolism and bleeding events (those with prevalence ≥ 5%), all-cause baseline HRU and costs.

^bFor continuous variables, the standardized difference was 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.

^cFor dichotomous variables, the standardized difference was 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].

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

Table 3. All-cause healthcare resource utilization of the rivaroxaban and apixaban cohorts – up to 18 and 24 months follow-up.

HRU measures	Frequency of HRU		Rate (PPPY)		Rate Ratio^a (95% CI)^b [A]/[B]	p-value^b
	Rivaroxaban	Apixaban	Rivaroxaban [A]	Apixaban [B]
	(N = 23,822)	(N = 53,666)	(N = 23,822)	(N = 53,666)
Up to 18 Months
Unweighted Cohort
Observation period,^c days, mean ± SD [median]	368 ± 176 [397]	340 ± 179 [340]
Total person-years	24,047	50,045
Hospitalizations	11,213	26,779	0.47	0.54	0.87 (0.84, 0.90)	<0.001
ER visits	24,072	55,052	1.00	1.10	0.91 (0.88, 0.94)	<0.001
Outpatient visits	465,222	1,077,633	19.3	21.5	0.90 (0.88, 0.91)	<0.001
Outpatient hospital visits	180,876	477,999	7.5	9.6	0.79 (0.76, 0.81)	<0.001
Office/physician visits	284,346	599,634	11.8	12.0	0.99 (0.97, 1.00)	0.112
Other visits^d	165,197	388,312	6.9	7.8	0.89 (0.86, 0.92)	<0.001
Weighted Cohort
Observation period,^c days, mean ± SD [median]	351 ± 177 [355]	348 ± 179 [354]
Total person-years	27,654	61,696
Hospitalizations	13,042	27,904	0.47	0.45	1.04 (1.00, 1.09)	0.072
ER visits	27,622	60,532	1.00	0.98	1.02 (0.98, 1.05)	0.377
Outpatient visits	539,750	1,232,203	19.5	20.0	0.98 (0.96, 0.99)	0.008
Outpatient hospital visits	214,828	512,514	7.8	8.3	0.94 (0.90, 0.97)	<0.001
Office/physician visits	324,922	719,689	11.7	11.7	1.01 (0.99, 1.02)	0.441
Other visits^d	203,728	455,353	7.4	7.4	1.00 (0.97, 1.03)	0.850
Up to 24 Months
Unweighted Cohort
Observation period,^e days, mean ± SD [median]	419 ± 234 [397]	382 ± 233 [340]
Total person-years	27,330	56,160
Hospitalizations	12,400	29,240	0.45	0.52	0.87 (0.84, 0.90)	<0.001
ER visits	26,745	60,286	0.98	1.07	0.91 (0.88, 0.94)	<0.001
Outpatient visits	516,550	1,183,156	18.9	21.1	0.90 (0.88, 0.91)	<0.001
Outpatient hospital visits	198,499	519,457	7.3	9.2	0.79 (0.76, 0.81)	<0.001
Office/physician visits	318,051	663,699	11.6	11.8	0.98 (0.97, 1.00)	0.076
Other visits^d	185,461	429,926	6.8	7.7	0.89 (0.86, 0.92)	<0.001
Weighted Cohort
Observation period,^e days, mean ± SD [median]	396 ± 233 [355]	392 ± 234 [354]
Total person-years	37,750	83,816
Hospitalizations	16,945	36,327	0.45	0.43	1.04 (0.99, 1.08)	0.104
ER visits	36,313	79,302	0.96	0.95	1.02 (0.98, 1.06)	0.429
Outpatient visits	711,456	1,623,067	18.8	19.4	0.97 (0.96, 0.99)	<0.001
Outpatient hospital visits	276,528	661,875	7.3	7.9	0.93 (0.89, 0.96)	<0.001
Office/physician visits	434,928	961,192	11.5	11.5	1.00 (0.99, 1.02)	0.669
Other visits^d	272,899	606,080	7.2	7.2	1.00 (0.97, 1.03)	0.962

CI, confidence interval; ER, emergency room; HRU, healthcare resource utilization; LOS, length of stay; PPPY, per patient per year.

^aRate ratios were obtained from Poisson regression models with log-link.

^bConfidence intervals and p-values were calculated using non-parametric bootstrap procedures with 499 replications.

^cThe observation period spanned from the index date to the earliest of: 18 months, end of continuous enrollment, death, or end of data availability.

^dIncludes visits such as home services and hospice.

^eThe observation period spanned from the index date to the earliest of: 24 months, end of continuous enrollment, death, or end of data availability.

Table 4. Healthcare cost components of the rivaroxaban and apixaban cohorts – up to 18 and 24 months follow-up.

Healthcare costs,^a $US 2019	Rivaroxaban [A]	Apixaban [B]	Cost difference	p-value^b
			(95% CI)^b
	(N = 23,822)	(N = 53,666)	[A] - [B]
Up to 18 months
Unweighted Cohorts
Observation period,^c days, mean ± SD [median]	368 ± 176 [397]	340 ± 179 [340]
All-cause total healthcare costs, PPPY, mean ± SD	$36,251 ± 58,451	$40,858 ± 73,162	−4,607 (−5,579; −3,734)	<0.001
Total medical costs	$30,053 ± 56,375	$34,171 ± 71,206	−4,118 (−5,076; −3,275)	<0.001
Hospitalization costs	$9,534 ± 32,239	$10,737 ± 35,716	−1,203 (−1,712; −772)	<0.001
ER visit costs	$3,551 ± 13,671	$4,104 ± 19,234	−554 (−779; −330)	<0.001
Outpatient visit costs	$14,804 ± 37,327	$16,717 ± 49,788	−1,913 (−2,546; −1,271)	<0.001
Outpatient hospital visit costs	$11,839 ± 33,055	$13,700 ± 46,443	−1,861 (−2,416; −1,341)	<0.001
Office/physician visit costs	$2,965 ± 14,723	$3,017 ± 15,847	−52 (−269; 201)	0.725
Other visit costs^d	$2,164 ± 8,968	$2,613 ± 13,553	−449 (−614; −265)	<0.001
Pharmacy costs	$6,197 ± 11,313	$6,687 ± 11,241	−489 (−675; −288)	<0.001
Weighted Cohorts
Observation period,^c days, mean ± SD [median]	351 ± 177 [355]	348 ± 179 [354]
All-cause total healthcare costs, PPPY, mean ± SD	$38,464 ± 62,881	$39,585 ± 69,247	−1,121 (−2,027; −249)	0.020
Total medical costs	$32,045 ± 60,558	$32,994 ± 67,291	−949 (−1,860; −92)	0.036
Hospitalization costs	$10,600 ± 34,427	$10,204 ± 34,826	396 (−119; 859)	0.112
ER visit costs	$3,996 ± 15,384	$3,892 ± 17,585	104 (−133; 370)	0.421
Outpatient visit costs	$14,933 ± 38,192	$16,415 ± 46,815	−1,482 (−2,127; −885)	<0.001
Outpatient hospital visit costs	$11,874 ± 33,651	$13,453 ± 43,449	−1,579 (−2,134; −1,046)	<0.001
Office/physician visit costs	$3,059 ± 15,167	$2,962 ± 15,373	97 (−115; 342)	0.409
Other visit costs^d	$2,516 ± 13,287	$2,484 ± 12,476	33 (−235; 321)	0.794
Pharmacy costs	$6,419 ± 12,607	$6,591 ± 11,038	−172 (−350; 32)	0.108
Up to 24 months
Unweighted Cohorts
Observation period,^edays, mean ± SD [median]	419 ± 234 [397]	382 ± 233 [340]
All-cause total healthcare costs, PPPY, mean ± SD	$35,310 ± 56,073	$39,847 ± 70,512	−4,538 (−5,454; −3,672)	<0.001
Total medical costs	$29,151 ± 53,912	$33,221 ± 68,533	−4,070 (−4,938; −3,221)	<0.001
Hospitalization costs	$9,308 ± 30,719	$10,522 ± 34,270	−1,215 (−1,650; −769)	<0.001
ER visit costs	$3,478 ± 13,000	$4,017 ± 18,559	−539 (−763; −316)	<0.001
Outpatient visit costs	$14,219 ± 35,666	$16,092 ± 47,736	−1,874 (−2,498; −1,277)	<0.001
Outpatient hospital visit costs	$11,282 ± 31,210	$13,127 ± 44,493	−1,844 (−2,396; −1,356)	<0.001
Office/physician visit costs	$2,936 ± 14,729	$2,965 ± 15,213	−29 (−254; 239)	0.838
Other visit costs^d	$2,146 ± 8,633	$2,589 ± 13,258	−443 (−623; −255)	<0.001
Pharmacy costs	$6,159 ± 11,122	$6,626 ± 11,148	−467 (−648; −271)	<0.001
Weighted Cohorts
Observation period,^e days, mean ± SD [median]	396 ± 233 [355]	392 ± 234 [354]
All-cause total healthcare costs, PPPY, mean ± SD	$37,482 ± 60,515	$38,594 ± 66,681	−1,111 (−1,983; −255)	0.020
Total medical costs	$31,110 ± 58,132	$32,058 ± 64,695	−948 (−1,818; −69)	0.040
Hospitalization costs	$10,332 ± 32,890	$10,000 ± 33,363	333 (−158; 761)	0.140
ER visit costs	$3,914 ± 14,693	$3,810 ± 16,996	104 (−128; 353)	0.381
Outpatient visit costs	$14,381 ± 36,754	$15,786 ± 44,810	−1,405 (−1,990; −822)	<0.001
Outpatient hospital visit costs	$11,351 ± 31,936	$12,873 ± 41,537	−1,522 (−2,011; −1,000)	<0.001
Office/physician visit costs	$3,030 ± 15,368	$2,913 ± 14,761	117 (−108; 391)	0.321
Other visit costs^d	$2,482 ± 12,696	$2,462 ± 12,199	20 (−226; 283)	0.886
Pharmacy costs	$6,372 ± 12,324	$6,536 ± 10,979	−164 (−335; 26)	0.112

CI, confidence interval; ER, emergency room; PPPY, per patient per year; SD, standard deviation.

^aCosts were inflation-adjusted to US$2019 using the US Medical Care consumer price index from the Bureau of Labor Statistics from the US Department of Labor.

^bConfidence intervals and p-values were generated based on non-parametric bootstrap procedures with 499 replications.

^cThe observation period spanned from the index date to the earliest of: 18 months, end of continuous enrollment, death, or end of data availability.

^dIncludes visits such as home services and hospice.

^eThe observation period spanned from the index date to the earliest of: 24 months, end of continuous enrollment, death, or end of data availability.