title: Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. Cost-effectiveness of pravastatin therapy for survivors of myocardial infarction with average cholesterol levels. Prediction of coronary heart disease using risk factor categories. Lifetime cost effectiveness of simvastatin in a range of risk groups and age groups derived from a randomised trial of 20 536 people Combination of direct and indirect evidence in mixed treatment comparisons. Cost-effectiveness of primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes: results from the Collaborative Atorvastatin Diabetes Study (CARDS) The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin Quality of life in Brazil: normative values for the Whoqol-bref in a southern general population sample Cost-effectiveness of rosuvastatin in the prevention of ischemic heart disease in Portugal. Cost-Effectiveness of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor Therapy in Older Patients with Myocardial Infarction
abstract: BACKGROUND Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events . Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol , we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment . METHODS We r and omly assigned 17,802 apparently healthy men and women with low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin , 20 mg daily , or placebo and followed them for the occurrence of the combined primary end point of myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes . RESULTS The trial was stopped after a median follow-up of 1.9 years ( maximum , 5.0 ) . Rosuvastatin reduced LDL cholesterol levels by 50 % and high-sensitivity C-reactive protein levels by 37 % . The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio for rosuvastatin , 0.56 ; 95 % confidence interval [ CI ] , 0.46 to 0.69 ; P<0.00001 ) , with corresponding rates of 0.17 and 0.37 for myocardial infa rct ion ( hazard ratio , 0.46 ; 95 % CI , 0.30 to 0.70 ; P=0.0002 ) , 0.18 and 0.34 for stroke ( hazard ratio , 0.52 ; 95 % CI , 0.34 to 0.79 ; P=0.002 ) , 0.41 and 0.77 for revascularization or unstable angina ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.70 ; P<0.00001 ) , 0.45 and 0.85 for the combined end point of myocardial infa rct ion , stroke , or death from cardiovascular causes ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.69 ; P<0.00001 ) , and 1.00 and 1.25 for death from any cause ( hazard ratio , 0.80 ; 95 % CI , 0.67 to 0.97 ; P=0.02 ) . Consistent effects were observed in all subgroups evaluated . The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes . CONCLUSIONS In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels , rosuvastatin significantly reduced the incidence of major cardiovascular events . ( Clinical Trials.gov number , NCT00239681 . BACKGROUND The objective of this study was to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels . METHODS We performed a cost-effectiveness analysis based on actual clinical , cost , and health-related quality -of-life data from the Cholesterol and Recurrent Events ( CARE ) trial . Survival and recurrent coronary heart disease events were modeled from trial data in Markov models , with the use of different assumptions regarding the long-term benefit of therapy . RESULTS Pravastatin therapy increased quality -adjusted life expectancy at an incremental cost of $ 16,000 to $ 32,000 per quality -adjusted life-year gained . In subgroup analyses , the cost-effectiveness of pravastatin therapy was more favorable for patients > 60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels > 125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy . CONCLUSIONS The cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels compares favorably with other interventions BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed  CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD Objectives To evaluate the cost effectiveness of 40 mg simvastatin daily continued for life in people of different ages with differing risks of vascular disease . Design A model developed from a r and omised trial was used to estimate lifetime risks of vascular events and costs of treatment and hospital admissions in the United Kingdom . Setting 69 hospitals in the UK . Participants 20 536 men and women ( aged 40 - 80 ) with coronary disease , other occlusive arterial disease , or diabetes . Interventions 40 mg simvastatin daily versus placebo for an average of 5 years . Main outcome measures Cost effectiveness of 40 mg simvastatin daily expressed as additional cost per life year gained . Major vascular event defined as non-fatal myocardial infa rct ion or death from coronary disease , any stroke , or revascularisation procedure . Results were extrapolated to younger and older age groups at lower risk of vascular disease than were studied directly , as well as to lifetime treatment . Results At the April 2005 UK price of � 4.87 ( € 7 ; $ 9 ) per 28 day pack of generic 40 mg simvastatin , lifetime treatment was cost saving in most age groups and vascular disease risk groups studied directly . Gains in life expectancy and cost savings decreased with increasing age and with decreasing risk of vascular disease . People aged 40 - 49 with 5 year risks of major vascular events of 42 % and 12 % at start of treatment gained 2.49 and 1.67 life years , respectively . Treatment with statins  remained cost saving or cost less than � 2500 per life year gained in people as young as 35 years or as old as 85 with 5 year risks of a major vascular event as low as 5 % at the start of treatment . Conclusions Treatment with statins  is cost effective in a wider population than is routinely treated at present Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Aims /hypothesisWe estimated the cost-effectiveness of atorvastatin treatment in the primary prevention of cardiovascular disease in patients with type 2 diabetes using data from the Collaborative Atorvastatin Diabetes Study (CARDS).Subjects and methods A total of 2,838 patients , who were aged 40 to 75 years and had type 2 diabetes without a documented history of cardiovascular disease and without elevated LDL-cholesterol , were recruited from 32 centres in the UK and Irel and and r and omly allocated to atorvastatin 10 mg daily ( n = 1,428 ) or placebo ( n = 1,410 ) . These subjects were followed-up for a median period of 3.9 years . Direct treatment costs and effectiveness were analysed to provide estimates of cost per endpoint-free year over the trial period for alternative definitions of endpoint , and of cost per life-year gained and cost per quality -adjusted life-year ( QALY ) gained over a patient ’s lifetime . Results Over the trial period , the incremental cost-effectiveness ratio ( ICER ) was estimated to be £ 7,608 per year free of any CARDS primary endpoint ; the ICER was calculated to be £ 4,896 per year free of any cardiovascular endpoint and £ 4,120 per year free of any study endpoint . Over lifetime , the incremental cost per life-year gained was £ 5,107 and the cost per QALY was £ 6,471 ( costs and benefits both discounted at 3.5 % ) . Conclusions /interpretation Primary prevention of cardiovascular disease with atorvastatin is a cost-effective intervention in patients with type 2 diabetes , with the ICER for this intervention falling within the current acceptance threshold ( £ 20,000 per QALY ) specified by the National Institute for Health and Clinical Excellence ( NICE ) Abstract Objective : To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia . Design : Economic benefit analysis based on data from the West of Scotl and coronary prevention study . Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated . Scottish record linkage data provided disease specific survival . Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotl and coronary prevention study . Subjects : Men with hypercholesterolaemia similar to the subjects in the West of Scotl and coronary prevention study . Main outcome : Cost consequences , the number of transitions from health to cardiovascular disease prevented , the number needed to start treatment , and cost per life year gained . Results : If 10 000 of these men started taking pravastatin  , 318 of them would not make the transition from health to cardiovascular disease ( number needed to treat , 31.4 ) , at a net discounted cost of £ 20 m over 5 years . These benefits imply an undiscounted gain of 2460 years of life , and thus £ 8121 per life year gained , or £ 20 375 per life year gained if benefits are discounted . Restriction to the 40 % of men at highest risk reduces the number needed to treat to 22.5 ( £ 5601 per life year gained ( undiscounted ) and £ 13 995 per life year gained ( discounted ) ) . Conclusions : In subjects without evidence of prior myocardial infa rct ion but who have hypercholesterolaemia , the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups . Key messages The West of Scotl and coronary prevention study showed that pravastatin can prevent cardiovascular disease in men with hypercholesterolaemia So far , reports have deemed this prevention unjustified due to adverse economic implication s This analysis , based on data from the West of Scotl and coronary prevention study and extensive data from the Scottish record linkage system , shows that using pravastatin in this way is worth considering because of its substantial clinical benefit at a reasonable cost Practitioners must now consider using pravastatin to prevent cardiovascular disease in men with hypercholesterolaemia Increased economic efficiency may be obtained by restricting prevention to patients with additional risk Purpose Normative data for WHOQOL-bref are scarce in the literature and unavailable in Latin American countries . The main objective of this study was to provide normative scores of WHOQOL-bref in a general population sample in Brazil and to describe differences in mean scores according to some socio-demographic characteristics . Methods WHOQOL-bref was applied to a r and omly selected sample of the general population of Porto Alegre . Participants were literate people aged 20 to 64 years . The question naires were self-administered in the presence of an interviewer in the respondent ’s home . Results The response rate was 68 % , and the final sample contained 751 respondents ( 38 % men , 62 % women ) .  Low quality of life was observed in the following subgroups : female gender , lower economic class , lower educational level , and the subgroup reporting a chronic medical condition . The mean scores of the WHOQOL-bref and percentiles of scores are reported as normative data for the general population . Conclusion Our results can be useful to research ers using the WHOQOL-bref to compare their results with normative data from a r and omly selected sample of general population . Additionally , the ability of WHOQOL-bref to discriminate different population subgroups makes it an important tool to identify vulnerable groups in epidemiological surveys OBJECTIVE To assess the cost-effectiveness of rosuvastatin in the treatment of hypercholesterolemia and the prevention of ischemic heart disease ( IHD ) in Portugal . METHODS A probabilistic Markov model was constructed to analyze the costs and consequences of lifetime treatment with rosuvastatin , atorvastatin , pravastatin , and simvastatin . For this purpose , the results from r and omized head-to-head trials evaluating low-density lipoprotein ( LDL ) changes were combined with the results from a meta- analysis defining the relationship between LDL levels and fatal and nonfatal IHD events . The incidence of myocardial infa rct ion ( MI ) was derived from a 9-year Portuguese observational study . The eligible population was defined as untreated individuals aged more than 35 years with LDL levels above 115 mg/dl .  Death rates due to IHD and other causes were obtained from official data . Re source use in the treatment of MI was estimated by a Delphi panel of eight Portuguese cardiologists with at least 15 years of clinical practice . Costs were calculated from the payers ' perspective . RESULTS Rosuvastatin  increases life expectancy between 5.5 and 12.1 days per patient . It is cost-saving when compared to atorvastatin , but it increases costs when assessed against pravastatin and simvastatin ( euro1,004 and euro684 per patient , respectively ) . Therefore , rosuvastatin is a dominant alternative compared to atorvastatin , having an incremental cost-effectiveness ratio of euro30,350 to pravastatin and euro39,340 to simvastatin . In the probabilistic sensitivity analysis , performed rosuvastatin always dominates atorvastatin and is associated with a cost per life-year gained inferior to euro50,000 in 95.7 % of the cases when compared to pravastatin and in 67.0 % simulations when assessed against simvastatin . CONCLUSIONS Rosuvastatin is a cost-effective alternative in the prevention of IHD in Portugal 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
target: 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: 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 .