fondaparinux and Hip-Fractures

The use of antithrombotic drugs for the prevention of venous thromboembolism (VTE) in patients undergoing surgery is presently based on solid principles and high-level scientific evidence. This article reviews current strategies of pharmacological thromboprophylaxis. The level of VTE risk following surgery depends on a variety of factors that the surgeon should take into account, including the type of surgery and the presence of additional risk factors, such as elderly age and cancer. In patients undergoing minor general surgery, early mobilization is sufficient as prophylaxis, whereas in those undergoing major general surgery, thromboprophylaxis with low molecular weight heparin (LMWH), low-dose unfractionated heparin, or the pentasaccharide fondaparinux is recommended. Patients undergoing major orthopedic surgery have a particularly high risk of VTE, and routine thromboprophylaxis with LMWH, fondaparinux, or a vitamin K antagonist (international normalized ratio target: 2.0 to 3.0) is the standard of care in this group of patients. Recently, two new oral anticoagulants, rivaroxaban (a factor Xa inhibitor) and dabigatran etexilate (a direct thrombin inhibitor) have been licensed to be used for thromboprophylaxis after orthopedic surgery in Europe. Mechanical methods of thromboprophylaxis (compression stockings, intermittent pneumatic compression, vena cava filters), not discussed in detail in this review, should always be considered in patients at high thrombotic risk, in association with the pharmacological strategies, or in cases of contraindications to anticoagulants, as in patients or procedures at high risk of bleeding.

Topics: Aged; Anticoagulants; Antithrombins; Arthroscopy; Bariatric Surgery; Benzimidazoles; Blood Coagulation Disorders, Inherited; Dabigatran; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Kidney; Knee; Laparoscopy; Morpholines; Neoplasms; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Thrombophilia; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Arthroscopy; Drug Administration Schedule; Fondaparinux; Hematoma, Epidural, Spinal; Hematoma, Subdural, Spinal; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Premedication; Punctures; Soft Tissue Injuries; Thromboembolism; Venous Thrombosis; Wounds and Injuries

Hip fracture surgery carries a high risk of venous thromboembolism and, until recently, was poorly investigated. The efficacy and safety of fondaparinux, a new synthetic antithrombotic, were investigated in two large, thromboprophylaxis studies. Results of the Penthifra study, which was a randomized, double-blind phase III trial, showed that 1 week of fondaparinux, compared with enoxaparin, significantly reduced venous thromboembolic events from 19.1% to 8.3% (relative risk reduction: 56.4%; P<.001) without increasing bleeding risk. Penthifra Plus results showed that extending fondaparinux prophylaxis from 1 to 4 weeks was well tolerated and, compared to placebo, significantly reduced delayed venous thromboembolism events from 35% to 1.4% (relative risk reduction: 95.9%; P<.001). Based on these findings, 4-week fondaparinux treatment may become the standard thromboprophylaxis after hip fracture surgery.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Clinical Trials, Phase III as Topic; Drug Administration Schedule; Enoxaparin; Female; Fondaparinux; Fracture Fixation, Internal; Hip Fractures; Humans; Incidence; Injury Severity Score; Male; Middle Aged; Polysaccharides; Postoperative Care; Postoperative Complications; Postoperative Hemorrhage; Primary Prevention; Prognosis; Radiography; Randomized Controlled Trials as Topic; Sex Factors; Survival Rate; Thromboembolism; Treatment Outcome

Orthopedic surgery remains a condition at high risk of venous thromboembolism (VTE). Fondaparinux, the first of a new class of synthetic selective factor Xa inhibitors, may further reduce this risk compared with currently available thromboprophylactic treatments.. A meta-analysis of 4 multicenter, randomized, double-blind trials in patients undergoing elective hip replacement, elective major knee surgery, and surgery for hip fracture (N = 7344) was performed to determine whether a subcutaneous 2.5-mg, once-daily regimen of fondaparinux sodium starting 6 hours after surgery was more effective and as safe as approved enoxaparin regimens in preventing VTE. The primary efficacy outcome was VTE up to day 11, defined as deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism. The primary safety outcome was major bleeding.. Fondaparinux significantly reduced the incidence of VTE by day 11 (182 [6.8%] of 2682 patients) compared with enoxaparin (371 [13.7%] of 2703 patients), with a common odds reduction of 55.2% (95% confidence interval, 45.8% to 63.1%; P<.001); this beneficial effect was consistent across all types of surgery and all subgroups. Although major bleeding occurred more frequently in the fondaparinux-treated group (P =.008), the incidence of clinically relevant bleeding (leading to death or reoperation or occurring in a critical organ) did not differ between groups.. In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily, starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Confidence Intervals; Double-Blind Method; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Fracture Fixation, Internal; Hip Fractures; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Orthopedic Procedures; Polysaccharides; Randomized Controlled Trials as Topic; Thromboembolism; Time Factors; Treatment Outcome; Venous Thrombosis

Hip fracture surgery (HFS) carries a high risk of venous thromboembolism (VTE) in the absence of thromboprophylactic treatment. Previous reports have suggested that fondaparinux sodium (FPX) administration decreases the incidence of VTE after HFS and total hip and knee arthroplasties. However, investigations of that effect in Japanese populations remain inadequate. We evaluated the efficacy of FPX after HFS in a prospective randomized controlled trial.. Subjects comprised 76 consecutive Japanese patients who underwent HFS and were randomly assigned to the FPX group, who received subcutaneous injections of FPX 2.5 mg/day for 14 days beginning the next after HFS, or the control group (non-FPX group). D-dimer values were measured on admission and 7 and 14 days after HFS. Subjects with D-dimer levels over the cutoff value (> 20 microg/ml on day 7) underwent enhanced computed tomography (CT) to evaluate the possibility of deep vein thrombosis (DVT) of the lower extremities. D-dimer values, the incidence of DVT, and side effects associated with a bleeding tendency (i.e., hematoma or massive bleeding) were compared between groups.. The FPX group showed significantly lower D-dimer levels than the non-FPX group at 7 and 14 days after HFS (P < 0.05). Only one case in the FPX group exceeded the D-dimer cutoff compared to 12 cases in the non-FPX group (P = 0.001). DVTs were found with enhanced CT in one case in the FPX group and in five cases in the non-FPX group. In the FPX group, symptomatic hematoma at the surgical site and/or decreased hemoglobin > 2 g/dl was noted in four cases (10.5%). Postoperative drainage volumes did not differ significantly between groups.. FPX administration demonstrated positive effects on the prevention of VTE after HFS. However, careful postoperative observation is warranted to prevent serious side effects after FPX administration.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Fibrin Fibrinogen Degradation Products; Fondaparinux; Fracture Fixation; Hip Fractures; Humans; Japan; Male; Polysaccharides; Venous Thromboembolism; Venous Thrombosis

Twenty-three patients with fondaparinux prophylaxis over 75 years of age who underwent hip fracture surgery were enrolled in the study. Fondaparinux sodium (2.5 mg) was administered subcutaneously 6 h postoperatively and then every 24 h for 28 days. Coagulation and inflammatory parameters were measured preoperatively, then 10 h, 2, 7, and 28 days postoperatively. Increased D-dimers, positive acute phase proteins, and IL-6, and decreased negative acute phase proteins were observed preoperatively (P < 0.05). Maximum values were reached 10 h postoperatively for IL-6 and D-dimer, and on postoperative days 2 and 7 for positive acute phase proteins (P < 0.05). Transferrin, prealbumin and antithrombin levels were lowest 10 h postoperatively and on postoperative day 2 (P < 0.05). Increased D-dimers, IL-6, and positive acute phase proteins, and decreased negative acute phase proteins persisted until postoperative day 28 (P < 0.05). Prothrombin fragments (F1 + 2) reached peak levels preoperatively and decreased gradually until postoperative day 28. Fondaparinux promoted the inhibition of thrombin generation, as documented by negative correlation between F1 + 2 and FXa inhibition (r = -0.46; P < 0.001). Fondaparinux-induced FXa inhibition increased gradually until postoperative day 28. This increase correlated positively with antithrombin activity (r = 0.4; P < 0.05). Fondaparinux prophylaxis counteracted pro-thrombogenic effect associated with hip fracture and subsequent surgery without severe bleeding complications.

Topics: Acute-Phase Proteins; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Factor Xa Inhibitors; Female; Fondaparinux; Hip Fractures; Humans; Inflammation Mediators; Injections, Subcutaneous; Male; Polysaccharides; Postoperative Complications; Time Factors; Venous Thromboembolism

Little is known about the efficacy of graduated compression stockings in preventing venous thromboembolism after hip surgery. We conducted a prospective, randomised single-blind study to determine whether the addition of compression stockings to fondaparinux conferred any additional benefit. The study included 874 patients, of whom 795 could be evaluated (400 in the fondaparinux group and 395 in the fondaparinux plus compression stocking group). Fondaparinux was given post-operatively for five to nine days, either alone or combined with wearing stockings, which were worn for a mean 42 days (35 to 49). The study outcomes were venous thromboembolism, or sudden death before day 42. Duplex ultrasonography was scheduled within a week of day 42. Safety outcomes were bleeding and death from venous thromboembolism. The prevalence of deep-vein thrombosis was similar in the two groups 5.5% (22 of 400) in the fondaparinux group and 4.8 (19 of 395) in the fondaparinux plus stocking group (odds ratio 0.88, 95% confidence interval 0.46 to 1.65, p = 0.69). Major bleeding occurred in only one patient. The addition of graduated compression stockings to fondaparinux appears to offer no additional benefit over the use of fondaparinux alone.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Fondaparinux; Hip Fractures; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Prospective Studies; Single-Blind Method; Stockings, Compression; Time Factors; Treatment Outcome; Ultrasonography; Venous Thrombosis

Fondaparinux efficacy for thromboprophylaxis was evaluated in predefined high-risk hip fracture patients. Patients received fondaparinux 2.5 mg for 7 days following surgery; 656 patients were randomized double blind to receive placebo or continue fondaparinux regimen for 21 additional days. Primary efficacy was venous thromboembolism (VTE) based on bilateral venography during the double-blind period. Total VTE was 1.4% (3 of 208 patients) for extended prophylaxis and 35% (77 of 220 patients) for short-term prophylaxis (P = 0.001), relative risk reduction (RRR) of 96%. Major bleeding occurred in 2% (8 of 327 patients) with extended prophylaxis and in 0.6% (2 of 329 patients) with short-term prophylaxis (P =.063). Risk of VTE was continued following short course fondaparinux in hip fracture patients, but was significantly reduced by extending prophylaxis, without significant risk of major bleeding.

Topics: Aged; Anticoagulants; Double-Blind Method; Female; Fondaparinux; Hip Fractures; Humans; Logistic Models; Male; Middle Aged; Polysaccharides; Treatment Outcome; Venous Thrombosis

The benefit of thromboprophylaxis for 1 month has never been evaluated in patients undergoing hip fracture surgery, a setting in the highest risk category for postoperative venous thromboembolism (VTE).. In a double-blind multicenter trial, 656 patients undergoing hip fracture surgery were randomly assigned to receive prophylaxis with a once-daily subcutaneous injection of either 2.5 mg of fondaparinux sodium or placebo for 19 to 23 days. Before randomization, all patients had received fondaparinux for 6 to 8 days. The primary efficacy outcome was VTE occurring during the double-blind period (deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism). The main safety outcome was major bleeding.. The primary efficacy outcome was assessed in 428 patients. Fondaparinux reduced the incidence of VTE compared with placebo from 35.0% (77/220) to 1.4% (3/208), with a relative reduction in risk of 95.9% (95% confidence interval, 87.2%-99.7%; P<.001). Similarly, the incidence of symptomatic VTE was significantly lower with fondaparinux (1/326; 0.3%) than with placebo (9/330; 2.7%). The relative reduction in risk was 88.8% (P =.02). Although there was a trend toward more major bleeding in the fondaparinux group than in the placebo group (P =.06), there were no differences between the 2 groups in the incidence of clinically relevant bleeding (leading to death, reoperation, or critical organ bleeding).. Extended prophylaxis with fondaparinux for 3 weeks after hip fracture surgery reduced the risk of VTE by 96% and was well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Double-Blind Method; Drug Administration Schedule; Female; Fibrinolytic Agents; Fondaparinux; Hip Fractures; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Venous Thrombosis

Surgery for hip fracture carries a high risk of venous thromboembolism, despite the use of current thromboprophylactic treatments. Fondaparinux, a synthetic pentasaccharide, is a new antithrombotic agent that may reduce this risk.. In a double-blind study, were randomly assigned 1711 consecutive patients undergoing surgery for fracture of the upper third of the femur to receive subcutaneous doses of either 2.5 mg of fondaparinux once daily, initiated postoperatively, or 40 mg of enoxaparin once daily, initiated preoperatively, for at least five days. The primary efficacy outcome was venous thromboembolism up to postoperative day 11. Venous thromboembolism was defined as deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or documented symptomatic pulmonary embolism. The main safety outcomes were major bleeding and mortality from all causes. The duration of follow-up was six weeks.. The incidence of venous thromboembolism by day 11 was 8.3 percent (52 of 626 patients) in the fondaparinux group and 19.1 percent (119 of 624 patients) in the enoxaparin group (P<0.001). The reduction in risk with fondaparinux was 56.4 percent (95 percent confidence interval, 39.0 to 70.3 percent). There were no significant differences between the two groups in the incidence of death or clinically relevant bleeding.. In patients undergoing surgery for hip fracture, fondaparinux was more effective than enoxaparin in preventing venous thromboembolism and equally safe.

Topics: Aged; Double-Blind Method; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Hip Fractures; Humans; Incidence; Injections, Subcutaneous; Male; Mortality; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Venous Thrombosis

Heparin-induced thrombocytopenia (HIT) is a severe complication caused by heparin. It is characterized by occult onset and missed diagnosis. Misdiagnosis easily occurs.. This paper reported an 85-year-old woman with an intertrochanteric fracture of the femur which was treated with low molecular weight heparin (LMWH) and fondaparinux sodium to prevent venous thrombosis. Then, the patient developed HIT. This is the first case report of HIT induced by LMWH and fondaparinux in a patient with a hip fracture. This case highlights the severity of HIT in elderly patients with hip fractures using LMWH and fondaparinux and the need for platelet monitoring in these patients.. LMWH was ceased in this HIT-confirmed patient, and non-heparin treatment was begun instead. Apixaban was given twice daily for therapeutic anticoagulation therapy. In the end, the platelet levels gradually returned to normal.. We should pay more attention to HIT and platelets during the perioperative period of orthopedic surgery, especially in elderly patients. Once the disease is confirmed, it is necessary to stop heparin-related drugs immediately and administer oral anticoagulants instead.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Femur; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Thrombocytopenia

Topics: Aged, 80 and over; Antibodies; Anticoagulants; Blood Platelets; Dalteparin; Female; Fondaparinux; Hip Fractures; Hirudins; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Morpholines; Peptide Fragments; Platelet Count; Polysaccharides; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombocytopenia; Venous Thrombosis

Despite the need for effective and safe thromboprophylactic drugs for patients with renal impairment, clinical trial data on anticoagulant agents are limited in this population. The study aim was to assess in the real-world setting the use of the once-daily 1.5 mg reduced dosage regimen of fondaparinux available for this context. In this prospective cohort study, patients with a creatinine clearance (CrCl) of 20-50 ml/minute, undergoing total hip (THR) or knee (TKR) replacement or hip fracture surgery (HFS) received fondaparinux thromboprophylaxis. Main clinical outcomes were bleeding (major/clinically relevant non-major), symptomatic venous thromboembolism (VTE) and death. Overall, 442 patients (353 women; median age: 82 years; 39.4% in ASA class ≥3; mean ± SD CrCl: 39.0 ± 8.0 ml/minute; 78% with additional risk factors for bleeding), undergoing THR (43.7%), TKR (27.6%), or HFS (28.7%) received fondaparinux 1.5 mg for a mean ± SD duration of 16.0 ± 12.5 days. At postoperative day 10, the rates (95% confidence interval) of major bleeding, clinically relevant bleeding and symptomatic VTE were 4.5% (2.8-6.9), 0.5% (0.1-1.6) and 0.5% (0.05-1.62), respectively; no fatal bleeding, bleeding into a critical organ, pulmonary embolism or proximal deep-vein thrombosis occurred. Corresponding rates at one month were 5.2%, 0.7% and 0.7%. One-month mortality was 2.3% (0.9-3.6). This large clinical prospective study provides for the first time, under conditions reflecting "real-world" routine clinical practice, data on the bleeding and VTE risks of thromboprophylaxis with fondaparinux 1.5 mg after major orthopaedic surgery in renally impaired patients. It shows that these patients constitute a very elderly and fragile population.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biomarkers; Creatinine; Female; Fondaparinux; Fracture Fixation; France; Hemorrhage; Hip Fractures; Humans; Kidney; Logistic Models; Male; Middle Aged; Multivariate Analysis; Orthopedic Procedures; Polysaccharides; Prospective Studies; Renal Insufficiency; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism

Topics: Anticoagulants; Austria; Drug Administration Schedule; Fondaparinux; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Injections; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Venous Thromboembolism

Clinical trials have shown differences in efficacy among anticoagulants used for venous thromboembolism (VTE) prophylaxis after hip fracture surgery, but the applicability of their results is limited by constraints of the clinical trial setting. We conducted this retrospective cohort study to assess VTE after hip fracture surgery in patients who received prophylaxis with dalteparin, enoxaparin, fondaparinux, or unfractionated heparin in a hospital setting. After adjustments were made for demographic differences, risk for VTE was significantly higher for dalteparin (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.99-1.92), enoxaparin (OR, 1.4; 95% CI, 1.05-1.86), and unfractionated heparin (OR, 1.9; 95% CI, 1.39-2.58) compared with fondaparinux. These findings confirm the results of clinical trials in a real-world setting.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Cohort Studies; Dalteparin; Enoxaparin; Female; Follow-Up Studies; Fondaparinux; Fracture Fixation, Intramedullary; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Incidence; Logistic Models; Male; Odds Ratio; Polysaccharides; Postoperative Complications; Premedication; Probability; Radiography; Retrospective Studies; Risk Assessment; Treatment Failure; Treatment Outcome; Venous Thromboembolism

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.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cost-Benefit Analysis; Fondaparinux; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Models, Econometric; Outcome Assessment, Health Care; Polysaccharides; Sweden; Treatment Outcome; Venous Thromboembolism

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.. 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.. 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.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Enoxaparin; Female; Follow-Up Studies; Fondaparinux; Hip Fractures; Humans; Inpatients; Insurance, Health, Reimbursement; Length of Stay; Linear Models; Male; Norway; Polysaccharides; Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Fondaparinux; Hip Fractures; Humans; Polysaccharides; Postoperative Complications; Thrombosis

To determine the cost effectiveness of fondaparinux sodium compared with enoxaparin sodium for prophylaxis against venous thromboembolism in patients undergoing major orthopaedic surgery.. 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.. 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.. 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.

Topics: Aged; Aged, 80 and over; Anticoagulants; Clinical Trials as Topic; Cohort Studies; Cost-Benefit Analysis; Decision Support Techniques; Enoxaparin; Fondaparinux; Health Care Costs; Hip Fractures; Humans; Models, Economic; Orthopedic Procedures; Polysaccharides; Treatment Outcome; Venous Thrombosis

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Fondaparinux; Fracture Fixation, Internal; Hip Fractures; Humans; Polysaccharides; Thromboembolism; United Kingdom; Venous Thrombosis

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.. 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.. 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.. 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.. 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.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cohort Studies; Cost-Benefit Analysis; Enoxaparin; Fondaparinux; Hip Fractures; Humans; Models, Theoretical; Orthopedics; Polysaccharides; Sensitivity and Specificity; Thromboembolism; Treatment Outcome; Venous Thrombosis

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Controlled Clinical Trials as Topic; Fondaparinux; Fracture Fixation, Internal; Hip Fractures; Humans; Polysaccharides; Thromboembolism; Treatment Outcome; Venous Thrombosis

Topics: Drug Administration Schedule; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hip Fractures; Humans; Polysaccharides; Postoperative Complications; Thromboembolism; Venous Thrombosis