Torasemide: a pharmacoeconomic review of its use in chronic heart failure.

Torasemide is a loop diuretic used for the treatment of hypertension and for oedema in chronic heart failure (CHF), renal failure and cirrhosis. The efficacy of torasemide in reducing salt and water retention in CHF has been established in double-blind comparative studies against furosemide. Torasemide has been shown to be at least as effective as furosemide in terms of total volume of urine excreted and also has a longer duration of action. The efficacy of torasemide (in terms of improved CHF symptoms and reduced pulmonary congestion, oedema and bodyweight) has been shown in randomised controlled trials and confirmed in large postmarketing studies. In addition, data from postmarketing studies have shown that patients receiving torasemide had significantly reduced hospital admission rates compared with patients receiving furosemide. Pharmacoeconomic assessments of torasemide have focused on its effect in reducing hospitalisation. Hospitalisation costs due to CHF decreased by 86% during the 11.2-month period of torasemide treatment, compared with the 6-month period prior to treatment, in a US retrospective study assessing medical and pharmacy claims data. Overall, average monthly costs for patients decreased by 56.6% after 5.1 months (from $US1,897.28 to $US823.70 per patient per month; PPPM), and by 76% after 11.2 months (from $US1,944.76 to $US470.76 PPPM) of torasemide treatment. In the furosemide group, average monthly costs for patients increased moderately from $US227.28 to $US261.18 PPPM after 12 months. Direct comparison of the torasemide and furosemide study groups was not possible because the group receiving torasemide had much higher healthcare resource use at baseline. Compared with furosemide, torasemide was associated with reduced rates of hospital admissions for CHF and/or cardiovascular causes in 3 studies, a retrospective analysis conducted in Germany, a prospective US study of patients enrolled from hospital admissions and a decision-analysis model. As a result, the direct costs of treatment for CHF or cardiovascular diseases for patients treated with torasemide were less than those with furosemide. However, in the US study, there was no statistically significant difference in hospital admissions for all causes and/or in overall direct medical costs, although the study was not powered to show this. In another US study of managed care patients with New York Heart Association (NYHA) class II or III CHF, no difference in clinical or economic outcomes was observed between patients taking torasemide or furosemide; despite the higher acquisition costs for torasemide, total costs were similar for both groups. Torasemide was found to be more cost effective than furosemide in terms of cost per patient with improved functional (NYHA) class of CHF severity in a retrospective German analysis, although this measure is not ideal. This study also evaluated indirect costs (for loss of productivity of employed patients) and resultssuggest torasemide has a favourable effect in reducing days off work compared with furosemide, although the population of employed patients in the study was very small. Torasemide has been shown to improve some measures of quality of life in 2 studies. It was associated with higher quality-of-life scores than furosemide in a 6-month study, but the differences were only significant at month 4. In another study, torasemide significantly improved fatigue, but full study details are yet to be published. CONCLUSIONS: Despite the higher acquisition cost of torasemide over furosemide, pharmacoeconomic analyses have shown that torasemide is likely to reduce overall treatment costs of CHF by reducing hospital admissions and readmissions. Torasemide has generally shown clinical and economic advantages over furosemide, although more long term data are needed to confirm these results and to further investigate effects on quality of life. There are limitations to the currently available pharmacoeconomic data, but present data support the use of torasemide as a first-line option for diuretic therapy in patients with CHF presenting with oedema and especially in those patients not achieving relief of symptoms with furosemide.     

Cost-effectiveness analysis of formoterol versus salmeterol in patients with asthma.

OBJECTIVE: The aim of this study was to determine the relative economic consequences of treating asthmatics with twice daily dry powder formoterol 12 micrograms as compared with salmeterol 50 micrograms from a societal perspective. DESIGN AND SETTING: A randomised, 6-month, open-label study including 482 patients with asthma was conducted in Italy, Spain, France, Switzerland, the UK and Sweden. Medical costs included the costs of medications, physician services, emergency room visits, hospital admissions and lung function and other tests. Travel costs and costs of production loss were also calculated. Unit prices were estimated from external sources. To pool the costs of the 6 countries, European currencies were converted to US dollars using 1995 exchange rates. Outcome measures were the number of episode-free days (EFDs) and the number of patients reaching a clinically relevant improvement in quality of life as measured using the St. Georges Respiratory Questionnaire. MAIN OUTCOME MEASURES AND RESULTS: There were no significant differences between the 2 treatment arms in the frequency of emergency room visits, hospital admissions, use of rescue medication or contacts with general practitioners (GPs), specialists or nurses. Median medical costs over 6 months were $US828 per patient with formoterol and $US850 with salmeterol. This difference was not statistically significant. In both groups, about 60% of all days were episode-free. Average costs per EFD were about $US9 for both treatments. The average cost per patient reaching a clinically relevant improvement in quality of life was between $US1300 and $US1400. Incremental cost-effectiveness ratios were not calculated because both costs and outcomes were not significantly different. Asthma-related absenteeism ranged between 3 days and 6 months per patient in both groups. CONCLUSIONS: There was no evidence to suggest that either treatment was more cost effective than the other.     

Inpatient Costs of Major Cardiovascular Events

Objective

Many trials of new therapies for cardiovascular disease include economic measures to assess the impact of treatment on healthcare costs, however, it is difficult to compare results between trials due to variation in methods for assigning costs. Therefore we developed a standard library of inpatient hospital costs for major cardiovascular events commonly reported in trials for new cardiovascular therapies.

Design

Mean and median hospital charges for each event were calculated from Medicare admissions selected by ICD-9-CM codes from the most recent Healthcare Cost and Utilisation Project (HCUP) Nationwide Inpatient Sample (NIS) database available. Charges were converted to costs using the cost-to-charge ratio from the most recent Medicare cost report data and updated to 1999 using a model derived from the Medicare Payment Advisory Commission (MedPAC) forecast to recommend annual updates to Medicare.

Results

Total hospital costs for medical events ranged from $US3654 (1999 values) to $US7833; total hospital costs for surgery and procedures ranged from $US7054 to $US46 317. The distribution of hospital costs is skewed with median costs and lengths of stay lower than mean values. Costs for patients who died in the hospital were generally higher than costs for patients who were discharged.

Conclusions

The library of costs was calculated using a uniform method based on publicly available and easily accessible data and may be updated from year to year. This method provides standardised estimates of hospital costs that can be used in economic analyses of cardiovascular clinical trials.     

Direct costs of hip fractures in patients over 60 years of age in Belgium.

OBJECTIVE: Osteoporosis-related costs are now considered a major burden for health authorities in most developed countries. An accurate and exhaustive evaluation of these costs would be a major contribution to health economic studies evaluating the efficiency of screening and prevention strategies. Osteoporosis is the most frequent underlying cause of femoral neck fractures in the elderly; these fractures weigh heavily on healthcare budgets. However, in Belgium, very few data on the financial burden of hip fractures are available and no updated estimates have been made. The goal of this paper is to estimate the direct medical expenditures associated with hip fractures in Belgium in 1996. DESIGN AND SETTING: This 1-year population-based cross-sectional study is conducted from the social security perspective. The target population in this study are men and women aged 60 years and over. PATIENTS AND PARTICIPANTS: We selected patients who had been hospitalised for a hip fracture during the year 1996 who were also affiliated with a registered social security organisation (covering 25% of the Belgian population). The sample constituted 2374 patients. INTERVENTIONS: For each of these patients, we collected an exhaustive and detailed list of healthcare resource use as well as nursing home admissions following the hip fracture event. Cost items investigated in the analysis were inpatient hospital costs and outpatient costs. Mean annual costs per case recorded in the sample were then extrapolated to the whole country on the basis of an exhaustive list of diagnoses having lead to all countrywide hospitalisations (1,700,000 hospital stays/year). MAIN OUTCOME MEASURES AND RESULTS: The mean hospital inpatient costs for hip fracture were evaluated at 332,148 Belgian francs (BeF) [$US8977] per case and BeF4,367,746,200 ($US118,047,194) for the whole country (10 million inhabitants). Patients with a hip fracture experienced an annual BeF27,825 ($US752) extra outpatient cost during the year following this fracture event, after correcting for costs related to additional comorbidity already present before the hip fracture. Finally, after a proximal femoral neck fracture, the rate of nursing home admission was higher, both for men and women at any age compared with age- and gender-matched population. CONCLUSIONS: With a total cost (acute hospital and outpatient costs) of BeF4,667,894,950 ($US126,159,323) per year in Belgium, proximal femoral neck fracture should be considered a major health economic problem and appropriate measures to prevent this disease should be rapidly undertaken.     

Cost effectiveness of bisoprolol in the treatment of chronic congestive heart failure in Sweden: analysis using data from the Cardiac Insufficiency Bisoprolol Study II trial.

OBJECTIVE: To investigate the cost effectiveness of adding the beta-blocker bisoprolol to standard treatment in patients with congestive heart failure (CHF). DESIGN AND SETTING: A cost-effectiveness study was based on the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), a randomised clinical trial investigating the efficacy of adding bisoprolol to standard therapy of CHF. The cost-effectiveness analysis was carried out from a societal perspective. METHODS: Health effects were measured in terms of years of life gained. On the cost side, treatment costs for pharmaceuticals and hospitalisations were included. Data on healthcare resource consumption from CIBIS-II were used and were combined with average Swedish retail prices for medicines, and average costs for hospitalisations based on hospital admissions, in the base case. The costs of added years of life, i.e. consumption net of production during life-years gained were also included. RESULTS: If costs of added years of life were not included, then bisoprolol therapy increased life expectancy at an incremental cost of Swedish kronor (SEK) 13 094 (1999 values) per year of life gained. If costs of added years of life were included, then the incremental cost-effectiveness ratio of bisoprolol therapy was SEK 168 858 per year of life gained. CONCLUSIONS: For patients with CHF with the characteristics of those in CIBIS-II, the cost effectiveness of bisoprolol therapy compares favourably with that of other cardiovascular therapies.     

Cost-of-illness of epilepsy in Italy. Data from a multicentre observational study (Episcreen)

OBJECTIVE: To investigate the impact of epilepsy in Italy on healthcare resources, producing an average cost per patient per year of follow-up. DESIGN AND SETTING: The Episcreen Project is a multicentre longitudinal Italian observational study; its methodology, organisational network and case report form have been reported in detail elsewhere. Using a subset of patients with epilepsy from this project, we conducted a retrospective cost-of-illness analysis based on clinical records. The analysis was performed from the societal (community) perspective, including both direct and indirect costs. Hospital admissions, day-hospital visits, specialist visits, instrumental examinations, drugs and productivity losses because of visits and hospitalisation were analysed. Each cost variable was valued in 1996 Italian liras (L) using published national tariffs (except for drugs for which published prices were used). A sensitivity analysis was conducted on indirect costs to test the robustness of the assumption that 1 working day lost for each day hospital visit would produce a change of 0.3% in the weight of indirect costs. PATIENTS AND PARTICIPANTS: Patients analysed in this study were registered in the Episcreen database as at 21 November 1996. They were diagnosed with epilepsy at the last visit, had at least 1 follow-up visit (i.e. at least 1 visit after the enrolment visit), and had at least 12 months of follow-up. RESULTS: The average cost per patient per year was L2,726,116 ($US1767). The average cost per patient was higher for children than for adults [L3,629,997 ($US2353) and L2,362,134 ($US1531), respectively), and for newly diagnosed patients for whom the first diagnosis of epilepsy was addressed at the first Episcreen visit [adults: old referrals L1,304,353 ($US845), new referrals L6,901,374 ($US4473); children: old referrals L2,810,504 ($US1822), new referrals L7,814,400 ($US5065)]. Direct costs represented 87.6% of total costs. The major cost driver was hospitalisation (63.7%), followed by drugs (10.5%), day-hospital visits (4.1%), out-patient visits (3.85%), other tests (3.1%) and electroencephalographs (2.3%). Indirect costs (lost productivity) represented 12.4% of total costs. Sensitivity analysis showed that the results are sensitive to the value attributed to lost productivity. CONCLUSIONS: The cost of managing a patient with epilepsy in Italy is influenced by age, syndrome and modality of referral to the centre for epilepsy.     

Comparative effects of torasemide and furosemide in rats with heart failure

It has been reported that torasemide but not furosemide, may block the renin-angiotensin-aldosterone system and therefore it might attenuate myocardial remodeling accompanied by left ventricular (LV) dysfunction. We therefore compared the therapeutic effects of torasemide, a long-acting loop diuretic, and furosemide, a short-acting one, on the progression of LV remodeling in a rat model of chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM). CHF was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, rats were treated for 28 days with torasemide, furosemide, or vehicle. We investigated the effects on metabolic and neurohumoral parameters, cardiac fibrosis and remodeling in EAM rats. Diuresis was increased dose dependently by both torasemide and furosemide, showed an equipotent natriuretic effect. The urinary potassium excretion was significantly increased with furosemide in comparison to torasemide. Myocardial functional parameters were significantly improved by torasemide. Conversely, these parameters did not change in rats receiving furosemide. Torasemide suppressed LV fibrosis, myocardial protein levels of transforming growth factor-beta1, collagen III, and aldosterone synthase and improved survival rate to the control level, but furosemide did not. Moreover, both pharmacological interventions significantly elevated plasma angiotensin II and decreased atrial natriuretic peptide in a dose-dependent manner. Our results demonstrate that compared with furosemide, torasemide treatment significantly improved survival rate, LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.     

Stroke rehabilitation services to accelerate hospital discharge and provide home-based care: an overview and cost analysis

BACKGROUND: Limited information exists on the best way to organise stroke rehabilitation after hospital discharge and the relative costs of such services. OBJECTIVE: To review the evidence of the cost effectiveness of services that accelerate hospital discharge and provide home-based rehabilitation for patients with acute stroke. METHODS: A systematic review with economic analysis of published randomised clinical trials (available to March 2001) comparing early hospital discharge and domiciliary rehabilitation with usual care in patients with stroke was conducted. From included studies, data were extracted on study quality; major clinical outcomes including hospital stay, death, institutionalisation, disability, and readmission rates; and resource use associated with hospital stay, rehabilitation, and community services. The resources were priced using Australian dollars ($A) healthcare costs. The outcomes and costs of the new intervention were compared with standard care. RESULTS: Seven published trials involving 1277 patients (54% men; mean age 73 years) were identified. The pooled data showed that overall, a policy of early hospital discharge and domiciliary rehabilitation reduced total length of stay by 13 days [95% confidence interval (CI): -19 to -7 days]. There was no significant effect on mortality (odds ratio = 0.95; 95% CI: 0.65 to 1.38) or other clinical outcomes making a cost minimisation analysis for the economic analysis appropriate. The overall mean costs were approximately 15% lower for the early discharge intervention [$A16 016 ($US9941) versus $A18 350] ($US11 390)] compared with standard care. CONCLUSIONS: A policy of early hospital discharge and home-based rehabilitation for patients with stroke may reduce the use of hospital beds without compromising clinical outcomes. Our analysis shows this service to be a cost saving alternative to conventional in-hospital stroke rehabilitation for an important subgroup of patients with stroke-related disability.     

Cost analysis of the treatment of severe spinal spasticity with a continuous intrathecal baclofen infusion system.

OBJECTIVE: The purpose of our study was to analyse and evaluate the costs of continuous intrathecal baclofen administration as a modality in the treatment of severe spasticity in the Netherlands. DESIGN: A cost analysis was conducted as part of a prospective, multicentre, multidisciplinary, randomised and placebo-controlled clinical trial. The study covered the period from December 1991 to September 1995. The data on medical consumption and costs were collected over a 3-year period from different sources: administrative databases of health insurance companies, hospital registries and a patient survey. These data were structured by means of a flowchart analysis of the medical decision-making by specialists and general practitioners (GPs). They included data on in- and outpatient care, home care and care in nursing homes. The cost analysis was conducted using data from 18 patients included in the trial and from 15 so-called 'match' patients. The latter group are patients with comparable diseases leading to spasticity and living in comparable circumstances. Next to absolute costs (direct and indirect) of care and treatment for the 2 groups of patients, cost differences between the 2 groups were considered (differential cost analysis). SETTING: Per patient cost data, collected prospectively for 2 years during the phase of clinical evaluation, and retrospectively 1 year before implantation. The data were collected on patients from in- and outpatient care, home care and care in nursing home settings. PATIENTS AND PARTICIPANTS: The trial patients (8 men) had a mean age of 46 years; 11 patients had multiple sclerosis and 7 patients had spinal cord injuries. The match patients (7 men) had a mean age of 48 years; 9 patients had multiple sclerosis and 6 patients had spinal cord injuries. INTERVENTIONS: Trial patients were treated with a subcutaneously implanted programmable continuous infusion pump (SynchroMed, Medtronic), filled with baclofen (a muscle relaxant) to treat patients with chronic disabling spasticity who did not respond to a maximum dose of oral baclofen, dantrolene and tizanidine. MAIN OUTCOME MEASURES AND RESULTS: An analysis of hospital stay between both groups showed a significant difference during the implantation year. The average number of hospital days per patient in the year in the treated group was 31.5 days and in the match group was 18.7 days. Significant cost differences between both groups in the year that started with pump implantation and the following year can be attributed mostly to the costs of implantation of the pump and related hospitalisation days. The total costs of patient selection, testing, implanting the pump and follow-up amounted to $US28,473 for the first year. Savings must be taken into consideration as well. The savings of direct costs were due to withdrawal of oral medication (estimated annual total of between $US1950 and $US2800 per patient). Indirect savings on employment and nursing home costs, amounted annually to $US1047 and $US5814, respectively. Scenarios make it possible to consider policy consequences. The case of 'extending' the indications for this treatment to a larger population has been calculated and visualised. CONCLUSIONS: The costs of the therapy (continuous intrathecal infusion of baclofen) can be attributed mostly to implantation of the pump and related hospitalisation days. Savings originated from withdrawal of oral medication, job preservation and avoidance or delay of admission to a nursing home.     

Cost of illness and disease severity in a cohort of French patients with Parkinson's disease.

OBJECTIVE: To assess the relationship between severity and progression of illness in Parkinson's disease and the use of healthcare resources. DESIGN AND SETTING: This was a prospective cost-of-illness study conducted in France based on clinical observation over a 6-month period of patients with Parkinson's disease treated in the hospital or community setting. Regression analyses were performed to construct the model that offered the best explanation for health expenditures using clinical and sociodemographic indicators. PATIENTS AND PARTICIPANTS: All patients included in the study had well-defined idiopathic Parkinson's disease, were aged > 35 years, were receiving treatment with levodopa or other antiparkinsonian agents, and were capable of completing questionnaires, alone or with the help of a household member. The final study population consisted of 294 patients, of whom 54 were enrolled by general practitioners and 240 by neurologists. INTERVENTIONS: Investigators completed a clinical questionnaire at the beginning and end of the 6-month observation period. Patients completed a questionnaire on their daily living conditions at the beginning and end of the study, and also completed monthly reports of healthcare use and loss of productivity. Patients with motor fluctuations also filled in fluctuation diaries on 4 consecutive days at the beginning and end of the 6-month period. Resource data collected included hospital stays, ancillary care, drug therapy, medical visits and transportation. Social costs were evaluated in nonmonetary terms, with the exception of costs of adapting the home environment. Transfer payments were analysed using reports from patients. MAIN OUTCOME MEASURES AND RESULTS: Hospital stays were the most expensive component of care (39% of costs), followed by ancillary care (30%) and drug therapy (22%). The mean medical cost was 308 euros (EUR) [$US357] for patients followed by a general practitioner and EUR2580 ($US2993) for patients followed by a neurologist. Costs also varied with age and motor fluctuations. Medical costs were strongly correlated with most clinical indicators and the cost generally progressed in line with the severity of the disease. The strongest correlation was between clinical indicators and ancillary care costs. CONCLUSIONS: These results confirm the importance of the social burden of Parkinson's disease. The regression results could be used to evaluate the benefit of novel treatments that reduce the intensity of motor fluctuations.     

Economic evaluation of oral ofloxacin versus standard parenteral therapy in the treatment of pneumonia

The purpose of this study was to examine how inpatient use of oral ofloxacin, a fluoroquinolone antibiotic, affects utilisation of healthcare resources in the treatment of pneumonia. We collected data via chart review from a recent multicentre trial that randomised hospitalised adult patients with pneumonia to oral ofloxacin or standard parenteral therapy of the investigators' choice. We followed a total of 126 patients from randomisation until rule-out of pneumonia, death, loss to follow-up, or 30 days following cure, whichever occurred first. For each patient, we collected data on all inpatient antibiotic usage, duration of stay in hospital, and the utilisation of selected healthcare services following discharge from hospital. While length of stay did not differ between ofloxacin and standard-therapy patients (9.2 vs 11.1 days, respectively; p = 0.28), the cost of inhospital antibiotic therapy for those who received ofloxacin was one-fifth that of patients who were randomised to parenteral therapy ($US47 vs $US268). Costs of outpatient antibiotic therapy were slightly higher for the group receiving ofloxacin ($US26 vs $US3). No difference was noted in the rate of hospital readmission during follow-up. Our study therefore suggests that the use of oral ofloxacin among inpatients with pneumonia reduces the costs of antibiotic treatment compared to standard parenteral therapy.     

Cost effectiveness of long-term treatment with eszopiclone for primary insomnia in adults: a decision analytical model

OBJECTIVE: Although the clinical benefits of pharmacological treatments for insomnia have been studied, no systematic assessment of their economic value has been reported. This analysis assessed, from a broad payer and societal perspective, the cost effectiveness of long-term treatment with eszopiclone (LUNESTA, Sepracor Inc., [Marlborough, MA, USA]) for chronic primary insomnia in adults in the US. METHODS: A decision analytical model was developed based on the reanalysis of a 6-month placebo-controlled trial, which demonstrated that eszopiclone 3mg significantly improved sleep and daytime function measures versus placebo in adults with primary insomnia. Patients were classified as either having remitted or not remitted from insomnia based upon a composite index of eight sleep and daytime function measures collected during the trial. These data were supplemented with quality-of-life and healthcare and lost productivity cost data from the published literature and medical and absenteeism claims databases. RESULTS: Compared with non-remitted patients, patients classified as remitted had lower monthly healthcare and productivity costs (in 2006 dollars) [a reduction of $US242 and $US182, respectively] and higher quality-adjusted life-year (QALY) weight (a net gain of 0.0810 on a scale ranging from 0 to 1). During the study, eszopiclone-treated patients were about 2.5 times more likely to have remitted than placebo-treated patients. Six months of eszopiclone treatment reduced direct (healthcare) and indirect (productivity) costs by an estimated $US245.13 and $US184.19 per patient, respectively. Eszopiclone use was associated with a cost of $US497.15 per patient over 6 months (including drug cost, dispensing fee, physician visit and time loss to receive care). Thus, after considering the above savings and the costs associated with eszopiclone treatment over 6 months, cost increased by $US252.02 (excluding productivity gains) and $US67.83 (including productivity gains) per person. However, eszopiclone treatment was also associated with a net QALY gain of 0.006831 per patient over the same period. Consequently, the incremental cost per QALY gained associated with eszopiclone was approximately $US9930 (including productivity gains [i.e. $US67.83 / 0.006831]) and $US36 894 (excluding productivity gains [i.e. $US252.02 / 0.006831]). Sensitivity analyses using a variety of scenarios suggested that eszopiclone is generally cost effective. CONCLUSIONS: This analysis suggested that long-term eszopiclone treatment was cost effective over the 6-month study period, particularly when the impact on productivity costs is considered. Given the increasing interest in new pharmacological interventions to manage insomnia, payers and clinicians alike should carefully consider the balance of health and economic benefits that these interventions offer. Accordingly, additional research in this area is warranted.     

The economic impact of Parkinson's disease. An estimation based on a 3-month prospective analysis

OBJECTIVE: This study prospectively assesses the medical costs of Parkinson's disease (PD). DESIGN: Over a period of 3 months (from July to September 1995), patients with PD documented all items of healthcare provision. These data were then used to calculate medical costs for an individual patient as well as the costs of PD. PATIENTS AND SETTING: We included 20 outpatients with idiopathic PD from the neurological outpatient clinic, Klinikum Grosshadern, Munich, and 20 patients from two office-based neurologists in South-West Germany. MAIN RESULTS: The mean 3-month medical cost of PD in 1995 deutschmarks (DM) was 5210 ($US3390, 2240 Pounds) consisting of DM1410 ($US920, 610 Pounds) for care and nursing, DM1580 ($US1030, 680 Pounds) for drug therapy, DM1320 ($US860, 570 Pounds) for inpatient hospital care, DM40 ($US26, 17 Pounds) for outpatient care and DM860 for other expenses ($US560, 370 Pounds). The expenditure was related to the disease evolution. Patients complaining of one-sided symptoms [Hoehn and Yahr stage I; (HY I)] were less expensive to treat (DM1930, $US1250, 830 Pounds) than patients who were severely incapacitated (HY V) [DM9740, $US6330, 4200 Pounds; HY V]. After 3 to 5 years of levodopa treatment approximately 50% of patients start to experience fluctuations in motor ability and dyskinesias [Unified Parkinson's disease rating scale, part IV (UPDRS IV)]. This onset of motor complications parallels an increase in costs. For patients who experienced motor fluctuations, annual costs were DM6550 ($US4260, 2820 Pounds) compared with DM3030 ($US1960, 1300 Pounds) for patients lacking this problem. Indirect non-medical costs were not calculated due to the limited number of patients. The impact of the disease on work, however, is clearly apparent from the patients' history: 19 out of 34 patients who had already stopped working attributed this to the disease, and only 6 patients were still working at the time of the survey. CONCLUSION: PD poses a major financial impact to society which is expected to increase in future years as the age distribution shifts to older age groups. On the basis of a prevalence of PD of 183 per 100,000, we calculated an annual expenditure of DM3.0 billion for the direct medical costs of PD in Germany.     

Medical cost savings from pentoxifylline therapy in chronic occlusive arterial disease

This article assesses the direct medical cost savings associated with therapeutic dosages of pentoxifylline therapy compared with lower dosages in treating chronic occlusive arterial disease (COAD). The savings accrue from elimination of invasive diagnostic measures or a number of surgical procedures received by patients with COAD during hospital admissions. Findings are based on a secondary analysis of results presented in a previously published report of a population based historical cohort study. Patients in this study were severely enough afflicted by the disease that most were under the care of vascular specialists and many underwent surgery to restore normal blood flow. Costs are based on charges from Medicare expenditures in 4 US states in 1989. A case-mix adjustment procedure was applied and a sensitivity analysis was conducted on key assumptions and variables in the cost savings model. Pentoxifylline therapy reduced average hospital costs per patient by $US1173 per year (1989 dollars). After further adjustment for the costs of outpatient visits, other related drugs and the drug acquisition cost, an overall saving of $US965 would still be realised with a patient who received the full therapeutic dose of pentoxifylline. Sensitivity analysis suggests total annual direct medical cost savings between $US69 and $US3090 per patient. Hence, under the most plausible assumptions regarding choice of procedures, study design and patient population, and considering the possibility that diagnostic and surgical costs are delayed but not prevented, pentoxifylline therapy substantially reduces direct medical costs.     

新型袢利尿剂托拉塞米

综述托拉塞米的药理作用、药动学、临床应用、药物不良反应和药物经济学。托拉塞米属吡啶磺酰脲类袢利尿剂，作用于髓袢升支粗段，抑制Cl^ 和Na^ 的重吸收，产生利尿、利钠和其他作用。其生物利用度高，半衰期相对较长，血浆蛋白结合率较高。临床试验表明，托拉塞米治疗高血压和慢性肾功能衰竭、肝功能不全或心力衰竭患者的水肿和其他症状有效，不良反应较轻。药物经济学分析表明，托拉塞米通过降低住院率和再住院率而降低总花费。     

Loop diuretics enhance the secretion of prostacyclin in vitro, in healthy persons, and in patients with chronic heart failure

Background: Previous studies suggest that the acute haemodynamic effects of loop diuretics are due to a direct dilation of blood vessels and are not related to diuretic properties, but possibly to prostaglandin secretion. Objectives: We investigated whether in vitro human endothelial and renal epithelial cells responded to torasemide or furosemide with enhanced secretion of the vasodilator prostaglandin prostacyclin (PGI₂). We also investigated the effects of loop diuretics on plasma concentrations of PGI₂ and its physiological antagonist thromboxane after 25 min of administration of drugs in 44 patients with congestive heart failure (CHF) and 44 healthy volunteers. Methods: The PGI₂ levels were measured after extraction in ethyl acetate by RIA as levels of 6-KetoPGF_1α, a stable metabolite from a non-enzymatic degradation. TxB2 concentration, the stable hydrolysis product of TxA2, was also measured by RIA. Results: In human endothelial and renal epithelial cells, both loop diuretics induced an increase of 6-KetoPGF_1α secretion that reached a peak after about 5 min and remained stable for 30 min of exposure to the drugs. The magnitude of the phenomenon was lesser in epithelial than in endothelial cells. Moreover, in both cell lines, there was a significantly higher secretion of 6-KetoPGF_1α to torasemide than furosemide (P < 0.05). Concentrations of 6-KetoPGF_1α at baseline were similar between the groups of CHF patients receiving the two different drugs. After 25 min of both drugs, 6-Keto-PGF_1α significantly increased (P < 0.01), and this was significantly higher in patients treated with 10 mg of torasemide (P < 0.05 vs furosemide). Levels of PGI₂ at baseline were lower in healthy controls than those reached by CHF patients and similar between groups. After 25 min of both drugs, PGI₂ plasma levels were significantly increased (P < 0.01). Baseline values of TxB2 were significantly higher in CHF patients compared with controls (P < 0.01 vs respective groups), and, more importantly, furosemide but not torasemide increased TxB2 levels in patients and controls (P < 0.05 vs baseline). Conclusions: Our study is the first demonstration in human tissue of increased secretion of PGI₂ both in vitro and in vivo, after torasemide or furosemide administration. This phenomenon, which may explain in part the vasodilatory effects of these drugs, was more evident with torasemide and was reached at lower concentrations of the drug. Accordingly, we also found that furosemide but not torasemide stimulated the release of the PGI₂ physiological antagonist thromboxane in CHF patients and healthy controls. Received: 8 May 1998 / Accepted in revised form: 14 August 1998     

呋塞米与托拉塞米间隔使用治疗慢性心力衰竭的临床观察

目的探讨呋塞米与托拉塞米间隔使用治疗慢性心力衰竭（CHF）的疗效。方法将符合纳入标准患者随机分成试验组和对照组。试验组先使用呋塞米片7 d,然后改为托拉塞米片7 d;对照组使用呋塞米片14 d。比较两组治疗14 d后总有效率、尿量、电解质及pro-BNP的差别。结果①试验组总有效率为89.66%,显著高于对照组（77.01%）,差异有统计学意义（χ^2=7.968,P=0.019）;②两组治疗后尿量较治疗前显著增加,差异有统计学意义（P〈0.05）,血钾和pro-BNP均较治疗前显著下降,差异有统计学意义（P〈0.05）;③治疗后试验组尿量和血钾显著高于对照组,差异有统计学意义（P〈0.05）,pro-BNP显著低于对照组,差异有统计学意义（P〈0.05）;④试验组总不良反应发生率及低钾血症发生率显著低于对照组,差异有统计学意义（P〈0.05）。结论呋塞米与托拉塞米间隔使用可提高CHF治疗的总有效率,增加尿量,减少电解质紊乱等不良反应。     

An economic evaluation of atorvastatin for primary prevention of cardiovascular events in type 2 diabetes

OBJECTIVE: The CARDS trial, a multicentre, randomized, controlled trial, found that atorvastatin 10 mg/day for patients with type 2 diabetes mellitus and normal low-density lipoprotein (LDL)-cholesterol significantly reduced cardiovascular (CV) events, including stroke. We estimated the cost effectiveness of atorvastatin as primary prevention against CV disease from the short-term and lifetime US payer perspectives. RESEARCH DESIGN AND METHODS: We constructed a decision analytic (Markov) model to evaluate long-term costs and outcomes for atorvastatin 10 mg/day versus no HMG-CoA reductase inhibitor (statin) therapy for patients with type 2 diabetes and no history of a CV event. CV event rates and survival were based on risk equations calibrated to CARDS and applied to a US type 2 diabetes population; the atorvastatin effect on CV events was based on hazard ratios from CARDS; direct medical care costs were based on US treatment patterns and published costs analyses of patients with diabetes. Costs were valued in $US, year 2005 values; costs and benefits were discounted at 3% per annum. RESULTS: Within the time horizon of the trial (5 years), the cost effectiveness of atorvastatin was $US137 276 per QALY. At 10 years, the incremental cost per QALY improved to $US3640 per QALY. At 25 years, overall costs were lower and QALYs higher in the atorvastatin arm. Costs of managing CV events were lower after 5 years for patients treated with atorvastatin. CONCLUSIONS: For patients with type 2 diabetes and one additional risk factor for CV disease, normal LDL-cholesterol and no history of a CV event, primary prevention with atorvastatin appears to be cost saving and improve outcomes over 25 years, although it is costly from a short-term US payer perspective. From both a medical and an economic viewpoint, primary prevention is desirable in this patient population.