Cost effectiveness of cilostazol compared with naftidrofuryl and pentoxifylline in the treatment of intermittent claudication in the UK

ABSTRACT

Objective: To estimate the cost effectiveness of cilostazol (Pletal) compared to naftidrofuryl and pentoxifylline (Trental) in the treatment of intermittent claudication in the UK.

Design and setting: This was a modelling study on the management of patients with intermittent claudication who are 40 years of age or above and have at least six months history of symptomatic intermittent claudication, secondary to lower extremity arterial occlusive disease. The study was performed from the perspective of the UK's National Health Service (NHS).

Methods: Clinical outcomes attributable to managing intermittent claudication were obtained from the published literature and resource utilisation estimates were derived from a panel of vascular surgeons. Using decision analytical techniques, a decision model was constructed depicting the management of intermittent claudication with cilostazol, naftidrofuryl and pentoxifylline over 24 weeks in the UK. The model was used to estimate the cost effectiveness (at 2002/2003 prices) of cilostazol relative to the other treatments.

Main outcome measures and results: Starting treatment with cilostazol instead of naftidrofuryl is expected to increase the percentage improvement in maximal walking distance by 32% (from 57% to 75%) for a 12% increase in NHS costs (from £801 to £895). Treatment with cilostazol instead of pentoxifylline is expected to increase the percentage improvement in maximal walking distance by 67% (from 45% to 75%) and reduce NHS costs by 2% (from £917 to £895). Treatment with naftidrofuryl instead of pentoxifylline is expected to increase the percentage improvement in maximal walking distance by 27% (from 45% to 57%) and decrease NHS costs by 14% (from £917 to £801).

Conclusion: Within the limitations of our model, starting treatment with cilostazol is expected to be a clinically more effective strategy for improving maximal walking distance at 24 weeks than starting treatment with naftidrofuryl or pentoxifylline and potentially the most cost effective strategy. Moreover, the acquisition cost of a drug should not be used as an indication of the cost effectiveness of a given method of care.     

Health economic impact of olopatadine compared to branded and generic sodium cromoglycate in the treatment of seasonal allergic conjunctivitis in the UK

OBJECTIVE: This study estimated the health economic impact of olopatadine (Opatanol) compared to branded cromoglycate (Opticrom) and generic sodium cromoglycate in the treatment of seasonal allergic conjunctivitis (SAC) in the UK. DESIGN AND SETTING: This was a modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: A decision model was constructed depicting the management of SAC sufferers who are 4 years of age or above over a typical allergy season of 4 months and considers the decision by a GP to initially treat a patient with olopatadine, branded or generic cromoglycate. The analysis assumed both drugs to be equally effective. Consequently, a cost-minimisation analysis was performed to identify the least costly alternative. MAIN OUTCOME MEASURES AND RESULTS: Starting treatment with olopatadine is expected to lead to a healthcare cost of 92 pounds sterling (95% CI: 46 pounds sterling; 150 pounds sterling) over 4 months compared to 109 pounds sterling (95% CI: 65 pounds sterling; 166 pounds sterling) with branded cromoglycate and 95 pounds sterling (95% CI: 51 pounds sterling; 152 pounds sterling) with generic cromoglycate, resulting in a 16% and 3% reduction in healthcare costs respectively over 4 months of treatment. This cost-difference is primarily due to fewer GP visits among olopatadine-treated patients. CONCLUSION: Use of olopatadine instead of branded or generic cromoglycate affords an economic benefit to the NHS. Hence, within the limitations of the model, olopatadine is the preferred first-line treatment for use in SAC sufferers, since it is expected to lead to fewer GP visits, thereby releasing healthcare resources for alternative use.     

Modelling the cost effectiveness of cholinesterase inhibitors in the management of mild to moderately severe Alzheimer's disease

OBJECTIVE: To estimate the cost effectiveness (from the UK NHS and personal social services perspective) of the cholinesterase inhibitors donepezil, rivastigmine and galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer's disease. Patients had a mean age of 74 years, a mean disease duration of 1 year and a mean Alzheimer's disease assessment scale-cognitive subscale score of 24. METHODS: A pharmacoeconomic model was used to predict long-term outcomes over a 5-year time horizon and to estimate the cost effectiveness of cholinesterase inhibitors for the management of Alzheimer's disease. The model structure is informed by a systematic review of the literature on the clinical and cost effectiveness of cholinesterase inhibitors and a review of the literature on the costs and outcomes associated with treatment for Alzheimer's disease. The main outcome measure used was the cost per quality-adjusted life-year (QALY) gained. All healthcare costs (excluding cholinesterase inhibitor costs) were indexed to pounds sterling (2003 values). Drug costs are 2005 values. Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results. RESULTS: The clinical benefits on cognition from treatment with cholinesterase inhibitors resulted in an incremental cost per QALY gained ranging from 53,780 pounds sterling to 74,735 pounds sterling, over 5 years (vs usual care). Uncertainty analysis suggests that the probability of any of these treatments having an incremental cost per QALY of < 30,000 pounds sterling is < 21%. The key determinants of cost effectiveness were the effectiveness of treatment, the mean treatment cost and the cost savings associated with an expected delay in disease progression. CONCLUSIONS: Results presented in this paper suggest that the use of cholinesterase inhibitors may not be a cost-effective use of NHS resources. Guidance from the National Institute for Health and Clinical Effectiveness (NICE) in the UK on their judgements surrounding the acceptability of technologies as an effective use of resources, indicates there would need to be special reasons for accepting cholinesterase inhibitors as a cost-effective use of NHS resources.     

Cilostazol

Cilostazol is an antiplatelet agent with vasodilating properties that has been used in the treatment of patients with peripheral ischaemia such as intermittent claudication. The drug inhibits platelet aggregation induced by ADP, collagen and arachidonic acid. Unlike aspirin (acetylsalicylic acid), cilostazol inhibits both primary and secondary aggregation. It also acts as a vascular vasodilator by inhibiting calcium-induced contractions while having no direct effect on contractile proteins. In double-blind randomised trials, patients with intermittent claudication receiving cilostazol showed significant improvements versus placebo in terms of time to initial pain and maximal walking or absolute claudication distance; these findings were confirmed by cilostazol patients' positive responses on subscales measuring physical functioning and quality of life. In a 24-week randomised double-blind trial in patients with intermittent claudication, cilostazol 100mg twice daily produced significant improvements in pain-free and maximum walking distances, compared with pentoxifylline (oxpentifylline) 400mg 3 times daily and placebo. Cilostazol has been well tolerated, with the most common adverse events being headache, diarrhoea, abnormal stools and dizziness.     

A probabilistic cost-effectiveness analysis of escitalopram, generic citalopram and venlafaxine as a first-line treatment of major depressive disorder in the UK

OBJECTIVES: To determine if escitalopram is cost-effective in the UK when compared with venlafaxine and generic citalopram in primary care treatment of Major Depressive Disorder (MDD). METHODS: A pre-existing cost-effectiveness model was adapted to reflect the practice in the UK. Adult patients (> 18 years) with MDD [baseline scores >/= 18 and 相似文献   

A cost-effectiveness analysis of docetaxel in the second-line treatment of non-small cell lung cancer

BACKGROUND: Whilst lung cancer is the most common form of cancer in England and Wales (annual incidence rate of 50 per 100,000) it does not always receive the policy attention accorded to other types of cancer, such as breast and colorectal. Nevertheless, the burden of lung cancer is significant and the UK NHS Plan for cancer has set out the government's commitment to improving all cancer services. The question faced by the NHS is which interventions are most cost effective in implementing this plan. OBJECTIVE: To develop a model to assess the economics of second-line treatment of non-small cell lung cancer (NSCLC) from the perspective of the UK NHS, based on the resources and outcomes from the pivotal clinical study comparing docetaxel 75 mg/m(2) with best supportive care (BSC). METHODS: The area under the survival curve for each treatment was analysed and the difference in mean survival between the docetaxel group and the BSC group was calculated as 3.82 months. Measurable incremental costs for the docetaxel group were largely driven by drug acquisition and administration. These cost drivers, as well as toxicity treatment costs and cost offsets, were varied in the sensitivity analysis. Although the overall timeframe for the model was 2 years, discounting was not applied as the resources and benefits of docetaxel use in this setting are realised relatively immediately. RESULTS: The base case cost-effectiveness analysis (mean values) reported a cost per life-year gained of 13,863 pounds sterling for docetaxel 75 mg/m(2) (year 2000/2001 values). Sensitivity analysis showed that the number of treatment cycles per patient, which affected total treatment cost, had most influence on the cost per life-year gained in the base case scenario. Using the 95% confidence intervals around the mean number of treatment cycles, the base case cost per life-year gained varied from 10,985 pounds sterling to 16,738 pounds sterling. Using the 95% confidence intervals around the mean difference in survival, to represent best and worst case scenarios, the cost per life-year saved ranged from 10,020 pounds sterling to 32,781 pounds sterling . CONCLUSION: This model suggests, with its underlying assumptions and data, docetaxel 75 mg/m(2) in 3-weekly cycles is a cost-effective second-line treatment, from the perspective of the NHS, for pretreated NSCLC in terms of survival gains made for a reasonable increase in costs.     

Naftidrofuryl: a review of its use in the treatment of intermittent claudication

Naftidrofuryl (Praxilene) is a vasodilator that has been used in the treatment of intermittent claudication for >30 years in Europe to improve walking distance and provide symptomatic relief. However, earlier trials had inconsistencies in design and the clinical relevance of the treatment effect has been controversial. Recent randomised, double-blind, placebo-controlled trials, however, have generally been conducted in accordance with updated methodology guidelines. In these studies, naftidrofuryl 200mg three times daily improved pain-free and maximal walking distances and health-related quality of life by a significantly greater extent than placebo in patients with intermittent claudication. The magnitude of these effects appears to support claims that the effects of naftidrofuryl are clinically relevant in these patients.     

Drug treatment of intermittent claudication

The US FDA has approved two drugs for the management of intermittent claudication: pentoxifylline and cilostazol. The mechanism of action that provides symptom relief with pentoxifylline is poorly understood but is thought to involve red blood cell deformability as well as a reduction in fibrinogen concentration, platelet adhesiveness and whole blood viscosity. The recommended dose of pentoxifylline is 400 mg three times daily with meals. Cilostazol is a potent, reversible, phosphodiesterase III inhibitor. The inhibition of phosphodiesterase allows for the increased availability of cyclic adenosine monophosphate (cAMP). cAMP mediates many agonist-induced platelet inhibitory, vasodilatory and vascular antiproliferative responses. Cilostazol, at a dose of 100 mg twice daily, is recommended to be taken 30 minutes before or 2 hours after breakfast and dinner. In addition to pentoxifylline and cilostazol, clinical trials indicate many other drugs may relieve the symptoms of intermittent claudication. Ginkgo biloba, available as an over-the-counter extract, provides symptom relief comparable to pentoxifylline. Two European agents, naftidrofuryl and buflomedil, also have efficacy that is reported to be similar to pentoxifylline. Policosanol is a mixture of fatty alcohols derived from honeybee wax which, according to very limited data, reduces symptoms of claudication. Amino acids, certain peptides and prostaglandins may have a therapeutic role. Finally, novel approaches including angiogenesis mediated by growth factors, are currently under investigation.     

Pharmacological approaches to the treatment of intermittent claudication.

Intermittent claudication is a common condition of the elderly, occurring in 3 to 20% of individuals over the age of 65 years. Although local disease is usually benign, life expectancy in patients with intermittent claudication is reduced by approximately 10 years due to associated cardiovascular mortality. Several classes of drugs have been used in intermittent claudication, but clinical studies evaluating their efficacy leave much to be desired. Pentoxifylline (oxpentifylline), a rheological agent, and naftidrofuryl, an enhancer of aerobic metabolism, are the 2 most widely investigated and utilised drugs. The combined results of 10 placebo-controlled studies with pentoxifylline and 4 with naftidrofuryl estimate increases in claudication distances of 51 and 42%, respectively. However, due to publication bias, these figures are probably overestimates of the true benefit from treatment with these drugs. It is likely that any benefit from pentoxifylline or naftidrofuryl is small and of little clinical importance. The suggestion that naftidrofuryl has greater efficacy in older patients remains unproven. Other classes of drugs including vasodilators, antiplatelet drugs, anticoagulants and prostaglandins have not been shown to be effective. Only 2 approaches to the management of intermittent claudication have been shown convincingly to be of benefit: stopping smoking and exercising regularly.     

The cost of treatment for post-herpetic neuralgia in the UK

Post-herpetic neuralgia (PHN) following acute shingles caused by the herpes simplex virus is a painful and often disabling condition. Treatment of the condition can involve a range of drug therapies. In addition, patients with continuing pain may make several visits to general practitioners and hospital outpatient departments. The costs of treatment for these patients may be substantial. The main objective of this study was to estimate the costs and consequences to the UK National Health Service (NHS) of the treatment of PHN following shingles, and the effect of the condition on patients' lives in terms of pain and time off usual activities such as work. The lifetime direct treatment costs of a cohort of people from onset of PHN to resolution of the disease or death were calculated. These costs were estimated from data on the type and quantity of health resources used, and the unit costs or prices of those resources. This study has shown that PHN can be a costly consequence of acute shingles. For patients attending a tertiary referral centre the lifetime cost was 770 British pounds sterling. For a 1-year incidence cohort of people with shingles in the UK, the lifetime costs of treating PHN are between 4.8 million British pounds sterling (incidence of 21 000 people) and 17.9 million British pounds sterling (incidence of 78 200 people). Efforts are needed to reduce the incidence or severity of PHN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modelling the cost implications of using carboxymethylcellulose dressing compared with gauze in the management of surgical wounds healing by secondary intention in the US and UK

OBJECTIVE: To estimate the costs of using carboxymethyl cellulose dressing (CMCD; Aquacel* Hydrofiber) compared to gauze in managing surgical wounds healing by secondary intention in the US and UK. STUDY DESIGN: This was a modelling study performed from the perspective of payers (i.e. the hospital and community sector in the US and the National Health Service (NHS) in the UK). METHODS: Clinical outcomes attributable to managing surgical wounds healing by secondary intention with gauze were obtained from the published literature in the English language. There were no published studies on wounds healing by secondary intention with CMCD. Hence, the analysis conservatively assumed that wound healing rates associated with gauze would be the same for CMCD. These data were combined with resource utilisation estimates derived from a panel of clinicians enabling us to perform decision modelling. The models were used to determine the expected direct healthcare costs eight weeks after the surgical wounds were dressed by CMCD or gauze and left to heal by secondary intention in the US and UK. RESULTS: All wounds are expected to heal within eight weeks, irrespective of dressing. Managing abscesses and other surgical wounds with CMCD instead of gauze in the US is expected to reduce costs by 4% in both wound types (i.e. $247 and $507 respectively) per patient over eight weeks. In the UK, managing abscesses and other surgical wounds with CMCD instead of gauze is expected to reduce costs by 30% (574 pounds) and 12% (581 pounds) respectively per patient over eight weeks. The lower cost of managing CMCD-treated patients is due to decreased nursing costs associated with a lower frequency of CMCD changes compared to gauze dressing changes. CONCLUSION: Dressing surgical wounds healing by secondary intention with CMCD instead of gauze is expected to lead to a reduction in healthcare costs in both the US and UK. Hence, the purchase price of a dressing is not indicative of the cost effectiveness of a given method of surgical wound care.     

Economic impact of low dose polyethylene glycol 3350 plus electrolytes compared with lactulose in the management of idiopathic constipation in the UK

OBJECTIVE: To estimate the economic impact of using low dose polyethyene glycol 3350 (PEG 3350) plus electrolytes (PEG+E) compared with lactulose in the treatment of idiopathic constipation in ambulant patients. DESIGN AND PERSPECTIVE: This was a decision analytic modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: The clinical outcomes from a previously reported single-blind, randomised, multicentre trial were used as the clinical basis for the analysis. These data were combined with resource utilisation estimates derived from a panel of six general practitioners (GPs) and four nurses enabling a decision model to be constructed depicting the management of idiopathic constipation with either PEG+E or lactulose over 3 months. The model was used to estimate the expected 3-monthly NHS cost of using either laxative to manage idiopathic constipation. MAIN OUTCOME MEASURES AND RESULTS: The expected 3-monthly NHS cost of using PEG+E or lactulose to manage idiopathic constipation was estimated to be 85 pound sterling and 96 pound sterling per patient, respectively (1999/2000 values). However, significantly more patients were successfully treated with PEG+E than lactulose (53% versus 24%; p < 0.001) at 3 months. GP visits were the primary cost driver for both PEG+E- and lactulose-treated patients, accounting for 56% (2.9 visits) and 73% (4.4 visits), respectively, of the expected NHS cost per patient at 3 months. Among PEG+E-treated patients, the acquisition cost of PEG+E was the secondary cost driver, accounting for 30% of the expected NHS cost per patient at 3 months, whereas the acquisition cost of lactulose accounted for only 11% of the expected NHS cost per lactulose-treated patient. District nurse domiciliary visits accounted for 4% and thyroid function tests for 2%. The costs of switched laxatives, concomitant laxatives, and gastroenterologist and colorectal surgeon visits collectively accounted for up to 9% of the total. CONCLUSIONS: The true cost of managing idiopathic constipation is impacted on by a broad range of resources and not only laxative acquisition costs. This study indicated that managing idiopathic constipation with PEG+E instead of lactulose reduces the expected 3-monthly NHS cost by 11 pound sterling per patient. Moreover, using PEG+E instead of lactulose is expected to double the percentage of patients successfully treated at 3 months. Hence, PEG+E is a dominant treatment compared with lactulose. This suggests that the decision to use either PEG+E or lactulose to treat idiopathic constipation should be based on efficacy, safety, patient preferences and total management costs, and not drug acquisition costs.     

Pharmacological management of intermittent claudication: a meta-analysis of randomised trials

Intermittent claudication, a symptom of atherosclerosis in the large vessels of the lower limbs, greatly affects patient mobility and quality of life. Medical therapy for a moderate form of this condition includes vasodilators, antiplatelet agents and alternative treatments such as ginkgo biloba.A meta-analysis of results from 52 trials (including 5088 patients) was conducted for all current medical therapies for intermittent claudication. After 24 weeks, some of the medical therapies were found to be more effective than placebo for the primary end-points of either pain-free walking distance or maximum walking distance. Vasodilators presented the best results in walking distance. Pentoxifylline offered better results than naftidrofuryl, although the treatment benefit, measured in additional metres walked with treatment than without, was modest. Antiplatelets, ginkgo biloba and levocarnitine were slightly more effective than placebo, although the treatment benefit was of limited clinical importance. On average, patients walked 60m further with therapy than without, and only about half of that added distance was pain-free. Very little consistent information was available for other clinical end-points, such as overall mortality and adverse effects. These data suggest that some of the medical therapy, pentoxifylline in particular, can only modestly increase functional status in patients with moderate intermittent claudication. There is a need for uniformity in research design and reporting of trials. A future trial comparing medical therapy with physical therapy is indicated.     

The cost effectiveness of tacrolimus versus microemulsified cyclosporin: a 10-year model of renal transplantation outcomes

INTRODUCTION AND OBJECTIVE: In 1983, the launch of cyclosporin was a significant clinical advance for organ transplant recipients. Subsequent drug research led to further advances with the introduction of cyclosporin microemulsion (cyclosporin ME) and tacrolimus. This paper presents the results from a long-term model comparing the clinical and economic outcomes associated with cyclosporin ME and tacrolimus immunosuppression for the prevention of graft rejection following renal transplantation. STUDY DESIGN: A model was developed to project the costs and outcomes over a 10-year period following transplantation. The model was based on the results of a prospective, randomised study of 179 renal transplantation recipients receiving either cyclosporin ME or tacrolimus, which was conducted by the Welsh Transplantation Research Group (median follow-up: 2.7 years). METHODS: The short-term costs and outcomes were the averages from the actual head-to-head trial data. From this, the long-term costs and outcomes were extrapolated based on the rate of change in patient and graft survival at 3, 5 and 10 years post transplant, as reported in the 1995 United Kingdom Transplant Support Service Authority Renal Transplant Audit. PERSPECTIVE AND YEAR OF COST DATA: The analysis was conducted from the perspective of a UK transplant unit. Costs were at 1999 prices (pounds sterling 1 = dollars US 1.42 = Euro 1.5) and costs and outcomes were discounted at 6% and 1.5%, respectively. RESULTS: The model estimated that 10 years after transplantation, the proportion of patients surviving was 56% of the cyclosporin ME cohort and 64% of the tacrolimus cohort. The cumulative cost of maintenance therapy at 10 years was pounds sterling 23204 per patient maintained on cyclosporin ME versus pounds sterling 23803 per patient on tacrolimus. The cost per survivor at 10 years was pounds sterling 37000 (tacrolimus) versus pounds sterling 41000 (cyclosporin ME) and the cost per patient with a functioning graft was pounds sterling 39000 versus pounds sterling 45000. A Monte Carlo simulation of the model (10000 simulations) gave an average cost at 10 years of pounds sterling 23279 (SD pounds sterling 3457) for cyclosporin ME and pounds sterling 22841 (SD pounds sterling 3590) for tacrolimus. A (second order) probabilistic sensitivity analysis was also performed. The average cost at 10 years from a simulated cohort of 1000 was pounds sterling 23473 (SD pounds sterling 2154) for cyclosporin ME and pounds sterling 24087 (SD pounds sterling 2025) for tacrolimus. CONCLUSION: Renal transplant recipients maintained on tacrolimus have better short- and long-term outcomes than patients maintained on cyclosporin ME. The long-term use of tacrolimus is a more cost-effective solution in terms of the number of survivors, patients with a functioning graft and rejection-free patients.     

The costs and benefits of community thrombolysis for acute myocardial infarction : a decision-analytic model

BACKGROUND: There is evidence that the earlier a patient reaches hospital and receives thrombolysis, the better the outcome. The GREAT (Grampian Region Early Anistreplase Trial) directly addressed the issue of early thrombolysis by evaluating, in a randomised controlled trial, the efficacy of thrombolysis in the community compared with that administered in hospital. OBJECTIVE: This paper aimed to model the cost and benefits of community compared with hospital thrombolysis from the UK NHS perspective, using efficacy data from the GREAT. METHODS: A decision-analytic approach was used to model these two alternatives. Resource use and cost estimates were estimated for a single tertiary centre. Estimates of effectiveness in life-years were obtained from the 4-year follow-up for patients recruited to the GREAT, using declining exponential approximation of life expectancy. Costs are in pounds sterling, 2000/1 values. RESULTS: Community thrombolysis had an average life expectancy of 12.48 years and hospital thrombolysis had an average life expectancy of 12.39 years. Costs were 361 pounds sterling for community thrombolysis and 300 pounds sterling for hospital thrombolysis. Community thrombolysis led to an additional 0.09 years of life-expectancy gained compared with hospital thrombolysis at an additional cost of 61 pounds sterling per patient. Therefore, the incremental cost per life-year gained for the community thrombolysis service over the hospital thrombolysis service was 667 pounds sterling. Sensitivity analysis showed that estimates of cost per life-year gained were most sensitive to the estimates of survival. CONCLUSION: This model suggests that, from the UK NHS perspective, implementing community thrombolysis may lead to extra survival but at extra cost over hospital thrombolysis. Although the incremental cost per life-year is modest, judgements still have to be made, however, as to whether the extra benefits estimated are worth the additional resources required. This requires consideration of the local context in which the service may be introduced.     

An economic evaluation of the costs and benefits of heparin rationalisation in a hospital pharmacy

AIM: To estimate the costs and benefits for a UK hospital pharmacy of stocking a single low molecular weight heparin (LMWH), enoxaparin, compared to stocking unfractionated heparin (UFH) and stocking both UFH and multiple different LMWHs. METHODS: A decision-tree model was developed which considered the use of heparins for five indications: prophylaxis against venous thromboembolism (VTE) in major orthopaedic surgery; VTE prophylaxis in major general surgery; VTE prophylaxis in acute medical inpatients; treatment of diagnosed VTE; and anticoagulation for patients with unstable angina and non-ST-elevation myocardial infarction (UA/NSTEMI). Previously published cost-effectiveness analyses for each indication were combined into a single model and updated to 2002 prices. The number of patients given heparin in each indication was estimated from the pharmacy records of a large UK teaching hospital. The model estimated the use of drugs, staff time, clinical events and resource use resulting from anti-coagulation. Costs were estimated from the perspective of the hospital and the UK National Health Service. RESULTS: Total annual cost was estimated to be pounds sterling 3.2 m (single LMWH), pounds sterling 4.4 m (UFH only) and pounds sterling 3.7 m (multiple heparins). The largest expected cost savings from using a single LMWH compared to UFH only resulted from reduced hospital stay for DVT treatment, reduced revascularisation in UA/NSTEMI and fewer VTE events in orthopaedic surgery. Expected cost savings from using a single LMWH compared to multiple heparins were more modest CONCLUSION: Sub-optimal choice of anticoagulants may result in substantial excess costs elsewhere in the hospital.     

Cardiovascular prophylaxis with aspirin: costs of supply and management of upper gastrointestinal and renal toxicity

AIMS: To determine the cost to the NHS of prescribed low-dose aspirin. METHODS: This was a population based observational cohort study. Patients from Tayside Scotland (17 244 new users of dispensed aspirin each with 10 matched comparators) were included. A pragmatic analysis totalled costs from the start to end of the study and compared these with a matched cohort of aspirin nonusers to estimate excess costs. Fastidious analyses were done of subjects with no prior history of upper gastrointestinal (UGI) or renal disease where the cost that occurred during aspirin exposure, the 30 days following aspirin exposure and subsequent nonexposure was calculated adjusting for risk factors in each period. RESULTS: Subjects took aspirin for only 1.18 of the 2.53 years follow-up (47% compliance). Aspirin use cost an additional 49.86 UK pounds per year (pragmatic analysis) made up of 1.96 UK pounds for aspirin tablets (4%), 5.49 UK pounds for dispensing costs (11%), 24.60 UK pounds for UGI complications (49%) and 17.81 UK pounds for renal complications (36%). The costs for managing complications were substantially lower in the fastidious analysis (2.66 UK pounds for UGI complications and 2.92 UK pounds for renal complications). Assuming that the antiplatelet trial meta-analysis is an accurate assessment of the benefits of aspirin, the costs of preventing one vascular event lay between 62 500 UK pounds (primary prevention, pragmatic analysis) and 867 UK pounds (secondary prevention, fastidious analysis). These costs may be underestimates due to the low compliance observed. CONCLUSIONS: Compliance with aspirin was poor. Serious adverse events were uncommon but despite this aspirin cost the NHS between 6 and 25 times the cost of aspirin tablets due to dispensing costs and the cost of managing adverse effects.     

Cilostazol and peripheral arterial disease

Peripheral arterial disease is both common and disabling. Contemporary management of peripheral arterial disease is multimodal, encompassing both medical and interventional treatments. Cilostazol (Pletal), a 2-oxoquinolone derivative, is currently licensed in the UK for the treatment of patients with intermittent claudication to improve their walking distance in the absence of tissue necrosis or rest pain. The therapeutic effects of cilostazol are thought to be mediated through antiplatelet, antiproliferative and vasodilatory activities. This review aims to provide an overview of the management of peripheral arterial disease focusing upon cilostazol pharmacotherapy.     

Oral vasoactive medication in intermittent claudication: utile or futile?

Objective: To evaluate the role of orally administered vasoactive medication in the management of intermittent claudication. Setting: We limited our study to the products on the market in Belgium: cinnarizine, cyclandelate, isoxsuprine, naftidrofuryl, pentoxifylline, xanthinol nicotinate and buflomedil. Data sources: We conducted a systematic literature search involving Medline, International Pharmaceutical Abstracts, the Cochrane Library, direct contact with marketing companies and key authors, snowballing and Science Citation Index search. We looked for randomised placebo-controlled trials (RCTs) in patients with Fontaine stage II, in which pain-free and/or maximal walking distance were measured using a standardised exercise test. For isoxsuprine and xanthinol nicotinate, no trials conforming to these criteria were found. Thirty-six trials on cinnarizine, cyclandelate, buflomedil, naftidrofuryl and pentoxifylline met our inclusion criteria. Study selection: After quality assessment, 26 trials were excluded, mainly because of short trial duration (less than 12 weeks), small sample size (less than 30 patients) and/or failure to report details on variability (standard deviation or confidence limits). For cinnarizine and cyclandelate, none of the three selected RCTs was included. Data extraction: For buflomedil, of six published RCTs, two were included after quality assessment, each showing a marginally positive effect of buflomedil versus placebo. For naftidrofuryl, nine RCTs were selected; six were included of which five showed a significant positive result. The likelihood of publication bias and the heterogeneity of the results within and between trials precluded a meta-analysis. For pentoxifylline, of the 18 selected RCTs, only two could be included, both with inconclusive results. Conclusion: A national consensus conference, based on this review, concluded that health resources should be allocated to prevention and rehabilitation of intermittent claudication rather than to reimbursement of these products with doubtful efficacy. Received: 11 November 1999 / Accepted in revised form: 10 February 2000