A tale of two centers: Is low-molecular-weight heparin really superior for prevention of posttraumatic venous thromboembolism?

BACKGROUND: Low-molecular-weight heparin (LMWH) is widely used for venous thromboembolism chemoprophylaxis following injury. However, unfractionated heparin (UFH) is a less expensive option. We compared LMWH and UFH for prevention of posttraumatic deep venous thrombosis (DVT) and pulmonary embolism (PE). METHODS: Trauma patients 15 years or older with at least one administration of venous thromboembolism chemoprophylaxis at two level I trauma centers with similar DVT-screening protocols were identified. Center 1 administered UFH every 8 hours for chemoprophylaxis, and center 2 used twice-daily antifactor Xa-adjusted LMWH. Clinical characteristics and primary chemoprophylaxis agent were evaluated in a two-level logistic regression model. Primary outcome was incidence of DVT and PE. RESULTS: There were 3,654 patients: 1,155 at center 1 and 2,499 at center 2. The unadjusted DVT rate at center 1 was lower than at center 2 (3.5% vs. 5.0%; p = 0.04); PE rates did not significantly differ (0.4% vs. 0.6%; p = 0.64). Patients at center 2 were older (mean, 50.3 vs. 47.3 years; p < 0.001) and had higher Injury Severity Scores (median, 10 vs. 9; p < 0.001), longer stays in the hospital (mean, 9.4 vs. 7.0 days; p < 0.001) and intensive care unit (mean, 3.0 vs. 1.3 days; p < 0.001), and a higher mortality rate (1.6% vs. 0.6%, p = 0.02) than patients at center 1. Center 1's patients received their first dose of chemoprophylaxis earlier than patients at center 2 (median, 1.0 vs. 1.7 days; p < 0.001). After risk adjustment and accounting for center effects, primary chemoprophylaxis agent was not associated with risk of DVT (odds ratio, 1.01; 95% confidence interval, 0.69-1.48; p = 0.949). Cost calculations showed that UFH was less expensive than LMWH. CONCLUSION: Primary utilization of UFH is not inferior to LMWH for posttraumatic DVT chemoprophylaxis and rates of PE are similar. Given that UFH is lower in cost, the choice of this chemoprophylaxis agent may have major economic implications. LEVEL OF EVIDENCE: Prognostic and epidemiological, level II; Therapeutic, level III.

[The cost of pulmonary thromboembolism treatment]. / Pulmoner tromboemboli tedavisinde maliyet.

INTRODUCTION: Primary aim of this study is to determine the financial burden of Vitamin K Antagonists (VKA), low molecular weight heparins (LMWH) and new oral anticoagulants (NOAC) which are used in the treatment of the pulmonary thromboembolism (PTE). Secondary aim is to show long term complications of the treatment options. MATERIALS AND METHODS: The patients who are diagnosed with PTE between May 2016 and March 2018 at Faculty of Medicine Karadeniz Technical University Hospital were observed prospectively. Hospitalization costs were calculated on patients who were treated only for PTE by hospitalized in the Chest Diseases Service in the acute period. Maintenance costs were calculated over all patients who regulary admitted to our outpatient clinic with the diagnosis of PTE. Data were presented as mean ± SD and median ± interquartilee range. A p-value of <0.05 was accepted to be significant. RESULT: Fifty five (37.2%) of the patients were male, 93 (62.8%) were female and the median age was 68 (range 18-95). The median hospitalization time and cost of patients who are discharged with VKA (n: 22) compared with patients discharged with LMWH (n: 22) was found to be increased (1316.82 TL 7,5 days / 803.36 TL, 5 days p<0.001). Statistical analysis could not be performed with NOAC (n: 2). In the analysis of sixth month costs, LMWH cost was found to be higher than VKA cost (6.927.15 ± 2.687.67 TL/698.29 ± 483.51 TL p<0.001). However VKA treatment tended to be less expensive than treatment with NOACs (698.29 ± 483.51 TL/1.050.81 ± 300.28 TL p= 0.140). CONCLUSIONS: In the acute period of PTE, VKA increases the length of hospitalization and hospital costs in patients treated at the hospital. In the maintenance period, VKA tends to have a lower cost compared to NOACs.

Are direct oral anticoagulants an economically attractive alternative to low molecular weight heparins in lung cancer associated venous thromboembolism management?

Venous thromboembolism is highly prevalent in lung cancer patients. Low molecular weight heparins are recommended for long term treatment of cancer associated venous thromboembolism. Direct oral anticoagulants are however an interesting alternative as they are administered orally and don't require monitoring. There are currently studies comparing both their efficacy and tolerance for cancer patients and more and more guidelines suggest considering direct oral anticoagulants for cancer associated venous thromboembolism treatment. The objective of this study was to evaluate the budgetary impact that direct oral anticoagulants use would have for lung cancer associated venous thromboembolism treatment and prevention in France. An economic model was made to evaluate the cost of venous thromboembolism treatment and prevention among patients with primary lung cancer in France by two strategies: current guidelines versus direct oral anticoagulants use. The model was fed with clinical and economic data extracted from the French national health information system. The analysis was conducted from the national mandatory Health insurance point of view. The time horizon of the study was the evaluation of the annual management cost. Lung cancer associated venous thromboembolism management's mean cost was estimated of 836€ per patient, that is a total cost of about 40 million euros per year at a national level. A 76% decrease of this cost can be expected with direct oral anticoagulants use. However, despite their benefits, these treatments raise new issues (medication interactions, bleeding management), and would likely not be recommended for all patients.

Total costs of treating venous thromboembolism: implication of different cost perspectives in a Danish setting.

Aim: Optimal use of scarce resources is a focus in the healthcare sector, as resources devoted to health care are limited. Costs and health economic analyses can help guide decision-making concerning treatments. One important factor is the choice of cost perspective that can range from a focus on narrow drug budget costs to broader economic perspectives. In the case of treatment with oral anticoagulants in patients with venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, the aim of this cost analysis was to illustrate the differences in costs when applying different cost perspectives.Methods: In a cost analysis, pairwise comparisons of average costs of 6 months standard treatment with either a low molecular weight heparin parenteral anticoagulant (LMWH) and a Vitamin K Antagonist (VKA) versus one of the non-vitamin K oral anticoagulants [NOACs; dabigatran etexilate, rivaroxaban, apixaban, and edoxaban) used in daily clinical practice in Denmark for VTE patients were carried out. Each analysis included the results from five different cost analyses with increasingly broader cost perspectives going from the narrowest "drug cost only" perspective to the broadest "societal" perspective.Results: Focusing on "drug costs only", LMWH/VKA was associated with the lowest costs compared to all NOACs. However, including the economic impact of preventing recurrent VTE and limit bleedings, apixaban and rivaroxaban resulted in slightly lower health care costs than LMWH/VKA. When applying the "societal perspective", the total costs saved with apixaban and rivaroxaban compared to LMWH/VKA further increased, with apixaban having the lowest total costs.Conclusions: The present study's case of oral anticoagulants in VTE treatment illustrated the importance of the cost perspective in the choice of therapy. If decision-making were based on drug costs only, instead of applying a health care sector or societal cost perspective, suboptimal decisions may be likely.

A Review of Two Heparin Prophylaxes for Trauma.

Venous thromboembolism (VTE) prophylaxis has a significant impact on mortality and morbidity in trauma patients. This article reviews 9 published studies that investigate and compare low-dose unfractionated heparin (LDUH) with low-molecular-weight heparin (LMWH) for prophylaxis of VTE in the trauma patient population in terms of efficacy, safety, and cost. There is no difference between LDUH and LMWH for VTE prophylaxis. Four databases were utilized to find 9 relevant studies whose patient population was adult trauma patients: PubMed, CINAHL, EMBASE and Scopus. Two studies found statistically significant differences in deep venous thrombosis, and 3 found differences in pulmonary embolism between LDUH and LMWH. Only 1 study demonstrated a significant difference in bleeding complications between the 2 treatment regimens. Two statedthat using LDUH resulted in remarkable cost savings versus LMWH. The 9 studies all came to different conclusions. Contrary findings may have been affected by population variety, different dosing regimens, various applications of mechanical VTE prophylaxis, and/or different VTE-screening tools. All of the studies had major variances leading to conflicting results, which made this review unable to draw concrete conclusions. Limitations of each study, population variety, and disparity of dosing regimens made it difficult for this review to make recommendations for practice.

Impact of removal and restriction of me-too medicines in a hospital drug formulary on in- and outpatient drug prescriptions: interrupted time series design with comparison group.

BACKGROUND: The study covered in- and out-of-hospital care in a region in north-western Spain. The intervention evaluated took the form of a change in the hospital drugs formulary. Before the intervention, the formulary contained four of the five low molecular weight heparins (LMWHs) marketed in Spain. The intervention consisted of withdrawing two LMWHs (bemiparin and dalteparin) from the formulary and restricting the use of another (tinzaparin), leaving only enoxaparin as an unrestricted prescription LMWH. Accordingly, the aim of this study was to evaluate the effect on in- and outpatient drug prescriptions of removing and restricting the use of several LMWHs in a hospital drugs formulary. METHODS: We used a natural, before-after, quasi-experimental design with a control group and monthly data from January 2011 to December 2016. Based on data drawn from official Public Health Service sources, the following dependent variables were extracted: defined daily doses (DDD) per 1000 inhabitants per day (DDD/TID), DDD per 100 stays per day, and expenditure per DDD. RESULTS: The two compounds that were removed from the formulary registered an immediate decrease at both an intra- and out-of-hospital level (66.6% and 55.6% for bemiparin and 73.0% and 92.2% for dalteparin, respectively); similarly, the compound that was restricted also registered an immediate decrease (36.1% and 9.0% at the in- and outpatient levels, respectively); in contrast, the remaining LMWH (enoxaparin) registered an immediate, significant increase at both levels (44.9% and 32.6%, respectively). The intervention led to an immediate reduction of 6.8% and a change in trend in out-of-hospital cost/DDD; it also avoided an expenditure of €477,317.1 in the 21 months following the intervention. CONCLUSIONS: The results indicate that changes made in a hospital drugs formulary towards more efficient medications may lead to better use of pharmacotherapeutic resources in its health catchment area.

Healthcare resource utilization and costs associated with venous thromboembolism in cancer patients treated with anticoagulants.

Objective: The standard of care for cancer-related venous thromboembolism (VTE) has been low molecular weight heparin (LMWH), but oral anticoagulants are also widely prescribed. This study compared VTE-related healthcare resource utilization and costs of cancer patients treated with anticoagulants. Methods: Claims data from Humana Database (January 1, 2013-May 31, 2015) were analyzed. Based on the first anticoagulant received, patients were classified into LMWH, warfarin, or rivaroxaban cohorts. Characteristics were evaluated during the 6 months pre-index date (i.e. the first VTE); VTE-related resource utilization and costs were evaluated during follow-up. Cohorts were compared using rate ratios, and p-values and 95% confidence intervals were calculated. Healthcare costs were evaluated per-patient-per-year (PPPY) and compared using mean cost differences. Results: A total of 2,428 patients (LMWH: n = 660; warfarin: n = 1,061; rivaroxaban: n = 707) were included. Compared to patients treated with LMWH, patients treated with rivaroxaban had significantly fewer VTE-related hospitalizations, hospitalization days, and emergency room and outpatient visits, resulting in an increase of $12,000 VTE-related healthcare costs PPPY with LMWH vs rivaroxaban. Patients treated with rivaroxaban had significantly lower VTE-related resource utilization compared to patients treated with warfarin; however, VTE-related costs were similar between cohorts. The higher drug costs ($1,519) were offset by significantly lower outpatient (-$1,039) and hospitalization costs (-$522) in rivaroxaban relative to the warfarin cohort. Conclusions: Healthcare resource use and costs associated with VTE treatment in cancer patients are highest with LMWH relative to warfarin and rivaroxaban.

Barriers and facilitators to adopting high value practices and de-adopting low value practices in Canadian intensive care units: a multimethod study.

OBJECTIVE: To compare and contrast illustrative examples of the adoption of high value practices and the de-adoption of low value practices. DESIGN: (1) Retrospective, population-based audit of low molecular weight heparin (LMWH) for venous thromboembolism (VTE) prophylaxis (high value practice) and albumin for fluid resuscitation (low value practice) and (2) cross-sectional survey of healthcare providers. SETTING: Data were collected from nine adult medical-surgical intensive care units (ICUs) in two large Canadian cities. Patients are managed in these ICUs by a group of multiprofessional and multidisciplinary healthcare providers. PARTICIPANTS: Participants included 6946 ICU admissions and 309 healthcare providers from the same ICUs. MAIN OUTCOME MEASURES: (1) The use of LMWH for VTE prophylaxis (per cent ICU days) and albumin for fluid resuscitation (per cent of patients); and (2) provider knowledge of evidence underpinning these practices, and barriers and facilitators to adopt and de-adopt these practices. RESULTS: LMWH was administered on 38.7% of ICU days, and 20.0% of patients received albumin.Most participants had knowledge of evidence underpinning VTE prophylaxis and fluid resuscitation (59.1% and 84.2%, respectively). Providers perceived these practices to be followed. The most commonly reported barrier to adoption was insufficient knowledge/understanding (32.8%), and to de-adoption was clinical leader preferences (33.2%). On-site education was the most commonly identified facilitator for adoption and de-adoption (67.8% and 68.6%, respectively). CONCLUSIONS: Despite knowledge of and self-reported adherence to best practices, the audit demonstrated opportunity to improve. Provider-reported barriers and facilitators to adoption and de-adoption are broadly similar.

Comparative effectiveness of direct oral anticoagulants versus low-molecular weight heparins for the prevention of venous thromboembolism after total hip or knee replacement: A nationwide database cohort study.

BACKGROUND: Venous thromboembolism (VTE) after total knee or hip replacement (TKR, THR) is usually prevented with low-molecular weight heparin (LMWH), and increasingly by direct oral anticoagulants (DOAC). The aim of the present study was to compare the benefit-risk and medical costs of DOAC vs. LMWH in a real-life setting. METHODS: All patients with THR or TKR in France between Jan-1st 2013 and Sep-30th 2014, discharged to home, were identified and followed-up for 3 months in the French nationwide claims database, SNDS. DOAC users were 1:1 matched with LWMH users on gender, age and propensity score. Relative risks (RR) of hospitalized VTE, hospitalized bleeding and death were estimated using quasi-Poisson models. Medical costs were calculated according to the societal perspective, including total cost for outpatient claims and national DRG costs for hospitalisations. RESULTS: Most DOAC users (≥ 98.8%) were matched to a LMWH patient. For the 63,238 matched THR patients, the 3-month absolute risk of VTE was 0.9‰ with DOAC and 2.5‰ with LMWH (RR = 0.35 [0.23 to 0.54]), of bleeding 1.8‰ and 2.1‰ (0.88 [0.62-1.25]), death 0.7‰ and 1.1‰ (0.68 [0.40-1.15]). For the 31,440 matched TKR patients, risks were 1.6‰ and 2.3‰ (0.69 [0.42-1.16]) for VTE, 2.4‰ and 3.8‰ (0.64 [0.43 to 0.97]) for bleeding, and 0.6‰ and 0.8‰ (0.69 [0.30-1.62]) for all-cause death. Mean medical costs were 28% and 21% lower with DOAC than LMWH for THR and TKR, respectively. This nationwide study found a very low risk of VTE, hospitalized bleeding and death after THR or TKR discharge in patients with VTE prevention in real-life setting, with better benefit-risk profiles of DOAC compared to LMWH, and associated cost savings.

Routine Use of Low-Molecular-Weight Heparin For Deep Venous Thrombosis Prophylaxis After Foot and Ankle Surgery: A Cost-Effectiveness Analysis.

The purpose of the present study was to determine whether certain foot/ankle surgeries would benefit from the routine use of low-molecular-weight heparin (LMWH) as postoperative deep venous thrombosis prophylaxis. We conducted a formal cost-effectiveness analysis using a decision analytic tree to explore the healthcare costs and health outcomes associated with a scenario of no prophylaxis and a scenario of routine LMWH prophylaxis for 4 weeks. The 2 scenarios were compared for 5 procedures: (1) Achilles tendon repair (ATR), (2) total ankle arthroplasty (TAA), (3) hallux valgus surgery (HVS), (4) hindfoot arthrodesis (HA), and (5) ankle fracture surgery (AFS). The outcomes assessed included short- and long-term costs, quality-adjusted life-years (QALYs), and incremental cost per QALY gained. The costs were evaluated from the healthcare system perspective and are expressed in U.S. dollars at a 2015 price base. In the short term, routine prophylaxis was always associated with greater costs compared with no prophylaxis. For ATR, TAA, HA, and AFS, prophylaxis was associated with slightly better health outcomes; however, the gain in QALYs was minimal compared with the cost of prophylaxis (incremental cost-effectiveness ratio well above $50,000/QALY threshold). For HVS, prophylaxis was associated with both worse health outcomes and greater costs. In the long term, routine prophylaxis was always associated with worse health outcomes and either cost more (HA, AFS, HVS) or saved very little (ATR, TAA). We concluded that policies encouraging the routine use of LMWH after foot/ankle surgery are unlikely to be cost-effective. Decisions to perform prophylaxis should be on a case-by-case basis and should emphasize individual patient risk factors.

Advances in managing and preventing thromboembolic disease in cancer patients.

PURPOSE OF REVIEW: To update on new data for low-molecular weight heparins (LMWHs) and the direct oral anticoagulants (DOACs) for the treatment and prevention of cancer-associated thrombosis (CAT), to discuss progress with the risk-adaptive management scores (RAMS) and update on increased dose primary thromboprophylaxis (IDPTP). RECENT FINDINGS: In a pooled meta-analysis of 1132 cancer patients who received DOACs vs. vitamin K analogues (VKAs), recurrence of venous thromboembolism (VTE) was reduced from 6.0% on VKA schedules to 3.9% on DOACs. In a randomized trial of warfarin vs. once daily sc. tinzaparin (175 IU/kg), cumulative 6-month VTE incidence reduced from 10.5 to 7.2% [hazard ratio, 0.65 (95% confidence interval, 0.41-1.03); P = 0.07]. Despite early suggestions that DOACs may have a role in CAT, 3-6 months of LMWH remain the standard for initial treatment of CAT. A prospective comparison of RAMS found the Vienna CATS or the PROTECHT scores superior to the Khorana score but concluded that RAMS did not perform well enough to be used in the clinic. An efficacy scale of LMWHs in pancreatic cancer facilitates IDPTP. Practical implementation of IDPTP was needed to control the 40% VTE incidence of the HALO-109-202 study in metastatic pancreatic cancer. SUMMARY: DOACs have some encouraging data, but LMWHs remain the standard for CAT treatment. RAMS generated to predict VTE occurrence or recurrence are still of unproven significance and IDPTP for advanced pancreatic cancer has tools and guidance for implementation.

Cost-effectiveness analysis of rivaroxaban for treatment and secondary prevention of venous thromboembolism in the Netherlands.

BACKGROUND: Until recently, standard treatment of venous thromboembolism (VTE) concerned a combination of short-term low-molecular-weight heparin (LMWH) and long-term vitamin-K antagonist (VKA). Risk of bleeding and the requirement for regular anticoagulation monitoring are, however, limiting their use. Rivaroxaban is a novel oral anticoagulant associated with a significantly lower risk of major bleeds (hazard ratio = 0.54, 95% confidence interval = 0.37-0.79) compared to LMWH/VKA therapy, and does not require regular anticoagulation monitoring. AIMS: To evaluate the health economic consequences of treating acute VTE patients with rivaroxaban compared to treatment with LMWH/VKA, viewed from the Dutch societal perspective. METHODS: A life-time Markov model was populated with the findings of the EINSTEIN phase III clinical trial to analyze cost-effectiveness of rivaroxaban therapy in treatment and prevention of VTE from a Dutch societal perspective. Primary model outcomes were total and incremental quality-adjusted life years (QALYs), as well as life expectancy and costs. RESULTS: Over a patient's lifetime, rivaroxaban was shown to be dominant, with health gains of 0.047 QALYs and cost savings of €304 compared to LMWH/VKA therapy. Dominance was robustly present in all sensitivity analyses. Major drivers of the differences between the two treatment arms were related to anticoagulation monitoring (medical costs, travel costs, and loss of productivity) and the occurrence of major bleeds. CONCLUSION: Rivaroxaban treatment of patients with venous thromboembolism results in health gains and cost savings compared to LMWH/VKA therapy. This conclusion holds for the Dutch setting, both for the societal perspective, as well as the healthcare perspective.

Cost-effectiveness Analysis for Apixaban in the Acute Treatment and Prevention of Venous Thromboembolism in the Netherlands.

PURPOSE: Low-molecular weight heparin (LMWH) followed by vitamin K antagonists (VKAs) are the current standard treatment of acute venous thromboembolism (VTE) and prevention of recurrent VTE. The direct oral anticoagulant apixaban was recently found noninferior in efficacy and superior in preventing major bleeding compared with LMWH/VKAs in the AMPLIFY (Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy) trial. The objective of this study was to calculate the cost-effectiveness of apixaban compared with LMWH/VKA in the treatment of acute VTE and prevention of recurrent VTE in the Netherlands. METHODS: A Markov model was designed to simulate a cohort of 1,000 VTE patients receiving either apixaban or LMWH/VKA. Transition probabilities, costs, and utilities were obtained from the AMPLIFY trial and other literature. The incremental cost-effectiveness ratio (ICER) was calculated from the societal perspective; therefore, the model included both direct (inside and outside the health care sector) and indirect costs. In the univariate and probabilistic sensitivity analyses (PSAs) the robustness of the results was tested, and various additional scenario analyses were conducted. FINDINGS: In the base-case analysis, apixaban saved €236 and 0.044 quality-adjusted life years (QALYs) and 0.039 LYs were gained compared with LMWH/VKA. In the univariate sensitivity analysis the model appeared to be robust. The results of 2,000 iterations in the PSA found that the probability of apixaban being cost-effective at a willingness-to-pay threshold of €20,000/QALY was 100% and cost-saving was 94%. The scenario of 18-month treatment duration was the only scenario not indicating cost-savings with an ICER of €425/QALY. IMPLICATIONS: In acute anticoagulation use apixaban was found to be cost-saving. A longer anticoagulation period (18 months) resulted in a higher difference in drug costs, indicating a higher ICER. The cost-effectiveness of long-term or life-long use should be examined in future research.

Cost-effectiveness of apixaban versus low molecular weight heparin/vitamin k antagonist for the treatment of venous thromboembolism and the prevention of recurrences.

BACKGROUND: Prior analyses beyond clinical trials are yet to evaluate the projected lifetime benefit of apixaban treatment compared to low-molecular-weight heparin (LMWH)/vitamin K antagonist (VKA) for treatment of venous thromboembolism (VTE) and prevention of recurrences. The objective of this study is to assess the cost-effectiveness of initial plus extended treatment with apixaban versus LMWH/VKA for either initial treatment only or initial plus extended treatment. METHODS: A Markov cohort model was developed to evaluate the lifetime clinical and economic impact of treatment of VTE and prevention of recurrences with apixaban (starting at 10 mg BID for 1 week, then 5 mg BID for 6 months, then 2.5 mg BID for an additional 12 months) versus LMWH/VKA for 6 months and either no further treatment or extended treatment with VKA for an additional 12 months. Clinical event rates to inform the model were taken from the AMPLIFY and AMPLIFY-EXT trials and a network meta-analysis. Background mortality rates, costs, and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom National Health Service. The evaluated outcomes included the number of events avoided in a 1000-patient cohort, total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. RESULTS: Initial plus extended treatment with apixaban was superior to both treatment durations of LMWH/VKA in reducing the number of bleeding events, and was superior to initial LMWH/VKA for 6 months followed by no therapy, in reducing VTE recurrences. Apixaban treatment was cost-effective compared to 6-month treatment with LMWH/VKA at an incremental cost-effectiveness ratio (ICER) of £6692 per QALY. When initial LMWH/VKA was followed by further VKA therapy for an additional 12 months (i.e., total treatment duration of 18 months), apixaban was cost-effective at an ICER of £8528 per QALY gained. Sensitivity analysis suggested these findings were robust over a wide range of inputs and scenarios for the model. CONCLUSIONS: In the UK, initial plus extended treatment with apixaban for treatment of VTE and prevention of recurrences appears to be economical and a clinically effective alternative to LMWH/VKA, whether used for initial or initial plus extended treatment.

Low-molecular weight heparin versus vitamin K antagonists for the treatment of cancer-associated thrombosis: A cost-effectiveness analysis.

INTRODUCTION: Cancer-associated venous thromboembolism (VTE) is primarily treated with low-molecular weight heparin (LMWH), a strategy based on studies showing it to be superior to the vitamin K antagonist (VKA) warfarin for preventing VTE recurrence. Subsequent analyses suggest that the magnitude of this benefit might be less than previously determined. Neither patient-focused measures of utility nor the costs of each strategy have been evaluated in the current treatment era. METHODS: This is a cost-effectiveness analysis of VKA and LMWH for the treatment of cancer-associated thrombosis through use of a microsimulation model of outcomes for competing anticoagulation management strategies from a 2014 United States societal perspective. RESULTS: LMWH therapy added 0.27 QALYs relative to VKA treatment with an ICER of $217,007. One-way sensitivity analysis evaluating the utility of LMWH revealed that VKA was always the preferred strategy at a willingness to pay (WTP) threshold of $100,000 per QALY. Limitations include that the model incorporates a low VKA time in therapeutic range (TTR) and that the TTR in some centers may be higher thereby increasing the cost-effectiveness of the VKA strategy. Utilities for anticoagulation strategies were not derived from cancer patients, and preference is known to vary depending on how anticoagulation method is integrated with cancer treatment. CONCLUSIONS: Our findings suggest that compared to LMWH, warfarin is a more cost-effective strategy to treat cancer-associated VTE. Although LMWH is associated with a modest increase in life expectancy, this increase comes at significant cost.

Cost-effectiveness analysis of low-molecular-weight heparin versus aspirin thromboprophylaxis in patients newly diagnosed with multiple myeloma.

INTRODUCTION: The aim of this study was to assess the cost-effectiveness of low molecular weight heparin versus aspirin as primary thromboprophylaxis throughout chemotherapy for newly diagnosed multiple myeloma patients treated with protocols including thalidomide from the perspective of French health care providers. METHODS: We used a modeling approach combining data from the only randomized trial evaluating the efficacy of the two treatments and secondary sources for costs, and utility values. We performed a decision-tree analysis and our base case was a hypothetical cohort of 10,000 patients. A bootstrap resampling technique was used. The incremental cost-effectiveness ratio was calculated using estimated quality-adjusted life years as the efficacy outcome. Incremental costs and effectiveness were estimated for each strategy and the incremental cost-effectiveness ratio was calculated. One-way sensitivity analyses were performed. RESULTS: The number of quality-adjusted life years was estimated to be 0.300 with aspirin and 0.299 with heparin. The estimated gain with aspirin was therefore approximately one day. Over 6months, the mean total cost was € 1518 (SD=601) per patient in the heparin arm and € 273 (SD=1019) in the aspirin arm. This resulted in an incremental cost of € 1245 per patient treated with heparin. The incremental cost-effectiveness ratio for the aspirin versus heparin strategy was calculated to be - 687,398 € (95% CI, -13,457,369 to -225,385). CONCLUSIONS: Aspirin rather than heparin thromboprophylaxis, during the first six months of chemotherapy for myeloma, is associated with significant cost savings per patient and also with an unexpected slight increase in quality of life.

Rivaroxaban versus Heparin Bridging to Warfarin Therapy: Impact on Hospital Length of Stay and Treatment Costs for Low-Risk Patients with Pulmonary Embolism.

STUDY OBJECTIVE: To compare hospital length of stay (LOS) and hospital treatment costs in low-risk patients with pulmonary embolism (PE) anticoagulated with rivaroxaban or heparin bridging to warfarin therapy. DESIGN: Retrospective review of electronic health records and hospital billing records. SETTING: Large, teaching hospital in the northeastern United States. PATIENTS: One hundred ninety adults with objectively confirmed acute PE presenting to the emergency department between November 1, 2012, and May, 12, 2015, who were classified as low risk of early mortality and received anticoagulation with either rivaroxaban or heparin (i.e., unfractionated heparin or low-molecular-weight heparin) bridging to warfarin therapy were included in the analysis. Patients were identified as low risk by at least one of the following prediction rules: simplified Pulmonary Embolism Severity Index (sPESI; 115 patients), Hestia criteria (87 patients), or In-hospital Mortality for Pulmonary Embolism using Claims Data (IMPACT; 108 patients); these were not mutually exclusive, as patients could be classified as low risk by more than one risk stratification tool. MEASUREMENTS AND MAIN RESULTS: We divided low-risk patients identified by each prediction rule into two cohorts: those receiving rivaroxaban (allowing ≤ 2 days of prior heparin use) or heparin bridging to warfarin therapy. The primary end points for this study were LOS (number of days from the patient's arrival at our institution until discharge) and total hospital treatment costs (our institution's actual costs to provide treatment) for the index PE hospital encounter. Using multivariable generalized linear model regression (gamma-distributed error and log-link), we estimated differences in LOS and hospital costs (in 2015 U.S. dollars) between the two cohorts after covariate adjustment. Rivaroxaban was associated with significantly shorter adjusted LOS (range -2.1 to -4.3 days) and significantly lower index hospital costs (range -$3835 to -$7094) versus heparin bridging to warfarin, regardless of the prediction rule used to identify low-risk patients. CONCLUSION: Among low-risk PE patients identified by using sPESI, Hestia or IMPACT, rivaroxaban was associated with significantly shorter LOS and lower hospital treatment costs versus heparin bridging to warfarin.

Hospitalizations and Other Health Care Resource Utilization Among Patients with Deep Vein Thrombosis Treated with Rivaroxaban Versus Low-molecular-weight Heparin and Warfarin in the Outpatient Setting.

PURPOSE: Compared with low-molecular-weight heparin (LMWH) and warfarin, the oral anticoagulant rivaroxaban has advantages, such as simplified care, that may lead to less health care resource utilization. METHODS: A retrospective, matched-cohort analysis was conducted using claims dated between January 2011 and December 2013 from the Truven Health Analytics MarketScan databases. Adult patients who had a primary diagnosis of deep vein thrombosis (DVT) during an outpatient or emergency room (ER) visit after November 2, 2012, and who were treated with rivaroxaban or LMWH/warfarin on the same day, were identified. Patients were observed over 1, 2, 3, and 4 weeks after the DVT diagnosis. The mean numbers of hospitalizations for all causes and for venous thromboembolism (VTE) (which included those for DVT or pulmonary embolism), as well as other health care resource utilization (ER, outpatient, and other visits), and the associated health care costs and pharmacy costs, were evaluated and compared between cohorts using the Lin method. FINDINGS: All of the 512 rivaroxaban-treated patients were well matched with the LMWH/warfarin-treated patients. The mean numbers of all-cause hospitalizations were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (0.012 vs 0.032; P = 0.044) and 2 weeks (0.022 vs 0.048; P = 0.040). The corresponding mean numbers of VTE-related hospitalizations were significantly lower with rivaroxaban over 1 week (0.008 vs 0.028; P = 0.020), 2 weeks (0.016 vs 0.042; P = 0.020), and 4 weeks (0.034 vs 0.068; P = 0.036). The mean numbers of all-cause and VTE-related outpatient visits were also significantly lower in rivaroxaban users compared with those in LMWH/warfarin users over 1, 2, 3, and 4 weeks (all, P < 0.001). In terms of all-cause and VTE-related ER and other visits, no statistically significant differences were found between cohorts over the first 4 weeks. The associated mean all-cause total health care costs were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (US $2332 vs $3428; P < 0.001) and 2 weeks ($3108 vs $4524; P < 0.001); moreover, significantly lower mean costs related to all-cause hospitalizations (weeks 1 and 2) and pharmacy (weeks 1-4) were observed in patients treated with rivaroxaban, while no differences were found in costs related to ER visits (weeks 1-4), outpatient visits (weeks 1-4), or other visits (with the exception of week 1). IMPLICATIONS: Patients with DVT treated with rivaroxaban after an outpatient/ER visit had significantly lower mean numbers of hospitalizations and outpatient visits, as well as lower mean total, hospitalization, and pharmacy costs during the first 2 weeks of treatment compared with those in matched LMWH/warfarin users.

Cost-effectiveness analysis of apixaban compared to low-molecularweight heparins and vitamin k antagonists for treatment and secondary prevention of venous thromboembolism.

OBJECTIVE: Cost-effectiveness analysis of a 6-month treatment of apixaban (10 mg/12h, first 7 days; 5 mg/12h afterwards) for the treatment of the first event of venous thromboembolism (VTE) and prevention of recurrences, versus low-molecular-weight heparins/vitamin K antagonists treatment (LMWH/VKA). MATERIAL AND METHODS: A lifetime Markov model with 13 health states was used for describing the course of the disease. Efficacy and safety data were obtained from AMPLIFY and AMPLIFY-EXT clinical trials; health outcomes were measured as life years gained (LYG) and quality-adjusted life years (QALY). The chosen perspective of this analysis has been the Spanish National Health System (NHS). Drugs, management of VTE and complications costs were obtained from several Spanish data sources (€, 2014). A 3% discount rate was applied to health outcomes and costs. Univariate and probabilistic sensitivity analyses (SA) were performed in order to assess the robustness of the results. RESULTS: Apixaban was the most effective therapy with 7.182 LYG and 5.865 QALY, versus 7.160 LYG and 5.838 QALYs with LMWH/VKA. Furthermore, apixaban had a lower total cost (€13,374.70 vs €13,738.30). Probabilistic SA confirmed dominance of apixaban (led to better health outcomes with less associated costs) in 89% of the simulations. CONCLUSIONS: Apixaban 5 mg/12h versus LMWH/VKA was an efficient therapeutic strategy for the treatment and prevention of recurrences of VTE from the NHS perspective.

Objetivo: Analizar la relación coste-efectividad de 6 meses de tratamiento con apixaban (10 mg/12 h, 7 primeros días; 5 mg/12 h después) para el primer evento de tromboembolismo venoso (TEV) y prevención de recurrencias, frente a heparinas de bajo peso molecular/antagonistas de vitamina K (HBPM/ AVK). Material y métodos: Se ha empleado un modelo de Markov con 13 estados de salud que describen la evolución de la enfermedad a lo largo de la vida de los pacientes. Los datos de eficacia y seguridad se han obtenido de los ensayos clínicos AMPLIFY y AMPLIFY- EXT, calculándose los años de vida ganados (AVG) y los años de vida ajustados por calidad (AVAC) de las opciones terapéuticas evaluadas. En este análisis se adoptó la perspectiva del Sistema Nacional de Salud (SNS). El coste de la medicación, de las complicaciones y del manejo del TEV se obtuvo de distintas fuentes españolas (€, 2014). Se aplicó una tasa de descuento anual del 3% a costes y beneficios en salud. Se realizaron análisis de sensibilidad univariante y probabilístico (ASP) para evaluar la robustez de los resultados. Resultados: Apixaban generó mejores resultados en salud con 7,182 AVG y 5,865 AVAC, frente a 7,160 AVG y 5,838 AVAC para HBPM/AVK, y con menor coste total (13.374,70 € versus 13.738,30 €). El ASP confirmó la dominancia de apixaban (produce mejores resultados con menores costes asociados) en el 89% de las simulaciones. Conclusiones: Apixaban 5 mg/12 h versus HBPM/AVK fue una estrategia eficiente para el SNS en el tratamiento y prevención de recurrencias de TEV.