The economic implications of switching to rivaroxaban from enoxaparin plus vitamin K antagonist in the treatment of venous thromboembolism

Figures & data

Table 1. Baseline model assumptions.

Item	Baseline input	Calculation/notes
Plan size	1,000,000	N/A
# DVT/PE cases annually16	DVT: 0.21% PE: 0.10%	The report estimates 315 DVT/PE (DVT 67%; PE 33%) cases per 100,000 in the US. 315 * 0.67 (% DVT cases) = 211 Annual rate of DVT = 211 cases/100,000 population = 0.21% 315 * 0.33 (% PE cases) = 104 Annual rate of PE = 104 cases/100,000 people = 0.10%
Proportion of DVT/PE patients who receive drug treatment	DVT: 98.0% PE: 63.6%	DVT: The report estimates 98% of DVT patients receive drug treatment16. PE: Day 0 Kaplan-Meier survival estimate for all PE (63.6%)17.
Clinical Management Strategy	DVT and PE: Standard of care (100%) Rivaroxaban (0%)	STANDARD OF CARE (SOC): The use of low molecular weight heparin and warfarin RIVAROXABAN (RIVA): regimen specified by the EINSTEIN trials6^,14
Proportion of acute DVT/PE patients hospitalized18	DVT: Standard of care (53.1%) Rivaroxaban (50.6%) PE: Standard of care (89.9%) Rivaroxaban (89.7%)	Outcomes reported in the EINSTEIN DV T14 and EINSTEIN PE6 trials.
Proportion of acute DVT/PE patients not hospitalized18	DVT: Standard of care (46.9%) Rivaroxaban (49.4%) PE: Standard of care (10.1%) Rivaroxaban (10.3%)	Outcomes reported in the EINSTEIN DV T14 and EINSTEIN PE6 trials.
Mean Length of Stay (LOS), in days18	DVT: Standard of care (5.4 days) Rivaroxaban (4.7 days) PE: Standard of care (6.2 days) Rivaroxaban (4.5 days)	Outcomes reported from the North American EINSTEIN clinical trial program19.
% DVT/PE Recurrence	DVT: Standard of care (3.0%) Rivaroxaban (2.1%) PE: Standard of care (1.8%) Rivaroxaban (2.1%)	Outcomes reported in the EINSTEIN DV T14 and EINSTEIN PE6 trials.
% Major Bleeding Events	DVT: Standard of care (1.2%) Rivaroxaban (0.8%) PE: Standard of care (2.1%) Rivaroxaban (1.1%)	Outcomes reported in the EINSTEIN DV T14 and EINSTEIN PE6 trials.
% Non-major Bleeding Events	DVT: Standard of care (7.0%) Rivaroxaban (7.3%) PE: Standard of care (9.8%) Rivaroxaban (9.5%)	Outcomes reported in the EINSTEIN DV T14 and EINSTEIN PE6 trials.
Acute DVT event, hospital setting	Inpatient day ($1893) Maintenance, post-discharge ($7423)	INPATIENT DAY ($1893 in 2013 USD)20. Estimate from AHRQ 2010 national statistics for ICD-9-CM diagnosis codes 451.11–451.19, 451.2, 453.40–453.42, 453.8–453.89, 453.9. Mean cost of hospital stay ($8304 in 2010 USD)/mean length of stay (4.8 days). Estimate inflated to 2013 USD using the medical care services CPI-Index; inflation factor of 1.0945. MAINTENANCE ($7423 in 2013 USD)21. Maintenance costs associated with LMWH (enoxaparin), minus pharmacy and laboratory costs. Cost inflated to 2013 USD using the medical care services CPI-Index; inflation factor of 1.756. Costs from Spyropoulos et al.21, in 1998 USD (specific CPT codes not specified in the source document): – Hospital facility: $1397 – Professional fees (consultations): $86 – Ambulatory care: $1394 – Outpatient surgery: $138 – Professional fees (consultations): $294 – Home healthcare: $358 – Hospice: $560
Acute PE event, hospital setting	Inpatient day ($2246) Maintenance ($7423)	INPATIENT DAY ($2246/day in 2013 USD)20. Estimate from AHRQ 2010 national statistics for ICD-9-CM diagnosis codes 415.11–415.19. Mean cost of hospital stay ($11,083 in 2010 USD)/mean length of stay (5.4 days) Estimate inflated to 2013 USD using the medical care services CPI-Index; inflation factor of 1.0945. MAINTENANCE ($7423 in 2013 USD)21. Maintenance costs associated with LMWH (enoxaparin), minus pharmacy and laboratory costs. Cost inflated to 2013 USD using the medical care services CPI-Index; inflation factor of 1.756. Costs from Spyropoulos et al.21, in 1998 USD (specific CPT codes not specified in the source document): – Hospital facility: $1397 – Professional fees (consultations): $86 – Ambulatory care: $1394 – Outpatient surgery: $138 – Professional fees (consultations): $294 – Home healthcare: $358 – Hospice: $560
Acute DVT/PE event, outpatient setting	Initiating treatment ($6842) Maintenance ($7423)	INITIATING THERAPY ($6842 in 2013 USD). From 2011 Medicare Physician Fee Schedule, inflated to 2013 USD; inflation factor = 1.0622 (2011 USD; CPT)22: – CT angiography ($445; avg. 71275 non-facility), – chest x-ray ($47; avg. 71010, 71015, 71020–23, 71030, 71034, 71035 non-facility), – ECG ($20; 93000 non-facility), – IVC filter insertion ($2751; 37191 non-facility), – IVC filter removal ($1761; 37193 non-facility). From 2013 Clinical Diagnostic Lab fee schedule23: – D-dimer ($14; CPT 85380 non-facility). From AHRQ National Health Care Expenses 200924: – Emergency Visit, ($1318 in 2009 USD, inflated to $1492 using the medical care component of the CPI; inflation factor 1.1318). MAINTENANCE ($7423 in 2013 USD)21. Maintenance costs associated with LMWH (enoxaparin), minus pharmacy and laboratory costs. Cost inflated to 2013 USD using the medical care services CPI-Index; inflation factor of 1.756. Costs from Spyropoulos et al.21, in 1998 USD (CPT codes not specified in the source document): – Hospital facility: $1397 – Professional fees (consultations): $86 – Ambulatory care: $1394 – Outpatient surgery: $138 – Professional fees (consultations): $294 – Home healthcare: $358 – Hospice: $560
Efficacy: Recurrent Events7	Recurrent (DVT/PE) event cost ($19,209)	Overall mean cost of a recurrent DVT/PE event ($12,326 in 2001 USD). Estimate inflated to 2013 USD using the medical care services CPI Index factor of 1.5584.
Safety: Bleed Events7	Major bleeding ($23,904)	Mean cost of bleed event ($15,339 in 2001 USD). Estimate inflated to 2013 USD using the medical care services CPI-Index; inflation factor of 1.5584.
Safety: Bleed Events7	Clinically relevant non-major bleeding ($372)	Mean cost of a bleed event ($239 in 2001 USD). Estimate inflated to 2013 USD using the medical care services CPI-Index; inflation factor of 1.5584.
Anticoagulation: Duration of therapy following acute event (DVT)	3-month: 11.9% 6-month: 62.8% 12-month: 25.3%	Following an acute DVT event, patients may receive 3-, 6-, or 12-months of anti-coagulation therapy. Estimates drawn from the EINSTEIN DVT trial14.
Anticoagulation: Duration of therapy following acute event (PE)	3-month: 5.2% 6-month: 57.4% 12-month: 37.4%	Following an acute PE event, patients may receive 3-, 6-, or 12-months of anti-coagulation therapy. Estimates drawn from the EINSTEIN PE trial6.
Anticoagulation: Standard of Care (SOC)	LMWH, daily cost ($88) warfarin, monthly cost ($3.60)	Patients who receive standard of care (SOC) are assumed to receive 8 days of LMWH plus 3-, 6-, or 12-months of generic warfarin. LMWH, daily cost25: Assume 8 days of LMWH therapy, and 80 mg BID (average weight of 80 kg; observed average weight in the EINSTEIN trial6^,14 slightly higher). Model value of $88. Warfarin, monthly cost26: Warfarin 1 mg daily cost is $0.12/day. Monthly cost calculated as ($0.12 * 30 days * 12 months) = $3.60. Model value of $0.12 adjusted to 2013 USD using the medical care component of CPI (inflation factor = 1.0246).
Anticoagulation: SOC outpatient monitoring cost	Anticoagulation visit with prothrombin time and international normalized ratio ($69.70)	Schedule of anti-coagulation clinic visits and laboratory testing for Prothrombin Time and International Normalized Ratio (PT with INR)27: SOC treatment initiation (outpatients only): The model assumes seven anti-coagulation visits with INR test in the first 2 weeks following the start of warfarin. SOC treatment monitoring (all patients): Two anti-coagulation visits with INR test are assumed for each month of warfarin therapy after treatment initiation. Total tests (SOC arm only) are 6 tests (3-month regimen); 12 tests (6-month regimen) and 24 tests (12-month regimen). From 2013 Physician Fee Schedule28: – Office/outpatient visit established ($20.41, CPT 99211 non-facility; $43.89, CPT 99212 non-facility). From 2013 Clinical Diagnostic Lab fee schedule23: – PT with INR ($5.40; CPT 85610 non-facility).
Anticoagulation: rivaroxaban (RIVA)	RIVA 15 mg BID, daily cost ($19.10) RIVA 20 mg QD, daily cost ($9.55)	Patients who receive RIVA are assumed to receive 21 days of RIVA 15 mg BID plus 69 days (3-months), 159 days (6-months) or 339 days (12-months) of RIVA 20 mg QD. Cost of RIVA regimen (2014 USD)29: RIVA 15 mg BID regimen: $9.55 *2. RIVA 20 mg QD regimen $9.55.

Table 2. DVT and PE outcomes.

	Treated DVT (n = 2068)			Treated PE (n = 636)
	Original scenario	Projected scenario (switching 25% to RIVA)	Difference	Original scenario	Projected scenario (switching 25% to RIVA)	Difference
% Patients treated with:
Standard of Care (LMWH/warfarin)	100%	75%	–	100%	75%	–
Rivaroxaban	0%	25%	–	0%	25%	–
Acute event
Inpatient setting
Count: Patients (#, %)	1098 [53.1%]	1085 [52.5%]	(13)	572 [89.9%]	571 [89.8%]	(1)
Inpatient days	5929	5676	(253)	3545	3301	(244)
Sub-total: inpatient	$19,374,461	$18,799,804	($574,657)	$12,206,132	$11,654,781	($551,351)
Outpatient setting
Count: Patients (#, %)	970 [46.9%]	983 [47.5%]	13	64 [10.1%]	65 [10.2%]	1
Subtotal: outpatient	$13,834,171	$14,018,529	$184,358	$916,327	$920,862	$4535
Total: Acute events	$33,208,632	$32,818,333	($390,299)	$13,122,459	$12,575,643	($546,816)
Recurrent events
Count: Events (#, %)	62.03 [3.0%]	57.38 [2.8%]	(4.65)	11.58 [1.8%]	11.97 [1.9%]	0.4
Total: Recurrent events	$1,191,611	$1,102,240	($89,371)	$222,348	$229,984	$7636
Bleeding events
Count: Major Bleeds (#, %)	24.81 [1.2%]	22.75 [1.1%]	(2.07)	13.99 [2.2%]	12.24 [1.9%]	(1.75)
Sub-total major bleeds	$593,144	$543,716	($49,428)	$334,465	$292,657	($41,808)
Count: Non-major Bleeds (#, %)	144.75 [7.0%]	146.30 [7.1%]	1.55	62.33 [9.8%]	61.85 [9.7%]	(0.48)
Sub-total non-major bleeds	$53,846	$54,422	$576	$23,186	$23,009	($177)
Total: Bleed events	$646,990	$598,138	($48,852)	$357,651	$315,666	($41,985)
Anti-coagulation
Standard of Care (LMWH/warfarin)	$1,509,027	$1,131,770	($377,257)	$466,262	$349,697	($116,566)
Standard of Care (monitoring)*	$2,536,890	$1,902,668	($634,223)	$748,410	$561,307	($187,102)
Rivaroxaban	$0	$1,164,036	$1,164,036	$0	$400,324	$400,324
Total: Anti-coagulation	$4,045,917	$4,189,473	$152,556	$1,214,672	$1,311,328	$96,656
Grand total	$39,093,150	$38,717,184	($375,966)	$14,917,130	$14,432,621	($484,509)

2013 USD. DVT, deep vein thrombosis; LMWH, low molecular weight heparin; PE, pulmonary embolism; RIVA, rivaroxaban.

*Anti-coagulation clinic visit and prothrombin time with international normalized ratio laboratory monitoring.

Figure 1. Per patient costs of DVT over 1 year. *Original scenario (100% LMWH/warfarin): 1-year total = $18,904; **Projected scenario (75% LMWH/warfarin; 25% RIVA): 1-year total = $18,722. 2013 USD. DVT, deep vein thrombosis; LMWH, low molecular weight heparin; PE, pulmonary embolism; RIVA, rivaroxaban.

Figure 2. Per patient costs of PE over 1 year. *Original scenario (100% LMWH/warfarin): 1-year total = $23,455; **Projected scenario (75% LMWH/warfarin; 25% RIVA): 1-year total = $22,693. 2013 USD. DVT, deep vein thrombosis; LMWH, low molecular weight heparin; PE, pulmonary embolism; RIVA, rivaroxaban.

Table 3. Effect on direct care of a shift to oral anti-coagulation with rivaroxaban (treated DVT/PE).

	Standard of care	Effects of a shift to oral anti-coagulation with rivaroxaban
% of patients on therapy	100%	1%	5%	10%	25%
Acute DVT/PE event
Inpatient setting
LOS (days)	9474	(20)	(99)	(199)	(497)
In hospital ($)	$31,580,593	($45,040)	($225,201)	($450,403)	($1,126,008)
Outpatient setting
Outpatient ($)	$14,750,498	$7,555	$37,779	$75,557	$188,893
Total: Acute DVT/PE	$46,331,091	($37,485)	($187,422)	($374,846)	($937,115)
Efficacy
Recurrent events following acute DVT/PE (#)	73.61	(0.17)	(0.85)	(1.70)	(4.26)
Recurrent events following acute DVT/PE ($)	$1,413,959	($3270)	($16,347)	($32,694)	($81,735)
Safety (1 year)
Major bleed events (#)	38.81	(0.15)	(0.76)	(1.53)	(3.82)
Major bleed events ($)	$927,609	($3650)	($18,247)	($36,494)	($91,236)
Non-major bleed events (#)	207.07	0.04	0.21	0.43	1.07
Non-major bleed events ($)	$77,032	$16	$80	$159	$399
Total: Bleed event costs	$1,004,641	($3634)	($18,167)	($36,335)	($90,837)
Anti-coagulation
Standard of Care (LMWH/warfarin)	$1,975,289	($19,753)	($98,764)	($197,529)	($493,822)
Standard of Care (monitoring)*	$3,285,300	($32,853)	($164,256)	($328,530)	($821,325)
Rivaroxaban	–	$62,574	$312,872	$625,744	$1,564,360
Total: Anticoagulation	$5,260,589	$9968	$49,842	$99,685	$249,212
Incremental difference in cost following shift to rivaroxaban	–	($34,421)	($172,094)	($344,190)	($860,475)

2013 USD. DVT, deep vein thrombosis; LOS, length of stay; PE, pulmonary embolism; VTE, venous thromboembolism.

*Anti-coagulation clinic visit with prothrombin time and international normalized ratio laboratory monitoring.

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