Published online before print March 5, 2009, doi: 10.1161/CIRCOUTCOMES.108.808469
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original Articles |
Statin Cost-Effectiveness in the United States for People at Different Vascular Risk Levels
MRC/BHF Heart Protection Study Collaborative Group committees, collaborators, and participating hospitals are listed in the online appendix.
Correspondence to Heart Protection Study, Clinical Trial Service Unit and Epidemiological Studies Unit, Richard Doll Building, Old Road Campus, Headington, Oxford OX3 7LF, United Kingdom. E-mail hps{at}ctsu.ox.ac.uk
Received July 18, 2008; accepted December 1, 2008.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionAppendixReferences |
|---|
Background— Statins reduce the rates of heart attacks, strokes, and revascularization procedures (ie, major vascular events) in a wide range of circumstances. Randomized controlled trial data from 20 536 adults have been used to estimate the cost-effectiveness of prescribing statin therapy in the United States for people at different levels of vascular disease risk and to explore whether wider use of generic statins beyond the populations currently recommended for treatment in clinical guidelines is indicated.
Methods and Results— Randomized controlled trial data, an internally validated vascular disease model, and US costs of statin therapy and other medical care were used to project lifetime risks of vascular events and evaluate the cost-effectiveness of 40 mg simvastatin daily. For an average of 5 years, allocation to simvastatin reduced the estimated US costs of hospitalizations for vascular events by 
20% (95% CI, 15 to 24) in the different subcategories of participants studied. At a daily cost of $1 for 40 mg generic simvastatin, the estimated costs of preventing a vascular death within the 5-year study period ranged from a net saving of $1300 (95% CI, $15 600 saving to $13 200 cost) among participants with a 42% 5-year major vascular event risk to a net cost of $216 500 ($123 700 to $460 000 cost) among those with a 12% 5-year risk. The costs per life year gained with lifetime simvastatin treatment ranged from $2500 (–$40 to $3820) in people aged 40 to 49 years with a 42% 5-year major vascular event risk to $10 990 ($9430 to $14 700) in people aged 70 years and older with a 12% 5-year risk.
Conclusions— Treatment with generic simvastatin appears to be cost-effective for a much wider population in the United States than that recommended by current guidelines.
Key Words: cost-benefit analysis • cardiovascular diseases • statin intervention
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
Large randomized trials have shown that lowering blood levels of low-density lipoprotein (LDL) cholesterol with statin therapy substantially reduces rates of heart attacks, strokes, and revascularization procedures for a wide range of individuals.1 The US Adult Treatment Panel III guidelines recommend the initiation of statin therapy for people with preexisting coronary heart disease or "risk equivalents" (ie, other clinical atherosclerotic disease, diabetes, or other risk factors) who are at a 10-year risk of nonfatal myocardial infarction or coronary death (major coronary events [MCE]) higher than 20%, and in those with LDL cholesterol levels above 130 mg/dL who are at a 10-year MCE risk of at least 10%.2,3 Previous reports from the Heart Protection Study (HPS) indicated that, in the United Kingdom, lower-priced generic 40 mg simvastatin daily is cost-effective for individuals aged 35 to 85 years at a 5-year risk of major vascular events (MVE, ie, nonfatal myocardial infarction or coronary death, any stroke or revascularization procedure) risk as low as 5% (ie,
1% per annum).4,5
Clinical Perspective see p 65
Generic statins are now available in the United States and, at generic prices, statins are expected to be cost-effective at lower levels of risk. Although HPS was conducted in the United Kingdom, its clinical findings are directly applicable to other parts of the world. By contrast, the previous cost-effectiveness estimates from HPS based on UK costs cannot be applied directly to the US setting, because the costs of health care and statin treatment may well differ. The objective of the present report is to use individual participant data from HPS and healthcare costs from the United States to estimate the cost-effectiveness of prescribing generic simvastatin in the US healthcare setting for people at different levels of vascular disease risk.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
In HPS, 20 536 UK men and women, aged
40 to 80 years, with blood total cholesterol concentrations of at least 135 mg/dL (3.5 mmol/L) and a medical history of coronary disease, cerebrovascular disease, other occlusive arterial disease, diabetes mellitus, or treated hypertension were randomized to 40 mg simvastatin daily or placebo for an average of 5 years.6 Following randomization, data were prospectively collected from participants about compliance with study statin, use of nonstudy statin, and all hospital admissions during and after the scheduled study treatment period. As in previous analyses,4,5 cost-effectiveness estimates are presented for trial participants grouped into similar-sized quintiles of estimated 5-year MVE risk that range from 12% to 42% (corresponding to 10-year risks of 8% to 39%, respectively, for MCEs, which are the basis of the Framingham risk score used to guide treatment2). Risk quintiles were further subdivided by age at randomization (40 to 49, 50 to 59, 60 to 69, and 70 years and older) to allow for the differential effect of age on both disease risk and life expectancy.
Costs
For all vascular-related hospital admissions in HPS, UK National Health Service Read codes of medical diagnoses and procedures7 were translated into International Classification of Diseases 9th Revision Clinical Modification codes. These International Classification of Diseases 9th Revision Clinical Modification codes were used, together with information about age, gender, and discharge status of patients, to assign a US Diagnosis Related Groups (DRGs) code for each admission (Centers for Medicare and Medicaid Services DRG grouper, October 2003). The 2004 average national Medicare payments per DRG8 were then used, together with Medicare daily and per-procedure physician reimbursements,9 to calculate the US costs of each hospital admission. The physician fees were estimated over the average length of hospitalization per DRG reported for Medicare patients8 and average Medicare facilities fees for initial and subsequent hospital care and hospital discharge.9 Physician fees for in-hospital diagnostic and surgical procedures were based on the number and type of procedures recorded during HPS hospital admissions, the general description of DRGs, and the Medicare reimbursements for these procedures.9 A sensitivity analysis used the 2001 MEDSTAT healthcare reimbursements per DRG,10 with a proportionally increased estimate of Medicare physician and procedure fees to assess cost-effectiveness of 40 mg simvastatin from the perspective of the private US healthcare insurer.
A daily price of $1 was used in the main analyses for the study simvastatin11 as well as for any nonstudy statin used during the study. Scenario analyses used the 2006 average US wholesale proprietary statin prices (eg, $5.25 for 40 mg simvastatin daily)12 and, for future lifetime use, a projected generic price of $0.20 for 40 mg simvastatin daily to explore the sensitivity of the cost-effectiveness results to drug cost. Although statin treatment affected the risk of an event occurring, it did not appear to affect the hospitalization costs conditional on an event having occurred (ie, the hospitalization costs of a particular event were not significantly different between those allocated statin or placebo).5 Costs of hospitalizations for nonvascular events or of concomitant medication were not included in the within-trial cost-effectiveness analyses, because these costs were not significantly different in the intention-to-treat comparison of simvastatin versus placebo.4,6 In the lifetime analysis, however, hospitalization costs for nonvascular conditions were included, based on a study of public insurer healthcare expenditures in the United States,13 because increased life expectancy with statin therapy could lead to higher lifetime nonvascular costs. These costs were proportionately increased when the perspective of US private healthcare insurers was used. A further scenario explored the effect of including nonhospital costs related to nonfatal stroke using data from a study by Lee et al.14 All costs were inflated to 2006 using the Medical Care Component of the Consumer Price Index.15
Within-Trial Cost-Effectiveness
Intention-to-treat comparisons were made for hospitalization and statin costs during the scheduled study treatment period. Previous analyses of HPS had indicated similar proportional reductions of 25% in the rate of MVEs with allocation to 40 mg simvastatin daily in different categories of participant.4,6 Across the different subgroups studied, similar proportional reductions of 22% in UK hospitalization costs associated with vascular events, and similar absolute differences in the costs of statin treatment, were also observed between the study treatment groups.4 Consequently, it was hypothesized that the proportional reductions in US hospitalization costs associated with vascular events, and the absolute differences in US costs of statin treatment between the study treatment groups, would also be similar across different subcategories of participant. Hence, the absolute reduction in the US costs of vascular event hospitalizations in any particular subgroup was derived by applying the overall proportional reduction in vascular event costs observed among all participants to the vascular event costs observed in the placebo group for that particular subgroup. Absolute reductions in vascular deaths within subgroups were estimated similarly.
Lifetime Cost-Effectiveness
Details have already been reported on the Markov vascular disease state transition model that was developed and validated using individual participant data from the 20 536 participants in HPS.5 In brief, baseline risk factors, allocation to statin or placebo, and within-study experience of vascular events were used to predict annual risks of 3 main types of events: (1) vascular death, defined as coronary death, fatal stroke, or other vascular death; (2) nonfatal MVE, defined as nonfatal myocardial infarction, nonfatal stroke, or arterial revascularization; and (3) other vascular event, defined as admission for angina, heart failure, or other cardiac or vascular problem. Statin therapy was estimated to affect vascular event risk as a consequence of the change it produced in LDL cholesterol. During the course of HPS, a proportion of participants allocated to simvastatin stopped taking statin therapy (18% by the end of the study), and a proportion of those allocated to placebo started taking nonstudy statin (32% by the end of the study).6 Thus, the observed LDL cholesterol difference between the 2 arms was gradually reduced during the trial compared with the difference achieved by full compliance. The treatment allocation variables in the annual vascular event risk models allowed for this noncompliance to estimate the effect of actually taking statin therapy. Separate treatment effects were evaluated for the 3 categories of vascular event, but these effects were the same for first and subsequent events in the same category. Annual rates of vascular events predicted from the model were internally validated against those observed during the 5-year scheduled treatment period of HPS.5 Mortality rates for nonvascular causes were estimated from official life-table data for the United States after removal of vascular deaths.16 A two-part regression model17 that included age, gender, disease history, and other individual baseline characteristics was used to evaluate annual hospitalization costs associated with the predicted vascular events in the Markov model.
The Markov model was used to predict the annual occurrence of vascular or nonvascular death, nonfatal MVEs and other vascular events, and the annual hospitalization costs with and without lifetime use of 40 mg simvastatin daily, and to evaluate the gains in life expectancy and lifetime cost-effectiveness of 40 mg simvastatin daily versus no statin treatment among people at different ages and underlying levels of vascular disease risk. Parameter uncertainty in the estimates of life years gained, hospitalization cost savings, and cost per life year gained was assessed by nonparametric bootstrapping of the event and cost equations used in the model.18 Future benefits (ie, vascular deaths avoided and life years gained) and costs were discounted at the recommended annual rate of 3%.19 The effects of changing selected analytic parameters on the cost-effectiveness estimates were assessed. First, the predicted life expectancy was adjusted for age- and gender-specific health-related quality of life derived from a representative sample of the US population in the Agency for Healthcare Research and Quality’s Medical Expenditure Panel Survey.20,21 Second, an assessment was carried out for the impact on cost-effectiveness estimates of persistent use of statin therapy declining to 35% by the sixth year after initiation (ie, persistence during each of the first 5 years of 80%, 70%, 60%, 50%, 40%, and 35% thereafter). Finally, the cost-effectiveness of lifetime use of generic 40 mg simvastatin at $0.20 per day was assessed. Further extrapolation was made (as in the UK setting5) to 5 years beyond the eligible age limits for HPS (ie, down to 35 years and up to 85 years) and to vascular risk down to a 5-year MVE risk of 5% (compared with the 12% risk in the lowest quintile of HPS). The analyses were performed using SAS, Stata, and Excel computer software programs.
The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
Within-Study Analysis
Random allocation to simvastatin in HPS produced a very highly significant 25% (95% CI, 20 to 29; P<0.0001) proportional reduction in the rate of MVE, with similar reductions of about one quarter observed in a variety of different subgroups,4 including quintiles of vascular disease risk (Figure 1A). There was also a highly significant 20% (CI, 15 to 24; P<0.0001) proportional reduction in the estimated US costs of hospitalizations for vascular events, with similar effects observed across the risk subgroups studied (Figure 1B).
|
The numbers of days per person on study or nonstudy statin treatment during the scheduled 5-year study period are reported in Table 1. At $1 per day for statin therapy, the overall difference in the discounted cost of statin use between the treatment groups was $1297 (SE 7) per person, with the absolute difference in statin costs in any of the risk subgroups not materially different from this overall estimate (Table 1). At 2006 average US wholesale statin prices (ie, $5.25 daily for 40 mg proprietary simvastatin), the difference in the discounted cost of statin use between the treatment groups would be increased to $7026 (SE 34) per person.
|
As simvastatin allocation was associated with similar proportional reductions in vascular events among people in the different subgroups studied, more vascular events and their associated costs were avoided in higher-risk groups, which offset more of the costs of statin therapy and yielded lower net costs of treatment in those at a higher risk (Table 2). The discounted incremental cost of simvastatin allocation ranged from a savings of $38 (SE 192) in the highest risk quintile to added costs of $859 (SE 71) in the lowest risk quintile. Similarly, although the overall cost of avoiding a vascular death was estimated to be $29 000 (95% CI, 10 700 to 67 800), this result masks substantial variation between the risk subgroups (Table 2). For example, among individuals with a 42% 5-year risk of MVEs, allocation to simvastatin was estimated to be cost saving, with an average net reduction in cost of $1300 (CI, $15 600 saving to $13 200 cost) per vascular death avoided. By contrast, among those with a 12% 5-year risk, the cost per vascular death avoided was estimated to be $216 500 (CI, $123 700 to $460 000 cost).
|
If the private insurer perspective of hospital costs is considered, then allocation to generic simvastatin appears to save money during the 5-year study treatment period in all but the lowest risk quintile subgroup (Table 3). The addition of nonhospital stroke-related Medicare costs did not materially change the main results (Table 3). The price of simvastatin has the largest impact on the findings: at the 2006 average US proprietary price of $5.25 daily, the cost of avoiding a vascular death with 40 mg simvastatin ranges between $191 600 and $1 660 900 in the highest and lowest risk quintiles (Table 3).
|
Lifetime Analysis
Assuming that the effect of statins on vascular events observed during HPS is maintained with continued treatment for the patient’s lifetime, the Markov model was used to project gains in life expectancy and the incremental cost of lifetime simvastatin therapy within quintiles of 5-year risk of MVE subdivided by age at initiation of treatment. The estimated discounted life years gained with 40 mg simvastatin daily ranged between 0.47 (CI, 0.26 to 0.68) years for people aged 70 years or older with a 12% 5-year MVE rate to 1.33 (CI, 0.76 to 1.89) years for those aged 40 to 49 years with a 42% 5-year MVE rate (Table 4; which also gives the age-related values for 10-year risk of MCE in these MVE risk groups). Although continued use of 40 mg generic simvastatin increased lifetime costs, the cost per life year gained was below $11 000 for each of the risk and age categories included in HPS. Indeed, the upper limits of the 95% CIs for all risk and age groups were below $15 000 per life year gained (Table 4).
|
Although HPS did not collect quality-of-life information, adjustments were made for age- and gender-specific health-related quality of life using data from a representative sample of the US population. The quality-adjusted estimates for lifetime use of 40 mg generic simvastatin daily (Table 5) did not differ materially from the unadjusted estimates. If the usual daily price of generic 40 mg simvastatin falls to $0.20, the additional cost per quality-adjusted life year is estimated to be under $5500 for people at a 5-year MVE risk of 12% (ie, lowest risk quintile in the HPS) or higher (Table 5). The estimated costs per life year gained if long-term persistence with 40 mg generic simvastatin daily declined to 35% after 5 years were also similar to those for continued lifetime treatment, with both costs and benefits proportionally reduced (Table 5). Again, however, the use of 40 mg proprietary simvastatin at $5.25 per day had a large impact, with estimates ranging from $19 100 to $52 300 per life year gained across the risk and age groups studied (Table 5). When the private insurer perspective of hospital costs was considered, the cost-effectiveness of lifetime use of 40 mg generic simvastatin daily remained similar, because the larger reductions in vascular hospitalization costs were offset by larger nonvascular hospitalization costs associated with the increased life expectancy produced by statin therapy (data not shown).
|
Further extrapolation indicates that lifetime use of generic 40 mg simvastatin daily is cost-effective for people below and above the age range represented in HPS, with levels of 5-year MVE risk down at least to 5% (see Italic figures of Table 6). The estimated costs per quality-adjusted life year gained ranged between
$20 200 and $18 700 for individuals at a 5-year MVE risk of 5% who were aged between 35 and 85 years at initiation. At a daily generic 40 mg simvastatin cost of $0.20, the additional cost per quality-adjusted life year for people at 1% MVE risk per annum is predicted to be under $4000 (data not shown).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
In common with other large statin trials, HPS has shown that statin therapy produces similar proportional reductions in vascular risk per mmol/L reduction in LDL cholesterol among a wide range of patients (including those at different levels of vascular risk and at different presenting levels of LDL cholesterol).1,6 The individual participant data from this large study involving 20 536 patients followed for an average of 5 years was used together with the US costs of hospitalizations to assess the cost-effectiveness of using statins in the United States for people at different cardiovascular disease risk and age of initiation of statin therapy. These analyses indicate that at generic prices of $1 per day, the initiation of lifetime 40 mg simvastatin daily in the United States (as in United Kingdom4,5) is very cost-effective for people aged between 40 and 80 years, who have 5-year risks of MVEs as low as 12% (corresponding to 10-year risks of MCE—which are the basis of Framingham risk score used to guide treatment2—of
10%). Indeed, even at a substantially higher proprietary price of $5.25 per day, 40 mg simvastatin daily still appears to be cost-effective in the United States for patients at such levels of risk, albeit with higher costs per life year gained. The within-trial analysis indicates that, from the perspective of a US private health insurer, the use of generic 40 mg simvastatin daily even for only 5 years will result in healthcare savings in 4 of the 5 risk groups studied because of the higher costs of the vascular event hospitalizations avoided. The intervention will also save costs within 5 years across the risk groups studied in the HPS if the usual daily price of generic simvastatin falls significantly, independently of the perspective of the analysis.
A recent study has indicated that, for most individuals who currently receive statin therapy in the United States, simvastatin is a viable treatment alternative for achieving the LDL cholesterol level goal currently recommended by the US Adult Treatment Panel III.22 The results reported here show that initiating generic simvastatin treatment in accordance with those recommendations is very cost-effective. Indeed, extrapolation beyond the age and risk levels studied in HPS indicates that generic simvastatin is likely to be very cost-effective in the United States for individuals with annual MVE risks down to 1%, which corresponds to 10-year risks of MCE of only 4% (Table 6). These results differ from a recent estimate of $270 000 per quality-adjusted year of life with the use of higher-priced branded statins to achieve LDL cholesterol levels of 160 mg/dL among people in the US population at a low-risk of coronary artery disease.23 By contrast, our results indicate that generic simvastatin is cost-effective for a much wider population than that currently recommended for routine statin treatment. The absolute risks of vascular events among the participants in HPS may differ from those of similar people in the US, but the estimates of cost-effectiveness reported for different levels of risk are likely to generalize to a wide range of settings using (as in the present analyses) appropriate local data to estimate the risks for particular individuals.
There are a number of possible limitations to these analyses. First, treatment patterns in the United States differ from those in the United Kingdom. For example, the rates of coronary artery bypass grafting and percutaneous coronary interventional procedures tend to be substantially higher in the United States.24–26 Although the impact on health outcomes is difficult to predict, these higher rates would have resulted in further savings in costs of hospitalizations with statin therapy. Second, costs for concomitant medications, primary care, and other outpatient care were not included in the analysis. No significant effects of simvastatin allocation on concomitant medication were observed in HPS, whereas no data on primary care and outpatient resource use were collected. Although the observed reduction in vascular events would have also been expected to have an impact on outpatient resource use, the related costs are likely to be small in comparison with the hospitalization costs.27 Third, HPS did not collect data on the quality of life of participants. Regular safety monitoring did show, however, that 40 mg simvastatin daily was not associated with significantly more reports of muscle (or other) symptoms, and the estimated excess risk of myopathy was only 1 per 10 000 patients per year of treatment.4 Although patients and doctors need to be aware that serious muscle problems can occur rarely,28 this does not materially affect the cost-effectiveness of routine statin use. Consequently, we have presented analyses adjusted only for age- and gender-specific health-related quality of life. No quality-of-life adjustment for cardiovascular events was carried out, but that would probably further improve the estimates of cost-effectiveness of statins. Fourth, interventions that produce larger reductions in LDL cholesterol are likely to produce larger reductions in vascular disease risk than those achieved with 40 mg simvastatin daily in HPS,29 but may well be more expensive (particularly when patents persist), and their cost-effectiveness requires further study. Finally, the base-case analysis was based on a generic price for simvastatin 40 mg of $1 per day, which is currently available in the United States. It is not yet known where the generic price will settle and, clearly, further reductions in the price of simvastatin would further improve its cost-effectiveness.
In conclusion, the use of 40 mg simvastatin daily in the United States appears to be very cost-effective for individuals (independent of their age) with annual risks of major coronary and other vascular events well below the levels currently required by national guidelines. As a consequence, existing guidelines should be modified to extend statin treatment to a much wider population.
|
Appendix |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
Writing Committee
Borislave Mihaylova, DPhil
Andrew Briggs, DPhil
Mark Hlatky, MD, FACC, FAHA
Jane Armitage, FFPH, FRCP
Sarah Parish, DPhil
Alastair Gray, PhD
Rory Collins, FMed Sci, FRCP, MSc
|
Acknowledgments |
|---|
The most important acknowledgement is to the participants in the study, to the doctors, nurses, and administrative staff in hospitals and general practices throughout the United Kingdom who assisted with its conduct.
Sources of Funding
The study was funded by the UK Medical Research Council, British Heart Foundation, Merck & Co (manufacturers of simvastatin), and Roche Vitamins Ltd (manufacturers of the vitamins).
Disclosures
The Clinical Trial Service Unit, University of Oxford (writing committee members: J. Armitage, S. Parish, R. Collins) has a staff policy of not accepting honoraria or other payments from the pharmaceutical industry, except for the reimbursement of costs to participate in scientific meetings. Staff in the Health Economics Research Centre, University of Oxford, Oxford, UK (writing committee members: B. Mihaylova, A. Gray) and Section of Public Health and Economic Evaluation, University of Glasgow, Glasgow, UK (writing committee member: A. Briggs) occasionally act as paid consultants to the pharmaceutical industry. M. Hlatky (Department of Health Research and Policy and Department of Medicine, Stanford University, Stanford, Calif.) has no disclosures to make. The Clinical Trial Service Unit and the Health Economics Research Centre have received research funding through the University of Oxford from Merck & Co.
The investigators were responsible for the study design, data collection, data analysis, data interpretation, and submission of the manuscript for publication, independently of all funding sources. Local ethics committee approval was obtained for each of the 69 UK hospitals participating in the trial.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendixReferences |
|---|
1. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet. 2005; 366: 1267–1278.[CrossRef][Medline]
2. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001; 285: 2486–2497.
3. Grundy SM, Cleeman JI, Merz CNB, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ, National Heart, Lung, and Blood Institute, American College of Cardiology Foundation, American Heart Association. Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004; 110: 227–239.
4. Heart Protection Study Collaborative Group. Cost-effectiveness of simvastatin in people at different levels of vascular disease risk: economic analysis of a randomised trial in 20 536 individuals. Lancet. 2005; 365: 1779–1785.[CrossRef][Medline]
5. Heart Protection Study Collaborative Group. Lifetime cost effectiveness of simvastatin in a range of risk groups and age groups derived from a randomised trial of 20,536 people. BMJ. 2006; 333: 1145–1148.
6. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360: 7–22.[CrossRef][Medline]
7. NHS Centre for Coding and Classification. Read codes and the terms projects: a brief guide. London: Department of Health; 1993.
8. Centers for Medicare & Medicaid Services. Medicare Fee for Service for Parts A & B. 2006. Available at http://www.cms.hhs.gov/MedicareFeeforSvcPartsAB/03_MEDPAR.asp#TopOfPage. Accessed on October 18, 2006.
9. Medicare Program: Revision to Payment Policies Under the Physician Fee Schedule for Calendar Year 2004. Federal Register 268. 2003.
10. MEDSTAT. DRG Guide: Descriptions and Normative Values. 2001. Ann Arbor, MI: The MEDSTAT Group, Inc.
11. Drugstore.com. 2008. Available at http://www.drugstore.com/. Accessed on April 3, 2008.
12. Red Book: Pharmacy’s Fundamental Reference, 110th ed. Montvale, NJ: Thomson Healthcare/Thomson PDR.
13. Hodgson TA, Cohen AJ. Medical expenditures for major diseases, 1995. Health Care Financ Rev. 1999; 21: 119–164.[Medline]
14. Lee WC, Christensen MC, Joshi AV, Pashos CL. Long-term cost of stroke subtypes among Medicare beneficiaries. Cerebrovasc Dis. 2007; 23: 57–65.[Medline]
15. Bureau of Labor Statistics. Consumer Price Index. 2007. Available at http://www.bls.gov/cpi/home.htm. U.S. Department of Labor. Accessed on May 9, 2007.
16. Compressed Mortality File (CMF) on CDC WONDER On-line Database 1999–2003. 2006. United States Department of Health and Human Services (US DHHS), Centers for Disease Control and Prevention (CDC), National Center for Health Statistics (NCHS), Office of Analysis and Epidemiology (OAE).
17. Mullahy J. Much ado about two: reconsidering retransformation and the two-part model in health econometrics. J Health Econ. 1998; 17: 247–281.[CrossRef][Medline]
18. Efron B, Tibshirani R. An introduction to the bootstrap. New York: Chapman & Hall; 1993.
19. Weinstein MC, Siegel JE, Gold MR, Kamlet MS, Russell LB. Recommendations of the Panel on Cost-effectiveness in Health and Medicine. JAMA. 1996; 276: 1253–1258.
20. Agency for Healthcare Research and Quality (AHRQ). The Medical Expenditure Panel Survey. 2007. Available at http://www.meps.ahrq.gov/mepsweb/. Agency for Healthcare Research and Quality (AHRQ). Accessed on October 10, 2006.
21. Shaw JW, Johnson JA, Coons SJ. US valuation of the EQ-5D health states: development and testing of the D1 valuation model. Medical Care. 2005; 43: 203–220.[CrossRef][Medline]
22. Willey V, Sweet B, Fang C, Cziraky M. Therapeutic substitution of statins: a real world data driven approach based on NCEP ATPIII low density lipoprotein cholesterol (LDL-C) goals. Pharmacoepidemiology Drug Safety. 2007; 16: S42.[CrossRef][Medline]
23. Kahn R, Robertson RM, Smith R, Eddy D. The impact of prevention on reducing the burden of cardiovascular disease. Circulation. 2008; 118: 576–585.
24. US National Hospital Discharge Survey. 2006. Available at http://www.cdc.gov/nchs/about/major/hdasd/nhds.htm.
25. Society of Cardiothoracic Surgeons of Great Britain and Ireland. UK Cardiac Surgical register. 2006. Available at http://www.scts.org. Accessed on May 20, 2007.
26. British Cardiovascular Intervention Society. PCI Database. 2005. Available at http://www.bcis.org.uk. Accessed on May 20, 2007.
27. UK Prospective Diabetes Study Group. Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40. BMJ. 1998; 317: 720–726.
28. Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003; 289: 1681–1690.
29. Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol. 2006; 48: 438–445.
|
Footnotes |
|---|
The online Data Supplement is available at http://circoutcomes.ahajournals.org/cgi/content/full/OUTCOMES.108.808469/DC1.
Related Article
Circ Cardiovasc Qual Outcomes 2009 2: 65-72.
This article has been cited by other articles:
 |
|
 |
|
  M. A. Hlatky and P. Heidenreich The year in epidemiology, health services research, and outcomes research. J. Am. Coll. Cardiol., December 15, 2009; 54(25): 2343 - 2351. [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Krumholz Questioning Conventional Wisdom Circ Cardiovasc Qual Outcomes, March 1, 2009; 2(2): 59 - 60. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||