At costs lower than $ 0.10 per pill , treating all persons with LDL cholesterol levels greater than 3.4 mmol/L ( > 130 mg/dL ) could be a better strategy .
Previous cost-effectiveness analyses ( 719 ) show that statin therapy is generally cost-effective for secondary prevention and for high-risk primary prevention but do not focus on population -level impact or average cost-effectiveness across the heterogeneous U.S. population , including such subgroups of patients as those with low risk but very high cholesterol levels .
Also , it is unclear whether the ATP III approach to risk stratification , in which risk is formally assessed only for patients with 2 or more established risk factors , is the simplest and most cost-effective way of targeting statin therapy .
The 2004 up date to ATP III ( 3 ) notes that treatment of high-risk subgroups may be useful even when cholesterol levels are low , which suggests that a more purely risk-based approach may be simpler and more cost-effective than the ATP III approach .
Context Which lipid-lowering policies with statins are cost-effective ?
Implication Optimum policies for lipid lowering with statins are highly dependent on statin costs .
The Editors Coronary heart disease ( CHD ) is the leading cause of death in the United States ( 1 ) .
Inhibitors of HMG-CoA reductase , known as statins , lower cholesterol and prevent CHD events and mortality ( 2 , 3 ) .
However , statins are expensive and sometimes cause side effects , which makes it difficult for patients , physicians , and policymakers to decide who should receive them .
The CHD Policy Model is a mathematical state-transition model of CHD in the United States that can be used to project event rates and costs related to CHD .
Aspirin, Statins, or Both Drugs for the Primary Prevention of Coronary Heart Disease Events in Men: A CostUtility Analysis
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
At costs lower than $ 0.10 per pill , treating all persons with LDL cholesterol levels greater than 3.4 mmol/L ( > 130 mg/dL ) could be a better strategy .
Previous cost-effectiveness analyses ( 719 ) show that statin therapy is generally cost-effective for secondary prevention and for high-risk primary prevention but do not focus on population -level impact or average cost-effectiveness across the heterogeneous U.S. population , including such subgroups of patients as those with low risk but very high cholesterol levels .
Also , it is unclear whether the ATP III approach to risk stratification , in which risk is formally assessed only for patients with 2 or more established risk factors , is the simplest and most cost-effective way of targeting statin therapy .
The 2004 up date to ATP III ( 3 ) notes that treatment of high-risk subgroups may be useful even when cholesterol levels are low , which suggests that a more purely risk-based approach may be simpler and more cost-effective than the ATP III approach .
Context Which lipid-lowering policies with statins are cost-effective ?
Implication Optimum policies for lipid lowering with statins are highly dependent on statin costs .
The Editors Coronary heart disease ( CHD ) is the leading cause of death in the United States ( 1 ) .
Inhibitors of HMG-CoA reductase , known as statins , lower cholesterol and prevent CHD events and mortality ( 2 , 3 ) .
However , statins are expensive and sometimes cause side effects , which makes it difficult for patients , physicians , and policymakers to decide who should receive them .
The CHD Policy Model is a mathematical state-transition model of CHD in the United States that can be used to project event rates and costs related to CHD .