Cost-effectiveness of fondaparinux versus enoxaparin in non-ST-elevation acute coronary syndrome in Canada (OASIS-5).

BACKGROUND: Acute coronary syndrome (ACS) refers to a spectrum of life-threatening cardiac diseases usually due to coronary artery plaque rupture, subsequent thrombin generation plaque activation and thrombus formation. To date, no economic analyses have been published about the use of fondaparinux in NSTE-ACS patients in Canada. The purpose of our study is to estimate the lifetime cost-effectiveness of fondaparinux compared to enoxaparin for non-ST-elevation acute coronary syndrome (NSTE-ACS) patients in a Canadian hospital setting. METHODS: As an extension of a previous published economic analysis for US patients, an event-based decision analytic model was constructed using clinical and resource use data from OASIS-5, a randomized trial of 20,078 patients from 41 countries. A public payer perspective in the hospital setting was adopted. Resource use data from the trial were valued using Canadian costs. A cost regression model was developed to estimate the mean cost of managing the clinical events over the 180 day period. Annual costs of long-term care for ACS patients were added after 180 days until death. Long-term survival was incorporated using Canadian life tables with further adjustment for additional risks associated with NSTE-ACS. Quality-of-life (utility) decrements from published sources were applied to clinical events. Lifetime costs (2009 CAD$) and quality-adjusted life-years (QALYs), discounted annually at 5 %, were estimated for the typical patient in OASIS-5 (i.e., at mean covariate values). RESULTS: The trial data showed that fondaparinux is protective against all clinical events observed in the trial. The model showed that: over 180 days, fondaparinux dominates enoxaparin, producing similar estimates of QALYs gained and saving $439; over a patient's lifetime, fondaparinux yields an ICER of $4293/QALY. Based on PSA, the probabilities that fondaparinux dominates enoxaparin (less costly and more effective) and that is cost-effective at a $50,000 threshold were 42 % and 96 %, respectively. CONCLUSIONS: In the Canadian hospital setting, fondaparinux is cost-effective when compared to enoxaparin for the treatment of NSTE-ACS. This result holds both in the immediate post-event period and over the lifetimes of patients.

Cost-Effectiveness Analysis of Fondaparinux vs Enoxaparin in Non-ST Elevation Acute Coronary Syndrome in Thailand.

BACKGROUND: Non-ST elevation acute coronary syndrome (NSTE-ACS) imposes a significant health and economic burden on a society. Anticoagulants are recommended as standard therapy by various clinical practice guidelines. Fondaparinux was introduced and evaluated in a number of large randomised, controlled trials. This study therefore aimed to determine the cost-effectiveness of fondaparinux versus enoxaparin in the treatment of NSTE-ACS in Thailand. METHODS: A two-part construct model comprising a one-year decision tree and a Markov model was developed to capture short and long-term costs and outcomes from the perspective of provider and society. Effectiveness data were derived from OASIS-5 trial while bleeding rates were derived from the Thai Acute Coronary Syndrome Registry (TACSR). Costs data were based on a Thai database and presented in the year of 2013. Both costs and outcomes were discounted by 3% annually. A series of sensitivity analyses were performed. RESULTS: The results showed that compared with enoxaparin, fondaparinux was a cost-saving strategy (lower cost with slightly higher effectiveness). Cost of revascularisation with major bleeding had a greater impact on the amount of cost saved both from societal and provider perspectives. With a threshold of 160,000 THB ((4,857.3 USD) per QALY in Thailand, fondaparinux was about 99% more cost-effective compared with enoxaparin. CONCLUSION: Fondaparinux should be considered as a cost-effective alternative when compared to enoxaparin for NSTE-ACS based on Thailand's context, especially in the era of limited healthcare resources.

By-product from decoction process of Hibiscus sabdariffa L. calyces as a source of polyphenols and dietary fiber.

BACKGROUND: Dietary fiber (DF) and antioxidant compounds are widely used as functional ingredients. The market in this field is competitive and the search for new types of quality ingredients for the food industry is intensifying. The aim of this study was to evaluate the composition and antioxidant activity of by-products generated during the decoction of calyces of four Mexican Hibiscus sabdariffa L. cultivars ('Criolla', 'China', 'Rosalis' and 'Tecoanapa') in order to assess them as a source of functional ingredients. RESULTS: Some calyx components were partially transferred to the beverage during the decoction process, while most were retained in the decoction residues. These by-products proved to be a good source of DF (407.4-457.0 g kg⁻¹ dry matter) and natural antioxidants (50.7-121.8 µmol Trolox equivalent g⁻¹ dry matter). CONCLUSION: The decoction process extracted some soluble carbohydrates, ash and some extractable polyphenols. The DF content changed in the dried residues, which could be considered as high-DF materials with a high proportion of soluble DF (∼20% of total DF) and considerable antioxidant capacity. These by-products could be used as an antioxidant DF source.

[A retrospective study of UFT and oral leucovorin plus PSK combination adjuvant chemotherapy in patients with stage III colon cancer].

OBJECTIVE: To perform a retrospective analysis of UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer in order to evaluate both treatment efficacy and toxicity. SUBJECTS: Between 2003 and 2009, 273 stage III colon cancer patients underwent surgery in our institute, and we studied 156 of them. RESULTS: Patients' median age was 72 years old; 87 men and 69 women. Of all patients, 119 had stage IIIa and 37 had stage IIIb. The 3-year disease, free survival rates for stage III, stage IIIa and stage IIIb patients were 73. 9%and 80. 6%and 51. 4%, respectively, and the 3-year overall survival rates for stage III was 97. 6%. With regard to toxicity, liver function disorder was observed in 9. 6%of the patients as the most frequent adverse event, but there was no grade 3 or 4 toxicity. CONCLUSION: UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer showed a good response especially for stage III a.

[Safety and economics of fondaparinux administration in the laparoscopic surgery].

BACKGROUND: The factor Xa inhibitor, fondaparinux was used for prevention of venous thromboembolism in the clinical setting. We evaluated the antithrombotic effect, complications and economic aspects of this agent in the patients undergoing laparoscopic surgery. METHODS: Forty one patients scheduled for laparoscopic abdominal surgery were divided into two groups. In group F (N = 33), patients received once-daily subcutaneous injection of fondaparinux (2.5 mg x day(-1)) for 4 postoperative days. In group E (N = 8), patients did not receive therapy. In group F, general anesthesia with transversus abdominis plane (TAP) block was administered during surgery, and general anesthesia with epidural anesthesia was performed in group E. We evaluated incidence of DVT (deep vein thrombosis), abnormal bleeding, other postoperative complications, and economic benefit to the hospital. RESULTS: In both groups, no patient developed DVT Abnormal bleeding was observed in 7 patients of group E. Postoperative complications and pain were not different between the two groups. The revenue in group F was 34,434 yen/patient lower than that of group E due to Japanease insulance system. CONCLUSIONS: No patients developed DVT and severe complications of fondaparinux after laparoscopic abdominal cancer surgery. However, revenue to the hospital decreased 34,434 yen/patient by use of analgestic method. We must consider cost-benefit in use of fondaparinux.

Fondaparinux versus Enoxaparin in non-ST-elevation acute coronary syndromes: short-term cost and long-term cost-effectiveness using data from the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators (OASIS-5) trial.

BACKGROUND: The study aimed to compare the short-term costs and long-term cost-effectiveness of 2 antithrombotics, fondaparinux and enoxaparin, for non-ST-elevation acute coronary syndrome in the United States. METHODS: It was based on a large randomized trial of 20,078 patients Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators [OASIS-5] comparing the therapies in these patients. In OASIS-5, fondaparinux patients had about half the rate of major bleeding 9 days after randomization and at least as good clinical outcomes (death, myocardial infarction, major bleeding and stroke) after 6 months of follow-up. Health care resource use and clinical efficacy data from the trial were incorporated into a cost-effectiveness model as applied to a general US health care system both for the time horizon of the study (6 months) and over the longer term. RESULTS: The 180-day cost analysis indicates that fondaparinux would generate a cost saving of $547 per patient (95% CI $207-$924). Sensitivity analysis suggested that savings could vary between $494 and $733. When 180-day cost and clinical results were extrapolated to long-term cost-effectiveness, fondaparinux was dominant (less costly and more effective in terms of quality-adjusted life-years) under most scenarios. CONCLUSIONS: Fondaparinux is a more cost-effective antithrombotic agent than enoxaparin in non-ST-elevation acute coronary syndrome. This is true across the range of event risks seen in OASIS-5.

Cost effectiveness of fondaparinux in non-ST-elevation acute coronary syndrome.

BACKGROUND: Fondaparinux has been shown to reduce the risk of major bleeding and 30-day mortality compared with enoxaparin, in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). However, its cost effectiveness is not well known. OBJECTIVE: To evaluate the effectiveness and economic attractiveness of fondaparinux relative to enoxaparin in patients with NSTE-ACS treated with triple antiplatelet therapy and early (non-urgent) invasive strategy. METHODS: The decision model compares two alternative strategies: subcutaneous (SC) enoxaparin (1 mg/kg 12 hourly) versus SC fondaparinux (2.5 mg/day) in NSTE-ACS patients pre-treated with triple antiplatelet therapy and early revascularization. Cost-effectiveness and cost-utility analyses were performed from a healthcare perspective, based on a Markov model with a time horizon of the patient lifespan. Univariate sensitivity analysis and probabilistic (Monte Carlo) microsimulation analysis were performed. RESULTS: In the base-case analysis (65 years, Thrombolysis In Myocardial Infarction [TIMI] score 4), the use of fondaparinux was associated with a significant reduction in major bleeding, a slight reduction in adverse cardiac events, and minor improvements in survival and QALYs, together with a small reduction in costs. The dominance of fondaparinux over enoxaparin remained unchanged in the univariate sensitivity analyses. According to Monte Carlo simulation, fondaparinux was cost saving in 99.9% of cases. CONCLUSION: Compared with enoxaparin, the use of fondaparinux in patients with NSTE-ACS managed with an early invasive strategy appears to be cost effective, even in patients with a low risk of bleeding.

Fondaparinux for the prevention or treatment of venous thromboembolism related to lower limb trauma: evidence today.

Patients with lower limb and pelvic trauma, or undergoing major orthopaedic surgery represent one of the highest risk groups for the development of venous thromboembolism (VTE). A significant number of pharmacological and mechanical agents have been used for the prophylaxis and treatment of VTE. Fondaparinux is a relative new pharmacological agent that selectively binds to antithrombin, and represents a new class of synthetic selective inhibitors of activated factor X. Eleven percent of the fondaparinux-related English language literature, between 2001 and 2007, refers to orthopaedic trauma, and was the sample assessed for this critical analysis review. The clinical studies evaluating the safety, efficacy, and financial implications associated with lower limb orthopaedic trauma show that fondaparinux has comparable results with the well-established use of enoxaparin. However, the scientific community has raised several issues regarding mostly fondaparinux's safety, timing of its 1(st) dose, bleeding side effects, duration of administration and lack of a reliable reversing agent. Further trials are necessary focusing on the safety and efficacy of this drug mostly in relation to clinical relevant outcomes and to different fields of trauma surgery (pelvis, long bone fractures and polytrauma patients).

Cost-effectiveness of extended prophylaxis with fondaparinux compared with low molecular weight heparin against venous thromboembolism in patients undergoing hip fracture surgery.

A model was developed to estimate costs and clinical effectiveness of fondaparinux compared with enoxaparin after hip fracture surgery in Sweden. Outcomes and costs of venous thromboembolism (VTE)-related care from a health care perspective were incorporated, with symptomatic deep-vein thrombosis and pulmonary embolism, recurrent VTE, post-thrombotic syndrome, major haemorrhage and all-cause death being included. Event probabilities were derived from fondaparinux clinical trial data and published data. VTE-related resource use and associated costs as well as costs of prophylaxis were based on local Swedish data. Extended prophylaxis with fondaparinux could avoid an additional 28 symptomatic VTE per 1,000 patients compared with extended prophylaxis with enoxaparin in hip fracture surgery patients. Although the prophylaxis costs were higher in the fondaparinux group, these were offset by the lower costs associated with treating fewer VTE, which thus indicates that extended fondaparinux prophylaxis is the dominant alternative when compared with enoxaparin in hip fracture surgery.

Review of fondaparinux sodium injection for the prevention of venous thromboembolism in patients undergoing surgery.

The antithrombin binding sequence of heparin, a pentasaccharide, has been synthesized as fondaparinux, an indirect, selective, and reversible factor Xa inhibitor. It can be administered subcutaneously, is well absorbed, and has a half-life of c. 17 hours permitting once-daily injection. It has been evaluated in an extensive study program in major orthopedic surgery, including hip fracture, and in major abdominal surgery with a large proportion of surgery for cancer. The effect is at least as effective as for low-molecular-weight heparins and it has also been shown effective for extended prophylaxis in hip fracture patients. Several thousands of patients have been studied and the substance is safe, although a slightly higher frequency of bleedings is found than in patients on low-molecular-weight heparins. There is no specific antidote but if necessary, recombinant activated factor VII can be used. Other side-effects are rare. Fondaparinux is cost saving and sometimes cost neutral when compared with enoxaparin.

Fondaparinux sodium compared with enoxaparin sodium: a cost-effectiveness analysis.

INTRODUCTION: Patients undergoing major orthopedic surgery face considerable risk of venous thromboembolism (VTE), which may be fatal unless they receive prophylactic treatment. Fondaparinux sodium is a new antithrombotic agent that is indicated for prophylaxis of VTE after major orthopedic surgery. This paper presents a cost-effectiveness analysis of fondaparinux sodium and enoxaparin sodium, the latter being the most commonly used agent for prophylaxis of VTE. METHODS: The analysis is based on an international simulation model, using Norwegian unit costs, and Norwegian data of 55 000 patients undergoing orthopedic surgery between 1999 and 2001. We estimated the expected incidence of VTE and VTE-related deaths, and expected costs of VTE-related care for each of the two prophylactic agents for different periods. RESULTS AND CONCLUSION: The results indicate that fondaparinux sodium is likely to be more effective than enoxaparin sodium in preventing the incidence of VTE. By day 90, fondaparinux sodium is expected to avoid 180 more VTE events, and between 8 and 33 more VTE-related deaths per 10,000 patients than enoxaparin sodium. Fondaparinux sodium is also a cost-saving option in short follow-up periods for hip fracture surgery. For extended follow-up periods (i.e. 5 years), fondaparinux sodium is also likely to represent the lower cost treatment option after total knee and hip replacement. The sensitivity analyses show that the main results are robust to changes in the most important parameters. Results are, however, sensitive to the price difference between the two drugs.

TIMERx: novel polysaccharide composites for controlled/programmed release of drugs in the gastrointestinal tract.

Over the last 100 years tablets have grown from first invention to becoming the world's leading medicinal form, by any measure. This article considers some of the reasons for the pre-eminence of pharmaceutical tablets. Particular attention has been given to the role of controlled-release tablets and to a very versatile hydrogel-based controlled-release technology, called TIMERx((R)). The unique nature of TIMERx intermolecular physical chemistry is described in relation to the technology's potential to provide any one of a number of different release profiles, ranging from zero order to chronotherapeutic release. The unusual nature of TIMERx technology lies in its ability to provide different release kinetics by the manipulation of molecular interactions. This 'molecular engine' replaces the need for complex processing or novel excipients and allows desired drug release profiles to be 'factory set' following a simple formulation development process. The article describes the physico-chemical interactions of TIMERx technology at a molecular level and how they can be manipulated by formulation considerations. The article describes how TIMERx technology has been developed to the point where today it underpins a number of marketed pharmaceutical CR products as well as products under development by Penwest Pharmaceuticals.

Cost considerations surrounding current and future anticoagulant therapies.

Because the costs of anticoagulation therapy are substantial and the difference between the risks and benefits of this therapy are often narrow, economic analyses are particularly valuable when weighing anticoagulation options. Economic analyses to date suggest that anticoagulation is most effective and results in the greatest cost savings when applied to populations at highest risk for thrombotic events. They also suggest that in situations where a more costly anticoagulant agent is available, that agent is cost-effective only if it is clearly more efficacious or if it substantially reduces costs in other areas, such as hospitalization. These principles should guide clinicians' choices of anticoagulation strategies.

The cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis against thromboembolism following major orthopedic surgery.

BACKGROUND: The selective antithrombotic fondaparinux is more effective than the low-molecular-weight heparin enoxaparin for prevention of venous thromboembolism (deep-vein thrombosis [DVT] or pulmonary embolism) in patients undergoing major orthopedic surgery, but its cost-effectiveness is undetermined. OBJECTIVES: To evaluate the cost-effectiveness of fondaparinux relative to enoxaparin as prophylaxis against venous thromboembolism (VTE) for patients undergoing total hip replacement, total knee replacement or hip fracture surgery in the UK. PATIENTS/METHODS: A decision analysis model was created simulating the impact of fondaparinux and enoxaparin on patient outcomes and costs over various time points up to 5 years following surgery. The main outcome measures were treatment costs per patient and the incidence of clinical VTE and VTE-related deaths. A weighted (combined) cohort reflects the proportion of patients undergoing these procedures in 2000/2001. RESULTS: In the combined cohort, compared with enoxaparin, fondaparinux is expected to produce 20 fewer clinical VTE events and 3.2 fewer VTE-related deaths per 1000 procedures at 5 years. Cost savings at 5 years are pound 27 per patient with fondaparinux (discounted at 6% per year). In each of the three surgical groups, fondaparinux leads to lower expected costs per patient and to a smaller number of VTE events and VTE-related deaths. RESULTS are sensitive to the price difference between fondaparinux and enoxaparin and variation in the rate of late DVT. The analysis is robust to variations in all other key parameters. CONCLUSIONS: Compared with enoxaparin, fondaparinux is more effective and reduces costs to the healthcare system. At current prices, fondaparinux is the recommended strategy in the UK for prophylaxis following major orthopedic surgery.

Pharmacoeconomics of thrombosis management.

Venous thromboembolism (VTE) is the cause of significant morbidity and mortality and may lead to other complications, including recurrent VTE and long-term postthrombotic syndrome. Venous thromboembolism represents a huge health economic burden of nearly 500 million dollars/year in the United States. Without adequate prophylaxis, patients undergoing major orthopedic surgery are at high risk of developing VTE. Prophylaxis with either unfractionated heparin or warfarin not only substantially reduces the risk of VTE after orthopedic surgery, but also is more cost-effective than no prophylaxis. Low-molecular-weight heparins (LMWHs) have been shown to be superior to unfractionated heparin or warfarin, and despite the fact that they are more expensive, they are cost-effective. Large-scale clinical trials have shown that fondaparinux further reduces the likelihood of VTE complications after major orthopedic surgery. A review of the pharmacoeconomic evaluations of fondaparinux leads to the conclusion that fondaparinux is a cost-effective alternative to LMWHs in VTE prophylaxis.

Pharmacoeconomic analysis of fondaparinux versus enoxaparin for the prevention of thromboembolic events in orthopedic surgery patients.

INTRODUCTION: Fondaparinux is a novel synthetic antithrombotic that has been evaluated for the prevention of venous thromboembolism (VTE). In four large trials in patients who underwent major hip or knee surgery, fondaparinux was found to have a good safety profile and be more effective than enoxaparin. To generate Canadian pharmacoeconomic data for fondaparinux, an internationally developed cohort deterministic model was used to estimate the costs and consequences of prophylaxis with fondaparinux compared with enoxaparin in the Canadian orthopedic surgical setting. DESIGN AND SETTING: A health economic advisory group was assembled to guide the pharmacoeconomic evaluation. Efficacy and safety data for fondaparinux relative to enoxaparin were abstracted from a meta-analysis of four randomized trials. Canadian cost data to populate the model were obtained from a resource-use survey of four large Canadian hospitals, from the Canadian Institute for Health Information (CIHI), and from the Canadian economic literature. Case-mix information obtained from CIHI was incorporated into the cohort deterministic model, which predicted the number of VTEs and bleeds following prophylaxis with fondaparinux or enoxaparin within 90 days of surgery, and the associated overall cost difference. The stability of the base-case findings was evaluated with sensitivity analyses. STUDY PERSPECTIVE: Canadian healthcare system perspective. MAIN OUTCOME MEASURES AND RESULTS: Assuming a case mix of 50,693 major hip or knee surgeries performed in Canada in 1999/2000 (as reported by CIHI), the model predicted that prophylaxis with fondaparinux would avoid an additional 16 symptomatic VTEs per 1000 patients over the first 90 days, with an average cost savings of Can 55 dollars per patient. These findings were stable when key economic and clinical parameters were varied, including bleeding events. CONCLUSIONS: Our results suggest that in Canada, prophylactic fondaparinux compared with enoxaparin avoids VTEs and is associated with lower costs in patients who undergo major hip or knee surgery.

A cost-effectiveness analysis of fondaparinux sodium compared with enoxaparin sodium as prophylaxis against venous thromboembolism: use in patients undergoing major orthopaedic surgery.

OBJECTIVE: To determine the cost effectiveness of fondaparinux sodium compared with enoxaparin sodium for prophylaxis against venous thromboembolism in patients undergoing major orthopaedic surgery. METHODS: Using a cohort simulation model, two primary analyses were conducted from the perspective of the US healthcare payer. Probabilities for a trial-based analysis were obtained from patients participating in the fondaparinux clinical trial programme supplemented with data from published literature. Probabilities for a label-based analysis were estimated for a hypothetical cohort of US patients receiving either fondaparinux or enoxaparin as recommended by US FDA-approved labelling. Resource use and costs were obtained from large US healthcare databases. Outcome measures were rates of symptomatic thromboembolic events and healthcare costs. Costs were in 2003 values. RESULTS: In the trial-based analysis, fondaparinux was estimated to prevent 15.1 symptomatic venous thromboembolic events (per 1,000 patients) at 3 months for patients undergoing major orthopaedic surgery compared with enoxaparin. The cost savings (per patient) of using fondaparinux over enoxaparin are US 61 dollars at 30 days, US 89 dollars at 3 months, and US 155 dollars at 5 years. In the label-based analysis, fondaparinux was estimated to prevent 17.8 venous thromboembolic events (per 1,000 patients) at 3 months compared with enoxaparin, producing savings per patient of US 25 dollars at discharge, US 112 dollars over 1 month, US 141 dollars over 3 months and US 234 dollars over 5 years. Results remain robust to clinically plausible variation in input parameters and assumptions. CONCLUSION: Our model suggests that fondaparinux, when compared with the current standard regimen of enoxaparin for prophylaxis of venous thromboembolism in major orthopaedic surgery, improves outcomes and is cost saving from a US healthcare-payer perspective over the broad range of assumptions evaluated.

Cost analysis of fondaparinux versus enoxaparin as venous thromboembolism prophylaxis in elective hip replacement surgery.

Patients undergoing hip arthroplasty are at high risk for developing venous thromboembolic events (VTE) postoperatively in the absence of prophylaxis. In this study, a cost analysis comparing efficacy and safety data from a published trial evaluating fondaparinux and enoxaparin as VTE prophylaxis in hip replacement patients was performed. Incremental cost effectiveness ratios were calculated to determine cost per VTE avoided. Additionally, cost per death averted and cost per life year gained were calculated. Fondaparinux proved to offer minor cost savings when compared with 30 mg enoxaparin every 12 h for costs per VTE avoided, costs per death averted, and costs per life year gained. Sensitivity analyses support these findings.