Cost-effectiveness of statin therapy for vascular event prevention in adults with elevated C-reactive protein: implications of JUPITER Cost-effectiveness of fondaparinux in patients with acute coronary syndrome without ST-segment elevation. Cost-Effectiveness and Population Impact of Statins for Primary Prevention in Adults Aged 75 Years or Older in the United States A pharmacoeconomic evaluation of statins in the treatment of hypercholesterolaemia in the primary care setting in Spain Cost-effectiveness of Simvastatin plus Ezetimibe for Cardiovascular Prevention in CKD: Results of the Study of Heart and Renal Protection (SHARP) Aspirin, Statins, or Both Drugs for the Primary Prevention of Coronary Heart Disease Events in Men: A CostUtility Analysis Cost-effectiveness of statins for primary prevention in patients newly diagnosed with type 2 diabetes in the Netherlands. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis Impact of switching from different treatment regimens to a fixed-dose combination pill (polypill) in patients with cardiovascular disease or similarly high risk Projected cost-effectiveness of ezetimibe/simvastatin compared with doubling the statin dose in the United Kingdom: findings from the INFORCE study.
Abstract Objectives : High-sensitivity C-reactive protein ( hs-CRP ) has been explored for use in predicting cardiovascular risk . The recent Justification for the Use of Statins in Primary Prevention : An Intervention Trial Evaluating Rosuvastatin ( JUPITER ) study found that statin therapy reduced cardiovascular events in those with low-density lipoprotein ( LDL ) cholesterol levels below current treatment thresholds ( ≤130 mg/dL , 3.4 mmol/L ) , but with elevated hs-CRP levels ( ≥2.0 mg/L ) . This study examines the cost-effectiveness of statin treatment for individuals with elevated hs-CRP but normal LDL cholesterol . Methods : A Markov decision-analytic model was conducted from the U.S. societal perspective . Data from JUPITER were used to estimate rates of myocardial infa rct ion , angina and stroke . Statin costs were based on generic simvastatin 80 mg , equipotent to the rosuvastatin 20 mg dose used in JUPITER . Primary prevention was the focus and secondary prevention was not modeled explicitly . Quality -adjusted life-years ( QALYs ) were calculated using nationally representative preference-based utility weights . One-way sensitivity analyses and multivariate probabilistic sensitivity analysis were used to explore uncertainty in model parameters as well as estimate the likelihood of cost-effectiveness when all event rates , costs and utilities were drawn r and omly from distributions reflecting uncertainty . Results : Statin therapy cost $ 10,889/QALY for vascular event prevention in this population . Results were sensitive to the cost of statin treatment . Based on 10,000 simulations , statin therapy was cost-effective in 99.5 % of simulations , using a willingness-to-pay threshold of $ 20,000/QALY , and 100 % of simulations using a threshold of $ 50,000/QALY . Conclusions : Treatment with statins in patients with elevated hs-CRP but normal cholesterol appears to be cost-effective . Limitations of this study include the assumption that an equipotent dose of simvastatin result ed in the same risk reduction  as rosuvastatin . Further , post-event states simulated the average experience of a patient . Continued statin use , subsequent events and /or heart failure were not explicitly modeled BACKGROUND The combined use of antithrombotic agents , antiplatelet agents and invasive strategies in acute coronary syndrome without ST-segment elevation ( ACSWSTE ) reduces cardiovascular events . Fondaparinux has demonstrated equivalence to enoxaparin in reducing cardiovascular events , but with a lower rate of bleeding in patients using fondaparinux .  OBJECTIVE Evaluate the cost-effectiveness of fondaparinux versus enoxaparin in patients with ACSWSTE in Brazil from the economic perspective of the Brazilian Unified Health System ( SUS ) . METHODS A decision analytic model was constructed to calculate the costs and consequences of the compared treatments . The model parameters were obtained from the OASIS-5 study ( N = 20,078 patients with ACSWSTE r and omized to fondaparinux or enoxaparin ) . The target outcome consisted of cardiovascular events ( i.e. , death , myocardial infa rct ion , refractory ischemia and major bleeding ) on days 9 , 30 and 180 after ACSWSTE . We evaluated all direct costs of treatment and ACSWSTE-related events . The year of the analysis was 2010 and the costs were described in reais ( R$ ) . RESULTS On day 9 , the cost of treatment per patient was R$ 2,768 for fondaparinux and R$ 2,852 for enoxaparin . Approximately 80 % of total costs were associated with invasive treatments . The drug costs accounted for 10 % of the total cost . The combined rates of cardiovascular events and major bleeding were 7.3 % and 9.0 % for fondaparinux and enoxaparin , respectively . Sensitivity analyses confirmed the initial results of the model . CONCLUSION The use of fondaparinux for the treatment of patients with ACSWSTE is superior to that of enoxaparin in terms of prevention of further cardiovascular events at lower cost Editors ' Notes Context Clinical guidelines provide conflicting recommendations about whether to prescribe statins in persons aged 75 years or older for primary prevention of unwanted cardiovascular outcomes . Contribution This study used information from clinical trials to model the tradeoffs between benefits and harms and found that using  statins  in all persons aged 75 to 94 years would prevent new myocardial infa rct ions and deaths from coronary heart disease at an acceptable cost . Caution Small increases in the frequency or severity of harms would negate the benefits . Implication Additional research is warranted to better underst and the tradeoffs between benefits and harms in this age group . Statins are commonly used in adults aged 75 years or older ( 1 ) . Despite their widespread use , evidence for their effectiveness for primary prevention in elderly adults is unclear , and guidelines for their use in this population are inconsistent . The recently published American College of Cardiology/American Heart Association ( ACC/AHA ) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults gave limited recommendations for statin use for primary prevention in adults aged 75 years or older ( 2 ) , noting that few data were available to indicate an atherosclerotic cardiovascular disease event reduction benefit in primary prevention among individuals > 75 years of age who do not have clinical year atherosclerotic cardiovascular disease , and suggesting that comorbid conditions , safety , and priorities of care are recommended for joint provider and patient decision making . The American Medical Directors Association , a professional group of long-term care providers , recommended that statins not be routinely prescribed in adults aged 70 years or older as part of the American Board of Internal Medicine Choosing Wisely campaign ( 3 ) . This recommendation was based on the lack of an association between high cholesterol levels and outcomes in older adults as well as the potential for an increased risk for statin-related adverse events , including cognitive impairment , falls , neuropathy , and muscle damage ( 3 ) . The variation in these treatment recommendations reflects uncertainty about the balance between the benefits and risks of statin use in older adults compared with younger adults as well as the more limited evidence base in this population . Adults aged 75 years or older have been underrepresented in trials of statins for primary prevention , so the effectiveness of statins is less clear in this population . Results from observational studies suggest that the associations between low-density lipoprotein ( LDL ) cholesterol levels and outcomes are attenuated in older adults ( 47 ) . Although the baseline risk for cardiovascular disease is increased in older adults , their life expectancy is shorter and their risks for competing mortality are greater . Finally , there has been concern about geriatric-specific adverse effects , especially functional limitation due to muscle pain , weakness , and mild cognitive impairment ( 816 ) . In the presence of uncertainty about the riskbenefit tradeoff , computer simulations can provide estimates of the potential benefits of various treatment strategies as well as the costs and potential risk for harms . We evaluated the population benefit and cost-effectiveness of statins in persons aged 75 years or older without a history of cardiovascular disease in the United States . This investigation was conducted using the Cardiovascular Disease Policy Model ( CVDPM ) , a Markov model of the U.S. population ( 17 ) . We simulated the impact of statins for primary prevention based on treatment of the high-risk groups identified by the ACC/AHA guidelines , the associated costs , and potential harms that could offset the potential cardiovascular benefits in the U.S. population of adults aged 75 to 94 years over the next 10 years . Methods The Model The CVDPM is an established state-transition ( Markov ) model of the incidence , prevalence , mortality , and cost of CHD and stroke in U.S. residents aged 35 to 94 years ( 17 ) . The present study was limited to adults aged 75 to 94 years . The model comprises 3 components . First , the demographic-epidemiologic submodel estimates the incidence of coronary heart disease ( CHD ) ( cardiac arrest , myocardial infa rct ion [ MI ] , angina , or CHD death ) , ischemic stroke , and death from other causes on the basis of age , sex , systolic blood pressure , smoking , high-density lipoprotein and LDL cholesterol levels , diabetes , body mass index , and statin use . Second , the bridge submodel characterizes the initial CHD or stroke event and related events in the subsequent 30 days . Third , the disease-history submodel predicts the number of subsequent CHD and stroke events , revascularization procedures , and deaths among patients with cardiovascular disease , stratified according to age , sex , and history of cardiovascular disease events . In addition , persons may exit the model at any stage through a non-CHD , nonstroke mortality function , allowing for competing risk . Modifiable components of the model include population distributions , risk factor levels , risk factor coefficients , event rates , case-fatality rates , costs , and disability adjustments ( 17 ) . Costs for stroke requiring hospitalization , CHD , and acute stroke rehabilitation were estimated using California hospital data ( 18 ) and were deflated using costcharge ratios and the ratio of the U.S. national average costs to the California average ( 19 , 20 ) . Age- and sex-specific background health care costs were estimated using national data ( 21 ) . All model costs were inflated to 2014 costs by using the medical component of the Consumer Price Index ( 22 ) . All disability weights associated with the CHD and stroke event states were based on the Global Burden of Disease Study ( 23 , 24 ) . Additional details are provided in the Appendix . Simulation Inputs We modeled the effect of statins on LDL cholesterol level based on PROSPER ( Prospect i ve Study of Pravastatin in the Elderly at Risk of Vascular Disease ) , a r and omized , placebo-controlled trial of 5804 men and women aged 70 to 82 years ( 25 ) . In that trial , the mean reduction in LDL cholesterol level was 34 % for participants with an average initial level of 147 mg/dL , consistent with the estimated effect of a moderate-dose statin in the 2013 ACC/AHA guideline ( 2 ) . We included 3 estimates for the effectiveness of a decrease in LDL cholesterol level on events . The primary estimates were derived by extrapolating the age-stratified effect sizes of a 1.0-mmol/L reduction in LDL cholesterol level from the Cholesterol Treatment Trialists ' meta- analysis ( 26 ) . We fit a regression line to the 3 age strata reported in that analysis ( 60 years , > 60 to 70 years , and > 70 years ) to estimate the effect sizes at ages 80 and 90 years . In a sensitivity analysis , we used a high estimate based on the age-pooled estimate of effect of a 1.0-mmol/L reduction in LDL cholesterol level on major coronary events in the meta- analysis . We used a low estimate based on the effect size from PROSPER for primary prevention ( 25 ) . Statin costs were derived from the National Average Drug Acquisition Cost ( NADAC ) data base ( 27 ) . Our primary cost estimate ( $ 5.59 for a 30-day supply ) was the average of the NADAC costs for the 4 moderate-dose statins that are available in generic form : atorvastatin , 10 mg ; simvastatin , 20 mg ; pravastatin , 40 mg ; and lovastatin , 40 mg . This cost estimate was $ 5.00 when indexed to 2010 dollars based on the medical component of the Consumer Price Index ( 22 ) . In addition , we used a low cost estimate of $ 4 per month , based on the price of generic statins from multiple discount retailers ( such as Walmart , Target , and Walgreens ) . For a high cost estimate , we used $ 30 for a 30-day supply ; the low and high cost estimates have been used similarly in other contemporary cost-effectiveness analyses ( 28 , 29 ) . Adults aged 65 years or older use a median of 4 medications ; therefore , we estimated the cost of an additional 0.25 physician visit per year for statin use , assuming that medication management could be covered in 1 visit ( 30 , 31 ) . We estimated 1 lipid panel per year for monitoring ( 32 ) . Event rates for myopathy and hemorrhagic stroke were estimated as 0.001 per statin-year of use , based on the ACC/AHA guideline statement ( 2 ) . Although many major and minor adverse effects have been reported to be associated with statin use , we focused on 2 that are important to geriatric population s and that have generated concern in the scientific literature : functional limitation due to muscle pain and weakness , and mild cognitive impairment ( 816 ) . Both are prevalent in older adults and can have a substantial effect on quality of life and the ability to live independently . A recent review of late-life activity limitations in the United States reported data on participants in 5 nationally representative surveys . The prevalence of limitations in activities of daily living was 27 % in adults aged 75 to 84 years and 45 % in those aged 85 years or older ( 33 ) . The population -weighted average of these estimates is 32 % for adults aged 75 to 94 years . Widely varying prevalence estimates for mild cognitive impairment have been reported due to the differential measures of this condition and the differences between population s. A recent review reported prevalence of mild cognitive impairment of 19 % to 28 % in studies of older U.S. adults ; we used the average of the 4 U.S. studies , which was 25 % ( 34 ) . Disability-adjusted life-years for the corresponding states were calculated as 1 minus the disability weights reported in the Global Burden of Disease Study ( 24 ) . Because the statin-associated relative risk for these adverse effects is uncertain , we assumed no elevated risk for these adverse effects in our base-case scenario . The goal of this investigation was not to evaluate the strength of the literature regarding the presence of these adverse Abstract 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 . Study design : The CE analysis was based on an open-label , prospect i ve , naturalistic , r and omised intervention study under usual care conditions in primary care setting s 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 ( ® ) per patient achieving the therapeutic goals , was ® 424.3 for atorvastatin , ® 503.5 for fluvastatin , ® 527.0 for simvastatin and ® 683.4 for pravastatin . The incremental CE ratios  for atorvastatin versus fluvastatin and simvastatin were ® 238.9 and ® 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 < ® 250 Background Simvastatin , 20 mg , plus ezetimibe , 10 mg , daily ( simvastatin plus ezetimibe ) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease ( CKD ) in the Study of Heart and Renal Protection ( SHARP ) , but its cost-effectiveness is unknown . Study Design Cost-effectiveness of simvastatin plus ezetimibe in SHARP , a r and omized controlled trial . Setting & Population 9,270 patients with CKD r and omly assigned to simvastatin plus ezetimibe versus placebo ; participants in categories by 5-year cardiovascular risk ( low , < 10 % ; medium , 10%-<20 % ; or high , ≥20 % ) and CKD stage ( 3 , 4 , 5 not on dialysis , or on dialysis therapy ) . Model , Perspective , & Timeline Assessment during SHARP follow-up from the UK perspective ; long-term projections . Intervention Simvastatin plus ezetimibe ( 2015 UK £ 1.19 per day ) during 4.9 years ’ median follow-up in SHARP ; scenario analyses with high-intensity statin regimens ( 2015 UK £ 0.05-£1.06 per day ) . Outcomes Additional health care costs per major atherosclerotic event avoided and per quality -adjusted life-year ( QALY ) gained . Results In SHARP , the proportional reductions per 1 mmol/L of low-density lipoprotein ( LDL ) cholesterol reduction  with simvastatin plus ezetimibe in all major atherosclerotic events of 20 % ( 95 % CI , 6%-32 % ) and in the costs of vascular hospital episodes of 17 % ( 95 % CI , 4%-28 % ) were similar across participant categories by cardiovascular risk and CKD stage . The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy . The net cost per major atherosclerotic event  avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from £ 157,060 in patients at low risk to £ 15,230 in those at high risk ( £ 30,500-£39,600 per QALY ) ; and from £ 47,280 in CKD stage 3 to £ 28,180 in patients on dialysis therapy ( £ 13,000-£43,300 per QALY ) . In scenario analyses , generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost . Limitations High-intensity statin-alone regimens were not studied in SHARP . Conclusions Simvastatin plus ezetimibe prevented atherosclerotic events in SHARP , but other less costly statin regimens are likely to be more cost-effective for reducing cardiovascular risk in CKD Context National guidelines recommend aspirin or statin drugs individually to reduce first coronary heart disease ( CHD )  events , but there are no guidelines about taking both . Contribution The authors used a Markov model to estimate the cost-effectiveness of aspirin , statins , both drugs , or neither in men . In patients with a 10-year risk for CHD of 7.5 % , aspirin alone reduced costs and lengthened life compared with no treatment . Adding a statin cost $ 56200 per additional quality -adjusted life-year at a 7.5 % risk but only $ 42500 at a 10 % risk . Caution s The authors ' analysis was limited to men . Implication s Therapy with aspirin alone is effective and cost-effective in men with an average level of risk for CHD . The addition of a statin is more cost-effective as risk increases . The Editors Aspirin and statin drugs have been shown to be effective for preventing first coronary heart disease ( CHD ) events ( 1 - 3 ) . Systematic review s and meta-analyses suggest that the relative risk reductions with both forms of therapy are similar in magnitude and seem to be independent and relatively constant across the range of underlying risk for CHD ( 2 - 5 ) . The absolute benefit from these treatments seems to be proportional to the patient 's underlying risk for CHD . National treatment guidelines recommend aspirin and statin drugs individually for the primary prevention of cardiovascular events in men who are at increased risk ( 4 , 6 , 7 ) . However , no U.S. guidelines have addressed how these drugs should be used together , and we are unaware of any previous analyses that have reported the cost-effectiveness of these drugs when used in combination for CHD prevention . To help inform clinical and policy decisions about primary CHD prevention , we performed a costutility analysis that examined the use of aspirin therapy , statin therapy , or combination therapy with both drugs in men with various underlying levels of risk for CHD . Methods To examine the cost and utility associated with aspirin and with statin use , we used Microsoft Excel 2002 for Windows ( Microsoft Corp. , Redmond , Washington ) to develop a Markov state-transition model . The model was design ed to simulate cohorts of initially healthy middle-aged men with no history of cardiovascular events and with various levels of 10-year risk for CHD ( Figure 1 ) . Figure 1 . General structure of the Markov model . Base-Case Scenario In our base-case scenario , we compared the effectiveness of 10 years of aspirin therapy , statin therapy , combination therapy with both drugs , and no therapy in 45-year-old men with a 10-year risk for CHD of 7.5 % . After 10 years , both groups adopted the treatment used in the intervention group . Although the differences in therapy were maintained for only 10 years , we examined the effects of these therapies over a lifetime . Model Assumptions All persons were initially healthy and progressed through the model in annual cycles . In each cycle , an individual remained healthy , had an initial cardiovascular event ( angina , myocardial infa rct ion , or stroke ) , experienced adverse effects from therapy ( gastrointestinal bleeding from aspirin or myopathy from statins ) , or died . We assumed that those who had cardiovascular events or adverse events stayed in the subacute state for the remainder of that cycle and then entered a postevent state . Adherence to treatment was assumed to be 100 % in the absence of adverse effects , although the treatment efficacy data were based on the actual rates of adherence in the clinical trials . Persons who had adverse effects from therapy stopped taking the offending medication ; their procession through the model was similar to that of healthy patients after the initial cycle . All costs and outcomes were discounted at 3 % in accordance with current consensus recommendations ( 8) . Model Parameters Model parameters , including base-case values , ranges , and references , are shown in Table 1 ( 1 - 3 , 9 - 29 ) . Table 1 . Base-Case Estimates and Ranges Used in Sensitivity Analyses Noncardiovascular Mortality Age-dependent noncardiovascular mortality rates were estimated from the National Vital Statistics life tables ( 31 ) . Rates were adjusted as the cohort aged over the time horizon of the analysis . Cardiovascular Event Rates Baseline risks for initial cardiovascular events ( myocardial infa rct ion , stroke , angina , and death from CHD ) were drawn from Framingham risk equations by using hypothetical scenarios of nonsmoking , nonhypertensive , nondiabetic men at different levels of risk for CHD ( Appendix Table ) ( 32 ) . Assuming an exponential distribution , we translated these 10-year risks into annual event-related transition probabilities . These probabilities were allowed to change over time to reflect increasing risk for CHD over the time horizon of the analysis . Appendix Table . Sample Baseline Characteristics of 45-Year-Old Men by Risk Level Because we were interested in primary prevention , we did not simulate or examine the details of a patient 's course after a primary , nonfatal event . Instead , we assigned them an increased risk for death , increased costs , and decreased utilities by using data from the literature regarding the average experience of patients after an initial event . The increased relative risk for death after an initial event ( Table 1 ) was drawn from population -based studies in the United Kingdom ( 12 , 16 ) and applied to the general mortality rates from the U.S. life tables to generate the estimated postevent mortality rates . We modified these event rates by assuming that all patients received optimal secondary prevention . Adverse Effects The excess risks for gastrointestinal bleeding with aspirin use and for myopathy with statin use were drawn from systematic review s of r and omized trials and a recent secondary data analysis ( 2 , 26 , 27 ) . Risks for gastrointestinal bleeding and myopathy in untreated patients were assumed to be zero so that only treatment-induced adverse events were counted . Because better data were not available , we estimated the risks for death from aspirin-related gastrointestinal bleeding and statin-induced myopathy and varied them in sensitivity analysis . Patients who had nonfatal adverse effects were not given therapy with alternate agents for primary prevention of CHD . Modeling Stroke Because many r and omized trials of aspirin prophylaxis did not distinguish by stroke type , we had difficulty estimating the precise effect of aspirin on ischemic and hemorrhagic strokes ( 30 ) . To account for this limitation , we used 2 approaches to model the effect of aspirin on stroke . In the base-case analysis , we followed the approach that was used in a recent meta- analysis ( 9 ) by including hemorrhagic stroke and ischemic stroke together in 1 estimate of the effect of aspirin on total stroke ( relative risk for stroke with aspirin , 1.06 ) . In an alternate scenario , we modeled hemorrhagic stroke and ischemic stroke as separate health states . We assumed that aspirin was associated with an excess annual risk of 20 hemorrhagic strokes per 100000 users on the basis of published meta-analyses and that one third of these hemorrhagic strokes would be fatal ( 19 , 30 , 33 ) . We conservatively assumed that aspirin had no effect on ischemic stroke ( 30 ) . The costs and utilities of ischemic stroke and hemorrhagic stroke were also considered separately . Treatment Efficacy We used summary relative risk estimates from existing meta-analyses or relative risks from individual trials to estimate the efficacy of aspirin and statin therapy , either alone or in combination , for preventing CHD events ( 3 , 24 , 29 ) . Where data were limited , we made conservative assumptions . The efficacy of the combined use of aspirin and statins was assumed to be independent on the basis of data from secondary prevention trials ( 5 ) . We did not model the effect of aspirin or statins on initial use of revascularization procedures in the absence of a cardiovascular event . All patients who survived an initial cardiovascular event were assumed to have received secondary preventive therapy with aspirin and a statin or with an alternate agent if  they could not tolerate  aspirin  or  statins . The effect of treatments on all-cause mortality was estimated from meta-analyses of secondary prevention trials ( 18 - 20 ) . Costs We conducted our analysis from the perspective of a third-party payer . State costs ( Table 1 ) , which were derived from data from the published literature and several recent national data bases , are expressed in 2003 dollars . To estimate the costs during the year in which an event occurred , we estimated acute care costs by drawing on data regarding hospital charges from the Healthcare Utilization Project data base and by converting these values to costs . To convert hospital charges to costs , we used the 1999 cost-to-charge ratio value of 0.4501 , which was derived from the Medicare Provider Analysis and Review of short-stay hospitals ( 28 ) . We then used the Medical Consumer Price Index to generate an inflation factor of 1.195 , which was applied to the 1999 cost figure to convert 1999 dollars to 2003 dollars ( 17 ) . In addition to the acute care costs , we assumed that each patient who survived an acute event would also incur one half of the estimated ongoing annual costs of care for the first year . Costs for subsequent years were based on ongoing costs of care that were drawn from the medical literature ( 22 - 25 ) . Drug costs were obtained from the 2003 Red Book average wholesale prices ( 21 ) . For our base-case analysis , we set the annual  statin cost to $ 730 by averaging the Red Book prices of simvastatin ( $ 922 for 10 mg/d ) and lovastatin ( $ 503 for 10 mg/d ) . The base-case cost of aspirin was based on an annual cost of $ 16 for Bayer aspirin ( Bayer Healthcare LLC , Morristown , New Jersey ) . The annual cost of generic aspirin  was estimated at approximately $ 6 ( 21 ) . We varied the costs of each drug over wide ranges in sensitivity analysis . To check our cost estimates , we compared our derived values with other cost estimates BACKGROUND Statins are lipid-lowering drugs that reduce the risk of cardiovascular events in patients with diabetes . OBJECTIVES The objective of this study was to determine whether statin treatment for primary prevention in newly diagnosed type 2 diabetes is cost-effective , taking nonadherence , baseline risk , and age into account . METHODS A cost-effectiveness analysis was performed by using a Markov model with a time horizon of 10 years . The baseline 10-year cardiovascular risk was estimated in a Dutch population of primary prevention patients with newly diagnosed diabetes from the Groningen Initiative to Analyse Type 2 Diabetes Treatment ( GIANTT ) data base , using the United Kingdom Prospect i ve Diabetes Study risk engine . Statin adherence was measured as pill days covered in the IADB.nl pharmacy research data base . Cost-effectiveness was measured in costs per quality -adjusted life-year ( QALY ) from the health care payers ' perspective . RESULTS For an average patient aged 60 years , the base case , statin treatment was highly cost-effective at € 2245 per QALY . Favorable cost-effectiveness was robust in sensitivity analysis . Differences in age and 10-year cardiovascular risk showed large differences in cost-effectiveness from almost € 100,000 per QALY to almost being cost saving . Treating all patients younger than 45 years at diabetes diagnosis was not cost-effective ( weighted cost-effectiveness of almost € 60,000 per QALY ) . CONCLUSIONS Despite the nonadherence levels observed in actual practice , statin treatment is cost-effective for primary prevention in patients newly diagnosed with type 2 diabetes . Because of large differences in cost-effectiveness according to different risk and age groups , the efficiency of the treatment could be increased by targeting patients with relatively higher cardiovascular risk and higher ages BACKGROUND Long-term statin treatment reduces the frequency of cardiovascular events , but safety and efficacy in patients with abnormal liver tests is unclear . We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation ( GREACE ) study population . METHODS GREACE was a prospect i ve , intention-to-treat study that r and omly assigned by a computer-generated r and omisation list 1600 patients with coronary heart disease ( aged < 75 years , with serum concentrations of LDL cholesterol > 2·6 mmol/L and triglycerides < 4·5 mmol/L ) at the Hippokration University Hospital , Thessaloniki , Greece to receive statin or usual care , which could include statins .  The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests ( defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal ) compared with patients with abnormal liver tests who did not receive a statin . This risk reduction was compared with that for patients treated ( or not ) with statin and normal liver tests . FINDINGS Of 437 patients with moderately abnormal liver tests at baseline , which were possibly associated with non-alcoholic fatty liver disease , 227 who were treated with a statin ( mainly atorvastatin 24 mg per day ) had substantial improvement in liver tests ( p<0·0001 ) whereas 210 not treated with a statin had further increases of liver enzyme concentrations . Cardiovascular events occurred in 22 ( 10 % ) of 227 patients with abnormal liver tests who received statin ( 3·2 events per 100 patient-years ) and 63 ( 30 % ) of 210 patients with abnormal liver tests who did not receive statin ( 10·0 events per 100 patient-years ; 68 % relative risk reduction , p<0·0001 ) . This cardiovascular disease benefit was greater ( p=0·0074 ) than it was in patients with normal liver tests ( 90 [ 14 % ] events in 653 patients receiving a statin [ 4·6 per 100 patient-years ] vs 117 [ 23 % ] in 510 patients not receiving a statin [ 7·6 per 100 patient-years ] ; 39 % relative risk reduction , p<0·0001 ) . Seven ( < 1 % ) of 880 participants  who received a statin discontinued statin treatment because of liver-related adverse effects ( transaminase concentrations more than three-times the upper limit of normal ) . INTERPRETATION Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease . FUNDING None Aims Cardiovascular fixed-dose combination pills , or polypills , may help address the widespread lack of access and adherence to proven medicines . Initiation of polypill-based care typically entails switching from current separately taken medications . Given the heterogeneity in usual care , there is interest in the impact of polypill treatment across different patterns of prior medication regimen . Methods A total of 2004 participants with established cardiovascular disease or estimated 5-year cardiovascular risk of over 15 % were r and omised to polypill-based treatment ( aspirin 75 mg , simvastatin 40 mg , lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg ) or usual care . Baseline medications were classified by potency relative to polypill components . Estimated cardiovascular risk reduction was calculated by combining risk factor changes with results seen in meta-analyses of previous r and omised trials . Results For cholesterol reduction conferred by polypills , there was a dose response across baseline statin groups , with mean low-density lipoprotein (LDL)-cholesterol differences of 0.37 , 0.22 , 0.14 and 0.07 mmol/L among patients taking no statin , less potent , equipotent and more potent statin at baseline , respectively . Similarly there were differences in mean systolic BP of 5.4 , 6.2 , 3.3 and 1.8 mmHg among patients taking 0 , 1 , 2 or 3 BP-lowering agents . Among patients taking more potent statins at baseline , there was no significant difference in LDL-cholesterol but there were benefits for BP and aspirin adherence . Similar results were seen among patients taking 3 BP-lowering agents at baseline . Switching to a polypill-based strategy result ed in estimated cardiovascular relative risk reductions across a wide range of usual care patterns of antiplatelet , statin and BP-lowering therapy prescribing . Conclusion Adherence benefits from switching to a polypill result ed in risk factor changes that were at least as good as usual care across a wide variety of treatment patterns , including equally potent or more potent regimens . The benefits of switching to polypill-based care were greatest among those stepped up from partial treatment or less potent treatment OBJECTIVE To evaluate the incremental cost-effectiveness ratio ( ICER ) of switching to ezetimibe/simvastatin ( Eze/Simva ) compared with doubling the submaximal statin doses , in patients with acute coronary syndrome ( ACS ) events in the INFORCE study . METHODS Lifetime treatment costs and benefits were computed using a Markov model . Model inputs included each patient 's cardiovascular risk factor profile and actual lipid values at baseline and 12 weeks ( endpoint ) . Cardiovascular event and drug costs were discounted at 3.5 % . Age-specific utilities were based on UK literature values and non-coronary heart disease mortality rates on the Office of National Statistics data . In the INFORCE study , 384 patients taking statins at stable doses for ≥6 weeks before hospital admission were stratified by statin dose/potency ( low , medium , and high ) and then r and omized to doubling the statin dose or switching to Eze/Simva 10/40 mg for 12 weeks . RESULTS The Eze/Simva  group ( n=195 ) had a higher mean baseline total cholesterol than the double-statin group ( n=189 ) . Analyses were adjusted for baseline characteristics . In the INFORCE study , Eze/Simva  reduced low-density lipoprotein cholesterol ( LDL-C ) by ∼30 % ( vs. 4 % with doubling statin doses ) and significantly enhanced LDL-C goal attainment . In the cost-effectiveness analysis , Eze/Simva conferred 0.218 incremental discounted quality -adjusted life year ( QALY ) at a discounted incremental cost of £ 2524 , for an ICER of £ 11,571/QALY ( 95 % confidence interval=£8181-£18,600/QALY ) . The ICER was £ 13,552/QALY , £ 11,930/QALY , and £ 10,148/QALY in the low- , medium- , and high-potency strata , respectively . CONCLUSIONS Switching to Eze/Simva 10/40 mg is projected to be a cost-effective treatment ( vs. double-statin ) in UK patients with ACS
Considering a reasonable WTP threshold , intermediate dose statin therapy is economically attractive , and should be a priority intervention in prevention of cardiovascular events in Brazil
BACKGROUND Statins have proven efficacy in the reduction of cardiovascular events , but the financial impact of its widespread use can be substantial .
OBJECTIVE To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System ( SUS ) perspective .