The effect of risk factor reductions between 1981 and 1990 on coronary heart disease incidence, prevalence, mortality and cost.

OBJECTIVES: We sought to estimate the impact and cost-effectiveness of risk factor reductions between 1981 and 1990. BACKGROUND: Coronary heart disease (CHD) mortality rates have declined dramatically, partly as a result of reductions in CHD risk factors. METHODS: We used the CHD Policy Model, a validated computer-simulation model, to estimate the effects of actual investments made to change coronary risk factors between 1981 and 1990, as well as the impact of these changes on the incidence, prevalence, mortality and costs of CHD during this period and projected to 2015. RESULTS: Observed changes in risk factors between 1981 and 1990 resulted in a reduction of CHD deaths by approximately 430,000 and overall deaths by approximately 740,000, with an estimated cost-effectiveness of about $44,000 per year of life saved during this period, based on the estimated actual costs of the interventions used. However, because much of the benefit of risk factor reductions is delayed, the estimated reductions for the 35-year period of 1981 to 2015 were 3.6 million CHD deaths and 1.2 million non-CHD deaths, at a cost of only about $5,400 per year of life saved. CONCLUSIONS: Aggregate efforts to reduce risk factors between 1981 and 1990 have led to substantial reductions in CHD and should be well worth the cost, largely because of population-wide changes in life-style and habits. Some interventions are much better investments than others, and attention to such issues could lead to better use of resources and better outcomes in the future.

Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease: effect of grain fortification and beyond.

CONTEXT: A high homocysteine level has been identified as an independent modifiable risk factor for coronary heart disease (CHD) events and death. Since January 1998, the US Food and Drug Administration has required that all enriched grain products contain 140 microg of folic acid per 100 g, a level considered to decrease homocysteine levels. OBJECTIVES: To examine the potential effect of grain fortification with folic acid on CHD events and to estimate the cost-effectiveness of additional vitamin supplementation (folic acid and cyanocobalamin) for CHD prevention. DESIGN AND SETTING: Cost-effectiveness analysis using the Coronary Heart Disease Policy Model, a validated, state-transition model of CHD events in adults aged 35 through 84 years. Data from the third National Health and Nutrition Examination Survey (NHANES III) were used to estimate age- and sex-specific differences in homocysteine levels. INTERVENTION: Hypothetical comparison between a diet that includes enriched grain products projected to increase folic acid intake by 100 microg/d with the same diet without folic acid fortification; and a comparison between vitamin therapy that consists of 1 mg of folic acid and 0.5 mg of cyanocobalamin and the diet that includes grains fortified with folic acid. MAIN OUTCOME MEASURES: Incidence of myocardial infarction and death from CHD, quality-adjusted life-years (QALYs) saved, and medical costs. RESULTS: Grain fortification with folic acid was predicted to decrease CHD events by 8% in women and 13% in men, with comparable reductions in CHD mortality. The model projected that, compared with grain fortification alone, treating all patients with known CHD with folic acid and cyanocobalamin over a 10-year period would result in 310 000 fewer deaths and lower costs. Over the same 10-year period, providing vitamin supplementation in addition to grain fortification to all men aged 45 years or older without known CHD was projected to save more than 300 000 QALYs, to save more than US $2 billion, and to be the preferred strategy. For women without CHD, the preferred vitamin supplementation strategy would be to treat all women older than 55 years, a strategy projected to save more than 140 000 QALYs over 10 years. CONCLUSIONS: Folic acid and cyanocobalamin supplementation may be cost-effective among many population subgroups and could have a major epidemiologic benefit for primary and secondary prevention of CHD if ongoing clinical trials confirm that homocysteine-lowering therapy decreases CHD event rates.

Health and economic benefits of increased beta-blocker use following myocardial infarction.

CONTEXT: beta-blockers are underused in patients who have myocardial infarction (MI), despite the proven efficacy of these agents. New evidence indicates that beta-blockers can have benefit in patients with conditions that have been considered relative contraindications. Understanding the consequences of underuse of beta-blockers is important because of the implications for current policy debates over quality-of-care measures and Medicare prescription drug coverage. OBJECTIVE: To examine the potential health and economic impact of increased use of beta-blockers in patients who have had MI. DESIGN AND SETTING: We used the Coronary Heart Disease (CHD) Policy Model, a computer-simulation Markov model of CHD in the US population, to estimate the epidemiological impact and cost-effectiveness of increased beta-blocker use from current to target levels among survivors of MI aged 35 to 84 years. Simulations included 1 cohort of MI survivors in 2000 followed up for 20 years and 20 successive annual cohorts of all first-MI survivors in 2000-2020. Mortality and morbidity from CHD were derived from published meta-analyses and recent studies. This analysis used a societal perspective. MAIN OUTCOME MEASURES: Prevented MIs, CHD mortality, life-years gained, and cost per quality-adjusted life-year (QALY) gained in 2000-2020. RESULTS: Initiating beta-blocker use for all MI survivors except those with absolute contraindications in 2000 and continuing treatment for 20 years would result in 4300 fewer CHD deaths, 3500 MIs prevented, and 45,000 life-years gained compared with current use. The incremental cost per QALY gained would be $4500. If this increase in beta-blocker use were implemented in all first-MI survivors annually over 20 years, beta-blockers would save $18 million and result in 72,000 fewer CHD deaths, 62,000 MIs prevented, and 447,000 life-years gained. Sensitivity analyses demonstrated that the cost-effectiveness of beta-blocker therapy would always be less than $11,000 per QALY gained, even under unfavorable assumptions, and may even be cost saving. Restricting beta-blockers only to ideal patients (those without absolute or relative contraindications) would reduce the epidemiological impact of beta-blocker therapy by about 60%. CONCLUSIONS: Our simulation indicates that increased use of beta-blockers after MI would lead to impressive gains in health and would be potentially cost saving. JAMA. 2000;284:2748-2754.

Cost-effectiveness of cholesterol-lowering therapies according to selected patient characteristics.

BACKGROUND: The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II) recommends treatment guidelines based on cholesterol level and number of risk factors. OBJECTIVE: To evaluate how the cost-effectiveness ratios of cholesterol-lowering therapies vary according to different risk factors. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Published data. TARGET POPULATION: Women and men 35 to 84 years of age with low-density lipoprotein cholesterol levels of 4.1 mmol/L or greater (> or =160 mg/dL), divided into 240 risk subgroups according to age, sex, and the presence or absence of four coronary heart disease risk factors (smoking status, blood pressure, low-density lipoprotein cholesterol level, and high-density lipoprotein cholesterol level). TIME HORIZON: 30 years. PERSPECTIVE: Societal. INTERVENTIONS: Step I diet, statin therapy, and no preventive treatment for primary and secondary prevention. OUTCOME MEASURES: Incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: Incremental cost-effectiveness ratios for primary prevention with step I diet ranged from $1900 per quality-adjusted life-year (QALY) gained to $500000 per QALY depending on risk subgroup characteristics. Primary prevention with a statin compared with diet therapy was $54000 per QALY to $1400000 per QALY. Secondary prevention with a statin cost less than $50000 per QALY for all risk subgroups. RESULTS OF SENSITIVITY ANALYSIS: The inclusion of niacin as a primary prevention option resulted in much less favorable incremental cost-effectiveness ratios for primary prevention with a statin (>$500000 per QALY). CONCLUSIONS: Cost-effectiveness of treatment strategies varies significantly when adjusted for age, sex, and the presence or absence of additional risk factors. Primary prevention with a step I diet seems to be cost-effective for most risk subgroups but may not be cost-effective for otherwise healthy young women. Primary prevention with a statin may not be cost-effective for younger men and women with few risk factors, given the option of secondary prevention and of primary prevention in older age ranges. Secondary prevention with a statin seems to be cost-effective for all risk subgroups and is cost-saving in some high-risk subgroups.

The relative influence of secondary versus primary prevention using the National Cholesterol Education Program Adult Treatment Panel II guidelines.

OBJECTIVES: This study was undertaken to project the population-wide effect of full implementation of the Adult Treatment Panel (ATP) II guidelines of the National Cholesterol Education Program (NCEP). BACKGROUND: The ATP II has proposed guidelines for cholesterol reduction, but the long-term epidemiologic influence of its components has not been fully examined. METHODS: We used a calibrated, validated simulation of the U.S. population, aged 35 to 84 years to estimate the potential for the NCEP guidelines, under varying assumptions, to reduce coronary heart disease morbidity and mortality and overall mortality from the years 2000 to 2020. RESULTS: Primary prevention would yield only about half of the benefits of secondary prevention despite requiring nearly twice as many person-years of treatment. The projected increase in quality-adjusted years of life per year of treatment for secondary prevention was 3- to 12-fold higher than for primary prevention. To yield population-wide epidemiologic benefits equivalent to NCEP recommendations for secondary prevention, primary prevention would require a nearly sixfold increase in the number of persons treated compared with NCEP recommendations. All benefits of universal success of the NCEP primary prevention "screen and treat" guidelines could be achieved by a 11 mg/dl (8%) population-wide reduction in low-density lipoprotein cholesterol levels among persons without preexisting coronary heart disease. CONCLUSIONS: The NCEP guidelines for targeted primary prevention can be a useful component of a rational public health strategy, but only as a complement to the more appealing strategies of secondary prevention and "across-the-board" programs to lower all cholesterol levels.

Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer's disease.

OBJECTIVE: To demonstrate the use of cost-effectiveness analysis to assess the economic impact of donepezil in the treatment of mild or moderate AD. BACKGROUND: Cost-effectiveness analyses show the relationship between resources used (costs) and health benefits achieved (effects) for an intervention compared with an alternative strategy. METHODS: We developed a model to estimate the incremental cost-effectiveness of donepezil compared with no treatment. We determined costs per quality-adjusted life-years gained, a measurement that enhances the comparability of diverse studies. The model projects the progression of AD patients into more severe disease stages and into nursing homes. Data from a randomized clinical trial of donepezil were used to assess the drug's impact on the 6-week probabilities of progression. Data on the costs and health-related quality of life associated with different disease stages and settings were taken from published estimates and our companion cross-sectional study, respectively. RESULTS: Donepezil costs are partially offset by a reduction in the costs of care due to enhancement in cognitive functioning and the delay to more costly disease stages and settings. The magnitude of this cost offset and of the effect of donepezil on health-related quality of life depends on the model's assumptions about the duration of the drug effect, where controlled data are lacking. If the drug effect exceeds 2 years, the model predicts that for mild AD the drug would pay for itself in terms of cost offsets. CONCLUSIONS: The results of the cost-effectiveness model presented here suggest that donepezil may be cost-effective but additional controlled data on long-term drug efficacy are needed.

The recent decline in mortality from coronary heart disease, 1980-1990. The effect of secular trends in risk factors and treatment.

OBJECTIVE: To examine whether secular trends in risk factor levels and improvements in treatment can account for the observed decline in coronary heart disease mortality in the United States from 1980 to 1990 and to analyze the proportional contribution of these changes. DATA SOURCES: Literature review, US statistics, health surveys, and ongoing clinical trials. STUDY SELECTION: Data representative of the US situation nationwide reported in adequate detail. DATA EXTRACTION: A computer-simulation state-transition model of the US population between the ages of 35 and 84 years was developed to forecast coronary mortality. The input variables were estimated such that the combination of values led to an adequate agreement with reported coronary mortality figures. Subsequently, secular trends were modeled. DATA SYNTHESIS: Actual coronary mortality in 1990 was 34% (127,000 deaths) lower than would be predicted if risk factor levels, case-fatality rates, and event rates in those with and without coronary disease remained the same as in 1980. When secular changes in these factors were included in the model, predicted coronary mortality in 1990 was within 3% (10,000 deaths) of the observed mortality and explained 92% of the decline; only 25% of the decline was explained by primary prevention, while 29% was explained by secondary reduction in risk factors in patients with coronary disease and 43% by other improvements in treatment in patients with coronary disease. CONCLUSIONS: These results suggest that primary and secondary risk factor reductions explain about 50% of the striking decline in coronary mortality in the United States between 1980 and 1990 but that more than 70% of the overall decline in mortality has occurred among patients with coronary disease.

Cost-effectiveness of populationwide educational approaches to reduce serum cholesterol levels.

BACKGROUND: The aim of the present study was to estimate the cost-effectiveness of populationwide approaches to reduce serum cholesterol levels in the US adult population. METHODS AND RESULTS: This cost-effectiveness analysis was made from data from the literature and the Coronary Heart Disease Policy Model and was based on the US population age 35 to 84 years. Study interventions were populationwide programs to reduce serum cholesterol levels with costs and cholesterol-lowering effects similar to those reported from the Stanford Three-Community Study, the Stanford Five-City Project, and in North Karelia, Finland. The main outcome measures were cost-effectiveness ratios, defined as the change in projected cost divided by the change in projected life-years when the population receives the intervention compared with the population without the intervention. A populationwide program with the costs ($4.95 per person per year) and cholesterol-lowering effects (an average 2% reduction in serum cholesterol levels) of the Stanford Five-City Project would prolong life at an estimated cost of only $3200 per year of life saved. Under a wide variety of assumptions, a populationwide program would achieve health benefits at a cost equivalent to that of many currently accepted medical interventions. Such programs would also lengthen life and save resources under many scenarios, especially if the program affected persons with preexisting heart disease or altered other coronary risk factors. CONCLUSIONS: Populationwide programs should be part of any national health strategy to reduce coronary heart disease.

Cost-effectiveness considerations in the treatment of heterozygous familial hypercholesterolemia with medications.

When used for the primary prevention of coronary heart disease in persons with heterozygous familial hypercholesterolemia (hFH), a hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor is projected to be effective and to have very favorable cost-effectiveness ratios at low-to-medium doses. For example, 20 mg of lovastatin per day is estimated to save lives and save money in all men ages 35-44 years with hFH and in women ages 35-44 years with hFH and any other risk factor. The estimated incremental cost effectiveness of 40 mg compared with 20 mg of lovastatin for individuals with hFH ages 35-44 years was less than $45,000 per year of life saved in men with > or = 1 other risk factors and women with > or = 2 other risk factors. The estimated incremental cost-effectiveness ratio of 80 mg compared with 40 mg/day was substantially higher ($100,000 or more per year of life saved) even in the highest risk persons. The estimated cost-effectiveness ratios for primary prevention in hFH were reasonably similar to the favorable ratios for secondary prevention in the general population but substantially better than the estimated ratios for primary prevention in other adults with high cholesterol levels. Any national recommendations regarding the use of medications for individuals with hFH must include cost considerations. Our analyses support the use of low-to-moderate doses of high-cost medications for primary prevention in these patients.

Uncovering psychiatric test information with graphical techniques of Exploratory Data Analysis.

This article illustrates how Exploratory Data Analysis (EDA) can complement conventional statistical methods in evaluating psychiatric tests. Using one recent EDA computer program, we evaluated the ability of repeated psychiatric screening tests (the General Health Questionnaire [GHQ]) to predict medical and psychiatric service use in a Health Maintenance Organization (HMO), the Harvard Community Health Plan (HCHP). Using a stratified random sample of 244 new HCHP enrollees and viewing three-dimensional graphs of their data from multiple perspectives, we found two subpopulations: low GHQ scorers, for whom the tests did not predict service use; and high scorers, for whom they did. Surprisingly, improving scores forecast increased use and chronically high scores predicted diminished use. Using another stratified random sample of 213 new HCHP enrollees, and with scatterplot matrices from another interactive computer program, we found that high and unchanging GHQ scores forecast HMO dropout. We examine possible interpretations--for example, that chronically distressed patients may become immobilized, diminish service use, and ultimately leave the HMO. We also explain how EDA methods may help uncover elusive results in other data (e.g., mental health outcomes).

Cost-effectiveness of HMG-CoA reductase inhibition for primary and secondary prevention of coronary heart disease.

To determine the cost-effectiveness of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (such as lovastatin) for the primary and secondary prevention of coronary heart disease, we used the Coronary Heart Disease Policy Model, a computer-stimulated model that estimates the risk factor-specific annual incidence of coronary heart disease and the risk of recurrent coronary events in persons with prevalent coronary heart disease. When used for secondary prevention, 20 mg/d of lovastatin was estimated to save lives and save costs in younger men with cholesterol levels above 250 mg/dL (6.47 mmol/L) and to have a favorable cost-effectiveness ratio regardless of the cholesterol level except in young women with cholesterol levels below 250 mg/dL (6.47 mmol/L). Doses of 40 mg/d of lovastatin had favorable incremental cost-effectiveness ratios in men with cholesterol levels above 250 mg/dL (6.47 mmol/L). By comparison, primary prevention had favorable cost-effectiveness ratios only in selected subgroups based on cholesterol levels and other established risk factors. We conclude that current national recommendations regarding medication for secondary prevention are not as aggressive as our projections would suggest, while recommendations regarding the use of medications for primary prevention should consider the cost of medication as well as the risk factor profile of the individual patient.

Performance of a five-item mental health screening test.

We compared the screening accuracy of a short, five-item version of the Mental Health Inventory (MHI-5) with that of the 18-item MHI, the 30-item version of the General Health Questionnaire (GHQ-30), and a 28-item Somatic Symptom Inventory (SSI-28). Subjects were newly enrolled members of a health maintenance organization (HMO), and the criterion diagnoses were those found through use of the Diagnostic Interview Schedule (DIS) in a stratified sample of respondents to an initial, mailed GHQ. To compare questionnaires, we used receiver operating characteristic analysis, comparing areas under curves through the method of Hanley and McNeil. The MHI-5 was as good as the MHI-18 and the GHQ-30, and better than the SSI-28, for detecting most significant DIS disorders, including major depression, affective disorders generally, and anxiety disorders. Areas under curve for the MHI-5 ranged from 0.739 (for anxiety disorders) to 0.892 (for major depression). Single items from the MHI also performed well. In this population, short screening questionnaires, and even single items, may detect the majority of people with DIS disorders while incurring acceptably low false-positive rates. Perhaps such extremely short questionnaires could more commonly reach use in actual practice than the longer versions have so far, permitting earlier assessment and more appropriate treatment of psychiatrically troubled patients in primary care settings.

A comparison of three psychiatric screening tests using receiver operating characteristic (ROC) analysis.

Self-administered screening questionnaires are available to assist primary care physicians in detecting undiagnosed depression and anxiety disorders. This study used receiver operating characteristic (ROC) analysis to evaluate three such tests: the General Health Questionnaire (GHQ), the Mental Health Inventory (MHI), and the Somatic Symptom Inventory (SSI). Stratified by the results of a preliminary GHQ, 364 health maintenance organization (HMO) members were given these tests and a Diagnostic Interview Schedule (DIS), the latter used as a "truth" standard for current psychiatric diagnosis. The MHI performed significantly better than the GHQ in detecting mental disorders generally and anxiety disorders in particular, and somewhat better in detecting affective disorders. The SSI performed best in detecting anxiety disorders and was significantly better than the GHQ. When subjects who had participated in a previous study involving repeated GHQ administration were excluded, sensitivity of all tests improved, especially the GHQ. We conclude that the MHI can be a useful tool for screening primary care patients, and that the SSI has additional predictive value with respect to anxiety disorders.

Elevation of serum uric acid as a clue to alcohol abuse.

Hyperuricemia in unselected admissions to a general hospital was found to be a significant correlate of alcohol abuse in male subjects. Unexplained elevation of the serum uric acid level should always stimulate inquiry for the behavioral features of alcoholism.

A sex difference in the serum vitamin B-12 levels of hospitalized alcoholics.

The relationship of elevated serum vitamin B-12 concentration to alcoholism in general hospital patients was studied both in a retrospective and in a prospective group of patients. Alcoholism was the most common disease correlate of vitamin B-12 elevations in females. Of the unselected female alcoholics, 61% had a serum vitamin B-12 concentration larger than or equal to 1000 ng/liter at the time of admission; only 17% of the nonalcoholics, whatever their other disease, exhibited such high values. The sensitivity of high B-12 levels for alcoholism in females paralleled that of high SGOT, GGT and MCV values. In contrast, males (approximately 70% of our alcoholics) far less often exhibited B-12 elevations even when SGOT, GGT and MCV were abnormally high. Elevation of serum B-12 concentration should always raise the suspicion of alcohol abuse, especially in females.