Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A cost-effectiveness analysis.

BACKGROUND: Low-molecular-weight heparins are effective for treating venous thrombosis, but their cost-effectiveness has not been rigorously assessed. OBJECTIVE: To evaluate the cost-effectiveness of low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. DESIGN: Decision model. DATA SOURCES: Probabilities for clinical outcomes were obtained from a meta-analysis of randomized trials. Cost estimates were derived from Medicare reimbursement and other sources. TARGET POPULATION: Two hypothetical cohorts of 60-year-old men with acute deep venous thrombosis. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTION: Fixed-dose low-molecular-weight heparin or adjusted-dose unfractionated heparin. OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. An in-patient hospital setting was used for the base-case analysis. Secondary analyses examined outpatient treatment with low-molecular-weight heparin. RESULTS OF BASE-CASE ANALYSIS: Total costs for inpatient treatment were $26,516 for low-molecular-weight heparin and $26,361 for unfractionated heparin. The cost of initial care was higher in patients who received low-molecular-weight heparin, but this was partly offset by reduced costs for early complications. Low-molecular-weight heparin treatment increased quality-adjusted life expectancy by approximately 0.02 years. The incremental cost-effectiveness of inpatient low-molecular-weight heparin treatment was $7820 per QALY gained. Treatment with low-molecular-weight heparin was cost saving when as few as 8% of patients were treated at home. RESULTS OF SENSITIVITY ANALYSIS: When late complications were assumed to occur 25% less frequently in patients who received unfractionated heparin, the incremental cost-effectiveness ratio increased to almost $75,000 per QALY gained. When late complications were assumed to occur 25% less frequently in patients who received low-molecular-weight heparin, this treatment resulted in a net cost savings. Inpatient low-molecular-weight heparin treatment became cost saving when its pharmacy cost was reduced by 31% or more, when it reduced the yearly incidence of late complications by at least 7%, when as few as 8% of patients were treated entirely as outpatients, or when at least 13% of patients were eligible for early discharge. CONCLUSIONS: Low-molecular-weight heparins are highly cost-effective for inpatient management of venous thrombosis. This treatment reduces costs when small numbers of patients are eligible for outpatient management.     

Comparison of four strategies for diagnosing deep vein thrombosis: a cost-effectiveness analysis

PURPOSE: Four strategies for the diagnosis of deep vein thrombosis have been validated recently. The strategies use various combinations of assessment of a patient's clinical probability of having deep venous thrombosis, serial lower limb venous compression ultrasonography, and measurement of plasma D-dimer levels. We compared the cost-effectiveness of these diagnostic strategies. MATERIALS AND METHODS: We performed a formal cost-effectiveness analysis using a decision-analysis model. Outcomes considered were costs per patient, 3-month quality-adjusted survival, number of lives saved per 1,000 patients, and incremental costs per quality-adjusted life-year (QALY) gained. RESULTS: Under baseline conditions, with a 24% prevalence of deep vein thrombosis in tested patients, the effectiveness of all strategies was similar (4.6 to 4.8 lives saved per 1,000 patients managed). The most expensive strategy was serial ultrasound (repeat ultrasound on day 7 in all patients with a normal initial ultrasound) at a cost-effectiveness of $10,716 per additional QALY. Performing a repeat ultrasound only in patients with an elevated D-dimer level (serial ultrasound with D-dimer) was somewhat less expensive at $10,281 per additional QALY. Taking clinical probability into account by repeating ultrasound only in patients with an intermediate clinical probability of deep vein thrombosis (risk-based serial ultrasound) yielded further savings and cost $10,090 per additional QALY. The least expensive and most cost-effective option was to perform D-dimer as the initial test, followed by a single ultrasound if the D-dimer level was abnormal, and by phlebography in patients with a normal ultrasound and a high clinical probability of deep vein thrombosis (D-dimer with risk-based single ultrasound) at $8,897 per additional QALY. This strategy allowed a 17% reduction in incremental costs compared with the most expensive algorithm and reduced resource consumption (70 ultrasound procedures per 100 patients managed vs 130 to 170 with the other diagnostic strategies). CONCLUSIONS: Combining clinical probability and D-dimer with a single ultrasound in the diagnostic workup of patients with possible deep vein thrombosis is highly cost-effective, allowing a reduction in costs and resource use without any substantial increase in mortality. Serial ultrasonography is less cost-effective.     

Treatment of venous thromboembolism with low-molecular-weight heparin

Summary There is now ample evidence to indicate that certain low-molecular-weight heparins given subcutaneously can replace continuous intravenous unfractionated heparin for the initial treatment of venous thromboembolism. The low-molecular-weight heparins have a predictably high absorption rate when given subcutaneously and a prolonged duration of action, permitting them to be given by a once or twice daily injection for the prevention or treatment of venous thrombosis. Furthermore, treatment does not require laboratory monitoring, thus eliminating the need for continuous IV infusion and permitting the early discharge of patients with venous thromboembolism. This should eventually lead to the outpatient treatment of venous thromboembolism. Studies to date indicate that low-molecular-weight heparin is more cost-effective than unfractionated heparin in the treatment of venous thromboembolism and the cost effectiveness will be increased by out-of-hospital treatment. At the present time, the findings associated with any individual lowmolecular-weight heparin preparation cannot be extrapolated to different low-molecular-weight heparins, and therefore each must be evaluated in separate clinical trials. The information to date is that low-molecular-weight heparin is safer and more effective than continuous intravenous unfractionated heparin in the treatment of proximal venous thrombosis. The decreased mortality rate seen in two clinical trials, particularly in patients with metastatic cancer, was quite unexpected. This requires further confirmation in larger prospective randomized trials.     

Cost-effectiveness of low-molecular-weight heparin in the treatment of proximal deep vein thrombosis

OBJECTIVE: To estimate the cost-effectiveness of low-molecular-weight heparin (LMWH) in the treatment of proximal lower extremity deep venous thrombosis. DESIGN: Cost-effectiveness analysis that includes the treatment of the index case and simulated 3-month follow-up. SETTING: Acute care facility. PATIENTS AND PARTICIPANTS: Hypothetical cohorts of 1,000 patients who present with proximal deep venous thrombosis. INTERVENTIONS: Intravenous unfractionated heparin (UH), LMWH (40% at home, 60% in hospital), or selective UH/LMWH (UH for hospitalized patients and LMWH for patients treated at home). MEASUREMENTS AND MAIN RESULTS: The outcomes were recurrent thrombosis, mortality, direct medical costs, and marginal cost-effectiveness ratios from the payer’s perspective. At the base-case and under most assumptions in the sensitivity analysis, the LMWH and the selective UH/LMWH strategies dominate the UH strategy i.e., they result in fewer cases of recurrent thrombosis and fewer deaths, and they save resources. The savings occur primarily by decreasing the length of stay. The LMWH strategy resulted in lower costs as compared with the UH strategy when the proportion of patients treated at home was more than 14%. Treating 1,000 patients with the LMWH strategy as compared with the UH/LMWH strategy would result in 10 fewer cases of recurrent thrombosis, 1.2 fewer deaths, at an additional cost of $96,822; the cost-effectiveness ratio was $9,667 and $80,685 per recurrent thrombosis or death prevented, respectively. CONCLUSIONS: Treatment with LMWH leads to savings and better outcomes as compared with UH in patients with lower extremity deep venous thrombosis. The selective UH/LMWH strategy is an alternative option. Presented in part at the 20th annual meeting, Society of General Internal Medicine, Washington, DC, May 1–3, 1997.     

Cost-effectiveness of ultrasound in preventing femoral venous catheter-associated pulmonary embolism

Femoral central venous catheter use is complicated by a high risk of deep venous thrombosis despite antithrombotic prophylaxis. Although some have recommended screening for femoral catheter-associated thrombosis to prevent pulmonary embolism (PE), this strategy's economic implications are unclear. Therefore, we used a decision model to evaluate the potential cost-effectiveness of a Doppler ultrasound-based screening strategy versus no ultrasound in averting thromboembolic complications associated with femoral catheters. The base-case analysis included a hypothetical cohort of 60-year-old medical patients treated for acute respiratory failure. The perspective was that of the health care payor, and the primary outcomes were quality-adjusted life expectancy, PE, and PE-associated deaths. The ultrasound strategy cost $8,688/quality-adjusted life-year (QALY) gained, $5,305/PE averted, and $99,286/PE death averted. The best- and worst-case scenarios, calculated in multiway sensitivity analyses by varying in-hospital mortality, deep venous thrombosis prevalence, and ultrasound accuracy, ranged from $1,170/QALY to $35,342/QALY, respectively. Probablistic analyses, in which variables with uncertain values were varied randomly within their ranges, demonstrated median costs of $12,793/QALY (interquartile range $8,176/QALY, $20,648/QALY). In summary, ultrasound screening may improve outcomes among the critically ill with femoral venous catheters at acceptable costs and could complement venous thrombosis primary prevention programs.     

Cost-effectiveness of prophylactic low molecular weight heparin in pregnant women with a prior history of venous thromboembolism

PURPOSE: Women with a history of prior venous thromboembolism have an increased risk for recurrence during pregnancy. Although thromboprophylaxis reduces this risk, recent evidence suggests that, in many cases, prophylaxis can be safely withheld because the estimated recurrence risk is very low. The balance of risks and benefits in women with different recurrence risks has not been examined. METHODS: We developed a Markov state transition decision analytic model to compare prophylactic low molecular weight heparin to expectant management for pregnant women with a single prior venous thromboembolism. A lifetime time horizon and societal perspective were assumed. Input data were obtained by literature review. Outcomes were expressed as U.S. dollars per quality-adjusted life-year (QALY). RESULTS: For "low-risk" women with a prior venous thromboembolism associated with a transient risk factor and no known thrombophilic condition (recurrence risk 0.5%), expectant management was both more effective and less costly than prophylaxis. For "high-risk" women with prior idiopathic venous thromboembolism or known thrombophilic condition (recurrence risk 5.9%), prophylaxis was associated with a reasonable cost-effectiveness ratio (USD 38,700 per QALY) given a risk of bleeding complications <1.0% (base case 0.5%). CONCLUSION: For low-risk women with prior venous thromboembolism, expectant management during pregnancy leads to better outcomes than administration of prophylactic low molecular weight heparin. For high-risk women, antepartum thromboprophylaxis is a cost-effective use of resources.     

Measuring the hemodynamic response to primary pharmacoprophylaxis of variceal bleeding: a cost-effectiveness analysis

OBJECTIVES: The hemodynamic response to ss-blockers alone or with nitrates is highly predictive of efficacy in prevention of variceal bleeding. Hemodynamic monitoring (HDM) requires catheterization of the hepatic vein and measurement of the hepatic venous pressure gradient, the difference between wedged and free hepatic venous pressure. The aim of this study was to compare HDM with no HDM in patients considered for primary pharmacoprophylaxis of esophageal variceal bleeding. METHODS: A decision model was constructed to compare HDM with no HDM in cirrhotic patients with moderate to large esophageal varices. Patients intolerant to beta-blocker therapy would undergo endoscopic variceal ligation; those with an inadequate hemodynamic response (HDR) to beta-blocker therapy could have nitrates added before ligation was considered. Variceal bleeding was treated with ligation, with transjugular intrahepatic portosystemic shunt (TIPS) reserved for refractory bleeding. Probabilities of treatment responses as well as risks of bleeding and mortality were based on published literature. Only direct costs were considered during the 5-yr time horizon. Outcomes were cost in United States dollars, survival length in life-years, and proportions of patients who experienced variceal bleeding, TIPS insertion, and mortality from any cause. RESULTS: In the base case analysis, HDM was either cost-saving ($2,523 US dollars /life-year gained) or cost-effective (incremental cost-effectiveness ratio of $5,200 US dollars/life-year saved) compared with no HDM, depending on whether nitrates were added to beta-blocker therapy. HDM reduced variceal bleeding by nearly 60% and had a small effect on all-cause mortality. In the sensitivity analysis, HDM was sensitive to the time horizon, as it was not cost-effective for a time horizon of <22 months and was not cost-saving before 49 months. The cost-effectiveness of HDM was not sensitive to reasonable variation in the probability of HDR to beta-blocker therapy, risk of bleeding, risk reduction with pharmacotherapy, or to the costs of HDM, bleeding, ligation, or TIPS. Probabilistic sensitivity analysis indicated that HDM was more effective and less costly 100% and 57% of the time, respectively. CONCLUSIONS: Compared with the current standard of no HDM, measuring the hemodynamic response of primary pharmacoprophylaxis substantially reduces the number of bleeding episodes and is cost-effective or cost-saving over a wide range of sensitivity analyses. A randomized trial of HDM is needed to verify its efficacy in clinical practice.     

Assessment of cost-effectiveness of universal hepatitis B immunization in a low-income country with intermediate endemicity using a Markov model

BACKGROUND/AIMS: Most countries with high hepatitis B (HB) virus endemicity and most high-income countries have introduced immunization programmes against this infection. However, several low-income countries with intermediate HB endemicity have not done so. We performed a cost-effectiveness analysis of universal childhood HB immunization in such countries using India as an example, since available data on this aspect are limited. METHODS: Marginal cost of every life-year and quality-adjusted life-year (QALY) gained with universal HB vaccination was calculated using a Markov model. Two types of analyses (including and excluding expenditure on treatment of long-term complications of HB infection) were done. Several sensitivity analyses and Monte-Carlo simulation were performed. RESULTS: Universal immunization reduced the HB carrier rate by 71%, and increased the number of years and QALY lived by a birth-cohort by 0.173 years (61.072 vs. 60.899 years) and 0.213 years (61.056 vs. 60.843 years), respectively. Marginal costs were US$16.27 per life-year gained and US$13.22 per QALY gained, much lower than annual per capita income. One-way sensitivity analysis and Monte-Carlo simulation confirmed the robustness of the conclusions. CONCLUSIONS: Universal HB immunization is highly cost-effective in low-income countries with intermediate endemicity rates.     

Clinical outcome and cost of hospital vs home treatment of proximal deep vein thrombosis with a low-molecular-weight heparin: the Vascular Midi-Pyrenees study

BACKGROUND: Low-molecular-weight heparins have been shown to be effective and safe in the treatment of deep vein thrombosis. To our knowledge, there have been no direct comparisons of such treatment on an outpatient vs an inpatient basis. OBJECTIVE: To conduct a randomized, comparative, multicenter trial to evaluate the clinical outcomes and treatment costs of deep vein thrombosis in the outpatient and inpatient settings. METHODS: Two hundred one patients presenting with proximal deep vein thrombosis, without known risk factors for pulmonary embolism or hemorrhagic complications, were randomized to receive a low-molecular-weight heparin at the registered dose followed by an oral anticoagulant for up to 6 months, either in the hospital for the first 10 days followed by treatment at home (n=102) or at home from the outset (n=99). The primary clinical outcome was the incidence of venous thromboembolism recurrence, pulmonary embolism, or major bleeding. The economic analysis was performed from the point of view of the health insurance company. Total costs of the 2 management strategies were calculated to compare the cost consequences during the first 10 days. RESULTS: No differences in clinical outcome were detectable between the 2 groups. There was no increase in the rates of primary efficacy outcome in the patients treated at home vs in the hospital (3.0% vs 3.9%), while a cost reduction of 56% was demonstrated for outpatient management. CONCLUSION: For patients with proximal deep vein thrombosis and no symptoms of pulmonary embolism or increased risk of major bleeding, home treatment using a low-molecular-weight heparin is an effective, safe, and cost-saving strategy.     

Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials.

BACKGROUND: Low-molecular-weight heparins may simplify the management of deep venous thrombosis. A critical clinical issue is whether this more convenient therapy is as safe and effective as treatment with unfractionated heparin. PURPOSE: To compare the safety and efficacy of low-molecular-weight heparins with those of unfractionated heparin for treatment of acute deep venous thrombosis. DATA SOURCES: Reviewers identified studies by searching MEDLINE, reviewing references from retrieved articles, scanning abstracts from conference proceedings, and contacting investigators and pharmaceutical companies. STUDY SELECTION: Randomized, controlled trials that compared a low-molecular-weight heparin preparation with unfractionated heparin for treatment of acute deep venous thrombosis. DATA EXTRACTION: Two reviewers extracted data independently. Reviewers evaluated study quality using a validated four-item instrument. DATA SYNTHESIS: Eleven of 37 studies met inclusion criteria for three major outcomes. Most studies used proper randomization procedures, but only one was double-blinded. Compared with unfractionated heparin, low-molecular-weight heparins reduced mortality rates over 3 to 6 months of patient follow-up (odds ratio, 0.71 [95% CI, 0.53 to 0.94]; P = 0.02). For major bleeding complications, the odds ratio favored low-molecular-weight heparins (0.57 [CI, 0.33 to 0.99]; P = 0.047), but the absolute risk reduction was small and not statistically significant (0.61% [CI, -0.04% to 1.26%]; P = 0.07). For preventing thromboembolic recurrences, low-molecular-weight heparins seemed as effective as unfractionated heparin (odds ratio, 0.85 [CI, 0.63 to 1.14]; P > 0.2). CONCLUSIONS: Low-molecular-weight heparin treatment reduces mortality rates after acute deep venous thrombosis. These drugs seem to be as safe as unfractionated heparin with respect to major bleeding complications and appear to be as effective in preventing thromboembolic recurrences.     

Outpatient Management of Venous Thromboembolic Disease with Subcutaneous Lepirudin: A Case Report

Outpatient treatment of deep venous thrombosis has gained widespread acceptance and is facilitated by the use of subcutaneous low molecular weight heparins (LMWH). We report two patients in whom subcutaneous lepirudin was used for long term anticoagulation after heart transplant or surgical pulmonary embolectomy because treatment with LMWH or warfarin was contraindicated, unsuccessful, or impractical. Neither bleeding complications nor recurrent thromboses developed. Subcutaneous lepirudin may be safely and effectively employed for the outpatient treatment of venous thrombosis in selected cases including patients with heparin-induced thrombocytopenia and in those who fail LMWH.     

The cost-effectiveness of hepatitis A vaccination in patients with chronic hepatitis C viral infection in the United States

OBJECTIVE: Hepatitis A vaccination is recommended for patients with chronic hepatitis C. Our aim was to analyze the cost-effectiveness of hepatitis A vaccination in these patients. The specific strategies evaluated were: no vaccination, targeted vaccination, and universal vaccination. METHODS: Clinical estimates were based on published data. Costs estimates were based on published data and institutional Medicare reimbursement rates. Health-related quality-of-life weights were derived from published data and expert estimates. The target population consisted of patients 45 yr of age with chronic hepatitis C followed every 6 months until death. We adopted a societal perspective. RESULTS: Compared with no vaccination, targeted vaccination was associated with an incremental cost-effectiveness ratio of $51,000 per quality-adjusted life-year. The incremental cost-effectiveness ratio of universal vaccination compared with targeted vaccination was $3,900,000 per quality-adjusted life-year. The results were particularly sensitive to the incidence of hepatitis A, probability of fulminant hepatic failure, and costs of hepatitis A antibody screening and vaccination. CONCLUSIONS: Targeted vaccination for hepatitis A in patients with chronic hepatitis C may be a cost-effective strategy to decrease the morbidity and mortality associated with hepatitis A superinfection. Universal vaccination is not a cost-effective alternative to targeted vaccination in this target population.     

Responding to a small-scale bioterrorist anthrax attack: cost-effectiveness analysis comparing preattack vaccination with postattack antibiotic treatment and vaccination

BACKGROUND: In 2001, a small-scale bioterrorism-related anthrax attack was perpetrated via the US mail. The optimal future response may require strategies different from those required in a large-scale attack. METHODS: We conducted a cost-effectiveness analysis using Monte Carlo simulation during a 10-year time frame from a societal perspective to determine the optimal response strategy for a small-scale anthrax attack perpetrated against US Postal Service distribution centers in a large metropolitan area. Three strategies were compared: preattack vaccination of all US distribution center postal workers, postattack antibiotic therapy followed by vaccination of exposed personnel, and postattack antibiotic therapy without vaccination of exposed personnel. Outcome measures were costs, quality-adjusted life-years, and incremental cost-effectiveness. The probabilities for anthrax exposure and infection; vaccine and antibiotic benefits, risks, and costs; and associated clinical outcomes were derived from the medical literature and from bioterrorism experts. RESULTS: Postattack antibiotic therapy and vaccination of exposed postal workers is the most cost-effective response compared with other strategies. The incremental cost-effectiveness is $59 558 per quality-adjusted life-year compared with postattack antibiotic therapy alone. Preattack vaccination of all distribution center workers is less effective and more costly than the other 2 strategies. Assuming complete adherence to preattack vaccination, the incremental cost-effectiveness compared with postattack antibiotic therapy alone is almost $2.6 million per quality-adjusted life-year. CONCLUSION: Despite uncertainties about a future anthrax attack and exposure risk, postattack antibiotic therapy and vaccination of exposed personnel seems to be the optimal response to an attack perpetrated through the US Postal Service.     

Cost-effectiveness of testing for hypercoagulability and effects on treatment strategies in patients with deep vein thrombosis

PURPOSE: Among patients with deep vein thrombosis, hypercoagulable conditions impart a substantial risk of recurrent thrombosis. We sought to determine the cost-effectiveness of testing for these disorders, as well as which tests should be selected and how results should be used. METHODS: Using a Markov state-transition model, strategies of testing or not testing for a hypercoagulable state followed by anticoagulation for 6 to 36 months were compared in a hypothetical cohort of patients with apparently idiopathic deep vein thrombosis who were followed for life. Strategies were compared based on lifetime costs, quality-adjusted life-years (QALYs), and marginal cost-effectiveness. RESULTS: In the base case, testing followed by 24 months of anticoagulation in patients with a hypercoagulable condition was more cost-effective ($54,820; 23.76 QALYs) than usual care, which comprised 6 months of anticoagulation without testing ($55,260; 23.72 QALYs). All hypercoagulable conditions tested were common enough and associated with a sufficient risk of recurrence to justify inclusion in a test panel. Twenty-four months of initial anticoagulation was preferred (<$50,000/QALY) for most conditions, whereas lifetime anticoagulation was preferred for patients with antiphospholipid antibody syndrome ($2928/QALY) or homozygous factor V Leiden mutation ($3804/QALY). Models using newer evidence on recurrence suggested 18 to 36 months of anticoagulation without testing as the preferred approach. CONCLUSION: Testing for hypercoagulable disorders in patients with idiopathic deep vein thrombosis followed by 2 years of anticoagulation in affected patients is cost-effective. A simpler approach of treating all patients with prolonged anticoagulation without testing is justified if data confirm the persistent risk of recurrent thrombosis.     

Cost-effectiveness of screening a population with chronic gastroesophageal reflux

BACKGROUND: Persons with chronic esophageal reflux are at increased risk for the development of Barrett's esophagus and adenocarcinoma. Recently developed ultrathin endoscopes are less expensive and better tolerated than standard endoscopes, they can be used without sedation, and are sensitive and specific for Barrett's esophagus. The cost-effectiveness of one-time screening strategies were evaluated for 50-year-old patients with chronic reflux: no screening, standard endoscopy, and screening by an ultrathin endoscope. METHODS: Markov models were created to simulate the clinical course for patients with chronic reflux. Costs and quality-adjusted life-years were estimated from cancer registry data, published medical data, and expert opinion. RESULTS: Under baseline assumptions, no screening resulted in average costs of $11,785 per person and 19.3226 quality-adjusted life-years. Ultrathin endoscopy screening resulted in costs of $12,119 per person and 19.3326 quality-adjusted life-years, yielding a marginal cost-effectiveness ratio of $55,764 per quality-adjusted life-year. Using standard endoscopy yielded costs of $12,332 with only slightly greater effectiveness, yielding a marginal cost-effectiveness ratio of $709,260 when compared with ultrathin endoscopy and $86,833 compared with no screening. Results were most sensitive to variation in the incidence of cancer in the population with Barrett's esophagus. CONCLUSIONS: Screening for Barrett's esophagus with ultrathin endoscopy is more cost-effective than standard endoscopy, and both strategies appear to improve quality-adjusted life-years among patients with chronic reflux at costs that are similar to those of other accepted preventive measures.     

Diagnosis of suspected coronary artery disease in women: a cost-effectiveness analysis.

BACKGROUND: The optimal strategy for the diagnosis of coronary artery disease (CAD) in women is not well defined. We compared the cost-effectiveness of several strategies for diagnosing CAD in women with chest pain. METHODS: We performed decision and cost-effectiveness analyses with simulations of 55-year-old ambulatory women with chest pain. With a Markov model, simulations of patients underwent exercise electrocardiography, exercise testing with thallium scintigraphy, exercise echocardiography, angiography, or no workup. RESULTS: Diagnosis with angiography cost less than $17, 000 per quality-adjusted life-year compared with exercise echocardiography if the patient had definite angina and less than $76,000 per life-year if she had probable angina. If she had nonspecific chest pain, diagnosis with exercise echocardiography increased life-years compared with no testing. CONCLUSIONS: Cost-effectiveness of first-line diagnostic strategy for diagnosis of CAD in women varies mostly according to pretest probability of CAD. Diagnosis of coronary artery disease with angiography is cost-effective in 55-year-old women with definite angina. In 55-year-old women with probable angina, diagnosis with angiography would increase quality-adjusted life-years but significantly increase costs. Use of exercise echocardiography as a first-line diagnosis for CAD is cost effective in 55-year-old women with probable angina and nonspecific chest pain.     

A cost-effectiveness threshold analysis of a multidisciplinary structured educational intervention in pediatric asthma

Objective: Asthma educational interventions have been shown to improve several clinically and economically important outcomes. However, these interventions are costly in themselves and could lead to even higher disease costs. A cost-effectiveness threshold analysis would be helpful in determining the threshold value of the cost of educational interventions, leading to these interventions being cost-effective. The aim of the present study was to perform a cost-effectiveness threshold analysis to determine the level at which the cost of a pediatric asthma educational intervention would be cost-effective and cost-saving. Methods: A Markov-type model was developed in order to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a single uncontrolled before-and-after study performed with Colombian asthmatic children. Cost data were obtained from official databases provided by the Colombian Ministry of Health. The main outcome was the variable “quality-adjusted life-years” (QALYs). Results: A deterministic threshold sensitivity analysis showed that the asthma educational intervention will be cost-saving to the health system if its cost is under US$513.20. Additionally, the analysis showed that the cost of the intervention would have to be below US$967.40 in order to be cost-effective. Conclusions: This study identified the level at which the cost of a pediatric asthma educational intervention will be cost-effective and cost-saving for the health system in Colombia. Our findings could be a useful aid for decision makers in efficiently allocating limited resources when planning asthma educational interventions for pediatric patients.     

Cost-effectiveness of biologic agents for treatment of autoimmune disorders: structured review of the literature

OBJECTIVE: Four new biologic treatments have been approved for several autoimmune disorders. Economic evaluations have been used to model their cost-effectiveness. METHODS: We conducted a structured literature review in Embase and PubMed to identify all relevant cost-effectiveness models investigating one or more of these 4 drugs in autoimmune disorders. RESULTS: Fifteen full economic evaluations were identified [13 for rheumatoid arthritis (RA), 2 for Crohn's disease (CD), and 1 for ankylosing spondylitis (AS)]. While several studies found adalimumab, etanercept, and infliximab to be cost-effective (using a threshold around $50,000/quality-adjusted life-year) for treatment of severe RA, not all studies concurred, and there was significant variation in the range of cost-effectiveness ratios reported. Neither study in CD found treatment with infliximab to be cost-effective. Only one study was identified in AS: treatment with infliximab was found to be cost-effective. CONCLUSION: Modeling treatment strategies in chronic relapsing diseases such as RA, CD, and AS presents particular challenges, as reflected in the variation in cost-effectiveness results reported. A reference case for economic evaluations, such as that suggested by the OMERACT (Outcome Measures in Rheumatology) Health Economics Working Group will facilitate comparison and interpretation of results.     

Randomized, controlled trial of low molecular weight heparinvs. no deep vein thrombosis prophylaxis for major colon and rectal surgery in Asian patients

PURPOSE: Routine deep venous thrombosis prophylaxis is controversial in Asian patients, because deep venous thrombosis incidence was considered negligible. Because of recent reports of significantly higher incidences, a randomized, controlled trial was conducted to assess the effectiveness and complications of enoxaparin prophylaxis (low molecular weight heparins) in major colorectal surgery. METHODS: Three hundred twenty consecutive patients were randomly assigned to control or low molecular weight heparins groups. Patients in the low molecular weight heparins group were given perioperative enoxaparin starting 12 hours before surgery. The surgeon (blinded) assessed for difficulties related to possible enoxaparin administration. Independent blinded observers performed daily clinical assessments and Doppler studies (at the 3rd and 5th postoperative day). Deep venous thrombosis was confirmed by duplex ultrasound, and pulmonary embolism was confirmed by lung scans or postmortem examinations. RESULTS: Deep venous thrombosis developed in 5 of 169 (3 percent) controls and 0 of 134 low molecular weight heparins patients (P=0.045). Three of the deep venous thrombosis patients had pulmonary embolism, which was fatal in one patient. The surgeons were unable to perceive any increased surgical difficulties in the low molecular weight heparins group. The bleeding-related complications were significantly higher in the low molecular weight heparins patients (controls, n=3 (1.8 percent); low molecular weight heparins, n=9 (6.7 percent)). However, apart from one subdural hematoma and two abdominal hemorrhages needing re-exploration, which also occurred in one of the controls, these complications were minor bruises at the wounds, drains, or injection sites. CONCLUSION: Deep venous thrombosis prophylaxis is needed in Asian patients undergoing major colorectal surgery.     

Orally active heparin and low-molecular-weight heparin

The heparins, (unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH)) given by subcutaneous or intravenous injection have been used extensively in the prevention and treatment of both venous and arterial thromboembolic disorders. The increasing use of the heparins, LMWHs in particular, in the out of hospital setting has stimulated interest in the development of orally absorbable antithrombotic agents that require little or no monitoring, and this includes the heparins. UFH or LMWH delivered orally has been shown to have an antithrombotic effect in animal thrombosis models although there is little change in plasma coagulation tests. The addition of a simple organic chemical N -(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) to UFH markedly enhances its absorption. A phase II study in patients undergoing total hip replacement indicated that SNAC heparin in two different doses was as effective and safe as UFH given subcutaneously. A phase III clinical trial comparing two doses of SNAC heparin given orally with LMWH by subcutaneous injection for the prevention of venous thromboembolism in patients undergoing total hip replacement is currently underway.