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

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

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

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

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

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

A Review of Two Heparin Prophylaxes for Trauma.

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

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

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

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

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

Estimation of clinical and economic effects of prophylaxis against venous thromboembolism in medical patients, including the effect of targeting patients at high-risk.

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.

Market entry of biosimilar low-molecular-weight heparins in Europe: opportunities and challenges.

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.

Clinical and health costs impact of progress in diagnosis and treatment in venous thromboembolic disease: evolution in 15 years.

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.

Cancer and coagulation.

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.

Catheter ablation for atrial fibrillation on uninterrupted warfarin: can it be done without echo guidance?

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.

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

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

Cost-effectiveness of prolonged thromboprophylaxis after cancer surgery.

BACKGROUND: Consensus guidelines recommend prolonged thromboprophylaxis for up to 4 weeks after major abdominopelvic cancer operations. Several factors impede widespread adoption of these guidelines. These include lack of awareness, cost, increased bleeding complications, increased incidence of heparin-induced thrombocytopenia, and poor patient compliance. METHODS: A cost-effectiveness model was constructed comparing four potential strategies to postdischarge thromboprophylaxis in surgical oncology patients: (1) low-molecular-weight heparin (LMWH) once daily; (2) low-dose unfractionated heparin (LDUH) three times daily; (3) oral aspirin once daily; or (4) no prolonged prophylaxis. Probabilities and costs were estimated on the basis of published literature and average Medicare reimbursement. The decision analysis was conducted from the perspective of the health care system, with the primary end point being cost per patient without venous thromboembolism (VTE). Sensitivity analyses tested the robustness of the results. RESULTS: LDUH was most cost-effective, saving $154 per patient without VTE compared with no prophylaxis. LMWH was not cost-effective, incurring a cost of $230 per patient without VTE compared with no prophylaxis. Aspirin was a viable alternative to LDUH, saving $123 compared with no prophylaxis. When poor compliance was considered, aspirin became the dominant strategy. Sensitivity analyses failed to show any instance where LMWH was cost-effective. In terms of population costs, widespread use of LDUH after discharge would save $30.3 million per year in the United States. CONCLUSIONS: Although all chemical prophylaxis is effective in preventing VTE in the outpatient setting after cancer surgery, either LDUH or aspirin are the most cost-effective, depending on patient compliance.

Low-molecular-weight heparins: pharmacoeconomic decision modeling based on meta-analysis data.

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.

Chronically anticoagulated patients who need surgery: can low-molecular-weight heparins really be used to "bridge" patients instead of intravenous unfractionated heparin?

Patients at high risk of arterial or venous thromboembolic events often receive chronic treatment with long-term oral anticoagulants such as warfarin. However, if these patients require an invasive procedure, they may require a temporary interruption of their warfarin therapy to minimize their bleeding risk during the procedure. As warfarin has a long half-life and an unpredictable pharmacokinetic profile, short-acting parenteral anticoagulants, such as unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH), may be of benefit in protecting the patient from thromboemboli while their warfarin dose is withheld. Such "bridging therapy" has traditionally been provided in-hospital with intravenous UFH; however, recent data have suggested that LMWH may be an effective alternative, with potential cost-savings due to the ability to provide bridging therapy in the outpatient setting.

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

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

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

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

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

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

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

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

Treatment of pulmonary embolism: The use of low-molecular-weight heparin in the inpatient and outpatient settings.

Pulmonary embolism (PE) remains a major clinical problem associated with considerable mortality and morbidity. In patients with PE, appropriate anticoagulant therapy has been shown to significantly reduce both recurrence and mortality. Low-molecular-weight heparin (LMWH) is at least as effective as unfractionated heparin (UFH) in the treatment of PE, with a similar risk of bleeding. Furthermore, LMWH offers more predictable pharmacokinetics and anticoagulant effects. As a result, current guidelines from both the American College of Chest Physicians and the joint American College of Physicians/American Academy of Family Physicians recommend the use of LMWH over UFH (in patients with submassive PE). Outpatient treatment with LMWH has been shown to be feasible in many patients, and offers the potential for cost-savings and improvements in health-related quality of life. Further data are needed to support an evidence-based recommendation for the use of LMWH in the outpatient treatment of PE.