Abstract
Objective:
Venous thromboembolism (VTE) impacts ∼900,000 individuals annually in the US, causing up to 100,000 deaths. Patients experiencing VTE have heightened risk of recurrence. Initial parenteral anti-coagulation is standard therapy for acute VTE followed by ≥3 months of warfarin, which introduces the risk of major bleeding. Balancing increased risks of bleeding and recurrent VTE remains challenging. Recent clinical trials suggest that rivaroxaban, an oral direct inhibitor of factor Xa, provides an effective, safe, simplified approach to treatment. This study considers the economic implications of these data.
Methods:
This study modeled inpatient, acute, and 1-year VTE costs for a hypothetical commercial plan with 1 million members. At baseline, all VTE patients receive standard therapy. Alternatively, 25% are instead treated with rivaroxaban. Model inputs are trial- and literature-based.
Results:
Standard therapy for VTE consumes 9474 inpatient days ($31.6 million). Added to that is treatment for 74 recurrences ($1.4 million); major and non-major bleed events ($1 million); and direct costs of anti-coagulation ($5.3 million). Alternatively, a 25% shift to oral anti-coagulation with rivaroxaban reduces inpatient days (by 5%); associated acute-care costs (by 2%); recurrences and costs (by 6%). Four major bleeding events are prevented, at the cost of one additional non-major bleeding event, which, taken together, reduce net utilization by 9%. Direct costs of anti-coagulation increase by 5%.
Conclusion:
The reduction in inpatient utilization, recurrences, and major bleeding resulting from a 25% shift from standard therapy to rivaroxaban following acute VTE would conserve ∼$860,475 for every 1 million commercial health plan enrollees.
Introduction
Deep-vein thrombosis (DVT) and pulmonary embolism (PE), together or separately, describe venous thromboembolism. As many as 900,000 peopleCitation1 are affected by DVT/PE each year in the US alone. Acute DVT/PE usually leads to hospitalization—an estimated 550,000 hospitalizationsCitation2 each year in the US—and can be fatalCitation3. The immediate goal of therapy for acute DVT/PE is to arrest the advancement of existing thrombiCitation4. This is usually accomplished with parenteral anti-coagulation using low-molecular-weight heparin (LMWH), fondaparinux, IV unfractionated heparin (UFH), or subcutaneous (SC) UFHCitation4–7. Longer-term therapeutic goals include secondary prevention, since patients who have experienced a first episode of DVT/PE have persistently elevated risk of new eventsCitation3,Citation8,Citation9. Toward this end, standard therapy usually overlaps and follows parenteral heparin with ≥3 months of warfarinCitation4. While warfarin prophylaxis is very effective for reducing the risk of DVT/PE recurrence, it introduces a risk of major bleeding as well as challenges to outpatient management (e.g., drug and food interactions; requirement for close patient monitoring and regular dose adjustments; individual variability in metabolism)Citation10. How best to balance the competing goals of preventing DVT/PE recurrence without introducing major bleeding is still a matter of clinical debateCitation10. Of related concern is the economic burdenCitation11–13 that acute hospitalization, anti-coagulation, re-admission, and extended outpatient management for DVT/PE place on health systems, which are motivated to emphasize safe and effective treatments for individual patients that are also cost-efficient within the context of the broader populations they serveCitation7.
Recent clinical trialsCitation5,Citation6,Citation14 have shown that rivaroxaban, a newly developed direct factor Xa inhibitor, is as effective as standard therapy for acute DVT/PE and, when continued into the outpatient setting, is effective in preventing recurrences while maintaining an acceptable risk of bleeding. As an orally active agent, rivaroxaban may also simplify therapy by overcoming the obstacles of parenteral anti-coagulation administration, and regular laboratory monitoring and dose adjustments made necessary by the use of warfarinCitation5,Citation6,Citation14. The goal of this study is to estimate the potential economic implications for a commercial health plan if these therapeutic obstacles in the care of patients with DVT/PE could be avoided.
Methods
We used a decision-analytic model constructed in Microsoft Excel to estimate the annual economic burden of acute and follow-up therapy for patients with DVT/PE in a hypothetical commercial plan. Decision analyses are commonly used to estimate the financial stream of consequences related to the uptake and diffusion of health technologiesCitation15. Increasingly, decision analyses are sought out by those who manage and plan healthcare budgets, such as administrators of national or regional healthcare programs or private insurance plans.
Our analysis was conducted from a health system perspective. It begins with a population of 1 million members in a hypothetical commercial health plan. Incidence and care patterns are set to approximate current clinical treatment patterns around the use of anti-coagulation for DVT and PE in the first year following an acute event, including care setting, length of hospital stay, and outpatient follow-up (). Estimates of therapeutic efficacy (DVT/PE recurrence) and safety (major bleed events; clinically relevant non-major bleed events) were drawn from recent clinical trialsCitation6,Citation14. Direct healthcare and anti-coagulation cost estimates are based on published literature, adjusted to 2013 US dollars, with the exception of drug costs (enoxaparin, warfarin, rivaroxaban), which reflect 2014 wholesale acquisition cost (WAC) pricing.
Table 1. Baseline model assumptions.
In the baseline (original) scenario, all patients with DVT/PE who receive drug therapy are assumed to be treated with a low molecular weight heparin (LMWH)/warfarin regimen per the current standard of care (). In the projected scenario (RIVA), a sub-set of treated patients are assumed to receive rivaroxaban in place of the standard regimen. Our starting assumption, for illustrative purposes, is that 25% of treated patients receive rivaroxaban; the remaining 75% of treated patients receive a standard LMWH/warfarin regimen. We report modeled results over a range of assumptions about the proportion of patients treated with rivaroxaban or standard therapy.
Results
DVT
In a hypothetical commercial health system with 1 million members, our baseline model considers that there would be 2110 patients with acute DVT over the course of a year, most (98%; n = 2068) of whom would receive drug treatment (). At baseline, where the model assumes that all patients receive acute care with a standard LMWH/warfarin regimen, an estimated 53.1% (n = 1098) would require acute care in the inpatient setting, with a mean length of stay (LOS) of 5.4 days (total of 5929 inpatient days). The remainder would be treated as outpatients. Direct care costs for treatment of these acute DVT events would consume ∼$33.2 million. The baseline analysis also anticipates 62 (3.0%) recurrent events, which would be treated at a cost of almost $1.2 million. Bleeding events (25 major events; 145 non-major events) would generate an additional $646,990 in direct healthcare utilization. The cost of anti-coagulation (LMWH, warfarin, laboratory monitoring) across the continuum of care adds an estimated $4 million. Together, this totals almost $39.1 million in direct care costs for patients with DVT.
Table 2. DVT and PE outcomes.
In the projected scenario—where the model assumes that 75% of patients receiving drug treatment for DVT would receive a standard LMWH/warfarin regimen, and 25% would receive rivaroxaban—total acute-care costs are an estimated $32.8 million, since slightly fewer (52.5%; n = 1085) cases would require acute care (mean LOS = 4.7 days; total of 5676 days) in the inpatient setting (). Recurrent events at 1 year would number 57 (2.8%), which would be treated at a cost of $1.1 million. Approximately two fewer (23) major bleed events would come at a cost of one more (146) clinically significant but non-major bleed events; management of these events would generate an additional $598,138 in direct healthcare utilization. Anti-coagulation (LMWH and warfarin with laboratory monitoring for 75% of patients; rivaroxaban, which does not require laboratory monitoring, for 25% of patients) in this scenario adds another $4.2 million. Taken together, this scenario projects an estimated $38.7 million in direct care costs for patients with DVT. Thus, the model estimates that shifting 25% of patients from a standard LMWH/warfarin regimen to RIVA would reduce inpatient and outpatient costs to treat DVT by ∼$376,000 (a savings of $182 per patient []).
PE
The same commercial health system is projected to encounter 1000 patients (0.10%) with PE over the course of 1 year, an estimated 364 of whom will expire at the time of the acute event before a decision to treat can be made (). Assuming the remaining 636 patients with PE receive a standard LMWH/warfarin regimen, the model anticipates that 572 (89.9%) will require acute inpatient care with a mean 6.2-day LOS (total of 3545 inpatient days), generating an estimated $12.2 million in inpatient care costs for the acute event. The remaining patients (10.1%) would be treated in the outpatient setting, costing another $916,327. Recurrent events (12 events; $222,348) and bleeding events (14 major; 62 non-major) add ∼$358,000; anti-coagulants (LMWH, warfarin) account for another $1.2 million. In all, the total 1-year direct care costs (acute care, recurrent PE, bleeding events, anti-coagulants) in this scenario are ∼$14.9 million for patients with PE.
If a portion (25%) of the 636 surviving patients with PE are instead treated with rivaroxaban (the remaining 75% receiving a standard LMWH/warfarin regimen), the model projects that one fewer patient would require inpatient treatment. With a mean LOS with rivaroxaban therapy of 4.5 days, increased use of rivaroxaban reduces the total number of inpatient days for the treated cohort by 244 during the acute event, generating ∼$551,000 savings in inpatient care costs for the acute event. Recurrent events (12 events; $229,984), bleeding events (12 major; 62 non-major; $315,666), and anti-coagulation ($1.3 million) bring the total 1-year direct care costs to $14.4 million for patients with PE. Thus, the model estimates that shifting 25% of patients from SOC to rivaroxaban would reduce inpatient and outpatient costs to treat PE by ∼$484,509 (a savings of $762 per patient []).
Overall (DVT and PE)
Taking the DVT and PE results together (), our baseline model projects that management of acute DVT/PE treatment (standard of care) would consume 9474 inpatient days (69% associated with DVT; 31% with PE) and nearly $31.6 million (2013 USD). Outpatient care for acute events would add ∼$15 million. Treatment for 74 recurrent events (84% DVT) would cost $1.4 million; major bleed events (39; 64% DVT) and non-major bleed events (207; 70% DVT) would require an additional $1 million to treat. Including the cost of anti-coagulation (LMWH, warfarin, laboratory monitoring), the total estimated cost of care for patients with DVT/PE in the SOC scenario exceeds $54 million.
In the projected (RIVA) scenario, a 25% shift to oral anti-coagulation with rivaroxaban reduced the number of inpatient days for acute management of DVT/PE to 8977 (63% DVT), a reduction of 497 days (5%). Associated inpatient and outpatient acute care costs totaled $45.4 million (72% DVT), a reduction of $937,000 (2%). Overall, recurrent events and costs were decreased by 6% (four events; $81,735). In the RIVA scenario, four (10%) major bleeding events were prevented, at the cost of one (0.5%) additional non-major bleeding event which, taken together, reduced net healthcare utilization to manage bleeding events by ∼$91,000. Including the cost of anti-coagulants (LMWH, warfarin, rivaroxaban), the total cost of care for patients with DVT/PE in the RIVA scenario was $53.7 million (a 2% reduction from baseline).
The model’s initial assumption that 25% of treated patients would receive rivaroxaban in place of a standard LMWH/warfarin regimen is merely an example. More, or fewer patients in a given commercial health plan might be managed using rivaroxaban. It is for these reasons that the model results given in are additive. Thus, our model anticipates that, compared to the baseline (100% LMWH/warfarin) scenario, a 26% (1% + 25%) shift to oral anti-coagulation with rivaroxaban would result in 517 days (20 + 497) inpatient management (a 5% reduction from the baseline scenario) and a $974,600 ($37,485 + $937,115) saving in total (inpatient and outpatient) care cost (a 2% reduction from baseline). Recurrent events would decrease by 4 (0.17 + 4.26); associated care costs of $85,000 ($3,270 + $81,735) for recurrent events represent a reduction of 6% compared to baseline. Overall, the 26% shift to oral anti-coagulation with rivaroxaban would prevent 4 (0.15 + 3.82) major bleeding events, offset by one additional (0.04 + 1.07) clinically relevant non-major bleeding event which, taken together, would reduce the net healthcare utilization to manage bleeding events by ∼$94,000 ($3634 + $90,837) compared to the baseline scenario in which all patients treated for DVT/PE receive a standard LMWH/warfarin regimen. Additionally, a 26% shift to oral anti-coagulation with rivaroxaban would require $259,180 ($9968 + $249,212) to cover the cost of anti-coagulation (LMWH, warfarin and laboratory monitoring; rivaroxaban). In all, the incremental difference of a 26% shift from LMWH/warfarin to rivaroxaban would represent savings of just under $900,000 ($34,421 + $860,475).
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).
Discussion
Venous thromboembolism (DVT/PE) introduces significant clinical and economic burdens to healthcare systemsCitation30, not only due to the need for acute treatment, but because individuals with DVT/PECitation1 are at increased risk of recurrent events. DVT/PE events can be fatalCitation3; indeed, about half of patients with acute DVT/PE are hospitalizedCitation2, owing to the need for parenteral therapy with LMWH.
In many cases, though, these hospitalizations may be longer than necessary. One study observed that, for a large proportion of patients with DVT/PE, hospital discharge was delayed (by a mean of 4.1 days) until parenteral therapy was discontinued, even though anti-coagulation might have been safely managed via the use of bridge therapy in an outpatient settingCitation31. Other studies have demonstrated similar findingsCitation32–36. These results point to a substantial missed economic opportunity to reduce hospital length-of-stay without compromising clinical outcomesCitation30,Citation31.
An array of pharmacoeconomics evaluations have attempted to quantify this opportunity in managed care and non-managed care settings. For example, a Canadian study of 39 patients with DVT estimated that the per-patient cost of inpatient parenteral anti-coagulation was $3266, compared with $584 per patient in a home care cohort treated with subcutaneous tinzaparin (1999 CAD; p < 0.00001)Citation37. A study of 201 patients in France found that outpatient LMWH treatment was associated with a 56% lower costs (1996 Fr) compared with inpatient LMWH treatmentCitation38. In each of these studies, the key cost saving factor for outpatient LMWH is the reduction in hospital stay or no need for any hospital-based careCitation30. At issue may be the clinical challenge of balancing the increased risks of major bleeding, the risk of recurrent events, and the complex management required to administer bridge therapy with warfarin, which itself introduces the risk of major bleedingCitation31. Still, outpatient treatment of DVT/PE offers an important opportunity to improve the overall cost-effectiveness of care for affected patients.
Recent clinical trials show that rivaroxaban, an oral direct inhibitor of factor Xa, is as effective as standard therapy for acute DVT/PE and, when continued into the outpatient setting, may provide an effective, safe, single-drug, and simplified approach to treatment. Our study used a decision-analytic model to estimate the potential economic implications for a commercial health plan resulting from increased use of rivaroxaban among a hypothetical cohort of patients with DVT/PE. Our model considers the implications of this shift in therapy for acute care as well as recurrent events and bleeding events in the year following the acute DVT/PE event. Rates of major bleed, non-major bleed, and recurrent events are estimated from clinical trials. DVT/PE prevalence and healthcare costs are drawn from published sources.
Our analysis suggests that, in a commercial health plan population of 1 million enrollees, if 25% of patients with DVT/PE were treated with rivaroxaban in place of a standard LMWH/warfarin regimen, the number of inpatient days for acute DVT/PE management would be reduced by 5% (497 days) and associated (inpatient and outpatient) care costs for the acute event would be reduced by 2% ($937,115). Recurrent DVT/PE events and costs would be decreased by 6% (four events; $82,000). In addition, four (10%) major bleeding events would be prevented, at the cost of one (0.5%) additional non-major bleeding event which, taken together, would reduce net healthcare utilization to manage bleeding events by ∼$91,000. Including the cost of anti-coagulants (LMWH, warfarin and laboratory monitoring; rivaroxaban), the total cost of care for patients with DVT/PE in this scenario would be reduced by 2% ($860,475). Economic benefits notwithstanding, any increase in bleeding events is not to be taken lightly. Further, because diagnosis-related bundled payments include many hospital services, savings may accrue to multiple stakeholders. Nevertheless, these results suggest a potentially important economic motivation to a health system for managing DVT/PE with agents that avoid obstacles to treatment in the outpatient setting.
Our model uses the example of rivaroxaban to estimate the magnitude of the opportunity to affect costs and outcomes in patients treated for DVT/PE. Our model is sensitive to several assumptions. First, the majority of the cost reduction in our analysis stems from the reduced inpatient length of stay associated with rivaroxaban compared to treatment with LMWH/warfarin that was demonstrated in US clinical trial data. Modeled results would be more extreme to the extent that lengths of stay for patients treated with LMWH/warfarin are longer than those observed in the US, as has been suggested by an analysis of global trial data collected in the EINSTEIN DVT and PE studiesCitation18. The same is true for the number of recurrent DVT/PE events as well as the net healthcare utilization required to manage bleeding events: the model will make more extreme forecasts to the extent that real-world differences between treatment with LMWH/warfarin and treatment with rivaroxaban are greater than those shown in the clinical trial experience cited here. In addition, while use of rivaroxaban obviates the need for the ongoing laboratory monitoring associated with the use of LMWH/warfarin, a comprehensive evaluation of drug costs is beyond the scope of this analysis. In general, novel anti-coagulants such as rivaroxaban have higher acquisition costs compared to warfarin, but potentially lower rates of adverse drug-related eventsCitation39 that may result in significant cost offsets. This hypothesis should be evaluated in rigorous models of therapeutic cost-effectiveness once data on the real-world performance of novel oral anti-coagulation become available.
Conclusion
Our model suggests that the reduction in inpatient utilization, recurrent events, and major bleed events resulting from a shift of 25% from standard therapy to oral anti-coagulation with rivaroxaban following an acute DVT/PE event would conserve ∼$860,475 for every 1 million members enrolled in a commercial health plan.
Transparency
Declaration of funding
This research was supported by Janssen Scientific Affairs, LLC.
Declaration of financial/other relationships
KO received consulting fees from Janssen Scientific Affairs, LLC for the development of this paper. AP and BB are employees of Janssen Scientific Affairs, LLC, a subsidiary of Johnson & Johnson (J&J). SM was an employee of Janssen Scientific Affairs, LLC at the time of this research. Janssen Pharmaceuticals, Inc. markets rivaroxaban.
Acknowledgments
The authors gratefully acknowledge Dr Nancy Neil for her writing assistance and support with the development of this manuscript.
References
- Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol 2008;28:370-2
- Centers for Disease Control and Prevention. Venous thromboembolism in adult hospitalizations - United States, 2007–2009. MMWR Morbidity and mortality weekly report 2012;61(22):401–4
- Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1-7
- Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e419S-94S . https://doi.org/http://www.ncbi.nlm.nih.gov/pubmed/22315268
- Prins MH, Lensing AW, Bauersachs R, et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thrombosis J 2013;11:21. https://doi.org/http://www.thrombosisjournal.com/content/11/1/21
- Buller HR, Prins MH, Lensin AW, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-97
- Bullano MF, Willey V, Hauch O, et al. Longitudinal evaluation of health plan cost per venous thromboembolism or bleed event in patients with a prior venous thromboembolism event during hospitalization. JMCP 2005;11:663-73
- Prandoni P, Villalta S, Bagatella P, et al. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients. Haematologica 1997;82:423-8
- Rodger MA, Kahn SR, Wells PS, et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ: Can Med Assoc Journal 2008;179:417-26
- Zhu T, Martinez I, Emmerich J. Venous thromboembolism: risk factors for recurrence. Arterioscler Thromb Vasc Biol 2009;29:298-310
- Lefebvre P, Laliberte F, Nutescu EA, et al. All-cause and potentially disease-related health care costs associated with venous thromboembolism in commercial, Medicare, and Medicaid beneficiaries. JMCP 2012;18:363-74
- MacDougall DA, Feliu AL, Boccuzzi SJ, et al. Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. AJHP: Off J Am Soc Health-System Pharm 2006;63(20 Suppl 6):S5-15
- Spyropoulos AC, Lin J. Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: an administrative claims analysis from 30 managed care organizations. JMCP 2007;13:475-86
- Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-510
- Mauskopf JA, Sullivan SD, Annemans L, et al. Principles of good practice for budget impact analysis: report of the ISPOR Task Force on good research practices—budget impact analysis. Value Health: J Int Soc Pharmacoecon Outcomes Res 2007;10:336-47
- Decision Resources. Venous Thromboembolism (January 2012). Data on file. Burlington, MA: 2012
- Heit JA, Silverstein MD, Mohr DN, et al. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study. Arch Intern Med 1999;159:445-53
- van Bellen B, Prins M, Bamber L, et al. Reduction in Initial Length of Stay with Rivaroxaban Single-Drug Regimen versus LMWH-VKA Standard of Care: Findings from the EINSTEIN Trial Program. Blood (ASH Annual Meeting Abstracts). 2012;120:Abstract 3419
- Bookhart BK, Haskell L, Bamber L, et al. Length of stay and economic consequences with rivaroxaban vs enoxaparin/vitamin K antagonist in patients with DVT and PE: findings from the North American EINSTEIN clinical trial program. J Med Econ 2014;17:691-5
- Agency for Healthcare Research and Quality (AHRQ). Healthcare Cost and Utilization Project (HCUP); Outcomes by ICD-9-CM diagnosis codes 451.11–451.19, 451.2, 453.40–453.42, 453.8–453.89, 453.9 (deep-vein thrombosis). 2010. Available at: http://hcupnet.ahrq.gov/HCUPnet.jsp?Parms=H4sIAAAAAAAAAKtMLE4sSvTzDDY0SHWJMEzMSjQxNUzyMzRM8oUwLDPAtBGQMk7yMzEAiYMYUAELKN_CEsK3TEuMdA1ODE5KTcoJcAxJTE5MyU7MTMtMBMI0CEjMSksFAGaE7yV3AAAAB240376632CFF7938732B923A9B8FA8046D6F964. Accessed July 24, 2013
- Spyropoulos AC, Hurley JS, Ciesla GN, et al. Management of acute proximal deep vein thrombosis: pharmacoeconomic evaluation of outpatient treatment with enoxaparin vs inpatient treatment with unfractionated heparin. Chest 2002;122:108-14
- Centers for Medicare & Medicaid Services (CMS). Medicare Physician Fee Schedule. 2011. Available at: http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/PFSlookup/index.html. Accessed November 18, 2013
- Centers for Medicare & Medicaid Services (CMS). Clinical Diagnostic Laboratory Fee Schedule. 2013. Available at: http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ClinicalLabFeeSched/clinlab.html. Accessed March 25, 2014
- Agency for Healthcare Research and Quality (AHRQ). National Health Care Expenses in the US Civilian Non-institutionalized Population, 2009, Statistical Brief #355. 2009. Available at: http://meps.ahrq.gov/mepsweb/data_files/publications/st355/stat355.pdf. Accessed September 4, 2012
- Analy$ource Online. Selected from NDDF data included with permission and copyrighted by First DataBank, Inc. 2014. Available at: http://www.analysource.com. Accessed March 11, 2014
- Truven Health Analytics. Red Book. 2012. Available at: http://micromedex.com/redbook. Accessed October 18, 2012
- Hirsh J, Fuster V, Ansell J, et al. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation 2003;107:1692-711
- Centers for Medicare & Medicaid Services (CMS). Clinical Diagnostic Physician Fee Schedule. 2013. Available at: http://www.cms.gov/apps/physician-fee-schedule/search/search-criteria.aspx. Accessed April 17, 2014
- Analy$ource Online. Selected from NDDF data included with permission and copyrighted by First DataBank, Inc. 2014. Available at: http://www.analysource.com. Accessed February 7, 2014
- Groce JB. Initial management of deep venous thrombosis in the outpatient setting. AJHP: Off J Am Soc Health-System Pharm 2008;65:866-74
- Tapson VF, Hyers TM, Waldo AL, et al. Antithrombotic therapy practices in US hospitals in an era of practice guidelines. Arch Intern Med 2005;165:1458-64
- Panis LJ, Gooskens M, Verheggen FW, et al. Predictors of inappropriate hospital stay: a clinical case study. Int J Quality Health Care J Int Soc Quality Health Care/ISQua 2003;15:57-65
- Arcelus JI, Caprini JA, Monreal M, et al. The management and outcome of acute venous thromboembolism: a prospective registry including 4011 patients. J Vasc Surg 2003;38:916-22
- Aujesky DA, Cornuz J, Bosson JL, et al. Uptake of new treatment strategies for deep vein thrombosis: an international audit. Int J Quality Health Care J Int Soc Quality Health Care/ISQua 2004;16:193-200
- Goldhaber SZ, Tapson VF. A prospective registry of 5451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004;93:259-62
- Smith BJ, Weekley JS, Pilotto L, et al. Cost comparison of at-home treatment of deep venous thrombosis with low molecular weight heparin to inpatient treatment with unfractionated heparin. Int Med J 2002;32:29-34
- Lee M, Pao D, Hsu T, et al. Cost savings and effectiveness of outpatient treatment with low molecular weight heparin of deep vein thrombosis in a community hospital. Can J Clin Pharmacol 2004;11:e17-27
- Boccalon H, Elias A, Chale JJ, et al. Clinical outcome and cost of hospital vs home treatment of proximal deep vein thrombosis with a low-molecular-weight heparin: the Vascular Midi-Pyrenees study. Arch Intern Med 2000;160:1769-73
- Miller CS, Grandi SM, Shimony A, et al. Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol 2012;110:453-60