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.     

Cost effectiveness of imatinib compared with interferon-alpha or hydroxycarbamide for first-line treatment of chronic myeloid leukaemia

OBJECTIVE: To evaluate the cost utility of imatinib compared with interferon (IFN)-alpha or hydroxycarbamide (hydroxyurea) for first-line treatment of chronic myeloid leukaemia. DESIGN AND SETTING: A cost-utility (Markov) model within the setting of the UK NHS and viewed from a health system perspective was adopted. Transition probabilities and relative risks were estimated from published literature. Costs of drug treatment, outpatient care, bone marrow biopsies, radiography, blood transfusions and inpatient care were obtained from the British National Formulary and local hospital databases. Costs (pound, year 2001-03 values) were discounted at 6%. Quality-of-life (QOL) data were obtained from the published literature and discounted at 1.5%. The main outcome measure was cost per QALY gained. Extensive one-way sensitivity analyses were performed along with probabilistic (stochastic) analysis. RESULTS: The incremental cost-effectiveness ratio (ICER) of imatinib, compared with IFNalpha, was pound26,180 per QALY gained (one-way sensitivity analyses ranged from pound19,449 to pound51,870) and compared with hydroxycarbamide was pound86,934 per QALY (one-way sensitivity analyses ranged from pound69,701 to pound147,095) [ pound1=$US1.691=euro1.535 as at 31 December 2002].Based on the probabilistic sensitivity analysis, 50% of the ICERs for imatinib, compared with IFNalpha, fell below a threshold of approximately pound31,000 per QALY gained. Fifty percent of ICERs for imatinib, compared with hydroxycarbamide, fell below approximately pound95,000 per QALY gained. CONCLUSIONS: This model suggests, given its underlying data and assumptions, that imatinib may be moderately cost effective when compared with IFNalpha but considerably less cost effective when compared with hydroxycarbamide. There are, however, many uncertainties due to the lack of long-term data.     

Cost-effectiveness of statins in the prevention of coronary heart disease events in middle-aged Finnish men

ABSTRACT

Objective: This study evaluated the long-term cost-effectiveness of atorvastatin 20?mg, rosuvastatin 10?mg and simvastatin 40?mg in primary and secondary prevention of CHD in Finland.

Research design and methods: The effect of statin therapy on the incidence of CHD and the expected total costs of the disease were described using a Markov state transition model. Due to the limited amount of evidence concerning mortality and morbidity for rosuvastatin, the model was used to transmute the efficiency data of all statins (decrease in total cholesterol) into long-term endpoints (myocardial infarction, death) using risk functions of the FINRISK and 4S studies. The study followed a characterized cohort of 55-year-old Finnish men with an average 3.3–6.6?%?baseline risk of dying from cardiovascular disease within a 10-year period.

Main outcome measures: Incremental cost-effectiveness ratios (ICERs) for atorvastatin and rosuvastatin, compared with simvastatin, measured as cost of life years gained (€/LYG) and cost of quality adjusted life years gained (€/QALY).

Results: The use of rosuvastatin increased the life expectancy by 0.27 years on average (LYG) compared with simvastatin, producing additional 0.08 quality-adjusted life-years (QALYs). Compared with simvastatin, the cost of one LYG with rosuvastatin was €10 834 and the cost of one QALY gained was €36 548 (discount rate 5?%?per annum). Corresponding figures for atorvastatin were €31 286/LYG and €105 599/QALY.

Conclusions: If the decision makers’ willingness to pay for a QALY gained is around €40 000 there is a high probability (?>?50?%?) that rosuvastatin represents a cost-effective form of therapy in the prevention of CHD in middle-aged men with an average 3.3–6.6?%?risk of dying within 10 years from cardiovascular disease. However, the true clinical impact of these results needs confirmation from on-going clinical trials, as the role of rosuvastatin in reducing clinical events is pending, but for simvastatin and atorvastatin established.     

An economic evaluation of fluvastatin used for the prevention of cardiac events following successful first percutaneous coronary intervention in the UK

AIMS: To estimate the costs, benefits and cost effectiveness, from the UK NHS perspective, of fluvastatin (relative to no HMG-CoA reductase inhibitor [statin]) for the secondary prevention of major adverse cardiac events following a successful first percutaneous coronary intervention (PCI). METHODS: A cost-effectiveness analysis was undertaken using efficacy data from the Lescol Intervention Prevention Study (LIPS). LIPS was a randomised, double-blind, placebo-controlled trial undertaken in 77 centres (predominantly in Europe). Patients included in the trial had moderate hypercholesterolaemia and had successfully undergone their first PCI. Fluvastatin (Lescol) 40 mg twice daily plus dietary counselling was given to the intervention group for up to 4 years; the control group received dietary counselling only. A Markov model was used to estimate the incremental costs per QALY gained over a 10-year period, with cost data drawn from the UK NHS (2002 values). Monte Carlo simulations and multivariate analysis were used to assess uncertainty. Costs were discounted at 6% per annum, and health outcomes at 1.5% per annum. RESULTS: On average, treatment with fluvastatin cost an additional pound 300 (SD pound 303) [euro 423; SD euro 428] per patient and resulted in an additional 0.092 (SD 0.06) QALYs per patient over 10 years compared with controls. The incremental cost per QALY gained with fluvastatin versus the control group was pound 3207 (SD pound 5,497) [euro 4,527; SD euro 7,759]. Fluvastatin was dominant (better outcomes and lower costs) in 15.9% of the simulations and was dominated in 2.9%. The key determinants of cost effectiveness were: the effectiveness of fluvastatin in reducing acute myocardial infarction, subsequent PCI, coronary artery bypass graft and cardiac deaths; the utility weight associated with a subsequent post-PCI state; the cost of fluvastatin; and the time horizon evaluated. CONCLUSIONS: Fluvastatin is the only statin which has proven effective in preventing major coronary adverse events in new PCI patients; other statins lack this evidence. This Markov model, with its underlying assumptions and data, suggests that fluvastatin is a viable and economically efficient pharmaceutical (relative to no statin) to reduce heart disease in the UK when given routinely to all patients following PCI.     

Cost-Effectiveness Analysis of Cholesterol-Lowering Therapies in Spain

OBJECTIVE: To assess the cost efficacy of atorvastatin, simvastatin, lovastatin, fluvastatin, pravastatin, and colestyramine in the reduction of low-density lipoprotein-cholesterol (LDL-C) levels and the cost per patient to achieve the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) therapeutic objectives in Spain. METHOD: The following treatments were evaluated: atorvastatin, simvastatin, and pravastatin 10-40 mg/day; lovastatin and fluvastatin 20-80 mg/day; and colestyramine 12-24 g/day. The cost effectiveness of these treatments was evaluated, in terms of cost per percentage of LDL-C reduction, by comparing annual treatment costs versus the efficacy of LDL-C reduction. Treatment costs included medication costs (2003 wholesale prices), control measures, and the treatment of adverse affects. The efficacy of HMG-CoA reductase inhibitors (statins) was obtained from a meta-analysis of results obtained from clinical trials published between 1993 and 2003 that met the following criteria: monotherapy; >16 weeks of treatment; randomized allocation of individuals to the intervention and comparator groups; dietary treatment for > or =3 months before administration of medication; and double-blind measurement of outcomes. Average and incremental cost-effectiveness ratios were calculated to assess the efficiency of cholesterol-lowering treatments. RESULTS: Efficacy, in terms of percentage of LDL-C reduction, ranged from 10% for colestyramine 12 g/day to 49% for atorvastatin 40 mg/day. Total annual treatment costs ranged from euro 321 for fluvastatin 20 mg/day to euro 1151 for atorvastatin 40 mg/day. Cost-effectiveness ratios, in terms of cost per percentage of LDL-C reduced, were: euro 11-23 for atorvastatin; euro 12-21 for simvastatin; euro 14-22 for lovastatin; euro 15-24 for fluvastatin; euro 21-42 for pravastatin; and euro 35-46 for colestyramine. Atorvastatin 10 mg/day was the most cost-effective treatment, followed by simvastatin 10 mg/day, lovastatin 20 mg/day, and fluvastatin 20 mg/day. Atorvastatin was the most cost-effective treatment in the achievement of the NCEP ATP III LDL-C reduction objectives in patients with high (<100 mg/dL) and moderate (<130 mg/dL) risk of coronary heart disease (CHD), with a cost per patient of euro 747 and euro 405 per year, respectively. Fluvastatin was the most cost-effective treatment in the achievement of the NCEP ATPIII therapeutic objective in patients with low-risk of CHD (LDL-C <160 mg/dL), with a cost per patient of euro 321. CONCLUSION: Atorvastatin 10 mg/day was the most cost-effective cholesterol-lowering drug, followed by simvastatin 10 mg/day, lovastatin 20 mg/day, and fluvastatin 20 mg/day. The preferred statin should be atorvastatin in patients with moderate-to-high CHD risk and fluvastatin in patients with low risk for CHD.     

Cost effectiveness of tumour necrosis factor-alpha inhibitors as first-line agents in rheumatoid arthritis

BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease with an unknown aetiology that results in >9 million physician visits and >250 000 hospitalisations per year in the US. Tumour necrosis factor-alpha (TNFalpha) inhibitors are effective agents in treating RA; however, their cost effectiveness as first-line agents has not been investigated. This study aimed to examine the cost effectiveness of using TNFalpha inhibitors (both as monotherapy and in combination with methotrexate) as first-line agents versus methotrexate (monotherapy) from a payer perspective. METHODS: A Markov model was developed utilising a discount rate of 3% per annum, a cycle length of 1 year and a lifetime time-horizon for a hypothetical cohort of US females aged 55-60 years who had been diagnosed with RA. The source of data for predicted probabilities, expected mortality rates and treatment costs in year 2005 US dollars (drug, toxicity, monitoring and hospitalisation) was from the literature. These costs are assigned in 5-year cycles (calculated from initial 1-year estimates) along with the effect on quality-adjusted life-years (QALYs), which were calculated using the Health Assessment Questionnaire score. Univariate sensitivity analyses were conducted on all relevant parameters. RESULTS: Adalimumab, etanercept, adalimumab plus methotrexate and infliximab plus methotrexate had incremental cost-effectiveness ratios (ICERs) versus methotrexate monotherapy of $US63 769, $US89 772, $US194 589 and $US409 523 per QALY, respectively. When taking into consideration age at diagnosis, the ICER for etanercept ranged from $US84 129 to $US96 225 per QALY. In considering males for the base-case age at diagnosis, the ICER for etanercept versus methotrexate was $US85 100 per QALY. The average lifetime cost across all treatment arms in a woman diagnosed between 55 and 60 years of age was $US211 702. CONCLUSION: While these ICERs cannot be used to directly compare one biological agent with another since there are no comparative trials, they do provide a valid comparison versus methotrexate as first-line agents. Depending where the cost-effectiveness threshold is drawn (i.e. whether it is considered to be $US50 000 or $US100 000 per QALY), etanercept and adalimumab may be considered relatively cost-effective first-line treatments for RA compared with methotrexate monotherapy.     

Economic impacts attributable to the early clinical benefit of atorvastatin therapy – a US managed care perspective

ABSTRACT

Objective: The clinical literature suggests that atorvastatin therapy achieves a reduction in major cardiovascular events within the first year of therapy. Aside from obvious clinical benefits, economic advantage may also result from this observation. The present analysis modeled the clinical and economic consequences of initiating atorvastatin versus generic simvastatin in defined US managed care organization patient populations.

Research design and methods: A cost-consequence model was developed to estimate the differential rate and associated costs of cardiovascular events occurring over 2 years using real world price and adherence data. Four defined patient populations were included from representative atorvastatin trials: (1) diabetes mellitus; (2) multiple risk factors; (3) coronary heart disease; and (4) acute coronary syndrome. Costs of care included drug costs and costs of managing cardiovascular events. Univariate sensitivity analyses and multivariate sensitivity analysis via Monte Carlo simulation were conducted to test the robustness of the results.

Main outcome measures: The number of cardiovascular events avoided per 100^?000 patients initiated on atorvastatin as compared with simvastatin, and total treatment costs.

Results: The model predicts that, relative to simvastatin, atorvastatin will prevent 941 (95% confidence interval [CI] 481–1367) cardiovascular events after 1 year and 1426 (95% CI 833–1987) events after 2 years, per 100?000 patients. This is expected to reduce the cost of cardiovascular events by $365 (95% CI $192–$527) and $552 (95% CI $327–$763) per patient (US$ 2006), respectively, offsetting 80% and 75% of the medication cost difference between atorvastatin and simvastatin after 1 and 2 years, respectively. The incremental costs associated with atorvastatin treatment were estimated at $94 (95% CI –$68 to $267) and $175 (95% CI –$37 to $399) per patient after 1 and 2 years, respectively. Results were sensitive to assumptions regarding simvastatin efficacy and drug acquisition costs.

Conclusions: Although the present analysis is based in part on indirect comparisons and on trials not designed or statistically powered to specifically test the early benefits hypothesis, it suggests that atorvastatin's assumed early reduction of cardiovascular events partly offsets the acquisition price difference between atorvastatin and generic simvastatin in various groups of high-risk patients newly initiated on statin treatment.     

A pharmacoeconomic evaluation of statins in the treatment of hypercholesterolaemia in the primary care setting in Spain

BACKGROUND: Cardiovascular disease is one of the leading causes of death and it has been shown that primary prevention with the HMG-CoA reductase inhibitor (statin) lipid-lowering drugs can reduce cardiovascular events. Acquisition costs vary between statins and this may be an important consideration in the overall cost effectiveness (CE) of different options. OBJECTIVE: To perform a CE study of the main statins used in Spain for primary prevention of cardiovascular disease in patients with high cholesterol levels [corrected] STUDY DESIGN: The CE analysis was based on an open-label, prospective, naturalistic, randomised intervention study under usual care conditions in primary care settings in patients with high cholesterol levels (total cholesterol [TC] >240 mg/dL, low-density lipoprotein cholesterol [LDL-C] >160 mg/dL) and one or more cardiovascular risk factors. The analysis was conducted from the perspective of the Spanish National Health System; the year of costing was 2001. PATIENTS: A total of 161 patients (49.7% males), mean age 65 +/- 10.3 years, without evidence of cardiovascular disease were included in the study. Of those, 82.1% were hypertensive, 37.1% had diabetes mellitus and 17.9% were smokers. INTERVENTIONS: Forty-eight patients received oral atorvastatin 10 mg/day, 32 received fluvastatin 40 mg/day, 44 received simvastatin 20 mg/day and 37 patients received pravastatin 20 mg/day for 6 months. MAIN MEASUREMENTS AND RESULTS: After 6 months, the therapeutic goals of LDL-C control, according to the recommendations of the Spanish Society of Arteriosclerosis--Consensus-2000, were reached in 62.5%, 43.8%, 45.5% and 40.5% of patients treated with atorvastatin, fluvastatin, simvastatin and pravastatin, respectively. The average CE ratio, expressed as the cost in euros (euro) per patient achieving the therapeutic goals, was euros 424.3 for atorvastatin, euros 503.5 for fluvastatin, euros 527.0 for simvastatin and euros 683.4 for pravastatin. The incremental CE ratios for atorvastatin versus fluvastatin and simvastatin were euros 238.9 and euros 149.5, respectively, per additional patient reaching therapeutic goals. Atorvastatin, fluvastatin and simvastatin all dominated pravastatin. CONCLUSIONS: All the statins studied have been shown to be effective for reducing both TC and LDL-C levels. In this study, atorvastatin was the most efficient drug, with the best CE ratio (cost per patient reaching therapeutic goals). Atorvastatin was more effective and less costly than pravastatin, and when compared with fluvastatin or simvastatin the additional cost per additional patient achieving therapeutic goals was 相似文献   

Infliximab: a pharmacoeconomic review of its use in rheumatoid arthritis

Infliximab (Remicade), a biological disease-modifying antirheumatic drug (DMARD), binds to and inhibits the activity of tumour necrosis factor-alpha, which is thought to play an important role in the pathophysiology of rheumatoid arthritis. Intravenous infliximab plus methotrexate is recommended in patients with rheumatoid arthritis who have not achieved satisfactory disease control with adequate courses of other DMARDs. Pharmacoeconomic analyses have been based on efficacy data from the pivotal placebo-controlled Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) trial in patients with active, refractory rheumatoid arthritis. Infliximab every 8 weeks plus methotrexate demonstrated rapid and sustainable improvements in clinical response, delayed radiographic progression, and/or improved functional status and health-related QOL compared with placebo plus methotrexate at weeks 30, 54 and 102. In cost-utility analyses of infliximab plus methotrexate conducted from a healthcare payer and/or societal perspective in the US, Europe, Portugal, Sweden and the UK, infliximab 3 mg/kg every 8 weeks plus methotrexate was associated with acceptable (<$US50,000 per discounted QALY gained) cost-utility ratios relative to methotrexate alone in patients with active, refractory rheumatoid arthritis. When only direct costs were considered, the lifetime incremental cost per discounted QALY gained with infliximab plus methotrexate relative to methotrexate alone was $US30,500-38,700 (year of costing 1998 or not reported; treatment duration 54 or 102 weeks or lifelong) in the US and Europe analyses, and euro39 500 (year of costing not reported; lifelong treatment) in the Portuguese analysis. The cost-utility ratios were more favourable when lost productivity costs or the additional benefit of infliximab on radiographic stabilisation were considered. In the Swedish and UK analyses with a 10-year time horizon, infliximab plus methotrexate for 1 or 2 years was associated with cost-utility ratios of euro28 600-56 100 (year of costing not reported) when direct costs were considered, and euro3440-48 200 when direct costs plus loss-of-productivity costs were considered. In conclusion, cost-utility analyses, which were based on modelling of data from the pivotal clinical trial of infliximab plus methotrexate, indicate that infliximab plus methotrexate is associated with acceptable cost-effectiveness ratios (<$US50,000 per discounted QALY gained) relative to methotrexate monotherapy in patients with active rheumatoid arthritis who have not responded to previous methotrexate or other DMARD therapy. The cost effectiveness of infliximab versus other DMARDs is at present unclear, but will be clarified when appropriate data from directly comparative clinical and/or pharmacoeconomic studies become available. In patients in whom adequate courses of other DMARDs have failed to achieve satisfactory disease control, infliximab plus methotrexate may prevent or delay disability, which may produce reductions in nondrug costs that can help offset its acquisition cost.     

Cost effectiveness of peginterferon alpha-2a plus ribavirin versus interferon alpha-2b plus ribavirin as initial therapy for treatment-naive chronic hepatitis C

INTRODUCTION: In adults with previously untreated chronic hepatitis C (CHC), the combination of peginterferon alpha-2a plus ribavirin produces a higher rate of sustained virological response (SVR) than interferon alpha-2b plus ribavirin, but it is still unproven whether this increase is cost effective. The objective of this study was to determine if the gain in SVR with peginterferon alpha-2a plus ribavirin is worth the incremental cost. METHODS: We constructed a Markov model of disease progression in which cohorts of patients received peginterferon alpha-2a plus ribavirin or interferon alpha-2b plus ribavirin for 48 weeks (hepatitis C virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genotype non-1 patients without fibrosis), and were followed for their expected lifetimes. The reference patient was a 45-year-old male with CHC without cirrhosis. The SVRs with peginterferon alpha-2a plus ribavirin and interferon alpha-2b plus ribavirin used to populate the model were 46% and 36% for patients infected with HCV genotype 1 and 76% and 61% for patients infected with HCV non-1 genotypes, respectively. QOL and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs were in 2002 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was reported from the perspective of the Italian National Health Service. RESULTS: In patients infected with HCV genotype 1, peginterferon alpha-2a plus ribavirin increased life-years (LYs) by 0.78 years and QALYs by 0.67 years, compared with interferon alpha-2b and ribavirin. The incremental cost per LY and QALY gained was euro9433 and euro10 894, respectively. In patients infected with HCV non-1 genotypes, peginterferon alpha-2a plus ribavirin increased LYs by 1.17 and QALY by 1.01 years, compared with interferon alpha-2b plus ribavirin. The incremental cost per LY and QALY gained was euro3261 and euro3766, respectively. Using genotype distribution estimates, the weighted average ICER for all genotypes was euro6811 per LY gained and euro7865 per QALY gained. CONCLUSION: Our model suggests that peginterferon alpha-2a plus ribavirin is cost effective compared with conventional interferon alpha-2b plus ribavirin for treatment of naive adults with CHC, regardless of HCV genotype, under a wide range of assumptions regarding treatment effectiveness and costs.     

Atorvastatin efficacy in the primary and secondary prevention of cardiovascular events

Atorvastatin has been extensively studied in the primary and secondary prevention of cardiovascular events, and may have some clinical advantages over various other statins in these respects. The principal primary prevention study of atorvastatin, ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm), revealed that atorvastatin reduced the relative risk of primary coronary heart disease (CHD) events by 36% (p = 0.0005) compared with placebo in patients with hypertension. Much published data confirm the secondary preventive benefits of atorvastatin in various clinical settings. The IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) and TNT (Treating to New Targets) trials demonstrate the preventive efficacy of atorvastatin in patients with stable CHD. Relative to simvastatin (in the IDEAL trial) and low-dosage atorvastatin (in the TNT trial), intensive atorvastatin therapy (80 mg/day) reduced the risk of nonfatal myocardial infarction (MI) by 17-22% (p < or = 0.02). Furthermore, the ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events) and GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation) trials highlight the benefits of atorvastatin in the 'real world' setting in patients with stable CHD. Compared with 'usual' care, atorvastatin reduced the risk of nonfatal MI by 47-59% (p < or = 0.0002).Moreover, the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering), PROVE-IT (PRavastatin Or atorVastatin Evaluation and Infection Therapy) and IDEAL-ACS (Acute Coronary Syndromes) studies outline the benefits of high-dosage atorvastatin therapy started within 24-96 hours, 10 days or 2 months, respectively, of an acute coronary syndrome. Relative to placebo, pravastatin and simvastatin, atorvastatin reduced the risk of death or major cardiovascular events by 16-18% (p < or = 0.048). In patients undergoing revascularisation procedures, the AVERT (Atorvastatin VErsus Revascularisation Treatment) study revealed that 18 months' administration of atorvastatin 80 mg/day was at least as effective as angioplasty plus usual care in reducing the risk of ischaemic events in low-risk patients with stable coronary artery disease. Furthermore, the ARMYDA (Atorvastatin for Reduction in MYocardial DAmage during angioplasty) and ARMYDA-3 trials showed that 7 days' administration of atorvastatin 40 mg/day before coronary intervention significantly reduced the risks of periprocedural myocardial damage (ARMYDA), postprocedural MI (p = 0.025; ARMYDA) and atrial fibrillation (p = 0.003; ARMYDA-3) versus placebo. In addition, it has been reported that C-reactive protein levels and the combined incidence of cardiovascular events (death, MI and target segment revascularisation during the 6-month follow-up) were significantly higher in coronaropathic patients undergoing non-surgical revascularisation procedures (stent implantation) not receiving statin therapy compared with those treated with atorvastatin (80mg). Overall, therefore, the marked efficacy of atorvastatin in the primary and secondary prevention of cardiovascular events underscores the pivotal place that this statin has in general cardiovascular disease management, and suggests even greater potential clinical utility for the drug in some clinical settings.     

Cost-effectiveness analysis of a lidocaine 5% medicated plaster compared with gabapentin and pregabalin for treating postherpetic neuralgia: a german perspective

OBJECTIVE: This study set out to assess the cost effectiveness of using a 5% lidocaine (lignocaine) medicated plaster for the treatment of postherpetic neuralgia (PHN) compared with gabapentin, pregabalin 300 mg/day or 600 mg/day in German primary care. The analysis took the perspective of the Statutory Health Insurance scheme (GKV). METHODS: A Markov model was used to calculate the costs (2007) and benefits of the lidocaine plaster, gabapentin 1800 mg/day and pregabalin 300 or 600 mg/day over a 6-month time horizon in elderly patients with PHN who experienced insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants. The model calculated the cost per quality-adjusted life-year (QALY) gained and the cost per additional month without symptoms or intolerable adverse effects. The majority of transition probabilities were obtained from randomized controlled trials identified from a systematic literature review. Further model inputs, including resource use, concomitant medication and long-term efficacy/adherence data, were obtained from a Delphi panel. Utility values were taken from a previous study and age adjusted. Cost data were obtained from official price tariffs. Mortality, indirect costs and costs associated with inpatient treatment were not considered in the present analysis due to the perspective and time horizon employed. RESULTS: Over the 6-month period modelled, the mean total therapy cost per patient treated with the lidocaine plaster was euro911, compared with euro728 for gabapentin, euro875 for pregabalin 300 mg/day and euro977 for pregabalin 600 mg/day. Treatment with the lidocaine plaster was related to greater numbers of QALYs and more months without symptoms or intolerable adverse effects (mean 0.300 QALYs and 4.06 months per patient) than with gabapentin (mean 0.247 QALYs and 2.72 months), pregabalin 300 mg/day (mean 0.253 QALYs and 3.02 months) or pregabalin 600 mg/day (mean 0.256 QALYs and 3.22 months). The lidocaine plaster cost euro3453/QALY gained and euro137 per additional month without adverse effects or symptoms relative to gabapentin and euro766/QALY and euro35 per month without adverse effects or symptoms relative to pregabalin 300 mg/day. The lidocaine plaster dominated pregabalin 600 mg/day, being less costly and more effective. Probabilistic sensitivity analysis indicated that there is a 99.36% chance that the lidocaine plaster is the most clinically effective treatment considered in the analysis and a 99.09% chance that the lidocaine plaster is the most cost-effective treatment of the four therapies considered in the analysis if the GKV is willing to pay at least euro20 000/QALY gained. Extensive deterministic sensitivity analyses demonstrated that the findings are robust. CONCLUSIONS: The 5% lidocaine-medicated plaster is a cost-effective treatment option for the management of PHN in Germany compared with gabapentin and both 300 and 600 mg/day of pregabalin.     

Changes to the Statin Prescribing Policy in Belgium

Background and Objective New policies in Belgium encourage prescribing of generic HMG-CoA reductase inhibitors (statins), but may lead to non-equivalent switching of patients from more potent second generation statins, as has occurred elsewhere. We sought to assess the potential health economic impact of the new policies. Design This was a cost-effectiveness analysis Methods A Markov model was constructed to simulate the onset of cardiovascular disease (CVD) and death among a representative cohort of 80 Belgian patients initially free of CVD and taking atorvastatin. Cardiovascular risks were estimated from calibrated Framingham equations, and utilities and costs from published data. Decision analysis assessed the potential impact of switching all 80 patients to simvastatin. Changes in lipid levels expected to arise from switching were based on a published meta-analysis. Results If the 80 patients remained on atorvastatin, the model predicted that 23 (29%) would develop CVD over 20 years. If they were switched to simvastatin, the predicted number was 25 (31%), equating to a ‘number needed to harm’ of 52. Switching would lead to a net cost saving of € 131 (2012) per subject, but also a loss of 0.03 quality-adjusted life-years (QALYs) per subject. These equated to a decremental cost-effectiveness ratio of €4777 per QALY lost. Sensitivity analyses indicated this result to be robust. Conclusion Recently introduced statin prescribing policies in Belgium are likely, as intended, to reduce statin costs, but also increase the burden of CVD due to non-equivalent switching. It would be cost effective to maintain patients on atorvastatin for primary prevention rather than switch them to simvastatin.     

Simvastatin after orthotopic heart transplantation. Costs and consequences.

OBJECTIVE: Recent data indicate that the combination of a low cholesterol diet and simvastatin following heart transplantation is associated with significant reduction of serum cholesterol levels, lower incidence of graft vessel disease (GVD) and significantly superior 4-year survival rates than dietary treatment alone. On the basis of this first randomised long term study evaluating survival as the clinical end-point, we investigated the cost effectiveness of the above regimens as well as the long term consequences for the patient and for heart transplantation as a high-tech procedure. DESIGN AND SETTING: The perspective of the economic analysis was that of the German health insurance fund. Life-years gained were calculated on the basis of the Kaplan-Meier survival curves from the 4-year clinical trial and from the International Society for Heart and Lung Transplantation (ISHLT) overall survival statistics. Incremental costs and incremental cost-effectiveness ratios were determined using various sources of data, and both costs and consequences were discounted by 3% per year. Sensitivity analyses using alternative assumptions were conducted in addition to the base-case analysis. PATIENTS AND PARTICIPANTS: As in the original clinical trial, the target population of the economic evaluation comprised all heart transplant recipients on standard triple immunosuppression consisting of cyclosporin, azathioprine and prednisolone, regardless of the postoperative serum lipid profile. INTERVENTIONS: The therapeutic regimens investigated in the analysis were the American Heart Association (AHA) step II diet plus simvastatin (titrated to a maximum dosage of 20 mg/day) and AHA step II diet alone. MAIN OUTCOME MEASURES AND RESULTS: Four years of treatment with simvastatin (mean dosage 8.11 mg/day) translated into an undiscounted survival benefit per patient of 2.27 life-years; 0.64 life-years within the trial period and 1.63 life-years thereafter. Discounted costs per year of life gained were $US1050 (sensitivity analyses $US800 to $US15,400) for simvastatin plus diet versus diet alone and $US18,010 (sensitivity analyses $US17,130 to $US21,090) for heart transplantation plus simvastatin versus no transplantation (all costs reflect 1997 values; $US1 = 1.747 Deutschmarks). CONCLUSIONS: Prevention of GVD with simvastatin after heart transplantation was cost effective in all the scenarios examined with impressive prolongation of life expectancy for the heart recipient. Simvastatin also achieved an internationally robust 21% improvement in the cost effectiveness of heart transplantation compared with historical cost-effectiveness data.     

Candesartan cilexetil: a pharmacoeconomic review of its use in chronic heart failure and hypertension

The addition of candesartan cilexetil (Atacand, Amias, Blopress, Kenzen, Ratacand) to standard therapy for chronic heart failure (CHF) provided important clinical benefits at little or no additional cost in France, Germany and the UK, according to a detailed economic analysis focusing on major cardiovascular events and prospectively collected resource-use data from the CHARM-Added and CHARM-Alternative trials in patients with CHF and left ventricular (LV) systolic dysfunction. Results of a corresponding cost-effectiveness analysis showed that candesartan cilexetil was either dominant over placebo or was associated with small incremental costs per life-year gained, depending on the country and whether individual trial or pooled data were used. Preliminary data from a US cost-effectiveness analysis based on CHARM data also showed favourable results for candesartan cilexetil. Two cost-effectiveness analyses of candesartan cilexetil in hypertension have been published, both conducted in Sweden. Data from the SCOPE trial in elderly patients with hypertension, which showed a significant reduction in nonfatal stroke with candesartan cilexetil-based therapy versus non-candesartan cilexetil-based treatment, were incorporated into a Markov model and an incremental cost-effectiveness ratio of euro12 824 per QALY gained was calculated (2001 value). Another modelled cost-effectiveness analysis of candesartan cilexetil was based on the ALPINE trial, in which the incidence of new-onset diabetes was significantly lower in patients with newly diagnosed hypertension who were randomised to candesartan cilexetil (with or without felodipine) than among those who received hydrochlorothiazide (with or without atenolol). Although candesartan cilexetil was dominant over hydrochlorothiazide, the ALPINE cost-effectiveness analysis relied on a small number of clinical events and did not evaluate the incremental cost of candesartan cilexetil per life-year or QALY gained. In conclusion, despite some inherent limitations, economic analyses incorporating CHARM data and conducted primarily in Europe have shown that candesartan cilexetil appears to be cost effective when added to standard CHF treatment in patients with CHF and compromised LV systolic function. The use of candesartan cilexetil as part of antihypertensive therapy in elderly patients with elevated blood pressure was also deemed to be cost effective in a Swedish analysis, primarily resulting from a reduced risk of nonfatal stroke (as shown in the SCOPE study); however, the generalisability of results to other contexts has not been established. Cost-effectiveness analyses comparing candesartan cilexetil with ACE inhibitors or other angiotensin receptor blockers in CHF or hypertension are lacking, and results reported for candesartan cilexetil in a Swedish economic analysis of ALPINE data focusing on outcomes for diabetes require confirmation and extension.     

Differences between statins on clinical endpoints: a population-based cohort study

OBJECTIVE: Many studies have shown differences between statins based on surrogate endpoints, but few have studied differences in reaching clinical endpoints.This study compares the risk of cardiovascular and cerebrovascular events between atorvastatin users and other statin users in daily general practice. RESEARCH DESIGN AND METHODS: A cohort study was performed in the Integrated Primary Care Information project database, a longitudinal general practice research database with electronic patient records of more than 500,000 individuals in The Netherlands. All new statin users in the period 1st September 1999 to 31st December 2002 were included. Multivariate Cox-regression analysis was used to compare the occurrence of the primary endpoint between atorvastatin users and other statin users. MAIN OUTCOME MEASURES: The primary endpoint was the composite outcome of fatal or non-fatal myocardial infarction, admission for unstable angina pectoris, fatal or non-fatal cerebrovascular accidents, or transient ischaemic events. RESULTS: 3499 new statin users were identified, including 797 patients with a history of cardiovascular disease. 1341 persons started with simvastatin (38.3%), 1154 with atorvastatin (33.0%), 811 with pravastatin (23.2%) and 193 with other statins (5.5%). The median follow-up was 1.9 years. Two hundred and thirty three patients (6.7%) experienced a primary endpoint. Atorvastatin users had a significantly lower risk of cardiovascular and cerebrovascular events than users of other statins (relative risk [RR]: 0.70, 95% confidence interval [CI]: 0.55-0.96). The relative risks of atorvastatin users compared to simvastatin and pravastatin users individually were 0.70 (95% CI: 0.48-1.02) and 0.78 (95% CI: 0.52-1.16), respectively. The protective effect of atorvastatin was more pronounced in persons without a history of cardiovascular or cerebrovascular events. CONCLUSION: Atorvastatin showed a more favourable effect on fatal and non-fatal cardiovascular and cerebrovascular events in the general population than other statins.     

Cost Effectiveness of Eplerenone in Patients with Heart Failure after Acute Myocardial Infarction Who were Taking Both ACE Inhibitors and β-Blockers

Background

The EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure and Survival Study) showed that the use of aldosterone blockade with eplerenone decreased mortality in patients with heart failure after acute myocardial infarction, and a subsequent analysis showed eplerenone to be highly cost effective in this population.

Objective

To assess the cost effectiveness of eplerenone in an EPHESUS subgroup population who were taking both ACE inhibitors and β-blockers (β-adrenoceptor antagonists) at baseline.

Intervention

In the EPHESUS, a total of 6632 patients were randomized to receive eplerenone 25–50 mg/day (n = 3319) or placebo (n = 3313) concurrently with standard therapy and were followed for up to 2.5 years. Of these, 4265 (64.3%) patients (eplerenone: n = 2113; placebo: n = 2152) were taking both ACE inhibitors and β-blockers at baseline.

Methods and Main Outcome Measures

Resource use after the initial hospitalization included additional hospitalizations, outpatient services, emergency room visits, and medications. Eplerenone was priced at an average wholesale price of $US3.60 per day (year 2004 value). Bootstrap methods were used to estimate the fraction of the joint distribution of the cost and effectiveness. A net-benefit regression model was used to derive the propensity score-adjusted cost-effectiveness curve. The incremental cost effectiveness of eplerenone in cost per life-year gained (LYG) and cost per quality-adjusted life-year (QALY) gained beyond the trial period was estimated using data from the Framingham Heart Study, the Saskatchewan Health database, and the Worcester Heart Attack Registry. Both costs and effectiveness were discounted at 3%. Allthough not all resource use could be accounted for, the overall perspective was societal.

Results

As in the overall EPHESUS population, the total direct treatment costs were higher in the eplerenone arm than the placebo arm for patients who were taking both ACE inhibitors and β-blockers ($US14 563 vs $US12 850, difference = $US1713; 95% CI 721, 2684). The number of LYGs with eplerenone compared with placebo was 0.1665 based on the Framingham data, 0.0979 using the Saskatchewan data, and 0.2172 using the Worcester data. The incremental cost-effectiveness ratio (ICER) was $US10 288/LYG with the Framingham data, $US17 506/LYG with the Saskatchewan data, and $US7888/LYG with the Worcester data (99% <$US50 000/LYG for all three sources). The ICERs were systematically higher when calculated as the cost per QALY gained ($US14 926, $US25 447, and $US11 393, respectively) as the utilities were below 1 with no difference between the treatment arms.

Conclusions

As for the overall EPHESUS population, aldosterone blockade with eplerenone is effective in reducing mortality and is cost effective in increasing years of life for the EPHESUS subgroup of patients who were taking both ACE inhibitors and β-blockers.     

The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin

OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin. PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease. CONCLUSIONS: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.     

Zoledronic acid: a pharmacoeconomic review of its use in the management of bone metastases

Zoledronic acid (Zometa is a third-generation nitrogen-containing parenteral bisphosphonate indicated for the treatment of bone metastases due to solid tumours or multiple myeloma and for hypercalcaemia of malignancy (HCM). In patients with advanced breast or prostate cancer, zoledronic acid 4 mg every 3-4 weeks for up to 15 months significantly reduced the proportion of patients with > or =1 skeletal-related event (SRE), excluding HCM, compared with placebo. In patients with advanced breast cancer or multiple myeloma, the incidence of SREs was similar in patients treated with zoledronic acid 4 mg or pamidronic acid 90 mg every 3-4 weeks for up to 25 months but, in breast cancer patients, zoledronic acid reduced the risk of SREs, including HCM, by an additional 20% compared with pamidronic acid.In modelled cost-utility studies comparing direct costs based on efficacy and resource-use data from these and/or other trials, results have varied. In the most recent study performed from the perspective of the UK NHS and modelled over a 10-year treatment period in women with advanced breast cancer, intravenous zoledronic acid and oral ibandronic acid were dominant over no treatment. Intravenous zoledronic acid was the most cost effective, in terms of incremental costs per QALY gained, followed by oral ibandronic acid, intravenous pamidronic acid and intravenous ibandronic acid. Two other modelled analyses in patients with advanced breast cancer, also conducted from the perspective of the NHS, evaluated the cost utility of three bisphosphonate therapies in patients receiving hormonal therapy or intravenous chemotherapy. Analyses were modelled over 14.3 months (i.e. expected survival) and assumptions varied markedly from results in clinical breast cancer trials. Also, efficacy assumptions for zoledronic acid were not based on clinical trials with the drug. The results of these analyses suggest that oral ibandronic acid is more cost effective than intravenous zoledronic acid and intravenous pamidronic acid in terms of incremental cost per QALY gained. In a global, 15-month modelled cost-effectiveness analysis of patients with advanced prostate cancer, conducted from a third-party perspective, the incremental cost per QALY gained for zoledronic acid versus no treatment was $US159 200 (year 2000 value), which is about 3-fold greater than commonly accepted thresholds for cost effectiveness.In conclusion, a recent modelled economic analysis suggests that intravenous zoledronic acid 4 mg is dominant relative to no treatment in the management of bone metastases in patients with advanced breast cancer. In contrast, in patients with advanced prostate cancer, the incremental cost per QALY gained for zoledronic acid 4 mg versus no treatment was predicted to be higher than commonly accepted thresholds. Compared with other bisphosphonates in the setting of advanced breast cancer, intravenous zoledronic acid was more cost effective than oral or intravenous ibandronic acid and intravenous pamidronic acid in one study, but less cost effective than oral ibandronic acid in another. Further efficacy and economic data comparing intravenous zoledronic acid with oral ibandronic acid are needed. Meanwhile, zoledronic acid appears to be the most cost effective intravenous bisphosphonate for the management of bone metastases in patients with advanced breast cancer and possibly in patients with different types of advanced solid tumours.     

Persistence of atorvastatin and simvastatin among patients with and without prior cardiovascular diseases: a US managed care study

ABSTRACT

Background: In clinical practice, persistence with statin therapy is poor. While little is known about relative persistence to specific statins, previous studies have observed greater persistence in patients who achieve greater degrees of lipid lowering. Identification of statin therapies which improve patient persistence has the potential to improve the quality of patient care and clinical outcomes. Therefore, we assessed patient persistence with atorvastatin and simvastatin in primary and secondary prevention patients enrolled in managed care.

Methods: New statin users aged ≥18 years, both with and without prior cardiovascular (CV) events within the 12 month pre-treatment period, were identified from a large national database of managed care patients. Patients initiated atorvastatin or simvastatin therapy from January 1, 2003 to September 30, 2005 and were continuously enrolled in a covered plan for at least 12 months before and after initiation of statin therapy. Subanalyses of patients ≥65 years were also conducted. Measures of interest included demographic and clinical characteristics of the study samples and persistence of statin utilization over the 1-year follow-up period. Persistence was defined as the number of days a patient remained on treatment in the first year following their index date, measured from the date of first fill to study end or the date of discontinuation.

Results: A total of 129 764 atorvastatin users and 45 558 simvastatin users without prior CV events were included in the study. For those patients with prior CV events, a total of 6888 atorvastatin users and 4443 simvastatin users were included in the study. Median persistence in patients without prior CV events was 50 days longer for patients initiating therapy with atorvastatin than simvastatin (207 vs. 157 days, p < 0.0001) and after adjusting for confounding factors, those treated with atorvastatin were 15% less likely to discontinue therapy during the first year than those treated with simvastatin (HR = 0.85; 95% CI 0.84, 0.86; p < 0.001). In secondary prevention patients median persistence was 85 days longer in atorvastatin patients than simvastatin patients (266 vs. 181 days, p < 0.0001) and atorvastatin patients were 22% less likely to discontinue therapy (HR = 0.78; 95% CI 0.75, 0.82; p < 0.001). Persistence was worse in the elderly patients, but the relative difference between atorvastatin and simvastatin was similar to the overall patient population.

Conclusions: In patients with and without prior CV disease, persistence is generally poor, even worse in the elderly, but significantly better for atorvastatin patients than simvastatin patients (p < 0.001). Further studies are required to determine whether this is due to differences in cost, effectiveness, side-effects, or other attributes of the statins.

Study limitations: Differences in persistence could be, in part, due to unmeasured confounders although all available variables were adjusted in multivariate analyses. Additionally, the claims database lacks some clinical data such as lipid levels, limiting assessments of statin efficacy, and does not include any reasons for discontinuation of therapy.