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. Impact of treatment completion, intolerance and adverse events on health system costs in a randomised trial of 4 months rifampin or 9 months isoniazid for latent TB Cost-effectiveness analysis of rosuvastatin versus atorvastatin, simvastatin, and pravastatin from a Canadian health system perspective. Cost-efficacy analysis of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors based on results of the STELLAR trial: clinical implications for therapeutic selection. Cost Effectiveness of Atorvastatin in Patients with Type 2 Diabetes Mellitus Cost-Effectiveness of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor Therapy in Older Patients with Myocardial Infarction Perioperative statin therapy is associated with a significant and dose-dependent reduction of adverse cardiovascular outcomes after coronary artery bypass graft surgery. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. An Economic Evaluation of Fluvastatin used for the Prevention of Cardiac Events Following Successful First Percutaneous Coronary Intervention in the UK Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia. Improving Adherence to Cardiovascular Therapies: An Economic Evaluation of a Randomized Pragmatic Trial. The Role of Statins in the Management of Nonalcoholic Fatty Liver Disease. Cost-effectiveness of entecavir versus lamivudine for the suppression of viral replication in chronic hepatitis B patients in Brazil. Lipids, Apolipoproteins, and Their Ratios in Relation to Cardiovascular Events With Statin Treatment
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 Rationale Treatment for latent tuberculosis infection with isoniazid for 9 months ( 9INH ) has poor completion and serious adverse events , while treatment for 4 months with daily rifampin ( 4RIF ) has significantly higher completion and fewer adverse events . Objectives To compare the health system costs of 4RIF and 9INH . Methods In a r and omised trial conducted in five Canadian centres , one Brazilian and one Saudi Arabian centre , consenting subjects were r and omised to receive 4RIF or 9INH .  Health system costs were estimated from healthcare utilisation including scheduled and unscheduled visits , investigations and drugs . All activities for all subjects were evaluated using financial information from 2007 from the Montreal Chest Institute . Costs were expressed in Canadian dollars . Results Total health system cost per patient allocated to 4RIF was $ 854 compared with $ 970 for 9INH ( p<0.0001 ) . The average cost per patient for the 328 of 420 ( 78 % ) who completed 4RIF therapy was $ 1094 compared with $ 1625 for the 254 of 427 ( 60 % ) completing 9INH ( p<0.0001 ) . Costs were modestly increased in patients with minor intolerance and substantially increased if the treating physician stopped treatment because of possible adverse events . Total costs related to management of adverse events with 9INH were $ 48 142 compared with $ 25 684 for 4RIF ( p=0.008 ) . Using these data , incremental cost-effectiveness analyses showed that 4RIF would be cost saving and prevent more cases within 2 years if efficacy exceeded 74 % , and cost saving if efficacy exceeded 65 % . Conclusions The 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events . RCT registration number NCT00170209 OBJECTIVE The primary objective of this study was to assess the cost-effectiveness of the most commonly prescribed doses of rosuvastatin , atorvastatin , simvastatin , and pravastatin for managing various lipid parameters in patients with hypercholesterolemia over a 1-year time horizon from a Canadian health care perspective . METHODS Incremental cost-effectiveness ratios ( ICERs ) were estimated for br and ed rosuvastatin compared with br and ed atorvastatin , generic simvastatin , and generic pravastatin in patients with hypercholesterolemia in terms of percent reduction in low-density lipoprotein cholesterol ( LDL-C ) and total cholesterol (TC)/high-density lipoprotein cholesterol ( HDL-C ) ratio , as well as in TC , HDL-C , triglycerides ( TG ) , apolipoprotein ( Apo ) B , the ApoB/ApoA-I ratio , and attainment of the Canadian LDL-C goal . The pharmacoeconomic model was constructed for a 1-year time horizon using efficacy data from a r and omized , open-label trial including 2268 adults and the wholesale acquisition costs of br and ed rosuvastatin and atorvastatin and generic simvastatin and pravastatin in British Columbia . RESULTS The most commonly prescribed doses of each of the 4 statins in British Columbia were as follows : rosuvastatin 10 mg ( 75.8 % of all rosuvastatin doses ) ; atorvastatin 10 and 20 mg ( 46.4 % and 35.3 % , respectively , of all atorvastatin doses ) ; simvastatin 20 and 40 mg ( 42.5 % and 31.8 % , respectively , of all simvastatin doses ) ; and pravastatin 20 and 40 mg ( 55.0 % and 34.1 % , respectively , of all pravastatin doses ) . Rosuvastatin 10 mg was dominant ( ie , was more effective at a lower cost ) relative to atorvastatin 10 and 20 mg , simvastatin 20 and 40 mg , and pravastatin 40 mg in terms of reductions in LDL-C , TC/ HDL-C ratio , TC , ApoB , and ApoB/ApoA-I ratio , increases in HDL-C , and attainment of the LDL-C goal . Compared with pravastatin 20 mg , the ICER per percent reduction in LDL-C , TC/HDL-C ratio , TC , TG , ApoB , or ApoB/ApoA-I or increase in HDL-C ranged from $ 3.89 to $ 26.07 ; the value for 1 additional patient achieving the LDL-C goal was $ 419.75 . When the statin doses were aggregated based on the Canadian statin-utilization pattern , rosuvastatin was dominant relative to atorvastatin on all effectiveness measures evaluated . When rosuvastatin was compared with generic simvastatin and pravastatin , the annual costs for 1 additional patient achieving the LDL-C goal were $ 144.51 and $ 373.91 , respectively . Based on the sensitivity analysis , rosuvastatin was associated with the highest probability of cost-effectiveness compared with the other statins over a broad range of monetary values per unit of clinical effect . CONCLUSION When percent changes in lipid parameters and rates of LDL-C goal attainment were considered in patients with hypercholesterolemia in British Columbia , rosuvastatin 10 mg was more cost-effective than the most frequently used doses of atorvastatin ( 10 and 20 mg ) , generic simvastatin ( 20 and 40 mg ) , and generic pravastatin ( 20 and 40 mg ) STUDY OBJECTIVE To compare the cost/1 % reduction in  low-density lipoprotein cholesterol ( LDL )  and the cost/patient achieving the National Cholesterol Education Program Adult Treatment Panel III ( NCEP ATP III ) LDL goal based on the results of the  Statin Therapies  for Elevated Lipid Levels Compared Across Doses to Rosuvastatin ( STELLAR ) trial . DESIGN Cost-efficacy analysis . INTERVENTION Investigators in the STELLAR trial evaluated percentage reductions in LDL and achievement of the ATP III LDL goal for various doses of atorvastatin , pravastatin , rosuvastatin , and simvastatin . We derived efficacy estimates for these four statins from the results of this trial . We also derived drug acquisition costs from the average wholesale prices to estimate the cost/1 % reduction in LDL levels and the cost/patient achieving the ATP III LDL goal . MEASUREMENTS AND MAIN RESULTS In the STELLAR trial , doses of rosuvastatin produced reductions in LDL significantly greater than those of equivalent milligram/milligram doses of atorvastatin , simvastatin , or pravastatin . The annual acquisition cost/percentage LDL reduction was lower with rosuvastatin at doses of 10 mg ( 20.92 dollars ) , 20 mg ( 18.28 dollars ) , and 40 mg ( 17.42 dollars ) than with the other statins analyzed . Rosuvastatin also had a lower average cost/patient achieving the ATP III LDL goal over 6 weeks than that of the other statins . CONCLUSION Although the long-term clinical benefits and safety data from the increased LDL reduction achieved with rosuvastatin remain uncertain , rosuvastatin may be the most cost-effective statin among those analyzed in terms of acquisition cost/1 % reduction in LDL levels and in terms of patients achieving ATP III LDL goals . On the basis of the efficacy estimates from the STELLAR trial in conjunction with acquisition cost , a potential cost savings could be realized from the use of rosuvastatin Abstract Background and Objective : Patients with type 2 diabetes mellitus have a high risk of developing cardiovascular ( CV ) disease . The clinical benefit of use of statins in patients with type 2 diabetes has been demonstrated in several r and omized , controlled trials , including the CARDS clinical trial . Based on the clinical CARDS data , the favourable cost effectiveness of atorvastatin 10 mg in patients with type 2 diabetes has been demonstrated in countries such as the UK and France . This study aim ed to estimate the cost effectiveness in the Belgian setting of atorvastatin 10 mg compared with no treatment for the primary prevention of CV events in type 2 diabetes patients without a history of CV disease . Methods : A Markov model with 1-year cycles was developed to simulate the CV event and death risk according to the therapeutic approach initiated . The transition probabilities for CV events in the ‘ no statin treatment ’ group were derived from the risk equations reported from the large UKPDS . Risk reductions from the CARDS clinical trial were used to adjust these CV event probabilities in the atorvastatin 10 mg treatment group . The characteristics of type 2 diabetes patients without a CV history were derived from the Belgian OCAPI survey . The public healthcare payers ’ perspective was taken into account for costing . The direct medical costs of CV events were based on the Public Health Authorities ’ hospital data base for acute care costs and on the literature for the follow-up costs . The impact on the reimbursement system of generic entry to the market was considered in the drug cost . Costs were valued as at year 2009 ; costs and outcomes were discounted at 3 % and 1.5 % , respectively . Results : Based on a 5-year time horizon , atorvastatin was demonstrated to be cost effective with an incremental cost/ quality -adjusted life-year ( QALY ) of € 16 681 . Over a lifetime horizon ( 25 years ) , atorvastatin was demonstrated to be a cost-saving therapeutic intervention . At a threshold of € 30 000/QALY , atorvastatin had a 98.8 % probability of being cost effective . Conclusion : Compared with ‘ no treatment ’ , use of atorvastatin 10 mg as a primary prevention intervention in Belgian type 2 diabetes patients not only improves CV outcomes , but also appears to be cost saving over a lifetime horizon Recent large-scale r and omized , controlled trials of 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors ( statins ) have shown statistically significant reductions in cardiovascular events , strokes , and total mortality among selected groups , including patients with risk factors for vascular disease or a history of vascular disease ( 1 - 5 ) . In addition , cost-effectiveness analyses of the Sc and inavian Simvastatin Survival Study and the West of Scotl and Coronary Prevention Study have shown favorable cost-effectiveness ratios ( 6 , 7 ) . A limitation of the r and omized , controlled trials of statin therapy published to date , however , has been their failure to enroll patients older than 75 years of age . Ongoing r and omized , controlled trials are including patients in this age category , but results will not be available for some time ( 8 , 9 ) . Meanwhile , analyses of data from two secondary prevention trials , the Sc and inavian Simvastatin Survival Study and the Cholesterol and Recurrent Events ( CARE ) trial , have found that participants 65 to 70 years of age and those 65 to 75 years of age , respectively , experienced statistically significant reductions in cardiac end points similar to those seen in trial participants as a whole ( 10 , 11 ) . These results raise the prospect of extending the use of statins to patients older than 75 years of age with established coronary heart disease ( 12 ) . Although the issue of efficacy in patients older than 75 years of age will not be resolved definitively until trials of patients in this age group are published , decision-analytic models can test various assumptions about efficacy to gauge the potential cost-effectiveness of statins in this context . We modeled the cost-effectiveness of  statin therapy in a hypothetical cohort of patients 75 to 84 years of age with a history of myocardial infa rct ion by extrapolating results from published r and omized , controlled trials and epidemiologic data . Methods Model We compared two strategies for patients 75 to 84 years of age with previous myocardial infa rct ion :  usual care and initiation of HMG-CoA reductase inhibitor therapy . We developed a Markov model ( 13 ) and conducted a cohort simulation to track costs and health outcomes for hypothetical patients r and omly assigned to one of these strategies . In this model , patients can occupy one of six health states : baseline ( history of at least one myocardial infa rct ion ) , recurrent myocardial infa rct ion , postrecurrent myocardial infa rct ion , stroke , post-stroke , or dead ( Figure 1 ) . The model was not configured to deal with multiple events ( such as recurrent myocardial infa rct ion after stroke ) because such sequences of events occur infrequently enough to have a small effect on the overall analysis . Other health states , such as congestive heart failure , were not modeled explicitly but were averaged into the mortality estimates and quality -of-life weights . The model was constructed by using DATA 3.5 software ( TreeAge Software , Williamstown , Massachusetts ) . We adopted the societal perspective in all analyses . Figure 1 . Markov model . MI Transition Probabilities Each state of the model has an associated mortality rate that specifies the probability of dying in any given cycle ( Table 1 ) . These mortality rates were determined by using mortality risk ratios relative to all-cause mortality for an age-matched unselected population ; all-cause mortality rates were obtained from vital statistics data ( 14 ) . We chose to use mortality risk ratios ( multiplicative model ) rather than excess mortality ( additive model ) because a multiplicative model better captures how the risk for death from coronary heart disease changes with age ( 15 , 16 ) . Table 1 . Variables Governing Transition Probabilities for the Markov Model For purpose s of calibration , we initially created a two-state ( alive or dead ) Markov model , with mortality rates based on the 10-year survival curve after acute myocardial infa rct ion for patients 75 to 84 years of age ( 17 ) . The life expectancy of patients in the calibration model was then used as a benchmark to calibrate life expectancy for patients in the usual care strategy of the full six-state model . In the six-state model , we differentiated between death after recurrent myocardial infa rct ion or stroke and death from nonmyocardial infa rct ion or nonstroke causes because statins , by preventing both myocardial infa rct ion and stroke ( 2 ) , also prevent death after these events . Because patients with a history of myocardial infa rct ion have a higher chance of dying of coronary heart disease that is unrelated to recurrent myocardial infa rct ion ( for example , arrhythmia ) , this cohort has a higher risk for death from causes other than myocardial infa rct ion or stroke than does an unselected population . Long-term mortality after recurrent myocardial infa rct ion was adjusted upward to account for the additional risk for death after a recurrent event , on the basis of hazard ratios for coronary heart disease death as a function of nonfatal reinfa rct ion ( 18 ) . We converted these ratios into a hazard ratio for total mortality on the basis of data from the same trial indicating that coronary heart disease caused 76 % of deaths ( 19 ) and on the assumption of no excess risk for noncoronary heart disease death in patients with reinfa rct ion . Mortality rates after stroke were based on published data from the Oxfordshire Community Stroke Project ( 20 ) . Transition probabilities to recurrent myocardial infa rct ion or stroke from the baseline state are based on data describing reinfa rct ion rates ( 21 ) and stroke rates ( 22 , 23 ) . All of the data used to determine transition probabilities are population -based and specific to patients older than 75 years of age , with the exception of data from a clinical trial of patients up to 75 years of age ( 18 , 19 ) . We used data from a follow-up study of patients 65 to 75 years of age in the CARE trial to estimate the relative risk reduction conferred by statin therapy for the end points of myocardial infa rct ion ( fatal and nonfatal combined ) and stroke ( 11 ) . This study stratified patients in the CARE trial into those younger than 65 years of age and those 65 to 75 years of age and found that the latter group experienced statistically significant and clinical ly important reductions in cardiac and cerebrovascular events . Our base-case analysis used the mean estimates of relative risk reduction published in this study for patients 65 to 75 years of age , and the sensitivity analysis used the 95 % confidence limits . We applied risk reductions due to statin therapy to only two transitions out of the baseline state : recurrent myocardial infa rct ion and stroke . Because we did not explicitly model multiple strokes or recurrent myocardial infa rct ion , the model is based on the assumption that patients discontinue statin therapy after their first stroke or recurrent myocardial infa rct ion and no longer experience any additional costs or benefits of statin therapy . We also assumed that patients in the baseline state who are receiving statin therapy continue to accrue the benefits and costs associated with this therapy for the duration of their time in the baseline state . In a sensitivity analysis , we limited benefits of statin therapy to the first 5 years in the baseline state ; this time frame is similar to the duration of follow-up for the large r and omized , controlled trials of statin therapy ( 1 - 5 ) . Under this scenario , after 5 years , patients experience the same event rates and mortality rates as those not using statin therapy but continue to accrue the costs of drug while in the baseline state . This conservative analysis was conducted to examine the consequences of continuing to take a drug that in fact provides no additional benefit beyond the period for which it has been studied . Health-Related Quality of Life The model measured health effects in terms of quality -adjusted life expectancy . The health-related quality -of-life weights for the health states ( Table 2 ) were derived from time-tradeoff scores collected from patients with myocardial infa rct ion in the quality -of-life sub study of Global Use of Strategies to Open Occluded Coronary Arteries ( GUSTO-I ) ( 24 ) , which included patients older than 75 years of age . That study reported quality -of-life scores in patients who experienced various levels of disability from in-hospital stroke after myocardial infa rct ion and in patients who did not have a stroke . The quality -of-life weight ( utility ) for stroke was derived from the mean time-tradeoff utility for patients with ischemic stroke in GUSTO-I because these represent most nonfatal strokes . Bounds for sensitivity analysis were based on quality -of-life estimates approximately 1 SD from the mean . We also conducted a sensitivity analysis in which health states were not adjusted for quality -of-life differences . Table 2 . Utilities , Costs , and Discount Rate The base-case model assumed no disutility associated with statin use . This assumption was based on two studies of pravastatin that included patients older than 75 years of age and showed that pravastatin was well tolerated , with an incidence of adverse events similar to that of placebo ( 25 , 26 ) . However , because we know of no published studies of utilities in patients receiving statins , we performed a sensitivity analysis using a utility decrement of 0.013 in patients taking statins  . This number represents the utility decrement related to taking warfarin , a drug associated with considerably more inconvenience ( monthly laboratory monitoring ) , lifestyle modification , and risk than statins ( 27 ) . Costs In the base-case model , we included the following direct medical costs for both strategies : hospitalizations for nonfatal and fatal myocardial infa rct ion , hospitalizations for stroke , and post-stroke institutional care ( nursing home and rehabilitation ) . Patients in the  statin  group also experienced yearly drug costs and the cost of two additional office visits and two hepatic function OBJECTIVE The aim of this study was to determine whether perioperative statin therapy was associated with a dose-dependent decrease in adverse cardiovascular events after coronary artery bypass graft ( CABG ) surgery . DESIGN A prospect i ve observational study . SETTING A cardiovascular anesthesia unit in a university hospital . PARTICIPANTS Four hundred eighteen consecutive patients undergoing CABG surgery between October 2004 and October 2005 . INTERVENTIONS Patients were divided in 2 groups depending on whether their preoperative treatment included statins or not . In patients receiving statins , high- and low-dose regimens were respectively defined as a regimen recognized to induce a theoretic reduction of low-density lipoprotein cholesterol level equal to 45 % ( n = 87 ) or < 45 % ( n = 258 ) . In treated patients , statin therapy was maintained until the day of surgery and was restarted soon thereafter . MEASUREMENTS AND MAIN RESULTS The measured endpoint was adverse in-hospital cardiovascular outcomes including heart failure and /or malignant arrhythmia and /or cardiac death . Stepwise logistic regression and a multivariate analysis of propensity-matched cohort were used for analysis of the findings . After adjustment for propensity score , statin therapy was found to produce a significant reduction in cardiovascular outcomes ( odds ratio = 0.56 ; 95 % confidence interval [ CI ] , 0.32 - 0.96 , p < 0.05 ) . By using multivariate analysis , the odds ratio for cardiovascular outcomes in patients receiving high-dose statins compared with those treated by low-dose statins was 0.62 ( 95 % CI , 0.41 - 0.93 ; p < 0.05 ) . CONCLUSION Statin therapy is associated with a significant and dose-dependent reduction in adverse cardiovascular events after CABG surgery . However , further r and omized trials still require confirming a causal association between statins and better postoperative outcomes and evaluating the tolerance of such perioperative therapy IMPORTANCE For patients with limited prognosis , some medication risks may outweigh the benefits , particularly when benefits take years to accrue ; statins are one example . Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy . OBJECTIVE To evaluate the safety , clinical , and cost impact of discontinuing statin medications for patients in the palliative care setting . DESIGN , SETTING , AND PARTICIPANTS This was a multicenter , parallel-group , unblinded , pragmatic clinical trial . Eligibility included adults with an estimated life expectancy of between 1 month and 1 year , statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease , recent deterioration in functional status , and no recent active cardiovascular disease . Participants were r and omized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year . The study was conducted from June 3 , 2011 , to May 2 , 2013 . All analyses were performed using an intent-to-treat approach . INTERVENTIONS Statin therapy was withdrawn from eligible patients who were r and omized to the discontinuation group . Patients in the continuation group continued to receive statins . MAIN OUTCOMES AND MEASURES Outcomes included death within 60 days ( primary outcome ) , survival , cardiovascular events , performance status , quality of life ( QOL ) , symptoms , number of nonstatin medications , and cost savings . RESULTS A total of 381 patients were enrolled ; 189 of these were r and omized to discontinue statins , and 192 were r and omized to continue therapy . Mean ( SD ) age was 74.1 ( 11.6 ) years , 22.0 % of the participants were cognitively impaired , and 48.8 % had cancer . The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different ( 23.8 % vs 20.3 % ; 90 % CI , -3.5 % to 10.5 % ; P=.36 ) and did not meet the noninferiority end point . Total QOL was better for the group discontinuing statin therapy ( mean McGill QOL score , 7.11 vs 6.85 ; P=.04 ) . Few participants experienced cardiovascular events ( 13 in the discontinuation group vs 11 in the continuation group ) . Mean cost savings were $ 3.37 per day and $ 716 per patient . CONCLUSIONS AND RELEVANCE This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL , use of fewer nonstatin medications , and a corresponding reduction in medication costs . Thoughtful patient-provider discussion s regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01415934 Abstract 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 r and omised , 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 £ 300 ( SD £ 303 ) [ € 423 ; SD € 428 ] per patient and result ed 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 £ 3207 ( SD £ 5497 ) [ € 4527 ; SD € 7759 ] . 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 infa rct ion , 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 BACKGROUND AND AIMS Substantial residual cardiovascular risks remain despite intensive statin treatment . Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins . K-877 ( pemafibrate ) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy . The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment . METHODS The objectives were investigated in two , multicentre , r and omised , double-blind ,  placebo-controlled  , parallel group comparison clinical trials : ( A ) K-877 0.1 , 0.2 , and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients , ( B ) K-877 0.2 ( fixed dose ) and 0.2 ( 0.4 ) ( conditional up-titration ) mg/day in combination with any statin for 24 weeks in 423 patients . RESULTS In both studies , we found a robust reduction in fasting triglyceride levels by approximately 50 % in all combination therapy groups , which was significant compared to the statin-monotherapy ( placebo ) groups ( p < 0.001 ) . High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy , i.e. small low-density lipoproteins decreased whereas larger ones increased , and larger high-density lipoproteins decreased whereas smaller ones increased . The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies . CONCLUSIONS These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment OBJECTIVE Preplanned economic analysis of a pragmatic trial using electronic-medical-record-linked interactive voice recognition ( IVR ) reminders for enhancing adherence to cardiovascular medications ( i.e. , statins , angiotensin-converting enzyme inhibitors [ ACEIs ] , and angiotensin receptor blockers [ ARBs ] ) . METHODS Three groups , usual care ( UC ) , IVR , and IVR plus educational material s ( IVR+ ) , with 21,752 suboptimally adherent patients underwent follow-up for 9.6 months on average . Costs to implement and deliver the intervention ( from a payer perspective ) were tracked during the trial . Medical care costs and outcomes were ascertained using electronic medical records . RESULTS Per-patient intervention costs ranged from $ 9 to $ 17 for IVR and from $ 36 to $ 47 for IVR+ . For ACEI/ARB , the incremental cost-effectiveness ratio for each percent adherence increase was about 3 times higher with IVR+ than with IVR ( $ 6 and $ 16 for IVR and IVR+ , respectively ) . For statins , the incremental cost-effectiveness ratio for each percent adherence increase was about 7 times higher with IVR+ than with IVR ( $ 6 and $ 43 for IVR and IVR+ , respectively ) . Considering potential cost offsets from reduced cardiovascular events , the probability of breakeven was the highest for UC , but the IVR-based interventions had a higher probability of breakeven for subgroups with a baseline low-density lipoprotein ( LDL ) level of more than 100 mg/dl and those with two or more calls . CONCLUSIONS We found that the use of an automated voice messaging system to promote adherence to ACEIs/ARBs and statins may be cost-effective , depending on a decision maker 's willingness to pay for unit increase in adherence . When considering changes in LDL level and downstream medical care offsets , UC is the optimal strategy for the general population . However , IVR-based interventions may be the optimal choice for those with elevated LDL values at baseline BACKGROUND Non-alcoholic fatty liver disease ( NAFLD ) and its advanced form non-alcoholic steatohepatitis ( NASH ) are the most common causes of elevated liver enzymes in the general population . NASH , and to a lesser extent NAFLD have been associated with increased liver-related , cardiovascular disease ( CVD ) , and allcause mortality . No effective treatment is widely acceptable . OBJECTIVE The purpose of this review is to summarize available data on the impact of statins on NAFLD and NASH . METHOD A comprehensive review of the literature was performed to identify studies assessing the effect of statin use in NAFLD/NASH . RESULTS Recent reports have shown that the use of statins in patients with elevated plasma aminotransferases may be beneficial . Post hoc data from three large prospect i ve r and omized clinical trials ( n>11 , 000 ) suggest that specific statins ( mainly atorvastatin ) ameliorate NAFLD/NASH and reduce CVD events twice as much as in those with normal liver function . Several biopsy studies have found that rosuvastatin use is related with significant histological ameliorating effects in the setting of NASH . Statin treatment may also protect from hepatocellular carcinoma ( HCC ) related to NAFLD/NASH . CONCLUSION Since NAFLD/NASH patients have high CVD risk , they will probably require a statin . Thus , why not select a specific statins ( atorvastatin or rosuvastatin , both generic now ) that offer a substantial liver- and CVDrelated adverse event reduction ? The administration of statins in these patients is as safe as in the general population Hepatitis B virus infection is an important public-health issue . Chronic patients have a higher risk of death due to complications , which increases health-care expenses in . Cost-effectiveness analysis of entecavir ( ETV ) versus lamivudine ( LVD ) for treatment of chronic hepatitis B , in e antigen (AgHBe)-positive and negative patients , based on two phase 3 , controlled and r and omized studies . A decision analysis model was developed , using the following endpoints : cost per patient with undetectable viral load and cost per quality life year ( QALY ) gained . Risks for complications ( compensated or decompensated cirrhosis and hepatocellular carcinoma ) were based on the cohort study REVEAL , published in 2006 . The REVEAL parameters were applied to the results of the viral load levels obtained from the clinical assay data . The complication costs were based on a study of the disease cost conducted in Brazil , in 2005 . The cost data were obtained predominantly from Sistema Unico de Saúde [ SUS - Brazilian public health system ] payment tables and drug price lists . The utility data were obtained from literature and life expectancy information was based on IBGE data . The analysis perspective was that of SUS . A discount rate of 3 % per year was used . For the horizon of time of 10 years , the ETV had an incremental cost of approximately two million Brazilian Reais ( R$ ) compared to LVD . Reducing the number of complications ,  ETV treatment reduced costs by around 3 million , reducing final costs by 1 million , for AgHBe-positive patients .  ETV also reduced the incremental cost per QALY gained .  ETV was found to be the most cost-effective alternative for AgHBe-positive and negative patients Background — Low-density lipoprotein ( LDL ) cholesterol is the principal target of lipid-lowering therapy , but recent evidence has suggested more appropriate targets . We compared the relationships of on-treatment levels of LDL cholesterol , non – high-density lipoprotein ( HDL ) cholesterol , and apolipoprotein B , as well as ratios of total/HDL cholesterol , LDL/HDL cholesterol , and apolipoprotein B/A-I , with the occurrence of cardiovascular events in patients receiving statin therapy .  Methods and Results — A post hoc analysis was performed that combined data from 2 prospect i ve , r and omized clinical trials in which 10 001 ( “ Treating to New Targets ” ) and 8888 ( “ Incremental Decrease in End Points through Aggressive Lipid Lowering ” ) patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment . In models with LDL cholesterol , non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome , whereas a positive relationship with LDL cholesterol was lost . In a model that contained non-HDL cholesterol and apolipoprotein B , neither was significant owing to collinearity . Total/HDL cholesterol ratio and the apolipoprotein B/A-I ratio in particular were each more closely associated with outcome than any of the individual proatherogenic lipoprotein parameters . Conclusions — In patients receiving statin therapy  , on-treatment levels of non-HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcome than levels of LDL cholesterol . Inclusion of measurements of the antiatherogenic lipoprotein fraction further strengthened the relationships . These data support the use of non-HDL cholesterol or apolipoprotein B as novel treatment targets for statin therapy . Given the absence of interventions that have been proven to consistently reduce cardiovascular disease risk through raising plasma levels of HDL cholesterol or apolipoprotein A-I , it seems premature to consider the ratio variables as clinical ly useful
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 .