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Background: With the increasing utilization of anticoagulants, the selection of appropriate anticoagulants has emerged as a significant quandary. The objective of this study was to evaluate recent trend in the utilization and expenditure of anticoagulants within a specific region, aiming to provide valuable insights into the optimal choice of anticoagulants across other healthcare facilities., Methods: The utilization of anticoagulants was retrospectively analyzed. The data on anticoagulant utilizations in tertiary-care hospitals within a district were collected from January 2019 to December 2023. The expenditure, defined daily doses (DDDs), and defined daily cost (DDC) were calculated. The trends in the utilization and expenditure of anticoagulants were examined using linear regression analysis., Results: From 2019 to 2023, the DDDs of rivaroxaban demonstrated a significant annual increase in most hospitals (p < 0.05). Only a few hospitals exhibited a gradual rise in the consumption of low molecular weight heparin (LMWH) over the same period (p < 0.05). The trend of heparin sodium and warfarin varied across different hospitals. The implementation of the centralized procurement policy, however, resulted in a decline in the consumption of rivaroxaban and LMWH in 2021 and 2022 respectively. The DDC value of rivaroxaban experienced a substantial decrease over the past five years (p = 0.020), declining from 55.20 Chinese Yuan (CNY) in 2019 to 4.28 CNY in 2023. Conversely, there was a slight increase noted in the DDC of heparin sodium during this time frame (p = 0.042)., Conclusion: Over the past five years (2019-2023), there has been an increase in the utilization of rivaroxaban and LMWH. However, their expenditure has decreased. In addition, the utilization and expenditure of warfarin and heparin sodium remained relatively stable. The application prospects of rivaroxaban and LMWH are promising., Competing Interests: The authors declare there are no conflicts of interest., (Copyright: © 2025 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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.

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.

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.

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.

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 The American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

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.

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.

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

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.

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., (© 2016 Pharmacotherapy Publications, Inc.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.)

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., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

The term 'biosimilars' is used to qualify products developed to be similar to an original biological drug. Biosimilars are much more complicated to develop than a generic version of small-molecule drugs and this is especially true for low-molecular-weight heparins (LMWHs). Evidence on the antithrombotic management of acute coronary syndromes (ACS) showed that the introduction into the market of biosimilars approved on the basis of simple biological criteria, without robust data from comparative clinical trials, may be hazardous. Moreover, the mixtures of LMWH polysaccharide chains, some immunoallergic properties and potential contamination during the extraction process raise safety concerns. As was the case for the biosimilar erythropoietin, there is the risk that only copies of the most commercially successful LMWHs will be marketed, thus jeopardizing the 'biodiversity' now ensured by the presence of several LMWHs, each with unique features that support the use of an individual LMWH as first-choice therapy in certain categories of patients., (© 2015 International Society on Thrombosis and Haemostasis.)

Purpose: To assess the cost-effectiveness of apixaban versus rivaroxaban, low-molecular-weight heparin (LMWH)/dabigatran, and LMWH/vitamin K antagonist (VKA) for the initial treatment and prevention of recurrent thromboembolic events in patients with venous thromboembolism (VTE)., Methods: A Markov model was developed to evaluate the pharmacoeconomic effect of 6 months of treatment with apixaban versus other anticoagulants over a lifetime horizon. Network meta-analyses were conducted using the results of the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy (AMPLIFY), EINSTEIN-pooled, and RE-COVER I and II trials for the following end points: recurrent VTE, major bleeds, clinically relevant non-major bleeds, and treatment discontinuations. The analysis was conducted from the perspective of the United Kingdom National Health Service. The outcomes evaluated were the number of events avoided in a 1000-patient cohort, total costs, life years, quality-adjusted life years (QALYs), and cost per QALY gained over a patient's lifetime., Findings: Treatment for 6 months with apixaban was projected to result in fewer recurrent VTE and bleeding events in comparison to rivaroxaban, LMWH/dabigatran, and LMWH/VKA. Apixaban was cost-effective compared with LMWH/VKA at an incremental cost-effectiveness ratio of £2520 per QALY gained and was a dominant (ie, lower costs and higher QALYs) alternative to either rivaroxaban or LMWH/dabigatran. Sensitivity analysis indicated that results were robust over a wide range of inputs., Implications: The assessment of the effects and costs of apixaban in this study predicted that apixaban is a dominant alternative to rivaroxaban and LMWH/dabigatran and a cost-effective alternative to LMWH/VKA for 6 months of treatment of VTE and the prevention of recurrence., (Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.)

Background: The clinical and economic effects of medical thromboprophylaxis (MT) using low molecular weight heparin in Australia are unknown., Aim: To estimate the effects of MT in Australia., Methods: A decision tree model of MT was populated with national data for medical admissions. The Prevention of Recurrent Venous Thromboembolism (PREVENT) trial was chosen as the primary data source because its design uniquely avoided bias caused by treatment of sub-clinical events. Clinical efficacy and costs were estimated compared with no prophylaxis, assuming full compliance and according to three definitions of eligibility. Effectiveness was estimated as thrombotic events saved, mortality from bleeding or pulmonary embolus (PE), cost and $/year of life saved. Model outputs were subjected to sensitivity analysis., Results: MT decreased thrombotic events, and the numbers avoided increased as eligibility broadened (deep vein thrombosis (DVT): 2597, 2771 and 3232 at restricted, intermediate and broad eligibility; PE: 454, 484 and 565 respectively). The annual cost of no prophylaxis was $88.7 m. Costs were reduced at most restricted eligibility (-$7.9 m), but increased by $3.0 and $32.1 m at broader eligibility. PE deaths declined, but this was offset by deaths from haemorrhage, causing a net increase (158, 299 and 672 respectively). Estimates were sensitive to the incidence of venous thromboembolic event (VTE), case-fatality rates for PE and bleeds and the relative risk reduction for PE with prophylaxis., Conclusions: Under PREVENT trial conditions, MT avoids up to 3200 DVT and 565 PE events annually, but may increase mortality., (© 2016 Royal Australasian College of Physicians.)

Background: For many years, the standard of care for patients diagnosed with deep vein thrombosis (DVT) has been low-molecular-weight heparin (LMWH) bridging to an oral Vitamin-K antagonist (VKA). The availability of new non-VKA oral anticoagulants (NOAC) agents as monotherapy may reduce the likelihood of hospitalization for DVT patients., Objective: To compare hospital visit costs of DVT patients treated with rivaroxaban and LMWH/warfarin., Methods: A retrospective claim analysis was conducted using the MarketScan Hospital Drug Database for care provided between January 2011 and December 2013. Adult patients using rivaroxaban or LMWH/warfarin with a primary diagnosis of DVT during the first day of a hospital visit were identified (i.e., index hospital visit). Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients. The hospital-visit cost difference between these groups was evaluated for the index hospital visit, as well as for total hospital-visit costs (i.e., including index and subsequent hospital visit costs)., Results: All rivaroxaban users (n = 134) in the database were well-matched with four LMWH/warfarin users (n = 536). The mean hospital-visit costs were $5257 for the rivaroxaban cohort and $6764 in the matched-cohort of patients using LMWH/warfarin. The $1508 cost difference was statistically significant between cohorts (95% CI = [-$2296; -$580]; p-value = 0.002). Total hospital-visit costs were lower for rivaroxaban compared to LMWH/warfarin users within 1, 2, 3, and 6 months after index visit (significantly lower within 1 and 3 months, p-values <0.05) LIMITATIONS: Limitations were inherent to administrative-claims data, completeness of baseline characteristics, adjustments restricted to observational factors, and lastly the sample size of the rivaroxaban cohort., Conclusion: The availability of rivaroxaban significantly reduced the costs of hospital visits in patients with DVT treated with rivaroxaban compared to LMWH/warfarin.

Background: Venous thromboembolism is common in cancer patients and requires anticoagulation with low-molecular-weight heparin (LMWH). Current data recommend LMWH for anticoagulation as far as 6 months, yet guidelines recommend LMWH beyond 6 months in patients who have ongoing or active cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study., Objectives: (1) To identify the most clinically and cost-effective length of anticoagulation with LMWH in the treatment of cancer-associated thrombosis (CAT); (2) to identify practicalities of conducting a full randomised controlled trial (RCT) with regard to recruitment, retention and outcome measurement; and (3) to explore the barriers for progressing to a full RCT., Design: The Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT) trial is a randomised, multicentre, feasibility mixed-methods study with three components: (1) a RCT comparing ongoing LMWH treatment for CAT with cessation of LMWH at 6 months' treatment (current licensed practice) in patients with locally advanced or metastatic cancer, consulted in three clinical settings (haematology outpatients, oncology outpatients and primary care); (2) a nested qualitative study, including focus groups with clinicians to investigate attitudes for recruiting to the study and identify the challenges of progressing to a full RCT, and semistructured interviews with patients and relatives to explore their attitudes towards participating in the study, and potential barriers and concerns to participation; and (3) a UK-wide survey exercise to develop a classification and enumeration system for the CAT models and pathways of care., Setting: A haematology outpatients department, an oncology outpatients department and primary care., Participants: Patients with ongoing active or metastatic cancer who have received 6 months of LMWH for CAT., Interventions: Ongoing LMWH treatment for CAT versus cessation of LMWH at 6 months' treatment in patients with locally advanced or metastatic cancer., Main Outcome Measures: (i) The number of eligible patients over 12 months; (ii) the number of recruited patients over 12 months (target recruitment rate of 30% of eligible patients); and (iii) the proportion of randomised participants with recurrent venous thromboembolisms (VTEs) during follow-up., Results: Following several delays in setting up the RCT component of the study, 5 out of 32 eligible patients consented to be randomised to the RCT suggesting progression to a full RCT was not feasible. Reasons for non-consenting were primarily based on a fixed preference for continuing or discontinuing treatment after 6 months of anticoagulation, and a fear of randomisation to their non-preferred option. Views were largely influenced by patients' initial experience of CAT. Focus groups with clinicians revealed that they would be reticent to recruit to such a study as they had fixed views of best management despite the lack of evidence. Patient pathway modelling suggested that there is a broad heterogeneity of practice with respect to CAT management and co-ordination, with no consensus on which specialty should best manage such cases., Conclusions: The results of the RCT reflect recruitment from the oncology site only and provide no recruitment data from haematology centres. However, it is unlikely that these other sites would have access to more eligible patients. The management of cancer-associated thrombosis beyond 6 months will remain a clinical challenge. As it is unlikely that a prospective study will successfully recruit, other strategies to accrue relevant data are necessary. Currently the LONGHEVA (Long-term treatment for cancer patients with deep-venous thrombosis or pulmonary embolism) registry is in development to prospectively evaluate this important and common clinical scenario., Study Registration: This study is registered as clinical trials.gov number NCT01817257 and International Standard Randomised Controlled Trial Number (ISRCTN) 37913976., Funding Details: Funding for the ALICAT trial was provided by the Health Technology Assessment programme (10/145/01) in response to a themed funding call. The study was designed in accordance with the initial funding brief and feedback from the review process.

Background: Target-specific anticoagulants such as rivaroxaban facilitate immediate discharge of low-risk venous thromboembolism (VTE; including deep vein thrombosis [DVT] and pulmonary embolism [PE]) allowing treatment at home instead of hospitalization., Objectives: The objective was to compare costs accrued over 6 months by patients diagnosed with low-risk VTE and treated at home with rivaroxaban versus usual care with heparin-warfarin., Methods: This case-control study calculated costs using the established charge-to-cost ratio from UB-04 billing claims of patients diagnosed at two metropolitan hospitals. Patients were defined as low risk by the Hestia criteria. All patients were anticoagulated for 6 months. Control patients were treated with usual care using low-molecular-weight heparin (LMWH) and then warfarin. Case patients were treated with an initial dose of rivaroxaban in the ED followed by same-day discharge home with rivaroxaban. Medians were compared by Mann-Whitney U-test., Results: Fifty cases and 47 controls were identified. Groups were well matched according to mean age, Charlson comorbidity score, and proportions by sex and location of thrombus. For all VTEs, median hospital charges for 6 months after diagnosis were $11,128 (interquartile range [IQR] = $8,110 to $23,390) for controls, compared with $4,787 (IQR = $3,042 to $7,596) for cases (Mann-Whitney U-test p < 0.001). Subgroup analyses of the first week of therapy, PE, DVT, and inpatient pharmacy costs retained significance, with costs for rivaroxaban-treated PE patients 57% lower than control PE patients (p < 0.001) and 56% lower for DVT patients (p = 0.003)., Conclusions: Cost of medical care was lower for low-risk VTE patients discharged immediately from the ED with rivaroxaban therapy compared with patients treated with LMWH-warfarin., (© 2015 by the Society for Academic Emergency Medicine.)

Bemiparin is a low molecular weight heparin (LMWH) indicated for the acute treatment of deep vein thrombosis with or without pulmonary embolism, for the prophylaxis of venous thromboembolism in surgical and non-surgical patients and for the prevention of clotting in the extracorporeal circuit during hemodialysis. Due to its excellent pharmacological profile-the second-generation LMWH with the lowest molecular weight, the longest half-life and the highest anti-Factor Xa/anti-Factor IIa activity ratio-it can be safely used in special categories of patients (children, elderly, patients with renal impairment and congestive heart failure). Several studies demonstrated its safety and efficacy, while cost analyses show the economic benefits of bemiparin treatment as compared to other heparins. Recent evidences suggested the application of bemiparin even in the management of diabetic foot ulcers. The aim of this narrative review was to evaluate literature according to results coming from studies involving bemiparin administration in various clinical conditions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: To analyze clinical characteristics of venous thromboembolisms (VTE) in gynecological malignancies, and to find a cost-effective prophylaxis procedure for post-operative VTE., Patients and Methods: We analyzed clinical characteristics of 751 patients who underwent definitive surgery for gynecologic malignancies, and cost-effectiveness of VTE prophylaxis., Results: VTE was diagnosed preoperatively in 4.5% of ovarian cancer cases, more frequently than any other type (p<0.005). Older age and greater length of operation were independent risk factors for postoperative VTE. To prevent eight VTEs in 738 malignant cases, which occurred during day 2 to 10, $617,783, $726,185, or $994,222 were necessary for continuous VTE prophylaxis, using either unfractionated heparin (UFH), low-molecular weight heparin or fondaparinux, respectively., Conclusion: A strategy which might be cost-effective for post-surgical management of gynecological malignances is use of UFH three times combined with graduated compression stockings and intermittent pneumatic compression, thorough SpO2 monitoring, and perioperative measurements of the circumference of both sides of thighs and calves., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The objective of this study was to identify the self-reported barriers to and facilitators of prescribing low-molecular-weight heparin (LMWH) thromboprophylaxis in the intensive care unit (ICU)., Methods: We conducted an interviewer-administered survey of 4 individuals per ICU (the ICU director, a bedside pharmacist, a thromboprophylaxis research coordinator, and physician site investigator) regarding LMWH thromboprophylaxis for medical-surgical patients in 27 ICUs in Canada and the United States. Items were generated by the research team and adapted from previous surveys, audits, qualitative studies, and quality improvement research. Respondents rated the barriers to LMWH use, facilitators (effectiveness, affordability, and acceptability thereof), and perceptions regarding LMWH use., Results: Respondents had 14.5 (SD, 7.7) years of ICU experience (response rate, 99%). The 5 most common barriers in descending order were as follows: drug acquisition cost, fear of bleeding, lack of resident education, concern about bioaccumulation in renal failure, and habit. The top 5 rated facilitators were preprinted orders, education, daily reminders, audit and feedback, and local quality improvement committee endorsement. Centers using preprinted orders (mean difference [P<.01]) and computerized physician order entry (P<.01) compared with those centers not using those tools reported higher affordability for these 2 facilitators. Compared with physicians and pharmacists, research coordinators considered ICU-specific audit and feedback of thromboprophylaxis rates to be a more effective, acceptable, and affordable facilitator (odds ratio, 6.67; 95% confidence interval, 1.97-22.53; P<.01). Facilitator acceptability ratings were similar within centers but differed across centers (P≤.01)., Conclusions: This multicenter survey found several barriers to use of LMWH including cost, concern about bleeding, and lack of resident knowledge of effectiveness. The diversity of reported facilitators suggests that large scale programs may address generic barriers but also need site-specific interprofessional knowledge translation activities., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Venous thromboembolism is common in patients with cancer and requires anticoagulation with low molecular weight heparin. Current data informs anticoagulation as far as six months, yet guidelines recommend anticoagulation beyond six months in patients who have locally advanced or metastatic cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study. ALICAT (Anticoagulation Length in Cancer Associated Thrombosis) is a feasibility study to identify the most clinically and cost effective length of anticoagulation with low molecular weight heparin in the treatment of cancer associated thrombosis., Methods/design: ALICAT is a randomized multi-centre phase two mixed-methods study with three components: a randomized controlled trial, embedded qualitative study and a survey investigating pathways of care. The randomized controlled trial will compare ongoing low molecular weight heparin treatment for cancer-associated thrombosis versus cessation of low molecular weight heparin at six months treatment (current licensed practice) in patients with locally advanced or metastatic cancer. The embedded qualitative study will include focus groups with clinicians to investigate attitudes to recruiting to the study, identify the challenges of progressing to a full randomized controlled trial, and also semi-structured interviews with patients and relatives/carers to explore their attitudes towards participating in the study and potential barriers and concerns to participation. Finally, a UK wide survey exercise will be undertaken to develop a classification and enumeration system for the cancer associated thrombosis models and pathways of care., Discussion: There is a lack of evidence determining the length of anticoagulation for patients with cancer associated thrombosis and subsequently treatment length varies. The ALICAT study will consider the feasibility of recruiting patients to a phase three trial., Trial Registration: Current Controlled Trials ISRCTN37913976.

Background: The prevalence of venous thromboembolism (VTE) has been increasing in China. However, the treatment pattern and economic burden of these patients have not been well-understood., Objective: The objective of this study was to examine the patient characteristics, treatment pattern, anticoagulant monitoring, and economic burden of VTE among hospitalized patients in China., Methods: Hospitalizations with a diagnosis of VTE [including deep vein thrombosis (DVT) or pulmonary embolism (PE)] between 1 January 2010 and 30 June 2013 were included. Descriptive analysis was conducted for patients' characteristics, anticoagulant treatment, international normalized ratio (INR) monitoring, and hospitalization cost [in 2013 Chinese yuan (Y) and US dollars (US$)]. Multivariate regressions were performed to assess factors associated with oral anticoagulant use and total costs of inpatient care., Results: A total of 1,047 VTE-related hospitalizations were selected. The sample had a mean age of 62.4 years, with 45.9 % female. About 46.3 % of hospitalizations used heparin only, 35.0 % used warfarin, 0.8 % used rivaroxaban, and 18.0 % did not use anticoagulants. Among hospitalizations where warfarin was used, 90.8 % received at least one INR test and only 30 % had the last INR within the target therapeutic range (2-3) before discharge. The mean (standard deviation) total cost per hospitalization was Y29,114 (43,772) [US$4,757 (7,152)]. PE, VTE as primary diagnosis, female, insurance coverage, anticoagulant treatment, co-morbidities, admission condition, and surgical procedure were significantly associated with inpatient costs., Conclusions: Conventional anticoagulants were most commonly used in the study sample. Under-monitoring and suboptimal care may be an issue for patients treated with warfarin. The average total inpatient cost of VTE-related hospitalizations is high.

Introduction: Major orthopedic surgery is associated with a high risk of venous thromboembolism (VTE). Anticoagulants are recommended to prevent VTE, and recently an oral direct factor Xa inhibitor (FXaI) was approved for this indication. We compared the cost-effectiveness of FXaIs with low-molecular-weight heparin (LMWH) in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery., Design: A decision-tree model was developed to compare the cost-effectiveness of oral direct FXaIs (rivaroxaban, apixaban, and edoxaban) to subcutaneous LMWHs (enoxaparin and dalteparin), with separate models for THR and TKR. The analysis was conducted over a 180-day postoperative time horizon from the U.S. Medicare perspective. The model was developed using TreeAge Pro 2011 (TreeAge Software Inc., Williamstown, MA, USA)., Methods: Efficacy and safety data (probabilities of distal and proximal deep vein thrombosis, symptomatic pulmonary embolism, and major bleeding) were derived from a systematic review and meta-analysis of phase II and III clinical trials. Costs and quality-adjusted life-years (QALYs) are reported. One-way and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty., Results: In the THR model, the average costs per patient for FXaIs and LMWHs were $18,762 and $18,897, respectively, and the QALYs were 0.938 and 0.932. In the TKR model, the average cost per patient for FXaIs and LMWHs were $18,804 and $18,991, respectively, and the QALYs were 0.935 and 0.931. In both models, FXaIs dominated LMWH (less costly and more efficacious). Neither model was sensitive to changes in any of the variables in the one-way sensitivity analyses. Probabilistic sensitivity analysis indicated that FXaIs were cost-effective in more than 99% of iterations in the THR population and in 98% of iterations in the TKR population assuming a willingness-to-pay threshold of $50,000/QALY., Conclusion: Oral direct FXaIs may be an economically dominant strategy compared with LMWHs for VTE prophylaxis in patients undergoing either THR or TKR surgery., (© 2013 Pharmacotherapy Publications, Inc.)

Background: The therapeutic and diagnostic approach in deep vein thrombosis (DVT) has changed enormously in the last two decades with the introduction of ultrasound, low-molecular-weight heparin (LMWH), and premature motion. The aim of this study is to evaluate these changes and analyze their clinical and economic aspects., Methods: We registered all inpatients with a diagnosis of DVT during 1994 (n=110) and 2009 (n=75) and their sociodemographic and clinical features in a descriptive observational design. We performed a comparison of diagnostic techniques, length of stay, inpatient complications, and costs thus derived for both series, based on 2009 prices, so that we could get comparable results., Results: Ninety-one percent of inpatients in 1994 were diagnosed by venography, whereas, in 2009, the diagnosis was based on clinical features, D-dimer, and ultrasound in 100% of patients. Inpatient treatment went from 7% LMWH in 1994 to 96% in 2009, and as outpatient from 82% acenocumarol to 90.6% LMWH. Complications decreased by 13.3%. Length of stay was 2.7 higher in 1994. Globally, the cost per patient decreased by 63.39%, based primarily on reduced length of stay., Conclusions: The current diagnostic and therapeutic approach in DVT allows for effective treatment, fewer complications, and a drastic reduction in inpatient costs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background/objectives: The most cost-effective periprocedural management of patients with mechanical heart valves (MHV) is uncertain. The objective was to compare the effectiveness, safety and costs for inpatient intravenous unfractionated heparin (IVUH) vs. outpatient low molecular weight heparin (LMWH) "bridging" as periprocedural anticoagulation management for MHV patients., Methods: In a case-cohort study, Olmsted County, MN residents with MHV who received outpatient periprocedural LMWH management (cases) over the 11-year period, 1997-2007, were matched to residents with MHV who received inpatient IVUH periprocedural management on valve location and type, and on procedure type. Patients were followed for 3 months following hospitalization to identify thromboembolism (TE) and major bleeding. Total costs from 30 days before to 90 days after the procedure were determined from the Olmsted County Healthcare Expenditure and Utilization Database. Outcomes were compared using survival analysis and costs were compared using the Wilcoxon rank sum., Results: 149 cases (100 aortic, 29 mitral, 20 both; 64% bileaflet) were compared to 149 cohort members (100 aortic, 29 mitral, 20 both; 75% bileaflet). While the 3-month cumulative incidence of TE did not differ significantly among cases (2.7%) and cohort members (4.7%; p = 0.36), major bleeding was significantly lower in cases (5.4% vs. 15.4%; p < 0.005). Total costs were significantly higher for cohort members ($50,984 vs. $39,347; p = 0.002) due to higher inpatient costs ($47,729 vs. $34,860; p = 0.0002)., Conclusions: Outpatient bridging LMWH therapy is equally effective, but safer and less costly than inpatient IVUH as periprocedural anticoagulation management for MHV patients., (© 2013.)

Background: Four low-molecular-weight heparins with different dosage regimens are allowed for venous thromboembolism prophylaxis in patients with a high risk of thromboembolism in Germany. If comparison is made purely on the basis of drug costs, multi-dose vials are the favourable solution. We try to answer the question whether the choice of low-molecular-weight heparin influences the compliance with the S2 guideline "Inpatient and outpatient thromboembolism prophylaxis in surgery and perioperative medicine." Beyond that we ask if multi-dose administration is superior to the pre-filled syringe when total costs are calculated on the basis of procedure and technical application., Patients and Methods: After training the nursing and medical staff in guideline-compliant implementation of thromboembolism prophylaxis with pre-filled certoparin safety syringes (03/09-05/09) or nadroparin (06/09-08/09) and enoxaparin (02/10-04/10) from multi-dose vials, we calculated the total costs on the basis of procedure and technical application. Furthermore, the satisfaction of the nursing staff was interrogated and the proportion of non-guideline-compliant prescriptions was determinated prospectively on the basis of a total of 388 patient files., Results: When total costs are calculated on the basis of procedure and technical application, the costs for nadroparin are 1.16 €/0.3 mL, 1.30 €/0.4 mL and 1.58 €/0.6 mL, for enoxaparin 1.04 €/20 and 1.42 €/40, and for certoparin 1.25 €/pre-filled safety syringe. The pre-filled certoparin safety syringe made a very good overall impression on the nursing staff (versus sufficient for nadroparin and enoxaparin). Guideline-compliance was achieved in 100 % with body weight- and risk-independent certoparin, in 79.4 % with risk-adapted enoxaparin, and in 66.4 % with body weight- and risk-dependent nadroparin., Conclusion: The complexity of the dosage regimen of a low-molecular-weight heparin has a decisive influence on guideline-compliance. By calculating total costs on the basis of procedure and technical application multi-dose vials only offer a price advantage in patients with a low or moderate risk of thromboembolism compared with pre-filled safety syringes in the venous thromboembolism prophylaxis of orthopaedic and trauma surgery patients., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: There is controversy regarding the most appropriate strategy to prevent venous thromboembolism following total joint arthroplasty. Our objective was to estimate the lifetime costs, quality-adjusted life-years (QALYs), and costs per QALY gained using low-molecular-weight heparin compared with low-dose aspirin for two weeks after total knee or total hip arthroplasty in patients with no history of venous thromboembolism., Methods: We used a Markov cohort model with health states of healthy after surgery, no postphlebitic syndrome after venous thromboembolism, postphlebitic syndrome after venous thromboembolism, and survival after intracranial hemorrhage to compare treatment with low-molecular-weight heparin or aspirin (160 mg) for fourteen days after total knee arthroplasty or total hip arthroplasty in patients with an age of fifty-five, sixty, sixty-five, seventy, seventy-five, eighty, or eighty-five years. We estimated lifetime costs, QALYs gained, and costs per QALY gained for both strategies, and applied a cost-effectiveness threshold of $100,000 (2010 U.S. dollars) per QALY gained., Results: For patients undergoing total hip arthroplasty at the ages of fifty-five and seventy years, costs per QALY gained for low-molecular-weight heparin compared with aspirin were $315,000 and $1.4 million, respectively. For those undergoing total hip arthroplasty at the age of eighty or eighty-five years, aspirin cost less and saved more QALYs than low-molecular-weight heparin. For patients undergoing total knee arthroplasty at the ages of fifty-five, seventy, and eighty-five years, costs per QALY gained with low-molecular-weight heparin were $36,000, $112,000, and $448,000, respectively. Probabilistic sensitivity analyses confirmed a low probability of low-molecular-weight heparin being cost-effective for patients undergoing total hip arthroplasty and for those with an age of eighty years or older undergoing total knee arthroplasty. For individuals younger than eighty years of age undergoing total knee arthroplasty, the cost-effectiveness of low-molecular-weight heparin compared with aspirin is uncertain., Conclusions: For patients with no history of venous thromboembolism, aspirin is a cost-effective choice for venous thromboembolism prophylaxis following total hip arthroplasty, but the preferred choice following total knee arthroplasty depends on age and is uncertain for those younger than eighty years old.

This article examines the market entry of biosimilar low-molecular-weight heparins (LMWHs) in Europe by focusing on regulatory requirements, pricing, reimbursement, prescribing, and dispensing. The window for biosimilar LMWHs to enter the market is narrow on the supply side because of several factors. These include (1) regulatory requirements, including a quality dossier, clinical and nonclinical studies, pharmacodynamic and pharmacokinetic studies, immunogenicity studies, and a comparability exercise (but a reduction in clinical data requirements might be plausible in some cases); (2) prices of originator LMWHs are lower than those of other biologic products; (3) European prices of originator LMWHs are lower than those observed in the rest of the world; (4) research and development and manufacturing costs are substantial; (5) costs of active pharmaceutical ingredients have increased following the heparin contamination crisis; and (6) biosimilar LMWHs may be subjected to generic medicine pricing regulations. Furthermore, there are limited opportunities for biosimilar LMWHs on the demand side. This is because, although LMWHs have a large market volume in Europe, demand-side incentives for biosimilar LMWHs are largely absent, and the questions about interchangeability and substitution between originator and biosimilar LMWHs have yet to be fully resolved., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objectives: To evaluate the real-world use of venous thromboembolism (VTE) prophylaxis among medical inpatients and the impact of VTE prophylaxis on outcomes and cost., Study Design: Retrospective analysis of patientlevel administrative claims data for medical inpatients at risk of VTE and linked outpatient data., Methods: Data were analyzed from patients admitted to the hospital from 2005 to 2007 (calendar years) with a primary diagnosis of chronic heart failure, thromboembolic stroke, severe lung disease, acute infection, or cancer (index hospitalization), according to whether they received VTE prophylaxis or not. The number of VTE events, time to VTE event, length of hospital stay, and number of major or minor bleeding events were analyzed from the index date until the end of follow-up (180 days postdischarge) or death., Results: Overall, 7127 of 13,293 patients (53.6%) received VTE prophylaxis. Prophylaxis significantly reduced the incidence of VTE compared with no prophylaxis (0.06% vs 3.44%, respectively; P <.00001) and increased the median time to VTE (182 vs 27 days, respectively). Prophylaxis also significantly reduced the incidence of VTE in the 180 days postdischarge. Readmission rates were similar between groups. Major bleeding occurred in 1.57% of patients receiving low molecular weight heparin + warfarin versus <.6% receiving any other form of prophylaxis. The development of VTE or major or minor bleeding events significantly increased total medical costs versus no VTE events (P <.0001) or no bleeding events (P <.0003)., Conclusions: This real-world analysis showed that thromboprophylaxis was underutilized in medical patients, even though the clinical and economic impact of VTE was significant.

Thromboembolism, including both venous and arterial events, occurs commonly amongst patients with cancer. The occurrence of thromboembolism has significant consequences for cancer patients, including direct and indirect associations with mortality, morbidity, requirement for long-term anticoagulant therapy and consumption of healthcare resources. Recent studies have resulted in a better understanding of clinical risk factors and biomarkers of cancer-associated thrombosis, and a risk assessment model incorporating both has now been validated in multiple settings. Thromboprophylaxis with either unfractionated heparin or low-molecular-weight heparins (LMWHs) has been shown to be safe and effective in high-risk settings such as hospitalization for medical illness and the postsurgical period. Emerging new data from randomized studies have focused on outpatient prophylaxis, suggesting potential benefits in this setting as well. Treatment of cancer-associated thrombosis requires long-term anticoagulation with LMWH. Results from ongoing and planned trials of novel anticoagulants in the cancer setting are awaited., (Copyright © 2012 Wiley Periodicals, Inc.)

Background and Objective: This is a safety and cost comparison study with an analysis of budgetary impact of ambulatory management of patients with cancer and deep vein thrombosis (DVT) compared with hospital management., Material and Methods: Prospective observational study of patients with known malignancy and diagnosed with DVT from 2003 to 2007. The outcome variables were mortality, relapse and bleeding in one month. We conducted an economic analysis to evaluate the comparative cost of ambulatory patients., Results: Three hundred and seventeen patients, 55 (17%) had cancer. The mean age of patients was 63 ± 11 years. There were 2 hemorrhagic events, 2 recurrences and 6 deaths in one month of follow-up. Of all patients, only 7 (13,7%) required hospitalization. All but one deaths were due to progression of the underlying disease. Economic analysis concluded that outpatient management is 6 times less expensive than hospital management, which would imply a cost reduction of 85%., Conclusions: Specialized outpatient treatment of cancer patients with DVT is safe and could save significant financial resources., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Background: The benefit of unfractionated heparin (UFH) added to aspirin in patients with acute coronary syndromes (ACS) was described more than 20 years ago. Ever since, a wide variety of anticoagulant drugs have become available for clinical use, including low-molecular-weight heparins (LMWH), direct thrombin inhibitors and selective factor Xa inhibitors., Objective: The aim of this study was to critically review the available evidence on the cost and incremental cost effectiveness of anticoagulants in patients with ACS., Methods: Studies were identified using specialist databases (UK NHS Economic Evaluation Database [NHS EED] and Cost-Effectiveness Analysis [CEA] Registry), PubMed and the reference lists of recovered articles. Only studies based on randomized controlled trials were considered for inclusion. Finally, 22 studies were included in the review., Results: Enoxaparin is the only LMWH that has been shown to reduce the risk of death or myocardial infarction in patients with non-ST-elevation ACS (NSTE-ACS). In economic studies based on the ESSENCE trial conducted in the late 1990s, enoxaparin was consistently associated with a lower risk of coronary events, a reduction in the number of revascularization procedures and a lower cost per patient than UFH. However, these results refer to patients managed conservatively, with little use of thienopyridines and glycoprotein IIb/IIIa inhibitors, and the results are difficult to extrapolate to moderate-to-high-risk patients managed with the present day early invasive strategy. Available studies of LMWH in ACS with persistent elevation of ST-segment (STE-ACS) are limited to patients treated with thrombolysis. In this scenario, enoxaparin was shown to be a dominant alternative compared with UFH in a study based on the ASSENT-3 study and was considered an economically attractive alternative in three studies based on the ExTRACT-TIMI 25 study. However, these results should be interpreted cautiously due to the heterogeneity of the supportive randomized trials and the possible underestimation of bleeding costs. The effectiveness and safety of bivalirudin, a direct thrombin inhibitor, were evaluated in the ACUITY study (NSTE-ACS patients managed invasively) and the HORIZONS-AMI study (STE acute myocardial infarction patients planned for primary percutaneous coronary intervention). Bivalirudin monotherapy was not inferior to heparin plus a glycoprotein IIb/IIIa inhibitor and reduced the risk of major bleeding. The economic evaluations based on these studies suggest that bivalirudin is an attractive alternative to heparin plus a glycoprotein-IIb/IIIa inhibitor. In the OASIS-5 trial, compared with enoxaparin, fondaparinux reduced the mortality in patients with NSTE-ACS, probably because of a reduced risk of bleeding. In three economic evaluations of fondaparinux versus enoxaparin based on this trial, fondaparinux was the dominant strategy in two of them, and still economically attractive in a third. Taken as a whole, the usefulness of economic studies of anticoagulants in patients with ACS is undermined by the quality of the evidence about their effectiveness and safety; the narrow spectrum of the analysed scenarios; the lack of economic evaluations based on systematic reviews; the limitations of sensitivity analyses reported by the available economic evaluations; and their substantial risk of commercial bias., Conclusions: The available studies suggest that enoxaparin is an economically attractive alternative compared with UFH in patients with NSTE-ACS treated conservatively and STE-ACS patients treated with thrombolysis. Bivalirudin in patients with ACS treated invasively is cost effective compared with heparin plus a glycoprotein IIb/IIIa inhibitor. In patients with NSTE-ACS, fondaparinux is cost effective compared with enoxaparin. The usefulness of these results for decision making in contemporary clinical practice is limited due to problems of internal and external validity.

Background: Prevention of in-hospital venous thromboembolism (VTE) is identified internationally as a priority to improve patient safety. Advocated alternatives include low-dose unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Although LMWHs are as effective as UFH, less frequent administration and potentially safer adverse effect profile associated with LMWHs might off-set greater drug acquisition costs. The objective of this study was to determine the most cost-effective thromboprophylaxis strategy for hospitalized medicine patients and specific subgroups in Canada., Methods: A decision-analytic model assessed costs and outcomes of LMWH compared to UFH for thromboprophylaxis in at-risk hospitalized medicine patients from an institutional perspective. The outcome of interest was the incremental cost-effectiveness ratio (ICER) for preventing deep vein thrombosis (DVT) and combined untoward events (pulmonary embolism [PE], major bleed, and death). The time horizon of the model was the hospital stay., Results: In the base-case analysis, LMWH thromboprophylaxis resulted in higher costs ($7.40), but 3.6 and 1.1 fewer DVT and untoward events per 1000 patients, respectively, with associated ICERs of $2042 and $6832. Results remained predominantly stable when alternative assumptions were evaluated in the sensitivity analysis. Low-molecular-weight heparin had the most favorable economic profile in patients with a history of DVT. In the probabilistic sensitivity analysis, in 33% of simulations LMWH was less costly and more effective, whereas the reverse was true for UFH only in 13% of simulations., Conclusions: Low-molecular-weight heparin administration is a cost-effective alternative for thromboprophylaxis strategy in Canadian hospitalized medicine patients.

Anticoagulation is required during hemodialysis to prevent thrombus formation within the extracorporeal circuit. The low-molecular-weight heparin tinzaparin is more expensive than unfractionated heparin (UFH) in Canada but more convenient to administer. We conducted a time-and-motion study to test the hypothesis that tinzaparin may reduce nursing time and total health care costs compared with UFH. Data on health care resource use associated with anticoagulation during hemodialysis for chronic renal failure were collected at an academic hospital in Quebec. Nursing time was recorded for 8 nurses performing 16 dialysis sessions for 4 patients receiving tinzaparin and 4 receiving UFH (2 dialysis sessions per patient). Nurses had ≥ 1 year of experience supervising hemodialysis. We estimated total annual costs of nursing time and health care resources (anticoagulants, medical supplies, and laboratory testing) associated with anticoagulation. In sensitivity analyses, drug costs were varied ± 30% of their base-case values. Estimated annual nursing times per patient were 0.8 vs. 11.5 hours in the first year and 0.6 vs. 10.2 hours in subsequent years for tinzaparin vs. UFH, respectively. Annual drug costs per patient were CAD 898.56 for tinzaparin and 546.75 for UFH. Estimated total annual costs were CAD 1061.03 vs. 1012.71 in the first year and CAD 917.75 vs. 895.23 in subsequent years for tinzaparin vs. UFH, respectively. Use of tinzaparin was cost saving relative to UFH if tinzaparin price was reduced 30%. Most of the price differential between tinzaparin and UFH is offset by substantial time savings to nephrology nurses., (© 2011 The Authors. Hemodialysis International © 2011 International Society for Hemodialysis.)

Introduction: Catheter ablation for atrial fibrillation is an effective treatment for symptomatic patients who have failed drug therapy. Recent studies using intracardiac echocardiography have demonstrated that ablation can be performed safely on uninterrupted warfarin and may be superior to bridging low molecular weight heparin (LMWH). We sought to assess the safety of an uninterrupted warfarin protocol using a simplified ablation protocol in a prospective controlled study., Methods: Two anticoagulation regimes for patients undergoing catheter ablation for atrial fibrillation were evaluated--a bridging LMWH group and an uninterrupted warfarin group. Bleeding complications were compared between the 2 groups., Results: In total 198 patients were evaluated (109 bridging LMWH, 89 uninterrupted warfarin). The preprocedure INR in the LMWH group (mean age 60.6 years, 72% male) was 1.2 ± 0.3 compared to 2.3 ± 0.5 in the uninterrupted warfarin group (mean age 60.9 years, 69% male). The primary outcome (a composite of major and minor bleeding complications) was observed in 78% in the LMWH group compared to 56% in the warfarin group (P = 0.001), mainly due to increased pain at the venous access site (41% vs 16%, P = 0.001). Two patients undergoing ablation on warfarin required pericardiocentesis for cardiac tamponade. Drug costs were lower in the warfarin group ($64.77 ± 31.86 vs $20.76 ± 15.60, P = 0.005), but the overall cost of treatment per patient (including bed occupancy costs) was similar in the LMWH group compared to the warfarin group ($883.96 ± 278.78 vs $816.59 ± 182.72, P = 0.06)., Conclusion: Catheter ablation for atrial fibrillation can be performed safely on uninterrupted warfarin without intracardiac echocardiography, with a reduced risk of bleeding complications., (© 2010 Wiley Periodicals, Inc.)

Venous thromboembolism (VTE; defined by deep-vein thrombosis, central venous catheter-related thrombosis or pulmonary embolism) is a major therapeutic issue in cancer patients. VTE is reported in 15-20% of patients with cancer and is an independent prognostic factor and a leading cause of death. In this population, low-molecular-weight heparins have been shown to be superior to vitamin K antagonists. The Italian Association of Medical Oncology, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, the French 'Institut National du Cancer', the European Society of Medical Oncology and the American College of Chest Physicians have all published specific guidelines, but their implementation is still low in clinical practice. Methodological assessment of these guidelines was performed using the Appraisal of Guidelines Research & Evaluation Instrument. None of the guidelines on thrombosis and cancer have sought for patients' preferences, nor were they tested among target users. VTE in cancer patients requires a multidisciplinary approach but downstream of the guidelines publication, the potential organisational barriers in applying the recommendations have not been discussed. Tolerance and cost-effectiveness of long-term use of low-molecular-weight heparin may account for the large heterogeneity seen in daily clinical practice. Homogenization of guidelines in international consensus working groups followed by educational and active implementation strategies would be very valuable in order to improve the care of VTE in cancer patients.

Subcutaneous bemiparin has been evaluated for the prevention of venous thromboembolism (VTE) in moderate to high-risk patients undergoing surgery, and for the acute and long-term treatment of established VTE. General and orthopaedic surgery is associated with VTE incidence rates of 15-60% in the absence of thromboprophylaxis and this can be reduced by over 70% with appropriate thromboembolic prophylaxis. Bemiparin was as effective as unfractionated heparin (UFH) in the prevention of VTE, when both were initiated preoperatively, but was associated with significantly fewer bleeding episodes than UFH. Bemiparin prophylaxis initiated postoperatively was at least as effective as bemiparin initiated preoperatively and was associated with a lower incidence of bleeding complications than preoperative initiation. In terms of patients with cancer undergoing abdominal or pelvic surgery, preliminary results from a recent study with bemiparin showed that extended prophylaxis for 4 weeks significantly reduced the rate of major VTE, without increasing bleeding risk, compared with prophylaxis for one week. Bemiparin, initiated postoperatively, was as effective as enoxaparin, initiated preoperatively, in the prevention of VTE in patients undergoing total knee replacement. The incidence of bleeding complications was similar between groups, although the incidence of injection site haematoma was significantly higher with enoxaparin than with bemiparin. Postoperative initiation of bemiparin thromboprophylaxis minimized the risk of spinal haematoma in patients using neuraxial anaesthesia (approximately 93% of patients). In addition, postoperative initiation is likely to reduce the total costs, because patients do not need to be admitted to hospital the day before surgery. Bemiparin was more effective than intravenous UFH in the acute treatment of established deep vein thrombosis (DVT) and was as effective as oral warfarin in the subsequent secondary prevention of VTE over 3 months of therapy, while bleeding complications over 3 months of therapy were similarly low. In a European study, acute treatment of DVT with bemiparin for one week followed by 12 weeks' secondary prevention with bemiparin (i.e. bemiparin/bemiparin) was associated with a cost saving of &U20AC;908 per patient compared with UFH/warfarin. Similarly, bemiparin/warfarin produced a cost saving of &U20AC;769 compared with UFH/warfarin. The savings were predominantly the result of reduced hospital stays during acute treatment with bemiparin. Bemiparin was also associated with increased quality-adjusted life expectancy. Observational studies in routine clinical practice demonstrated that outpatient treatment of acute VTE was as effective as inpatient treatment, but with lower costs, and bemiparin was as effective as vitamin K antagonists over 3 months for secondary prevention, with VTE recurrence rates of 0% and 0.3% over 3 months in separate studies. Bemiparin is thus an effective, well tolerated agent for thromboprophylaxis in surgery, and for the acute and long-term treatment of established VTE, having advantages over UFH and particular benefits as a result of initiating therapy postoperatively.

Objectives: The aim of this study was to compare efficacy, safety, and consumption of low-molecular-weight heparins with unfractionated heparin, and to develop a pharmacoeconomic decision model based on meta-analysis data., Methods: Review and meta-analysis were performed of published randomized control trials directly comparing the safety and efficacy of low-molecular-weight heparins (LMWHs)-that is, nadroparin, enoxaparin, and dalteparin-and unfractionated heparin (UFH) was performed by two reviewers using inclusion/exclusion criteria based on the research objectives. The value of fixed effects and random effects odds ratio (95 percent confidence interval) was calculated for each trial for the composite end point. Subsequently, a pharmacoeconomic decision modeling based on reference pricing methodology was implemented., Results: In comparison to UFH, all LMWHs have independently demonstrated greater safety and effectiveness. None of the LMWHs demonstrated a significant superiority over each other; therefore, the group of LMWHs was interchangeable and suitable for cost minimization analysis and reference price implementation. Being the least expensive option, dalteparin single DDD price was set as the reference. Introduction of reference pricing for LMWHs would decrease the total expenditure on LMWHs of approximately 30 percent and would result in total savings of 1.830-2.070 thousand LTL in the country of Lithuania (approximately 0.8 million USD) per year., Conclusions: The meta-analysis results of LMWHs could be used to support a policy on reference-based pricing and pharmacoeconomic decision modeling in healthcare institutions, which would allow a decrease in healthcare expenditures.