Cost-effectiveness of enoxaparin versus aspirin in the prevention of venous thromboembolism after total hip or knee arthroplasty: an analysis from the CRISTAL cluster-randomized trial.

Aims: The aim of this study was to evaluate the healthcare costs and benefits of enoxaparin compared to aspirin in the prevention of symptomatic venous thromboembolism (VTE) after total hip arthroplasty (THA) or total knee arthroplasty (TKA) using data from the CRISTAL trial. Methods: This trial-based economic analysis reports value for money as incremental cost per quality-adjusted life-year (QALY) gained in 2022 Australian dollars, compared to a single threshold value of AUD$70,000 per QALY. Event costs were estimated based on occurrence of VTEs and bleeds, and on published guidelines for treatment. Unit costs were taken from Australian sources. QALYs were estimated using CRISTAL six-month follow-up data. Sensitivity analyses are presented that vary the cost of VTE treatment, and extend the analyses to two years. Results: The CRISTAL trial found that enoxaparin was more effective than aspirin in preventing symptomatic VTE within 90 days of THA or TKA (risk difference 1.97% (95% confidence interval (CI) 0.54% to 3.41%; p = 0.007)). The additional cost after a THA or TKA was AUD$83 (95% CI 68 to 97) for enoxaparin, and enoxaparin resulted in an additional 0.002 QALYs (95% CI -0.002 to 0.005). Incremental cost per QALY gained was AUD$50,567 (95% CI 15,513, dominated) for enoxaparin. We can be 60% confident that the incremental cost per QALY does not exceed the willingness-to-pay threshold of AUD$70,000. Increasing the cost of VTE treatment and extension of costs and consequences to two years suggested greater confidence that enoxaparin is good value for money (70% and 63% confidence, respectively). Conclusion: This analysis provides strong evidence that enoxaparin thromboprophylaxis following THA or TKA reduced VTEs, but weak evidence of net economic benefits over aspirin. If the value of avoiding VTEs is high, and there is a strong likelihood of VTE-related health impairments, we can be more confident that enoxaparin is cost-effective compared to aspirin.

Prophylactic anticoagulation after minimally invasive hysterectomy for endometrial cancer: a cost-effectiveness analysis.

OBJECTIVE: To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer. METHODS: All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained. RESULTS: Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was ≥4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSIONS: In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.

Comparative Effectiveness and Costs of Enoxaparin Monotherapy Versus Unfractionated Heparin Monotherapy in Treating Acute Coronary Syndrome.

BACKGROUND: Enoxaparin and unfractionated heparin (UFH) are guideline-recommended anticoagulants for patients with acute coronary syndrome (ACS), including unstable angina (UA) and myocardial infarction with (STEMI) or without ST-segment elevation (NSTEMI). Prior efficacy and safety evidence are mainly from clinical trials. Economic data are insufficient. This study examined the differences in utilization, effectiveness, safety, and costs in treating ACS between enoxaparin and UFH monotherapy using real-world data. METHODS: Using data from 859 US hospitals, inpatients ≥ 18 years of age with a diagnosis of an initial episode of ACS between 2010 and 2016 were identified. Outcomes included 30-day risk of non-fatal myocardial infarction (MI), recurrent angina, in-hospital mortality, composite ischemic complication (having MI/recurrent angina/death), major bleeding, and costs. Multivariable regression was used to compare outcomes between enoxaparin and UFH monotherapy. RESULTS: Among 1,048,053 eligible patients (UA: 219,259; NSTEMI: 582,134; STEMI: 246,660), the prevalence of enoxaparin monotherapy was 12.0%, 13.9%, and 5.1%, and the prevalence of UFH monotherapy was 45.1%, 43.1% and 59.8%, for UA, NSTEMI, and STEMI patients, respectively. Enoxaparin was associated with a lower risk of ischemic complications and death among NSTEMI, but not in UA or STEMI patients, and with a lower risk of major bleeding in all patients. Cost savings per patient during index admission and 30-day follow-up for enoxaparin over UFH was $2972 for UA, $2475 for NSTEMI, and $3050 for STEMI. CONCLUSIONS: Enoxaparin was associated with a lower risk of ischemic complications (including death), lower costs, and better safety than UFH among NSTEMI patients. Improving upstream selection of anticoagulants in appropriate populations may help optimize clinical outcomes and costs.

Real-World Comparative Effectiveness and Cost Comparison of Thromboprophylactic Use of Enoxaparin versus Unfractionated Heparin in 376,858 Medically Ill Hospitalized US Patients.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication in medically ill inpatients. Enoxaparin or unfractionated heparin (UFH) thromboprophylaxis has been shown to reduce VTE in clinical trials; however, comparative effectiveness and differences in hospital costs are unknown in US hospital practice. OBJECTIVE: This study compared clinical and economic outcomes between enoxaparin and UFH thromboprophylaxis in medically ill inpatients. METHODS: A retrospective cohort study was conducted using the Premier Healthcare Database between 1 January 2010 and 30 September 2016. Inpatients aged ≥ 18 years with a ≥ 6-day hospital stay for serious medical conditions were included. Two patient groups receiving thromboprophylaxis were identified during hospitalization: one receiving enoxaparin and other receiving UFH. Regression models were constructed to compare VTE events, in-hospital mortality, pulmonary embolism (PE)-related mortality, major bleeding, and total hospital costs during both the index hospitalization and the 90-day readmission period between the two groups. RESULTS: A total of 242,474 and 134,384 inpatients received enoxaparin or UFH for thromboprophylaxis, respectively. Compared with UFH prophylaxis, enoxaparin was significantly associated with 15%, 9%, 33%, and 41% reduced odds of VTE, in-hospital mortality, PE-related mortality, and major bleeding, respectively, during index hospitalization, and 10% and 19% reduced odds of VTE and bleeding, respectively, during the readmission period. Mean total hospital costs were significantly lower in patients receiving enoxaparin prophylaxis than in those given UFH. CONCLUSIONS: Thromboprophylaxis with enoxaparin was associated with significantly reduced in-hospital VTE events, death, and major bleeding and lower hospital costs compared with UFH in hospitalized medically ill patients.

Multi-Criteria Model for Evaluating Drugs to Prevent Deep Venous Thrombosis Associated With Orthopedic Surgery: A Hospital-Based Case Study.

BACKGROUND: It's estimated that 40% to 60% of patients undergoing major orthopedic surgery of the hip or knee who do not receive thromboprophylaxis will develop deep venous thrombosis Instituto Nacional de Traumatologia e Ortopedia has established a guideline to prevent DVT with the administration of the Enoxaparin. Recently, institute stakeholders have been questioning this guideline as new oral anticoagulants that offer more comfort and efficacy, but present higher risk of bleeding, have been appearing in the market for treating deep venous thrombosis. OBJECTIVE: This study aims to validate the application of a multicriteria decision analysis in a real-world problem, the use of rivaroxaban and enoxaparin to prevent deep venous thrombosis. METHODS: The multicriteria method MACBETH (Measuring Attractiveness by a Categorical Based Evaluation Technique) was used in a decision conferencing process to develop an evaluation model for measuring the relative value of the drugs on each evaluation criterion, separately and globally. The model-building process was informed by a literature review and meta-analysis of randomized clinical trials with a critical appraisal of the evidence. RESULTS: We report a model-structure with eight criteria, each one associated with a weighting coefficient and value function. Following a simple additive aggregation process, the model-outputs showed that Rivaroxaban was considered a robust option for DVT. Sensitivity analysis and robustness analysis were performed and testify the consistency of the results. CONCLUSION: This article contributes to literature by showing how MACBETH method can be combined with scientific evidence and participatory group processes, for health technology assessment in hospitals.

Cost-effectiveness of apixaban for prevention of venous thromboembolic events in patients after gynecologic cancer surgery.

OBJECTIVE: The cost-effectiveness of apixaban was compared with enoxaparin for prevention of postoperative venothromboembolic events (VTE) in gynecologic oncology patients. Current guidelines recommend thromboprophylaxis with low molecular weight heparin for 28 days following gynecologic cancer surgery, but recent trials suggest that oral apixaban may be a safe, patient-preferred alternative. Apixaban was superior to enoxaparin in a Canadian cost-effectiveness analysis using orthopedics trial data. METHODS: Medication costs, adherence rates, event rates, event costs, and utility decrements were estimated using prior clinical trial data and literature review for input into a short-term decision model to simulate outcomes in a hypothetical cohort of 1000 patients. Incremental cost-effectiveness ratios (ICERs) were calculated as net cost difference per quality-adjusted life year (QALY) gained. Input values at which net costs and QALYs were equivalent and ICERs at upper and lower bounds were evaluated. RESULTS: Using aggregated costs, apixaban was less expensive and more effective than enoxaparin, and remained so or had high value in all scenarios on sensitivity analysis. Examining disaggregated ICERs, apixaban was cost-effective for deep venous thrombosis (DVT); of high value for clinically-relevant non-major bleeding (CRNMB) ($411); low value for major bleeding ($183,465), VTE-related death ($2,711,229), and all-cause mortality ($297,522); and not cost-effective for pulmonary embolism prevention. CONCLUSIONS: Apixaban is more cost-effective than enoxaparin for the prevention of postoperative VTE in patients with gynecologic cancer. This appears to be driven largely by DVT and CRNMB prevention.

Medicine wastage in a thromboprophylaxis protocol for ambulatory trauma patients.

Thromboprophylactic medicine is provided routinely to patients who present to emergency departments (EDs) with lower leg fractures as a preventive measure against forming blood clots in an immobilised limb. A large amount of medicine is provided to these patients at discharge, but once they have recovered their mobility the remaining medicine is unusable and must be destroyed. There is a lack of data to quantify this waste. This article reports a service evaluation that was conducted in an ED to investigate the wastage and the cost implications of this treatment protocol. It shows that over half the medicine dispensed is subsequently wasted and makes recommendations for changing dispensing practice.

Economic Evaluation of Rivaroxaban Versus Enoxaparin for Prevention of Venous Thromboembolism After Total Knee Replacement and Total Hip Replacement: A Systematic Review.

BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism (PE) together are called venous thromboembolism (VTE) and impose a high economic burden on healthcare systems. Thousands of people are hospitalized annually due to benign and treatable diseases but die due to PE; with the adoption of appropriate prevention, these deaths can be prevented. OBJECTIVE: To investigate the cost-effectiveness of using rivaroxaban versus enoxaparin in published economic analyses for prevention of VTE after total knee (TKR) or hip replacement (THR). METHOD: In a systematic review electronic searches were performed on various online databases, including PubMed, Web of science, Embase, Scopus, Health Economic Evaluations Database (HEED), and ProQuest. The inclusion criteria were: studies that were conducted on the cost-effectiveness of rivaroxaban versus enoxaparin for the prevention of VTE after TKR and THR; cost-effectiveness studies conducted using decision analysis models based on the economic evaluation approach; studies with available full-text papers; and studies written in English and published between 2007 and 2019. The exclusion criteria were: studies with partial cost effectiveness (such as effectiveness assessment, cost assessment, quality-of-life assessment); studies written in languages other than English; and all protocols, conference abstracts, and letters to the editor. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to qualitatively evaluate the studies. RESULTS: Of a total of 537 initial studies, nine papers met the inclusion criteria. The time scope of studies ranged from 3 months to 5 years. Among the selected studies, some studies had included discount rates (n = 4) and the other studies did not utilize discount rates and were set to zero percent by default (n = 5). In all studies, direct medical costs, including costs related to the prevention, diagnosis, and treatment of VTE and PE, and management and monitoring of treatment costs were reviewed. CONCLUSION: The results of this systematic review showed that using rivaroxaban in patients undergoing total knee or hip replacement reduced costs and increased quality of life. However, since most of the studies had been conducted in developed countries, it is not possible to generalize the results to developing countries. Nonetheless, given that rivaroxaban is administered orally and does not require continuous monitoring, it will be less costly for patients and health systems and is more appropriate to administer it as a thromboprophylactic drug following total knee or hip replacement surgery.

A Caprini Risk Score-Based Cost-Effectiveness Analysis of Enoxaparin for the Thromboprophylaxis of Patients After Nonorthopedic Surgery in a Chinese Healthcare Setting.

BACKGROUND: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important cause of post-surgery morbidity and mortality. However, it is unclear whether thromboprophylaxis with the low-molecular-weight heparin (LMWH) enoxaparin after non-orthopedic surgery could balance the cost and clinical outcomes or not. OBJECTIVES: The purpose of this research was to evaluate the cost-effectiveness of enoxaparin for the universal prophylaxis of VTE and associated long-term complications in patients after non-orthopedic surgery compared with no prevention in a Chinese healthcare setting. METHODS: A decision model, which included both acute VTE and long-term complications, was developed to assess the economic outcomes of the two strategies for patients after non-orthopedic surgery. Quality-adjusted life years (QALYs) and direct medical costs were measured over a 5-year horizon. Incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Compared with no prevention, patients under enoxaparin treatment with Caprini risk scores of 3-4, 5-6, 7-8, and ≥ 9 increased by 0.012, 0.017, 0.034, and 0.102 in QALYs, respectively. The results were either that ICERs of thromboprophylaxis with enoxaparin over no prevention were lower than the thresholds or that thromboprophylaxis with enoxaparin was dominant. For patients with a Caprini risk score ≥ 9, thromboprophylaxis with enoxaparin is dominant across the whole drug use duration range. The sensitivity analysis confirmed the results. CONCLUSIONS: As the first analysis evaluating the economic outcomes of enoxaparin in patients undergoing general non-orthopedic surgery, this study suggests that thromboprophylaxis with enoxaparin is highly cost-effective compared with no prevention in patients with Caprini risk score ≥ 3.

The cost-effectiveness and cost-utility analysis of the use of enoxaparin compared with heparin for venous thromboembolism prophylaxis in medical inpatients in Iran.

BACKGROUND: Moderate to high risk medical inpatients are at increased risk of Venous Thromboembolism (VTE). The present study aims to investigate the cost-effectiveness and cost-utility of using Enoxaparin compared to Heparin in VTE prophylaxis in medical inpatients, from Iranian payer's perspective. METHODS: Decision tree modeling technique was used to evaluate cost-effectiveness and cost-utility of the compared interventions. The main considered outcomes were Life Years Gained (LYG) for Cost-Effectiveness Analysis (CEA) and Quality-Adjusted Life Years (QALY) for Cost-Utility Analysis (CUA). Costs and consequences of the interventions were evaluated for a three-month period and reported as Incremental Cost-Effectiveness Ratios (ICERs). One-way and Probabilistic Sensitivity Analysis (PSA) were conducted to evaluate the robustness of the model due to uncertainty in the input data. RESULTS: In base case scenario (i.e. public tariff), incremental cost was $10.32, and incremental QALY and incremental LYG were 0.0001 and 0.0002 per patients respectively. Base case ICERs were 60,376 USD/QALY and 71,077 USD/LYG per patient. The results of the sensitivity analysis showed the robustness of the model. CONCLUSION: As the estimated ICER per QALY is more than three times the reported Gross Domestic Product (GDP) per capita by world bank for Iran in 2017 ($5415), the use of Enoxaparin for VTE prophylaxis in medical in patients doesn't seem to be a cost-effective intervention compared to the use of Heparin in Iran.

Cost-Effectiveness of Extended Thromboprophylaxis in Patients Undergoing Colorectal Surgery from a Canadian Health Care System Perspective.

BACKGROUND: There is increasing evidence to support extended thromboprophylaxis after colorectal surgery to minimize the incidence of postdischarge venous thromboembolic events. However, the absolute number of events is small, and extended thromboprophylaxis requires significant resources from the health care system. OBJECTIVE: This study aimed to determine the cost-effectiveness of extended thromboprophylaxis in patients undergoing colorectal surgery for malignancy or IBD. DESIGN: An individualized patient microsimulation model (1,000,000 patients; 1-month cycle length) comparing extended thromboprophylaxis (28-day course of enoxaparin) to standard management (inpatient administration only) after colorectal surgery was constructed. SETTINGS: The sources for this study were The American College of Surgeons National Surgical Quality Improvement Project Participant User File and literature searches. OUTCOMES: Costs (Canadian dollars), quality-adjusted life-years, and venous thromboembolism-related deaths prevented over a 1-year time horizon starting with hospital discharge were determined. The results were stratified by malignancy or IBD. RESULTS: In patients with malignancy, extended prophylaxis was associated with higher costs (+113$; 95% CI, 102-123), but increased quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), resulting in an incremental cost-effectiveness ratio of 2473$/quality-adjusted life-year. For IBD, extended prophylaxis also had higher costs (+116$; 95% CI, 109-123), more quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), and an incremental cost-effectiveness ratio of 2475$/quality-adjusted life-year. Extended prophylaxis prevented 16 (95% CI, 4-27) venous thromboembolism-related deaths per 100,000 patients and 22 (95% CI, 6-38) for malignancy and IBD. There was a 99.7% probability of cost-effectiveness at a willingness-to-pay threshold of 50,000$/quality-adjusted life-year. To account for statistical uncertainty around variables, sensitivity analysis was performed and found that extended prophylaxis is associated with lower overall costs when the incidence of postdischarge venous thromboembolic events reaches 1.8%. LIMITATIONS: Significant differences in health care systems may affect the generalizability of our results. CONCLUSIONS: Despite the rarity of venous thromboembolic events, extended thromboprophylaxis is a cost-effective strategy. See Video Abstract at http://links.lww.com/DCR/A976. COSTO-EFECTIVIDAD DE LA TROMBOPROFILAXIS EXTENDIDA EN PACIENTES SOMETIDOS A CIRUGÍA COLORRECTAL DESDE UNA PERSPECTIVA DEL SISTEMA DE SALUD CANADIENSE:: Cada vez hay más pruebas que apoyen la tromboprofilaxis extendida después de la cirugía colorrectal para minimizar la incidencia de eventos tromboembólicos venosos después del alta hospitalaria. Sin embargo, el número absoluto de eventos es pequeño y la tromboprofilaxis extendida requiere recursos significativos del sistema médico.Determinar la rentabilidad (relación costo-efectividad) de la tromboprofilaxis extendida en pacientes sometidos a cirugía colorrectal por neoplasia maligna o enfermedad inflamatoria intestinal.Un modelo de microsimulación de paciente individualizado (1,000,000 de pacientes; ciclo de 1 mes) que compara la tromboprofilaxis extendida (curso de enoxaparina de 28 días) con el tratamiento estándar (solo para pacientes hospitalizados) después de la cirugía colorrectal.Archivo de usuario participante del Proyecto de Mejoramiento de la Calidad Quirúrgica del Colegio Nacional de Cirujanos Americanos (ACS-NSQIP) y búsquedas bibliográficas.Costos (en dólares Canadienses), años de vida ajustados por la calidad y muertes relacionadas con el tromboembolismo venoso prevenidas en un horizonte temporal de 1 año a partir del alta hospitalaria. Los resultados fueron estratificados por malignidad o enfermedad inflamatoria intestinal.En pacientes con neoplasias malignas, la profilaxis extendida se asoció con costos más altos (+113 $; IC del 95%, 102-123), pero con un aumento de la calidad de vida ajustada por años de vida (+0.05; IC del 95%, 0.04-0.06), lo que resultó en un incremento de relación costo-efectividad de 2473 $/año de vida ajustado por calidad. Para la enfermedad inflamatoria intestinal, la profilaxis extendida también tuvo costos más altos (+116 $; 95% IC, 109-123), más años de vida ajustados por calidad (+0.05; 95% IC, 0.04-0.06) y una relación costo-efectividad incremental de 2475 $/año de vida ajustado por calidad. La profilaxis prolongada evitó 16 (95% IC, 4-27) muertes relacionadas con tromboembolismo venoso por cada 100,000 pacientes y 22 (95% IC, 6-38) por malignidad y enfermedad inflamatoria intestinal, respectivamente. Hubo un 99.7% de probabilidad de costo-efectividad en un límite de disposición a pagar de 50,000 $/año de vida ajustado por calidad. Para tener en cuenta la incertidumbre estadística en torno a los variables, se realizó un análisis de sensibilidad y se encontró que la profilaxis extendida se asocia con menores costos generales cuando la incidencia de eventos tromboembólicos venosos después del alta hospitalaria alcanza 1.8%.Las diferencias significativas en los sistemas de salud pueden afectar la generalización de nuestros resultados.A pesar de la escasez de eventos tromboembólicos venosos, la tromboprofilaxis extendida es una estrategia rentable. Vea el video del resumen en http://links.lww.com/DCR/A976.

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.

Capped antithrombin III dosing is cost effective in the management of asparaginase-associated thrombosis.

Asparaginase therapy induces a transient antithrombin III (ATIII) deficiency, which contributes to the risk of asparaginase-induced thrombosis. At Cincinnati Children's Hospital Medical Center, management of asparaginase-induced thrombosis includes ATIII supplementation during therapeutic anticoagulation with enoxaparin. Due to the expense associated with ATIII, a capped dosing approach for ATIII was evaluated in this population. Peak ATIII levels were obtained following capped doses to evaluate response. In this pilot evaluation, 11 patients received a total of 138 capped doses for a total cost savings of $803 782. This pilot evaluation represents the first reported analysis of capped ATIII dosing in oncology patients.

Cost-Effectiveness of Betrixaban Compared with Enoxaparin for Venous Thromboembolism Prophylaxis in Nonsurgical Patients with Acute Medical Illness in the United States.

BACKGROUND: Studies show that the risk of venous thromboembolism (VTE) continues post-discharge in nonsurgical patients with acute medical illness. Betrixaban is the first anticoagulant approved in the United States (US) for VTE prophylaxis extending beyond hospitalization. OBJECTIVE: The aim was to establish whether betrixaban for VTE prophylaxis in nonsurgical patients with acute medical illness at risk of VTE in the US is cost-effective compared with enoxaparin. METHODS: A cost-effectiveness analysis was conducted, estimating the cost per quality-adjusted life-year (QALY) gained with betrixaban (35-42 days) compared with enoxaparin (6-14 days) from a US payer perspective over a lifetime horizon. A decision tree (DT) estimated primary VTE events, thrombotic events, and treatment complications in the first 3 months based on data from the phase III Acute Medically Ill VTE Prevention with Extended Duration Betrixaban study. A Markov model estimated recurrent events and long-term complication risks from published literature. EuroQoL-5 Dimensions utility data and costs inflated to 2017 US dollars (US$) were from published literature. Results were discounted at 3.0% per annum. Deterministic and probabilistic sensitivity analyses explored uncertainty. RESULTS: Betrixaban dominated enoxaparin, with savings of US$784 and increased QALYs of 0.017 per patient. In addition, betrixaban dominated enoxaparin across all sensitivity analyses, but was most sensitive to utilities and DT probabilities. Furthermore, probabilistic sensitivity analysis found that betrixaban was more cost-effective than enoxaparin at all willingness-to-pay thresholds. CONCLUSION: Betrixaban can be considered cost-effective for nonsurgical patients with acute medical illness at risk of VTE, requiring longer VTE prophylaxis from hospitalization through post-discharge.

Análise de Custo-efetividade e Impacto Orçamentário de Anticoagulantes no Tratamento da Trombose Venosa Profunda em Pacientes Oncológicos / Analysis of Cost-effectiveness and Budget Impact of Anticoagulants in the Treatment of Deep Venous Thrombosis in Oncology Patients / Análisis de Costo-efectividad e Impacto Presupuestal de Anticoagulantes en el Tratamiento de la Trombosis Venosa Profunda en Pacientes Oncológicos

Introdução: A trombose venosa profunda é uma complicação comum e intimamente relacionada às neoplasias. Novos anticoagulantes orais foram lançados nos últimos anos, entre eles, a rivaroxabana. Objetivo: O estudo analisou o custo-efetividade e o impacto orçamentário da rivaroxabana versus enoxaparina. Método: Trata-se de uma coorte retrospectiva, realizada com população oncológica sob a perspectiva do Sistema Único de Saúde. Por meio do modelo de árvore de decisão, foram comparados desfechos de sangramento e retrombose, e custos do tratamento da trombose venosa profunda com rivaroxabana ou enoxaparina, em um horizonte temporal de sete meses. Custos diretos foram extraídos do Sistema de Gerenciamento da Sistema de Gerenciamento da Tabela de Procedimentos, Medicamentos, Órteses, Próteses e Materiais e Medicamentos Especiais do SUS (SIGTAP-SUS), e empregou-se a Planilha Brasileira de Impacto Orçamentário de tecnologias da saúde para avaliação do impacto orçamentário com base na população brasileira de 2017, em cinco anos. A análise de sensibilidade simulou cenários tanto na avaliação de custo-efetividade quanto na de impacto orçamentário. Resultados: Cento e cinquenta e três pacientes foram incluídos na análise de custo-efetividade com diversas neoplasias. A rivaroxabana demonstrou não inferioridade terapêutica comparada à enoxaparina. A razão de custo-efetividade incremental foi de R$ 5.521,71 por unidade de benefício ganho com a nova alternativa, rivaroxabana. Na análise de sensibilidade, a rivaroxabana manteve-se dominante. Foi demonstrada uma economia no impacto orçamentário incremental de R$ 85.950.791.129,21 com a utilização de rivaroxabana ao longo de cinco anos em comparação ao cenário de referência, e esta se manteve como opção mais econômica perante as análises de sensibilidade. Conclusão: A rivaroxabana, nesse contexto, apresentou-se como uma importante alternativa terapêutica.

Introduction: Deep vein thrombosis is a common complication and closely related to neoplasms. New oral anticoagulants have been launched in recent years, among them rivaroxaban. Objective: The study analyzed the cost-effectiveness and budget impact of rivaroxaban versus enoxaparin. Method: This is a retrospective cohort, performed with oncological population from the perspective of Sistema Único de Saúde (National Health System). The decision tree model compared outcomes of bleeding and rethrombosis, and costs of treatment of deep venous thrombosis with rivaroxaban or enoxaparin in a time horizon of seven months. Direct costs were extracted from the SIGTAP-SUS, and the Brazilian Spreadsheet for Budgetary Impact of Health Technologies was used to evaluate the budgetary impact based in the Brazilian population of 2017 over a five-year period. The sensitivity analysis simulated scenarios for both cost-effectiveness and budget impact assessments. Results: One hundred and fifty-three patients were included in the cost-effectiveness analysis with several neoplasms. Rivaroxaban demonstrated no therapeutic inferiority compared to enoxaparin. The incremental cost-effectiveness ratio was R$ 5,521.71 per benefit unit spared with the new alternative, rivaroxaban. In the sensitivity analysis, rivaroxaban remained dominant. An economy in incremental budget impact of R$ 85,950,791,129.21 was demonstrated with the use of rivaroxaban over five years in comparison to the reference scenario, and this continued as the most economic option in relation to sensitivity analyzes. Conclusion: In this context rivaroxaban was an important therapeutic alternative.

Introducción: La trombosis venosa profunda es una complicación común e íntimamente relacionada a las neoplasias. Los nuevos anticoagulantes orales. Objetivo: El estudio analizó el Costo-Efectividad y el Impacto Presupuestario de la rivaroxabana versus enoxaparina. Método: En el modelo de árbol de decisión se compararon los resultados de la hemorragia y la retrombosis, y los costos del tratamiento de la trombosis venosa profunda con rivaroxabana o enoxaparina, con una cohorte retrospectiva, realizada con población oncológica bajo la perspectiva del Sistema Único de Salud en un horizonte temporal de siete meses. Los costos directos fueron extraídos del SIGTAP-SUS, y se empleó la Planilla Brasileña de Impacto Presupuestario de Tecnologías de la Salud para evaluación del Impacto Presupuestario con base en la población brasileña de 2017 en un horizonte temporal de cinco años. El análisis de sensibilidad simuló escenarios tanto en la evaluación de Costo-Efectividad y en la de Impacto Presupuestario. Resultados: Ciento cincuenta y tres pacientes fueron incluidos en el análisis de Costo-Efectividad con diversas neoplasias. La rivaroxabana demostró no inferioridad terapéutica comparada a la enoxaparina. La razón de costo-efectividad incremental fue de R $ 5.521,71 por unidad de beneficio ganada con la nueva alternativa, rivaroxabana. En el análisis de sensibilidad, la rivaroxabana se mantuvo dominante. Se demostró una economía em el Impacto Presupuestario incremental de R$ 85.950.791.129,21 con la utilización de rivaroxabana a lo largo de 5 años en comparación al escenario de referencia, y ésta se mantuvo como opción más económica ante los análisis de sensibilidad. Conclusión: La rivaroxabana, en este contexto, se presentó como una importante alternativa terapéutica.

Hospital Resource Utilization and Costs Associated With Warfarin Versus Apixaban Treatment Among Patients Hospitalized for Venous Thromboembolism in the United States.

A real-world US database analysis was conducted to evaluate the hospital resource utilization and costs of patients hospitalized for venous thromboembolism (VTE) treated with warfarin versus apixaban. Additionally, 1-month readmissions were evaluated. Of 28 612 patients with VTE identified from the Premier Hospital database (August 2014-May 2016), 91% (N = 26 088) received warfarin and 9% (N = 2524) received apixaban. Outcomes were assessed after controlling for key patient/hospital characteristics. For index hospitalizations, the average length of stay (LOS) was longer (3.8 vs 3.1 days, P < .001; difference: 0.7 days) and mean hospitalization cost higher (US$3224 vs US$2,740, P < .001; difference: US$484) for warfarin versus apixaban-treated patients. During the 1-month follow-up period, warfarin treatment was associated with a greater risk of all-cause readmission (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 1.09-1.48, P = .003), major bleeding (MB)-related readmission (OR: 2.10; 95% CI: 1.03-4.27, P = .04), and any bleeding-related readmission (OR: 1.67; 95% CI: 1.09-2.56, P = .02) versus apixaban. The results of this real-world analysis show that compared to warfarin, apixaban treatment was associated with shorter index hospital stays, lower index hospitalization costs, and reduced risk of MB-related readmissions among hospitalized patients with VTE.

Meta-Analysis Comparing the Efficacy, Safety, and Cost-Benefit of Direct Acting Oral Anticoagulants Versus Enoxaparin Thromboprophylaxis to Prevent Venous Thromboembolism Among Hospitalized Patients.

Venous thromboembolism (VTE) is a potentially fatal complication of hospitalization. Thromboprophylaxis using subcutaneous low molecular weight heparin (LMWH) can result in local irritation, pain, and ecchymoses, leading to nonadherence. Direct acting oral anticoagulants (DOACs) are an alternative, but their efficacy and safety for short-term inpatient-only use versus LMWH, in medically hospitalized patients, has not been rigorously assessed. We performed a systematic review with meta-analyses and exploratory cost effectiveness analysis of Phase III randomized controlled trials comparing DOACs to LMWH for VTE prophylaxis to determine the risk and benefit of each. The primary efficacy end point (composite of total VTE and any-cause mortality) occurred in 1,321 of 10,978 (11.4%) of patients receiving DOAC prophylaxis and 1,084 of 10,600 (10.2%) with LMWH (odds ratio [OR] 0.84; 95% confidence interval [CI] 0.63 to 1.13). The primary safety end point (composite of major bleeding and clinically relevant bleeding) occurred in 519 of 16,131 (3.2%) of patients receiving DOACs and 381 of 14,616 (2.6%) with LMWH (OR 1.12; 95%CI 0.83 to 1.53). Subgroup analyses for efficacy (n = 9,233) and safety (n = 12,584) was conducted on patients randomized to Apixaban or LMWH. The primary efficacy end point occurred in 294 of 4618 (6.4%) patients on Apixaban and 383 of 4615 (8.3%) on Enoxaparin (OR 0.82; 95% CI 0.55 to 1.24). Major and clinically relevant bleeding occurred in 157 of 6278 (2.50%) and 185 of 6,306 (2.9%), respectively (OR 0.86; 95% CI 0.58 to 1.26). Exploratory cost effectiveness analysis suggested that Apixaban compared with Enoxaparin thromboprophylaxis could result in long-term cost savings. In conclusion, this systematic review of randomized controlled trials and meta-analysis, stratified by type of patients and drug, indicates noninferiority of DOACs in efficacy, safety, and cost for short-term VTE thromboprophylaxis among patients hospitalized for medical illness.

A RCT study of Rivaroxaban, low-molecular-weight heparin, and sequential medication regimens for the prevention of venous thrombosis after internal fixation of hip fracture.

The guidelines for the prevention of venous thromboembolism in orthopedic surgeries have reached a consensus on the postoperative conventional anticoagulation. However, the choice of anticoagulant drugs is yet controversial. The use of the drug rivaroxaban is expensive. Since the compliance of patients with low-molecular-weight heparin is considerably low, a cost-effective, efficacious and convenient anticoagulant program is essential. The present study investigated the efficacy, safety, patient compliance, and cost-effectiveness of low-molecular-weight heparin with sequential Rivaroxaban anticoagulant therapy in patients with a hip fracture, following internal fixation. A total of 287 patients with hip fractures were randomized into three groups: Rivaroxaban alone, Enoxaparin alone, and Enoxaparin followed by Rivaroxaban. The primary endpoint was the incidence of postoperative VTE, whereas the secondary endpoints were the compliance and treatment costs. Adverse reactions included bleeding and wound complications. The incidences of VTE were 5.21%, 14.74%, and 10.42% in the Rivaroxaban, low-molecular-weight heparin, and sequential therapy groups, respectively. The VTE-related mortality rates were 0%, 1.05%, and 1.04%. The average hospital stay was 12±8,15±7, and 11±5d, whereas the compliance rates of the three groups were 82.3%, 71.6%, and 88.5%, respectively. The incidences of adverse incisions were 14.6%, 4.2%, and 6.3% for the three groups examined. The effects and the incidence of postoperative bleeding in the treatment of low-molecular-weight heparin followed by Rivaroxaban did not differ significantly from that of Rivaroxaban alone. However, the postoperative drainage, the cost of treatment and the incidence of VTE reduced significantly, whereas the incidences of adverse incisions and the patient compliance were increased. TRIAL REGISTRATION: ChiCTR-INR-17010495.

Cost-Effectiveness Analysis of Rivaroxaban for Treatment of Deep Vein Thrombosis and Pulmonary Embolism in Greece.

BACKGROUND AND OBJECTIVE: Venous thromboembolism (VTE), comprising deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a major healthcare concern that results in substantial morbidity and mortality with great economic burden for healthcare systems. Hence, the need for effective and efficient treatment of patients with VTE is important for both clinical and economic reasons. The objective of this study was to evaluate the cost effectiveness of rivaroxaban compared to standard of care (SoC) with enoxaparin followed by dose-adjusted vitamin-K antagonists for the treatment of DVT and PE in Greece. METHODS: An existing Markov model was locally adapted from a third-party payer perspective to reflect the management and complications of DVT and PE in the course of 3-month cycles, up to death. The clinical inputs and utility values were extracted from published studies. Direct medical costs, obtained from local resources, were incorporated in the model and refer to year 2017. Both costs and outcomes were discounted at 3.5%. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was calculated. Probabilistic sensitivity analysis (PSA) was carried out to deal with uncertainty. RESULTS: The base-case analysis showed that rivaroxaban in 3- and 6-month treatment duration for DVT and PE, respectively, as this is the common clinical practice in Greece, was associated with a 0.02 and 0.01 increment in QALYs compared to SoC, respectively. Rivaroxaban was associated with a reduced total cost in DVT (€85) but with an additional total cost in PE (€2) compared to SoC. Therefore, rivaroxaban was a dominant (less costly, more effective) and cost-effective (ICER: €177) alternative over SoC for the management of DVT and PE, respectively. PSA revealed that the probability of rivaroxaban being cost effective at a threshold of €34,000 per QALY gained was 99% and 81% for DVT and PE, respectively. CONCLUSION: Rivaroxaban may represent a cost-effective option relative to SoC for the management of DVT and PE in Greece.

Cost-Effectiveness of Different Strategies for the Prevention of Venous Thromboembolism After Total Hip Replacement in China.

INTRODUCTION: The aim of this study was to evaluate the cost-effectiveness of rivaroxaban and apixaban versus enoxaparin for the universal prophylaxis of venous thromboembolism (VTE) and associated long-term complications in Chinese patients after total hip replacement (THR). METHODS: A decision model, which included both acute VTE (represented as a decision tree) and the long-term complications of VTE (represented as a Markov model), was developed to assess the economic outcomes of the three prophylactic strategies for Chinese patients after THR. Transition probabilities for acute VTE were derived from two randomized controlled studies, RECORD1 and ADVANCE3, of patients after THR. The transition probabilities of long-term complications after acute VTE, utilities, and costs were derived from the published literature and local healthcare settings. One-way and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty concerning the model parameters. The quality-adjusted life years (QALYs) and direct medical costs were reported over a 5-year horizon, and incremental cost-effectiveness ratios (ICERs) were also calculated. RESULTS: Thromboprophylaxis with apixaban was estimated to have a higher cost (US $178.70) and more health benefits (0.0025 QALY) than thromboprophylaxis with enoxaparin over a 5-year time horizon, which resulted in an ICER of US $71,244 per QALY gained and was more than three times the GDP per capita of China in 2014 (US $22,140). Owing to the higher cost and lower generated QALYs, rivaroxaban was inferior to enoxaparin among post-THR patients. The sensitivity analyses confirmed these results. CONCLUSIONS: The analysis found that apixaban was not cost-effective and that rivaroxaban was inferior to enoxaparin. This finding indicates that compared with enoxaparin, the use of apixaban for VTE prophylaxis after THR does not represent a good value for the cost at the acceptable threshold in China; in addition, the cost of rivaroxaban was higher with lower QALYs.