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Background— The diagnostic utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure has been documented. However, most of the data were derived from countries with high healthcare resource use, and randomized evidence for utility of NT-proBNP was lacking. Methods and Results— We tested the hypothesis that NT-proBNP testing improves the management of patients presenting with dyspnea to emergency departments in Canada by prospectively comparing the clinical and economic impact of a randomized management strategy either guided by NT-proBNP results or without knowledge of NT-proBNP concentrations. Five hundred patients presenting with dyspnea to 7 emergency departments were studied. The median NT-proBNP level among the 230 subjects with a final diagnosis of heart failure was 3697 compared with 212 pg/mL in those without heart failure ( P P =0.031), the number of patients rehospitalized over 60 days by 35% (51 to 33; P =0.046), and direct medical costs of all ED visits, hospitalizations, and subsequent outpatient services (US $6129 to US $5180 per patient; P =0.023) over 60 days from enrollment. Adding NT-proBNP to clinical judgment enhanced the accuracy of a diagnosis; the area under the receiver-operating characteristic curve increased from 0.83 to 0.90 ( P Conclusions— In a universal health coverage system mandating judicious use of healthcare resources, inclusion of NT-proBNP testing improves the management of patients presenting to emergency departments with dyspnea through improved diagnosis, cost savings, and improvement in selected outcomes.

Background. Although exercise training improves cardiovascular disease (CVD) risk factors, few studies have evaluated its potential long-term cost-effectiveness. Methods. Using the Cardiovascular Disease Life Expectancy Model, a validated disease simulation model, we calculated the life expectancy of average 35- to 74-year-old Canadians found in the 1992 Canadian Heart Health Survey. The impacts of exercise training on cardiovascular risk factors were estimated as a 4% decrease in low-density lipoprotein (LDL) cholesterol, a 5% increase in high-density lipoprotein (HDL) cholesterol, and a 6 mm Hg decrease in both systolic and diastolic blood pressure. Exercise adherence was estimated at 50% for the first year and 30% for all additional years. Costs for a supervised exercise program determined from Canadian sources and converted to US dollars were estimated at $605 for the first year (medical evaluation, stress test, exercise prescription, and program costs) and $367 for all additional years (program costs). For an unsupervised program, the costs were estimated at $311 for the first year and $73 for all additional years. Results. The cost-effectiveness (CE) of an unsupervised exercise program (1996 U.S. dollars) was less than $12,000 per year of life saved (YOLS) for all individuals. The CE of a supervised exercise program was less than $15,000/YOLS for men with CVD, and between $12,000 and $43,000 for women with CVD and men without CVD. Conclusions. Given the relatively few risks, substantial long-term benefits, and modest costs, an unsupervised exercise training program represents good value for all. A more expensive supervised exercise program is also cost-effective for most individuals with CVD.

Recent studies suggest that the benefit of lipid-lowering treatment for the primary and secondary prevention of cardiovascular disease (CVD) extends to individuals with average cholesterol levels, to women and to the elderly. However, the proportion of the general population for which treatment is cost-effective has not been evaluated.Using data provided by the Canadian Heart Health Survey, the level of CVD risk was estimated for a random sample of the total population. A cost-effectiveness ratio for simvastatin was then calculated for each individual in the sample. Lastly, the proportion of the total population for which lipid-lowering therapy would be cost-effective for primary and secondary prevention of CVD was estimated according to total cholesterol (TC) levels.Among the surveyed individuals who were 30 to 74 years of age, 2212 had CVD and 12,982 did not. Among those with a TC level higher than 6.2 mmol/L, the proportions of individuals for which lipid-lowering therapy was cost-effective (at a level of less than 50,000 dollars per year of life saved) were 85.6% of men and 28.7% of women for primary prevention, and 99.8% of men and 86.1% of women for secondary prevention. The estimated cost of one year of lipid-lowering treatment for all individuals in the population with a TC level higher than 6.2 mmol/L and for all individuals regardless of TC levels for whom treatment would be cost-effective was $1 billion and 3.9 billion dollars, respectively.Lipid-lowering treatment for CVD prevention is cost-effective for a high proportion of the population, even for primary prevention. As a result, the cost of population-wide treatment for only one year is high even among individuals with a TC level higher than 6.2 mmol/L. Such costs should be considered in health care policy decisions.

To estimate the cost-effectiveness ratio of highly-active antiretroviral therapy (HAART) in Canada.A before-and-after analysis to calculate incremental cost of life year gained (LYG) between 1991 and 1995 (pre-HAART period) and between 1997 and 2001 (HAART period) for non-AIDS and AIDS groups (CDC stage of HIV infection).For two Quebec HIV hospital clinics, mean inpatient (IP) days, outpatient (OP) visits and direct health care costs per patient-year (PPY) were calculated. Cox's proportional hazards models calculated disease progression, stratified by study periods and adjusted for gender, age at cohort entry, sexual orientation, injecting drug use and baseline CD4 cell count.For non-AIDS patients, mean IP days was 1.6 (pre-HAART period) compared with 0.8 PPY (HAART period); mean OP visits increased from 2.8 to 5.5 PPY. Total cost was US$ 4265 (pre-HAART period) and US$ 9445 PPY (HAART period) of which 66 and 84%, respectively were spent on antiretroviral drugs. Median progression time was 6.3 years in the pre-HAART period compared with 12.5 years in HAART period (log rank chi = 270, P0.0001). Incremental cost per LYG between periods was US$ 14 587. For AIDS patients, mean IP days decreased from 13.3 to 4.4 PPY between periods; OP visits increased from 8.3 to 9.2 PPY. Total costs increased from US$ 9099 to US$ 11 754 PPY, while expenditure on antiretroviral drugs increased from 29 to 72% of total cost. Median progression time was 3.8 years in the pre-HAART period, which increased to 13.3 years in the HAART period (log rank chi = 158, P0.0001); incremental cost per LYG between periods was US$ 12 813.HAART appeared a cost-effective intervention in Canada.

Osteoarthritis and hypertension are highly prevalent among older Americans. Anti-inflammatory medications can destabilize blood pressure control. We estimated the decreased cardiovascular risk, premature mortality, and direct health care costs that could be avoided if blood pressure control is not destabilized among hypertensive Americans taking cyclooxygenase-2 (COX-2)–specific inhibitors for osteoarthritis. Data from the Third National Health and Nutrition Examination Survey (NHANES III) provided the distribution of cardiovascular risk factors among American adults with osteoarthritis and hypertension. The Cardiovascular Disease Life Expectancy Model was used to estimate the impact of a 2.26% increase in systolic blood pressure on the basis of results of a randomized trial comparing COX-2–specific inhibitors. A similar analysis was completed for American adults with osteoarthritis and untreated hypertension (≥140/90 mm Hg). Among 7.3 million Americans with treated hypertension, maintaining blood pressure control would avoid >30 000 stroke deaths and 25 000 coronary deaths resulting in >449 000 person years of life saved and $1.4 billion in direct health care cost savings. When an additional 3.8 million Americans with untreated hypertension are considered, maintaining blood pressure control could prevent >47 000 stroke deaths, 39 000 coronary deaths, and result in 668 000 person years of life saved and >$2.4 billion in direct health care cost savings. We conclude that even a small increase in systolic blood pressure among hypertensive Americans with osteoarthritis may substantially increase the clinical and economic burden of cardiovascular disease. Maintaining blood pressure control may be associated with substantial benefits.

Purpose Diabetes mellitus is associated with an increased risk of cardiovascular disease. We compared the clinical effects of treating dyslipidemia in patients who had diabetes mellitus but no diagnosed cardiovascular disease with the effects of similar treatment in patients who had cardiovascular disease but no diabetes mellitus. Methods We estimated the number of adults (ages 30 to 74 years) requiring lipid therapy using data from the third National Health and Nutrition Examination Survey and current lipid treatment guidelines. Using the Cardiovascular Life Expectancy Model, we estimated the mean increase in life expectancy that would result from lowering low-density lipoprotein cholesterol levels by 35% and increasing high-density lipoprotein cholesterol levels by 8% based on results from the Scandinavian Simvastatin Survival Study. Results The mean number of years of life saved ranged from 3 to 3.4 years for men with diabetes versus 2.4 to 2.7 years for men with cardiovascular disease. In women, the estimated benefits were 1.6 to 2.4 years for those with diabetes versus 1.6 to 2.1 years for those with cardiovascular disease. Total population benefits were also substantial for patients with diabetes (25.4 million person-years of life saved) and those with cardiovascular disease (16.0 million person-years of life saved). Conclusion The clinical benefits of treating dyslipidemia in patients with diabetes should be at least equivalent to, if not more substantial than, the benefits observed among those with cardiovascular disease.

OBJECTIVE— Epidemiological studies have shown that the risk of myocardial infarction (MI) in diabetic patients without cardiovascular disease(CVD) is comparable to the risk of MI in patients with CVD. We used a validated Markov model to compare the long-term costs and benefits of treating dyslipidemia in diabetic patients without CVD versus treating CVD patients without diabetes in the U.S. The generalizability and robustness of these results were also compared across six other countries (Canada, France,Germany, Italy, Spain, and the U.K.). RESEARCH DESIGN AND METHODS— With use of the Cardiovascular Disease Life Expectancy Model, cost effectiveness simulations of simvastatin treatment were performed for men and women who were 40-70 years of age and had dyslipidemia. We forecast the long-term risk reduction in CVD events after treatment. On the basis of the Scandinavian Simvastatin Survival Study results, we assumed a 35% reduction in LDL cholesterol and an 8% rise in HDL cholesterol. RESULTS— In the U.S., treatment with simvastatin for CVD patients without diabetes was cost-effective, with estimates ranging from$8,799 to $21,628 per year of life saved (YOLS). Among diabetic individuals without CVD, lipid therapy also appeared to be cost-effective, with estimates ranging from $5,063 to $23,792 per YOLS. In the other countries studied, the cost effectiveness of treating diabetes in the absence of CVD was comparable to the cost effectiveness of treating CVD in the absence of diabetes. CONCLUSIONS— Among diabetic men and women who do not have CVD,lipid therapy is likely to be as effective and cost-effective as treating nondiabetic individuals with CVD.

Objective: To forecast the long-term benefits and costeffectiveness of lipid modification in the secondary prevention of cardiovascular disease. Methods: A validated model based on data from the Lipid Research Clinics cohort was used to estimate the benefits and cost-effectiveness of lipid modification with 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors (statins) based on results from the Scandinavian Simvastatin Survival Study (4S), including a 35% decrease in low-density-lipoprotein (LDL)–cholesterol levels and an 8% increase in high-density-lipoprotein (HDL)– cholesterol levels. After comparing the short-term outcomes predicted for the 4S with the results actually observed, we forecast the long-term risk of recurrent myocardial infarction, congestive heart failure, transient ischemic attacks, arrhythmias, and strokes and the need for surgical procedures such as coronary artery bypass grafting, catheterization, angioplasty, and pacemaker insertions. Outpatient follow-up care costs were estimated, as were the costs of hospital care and drug therapy. All costs were expressed in 1996 US dollars. Results: The short-term outcomes predicted for the 4S were consistent with the observed results. The longterm benefits of lipid modification among low-risk subjects (normotensive nonsmokers) with a baseline LDL/ HDL ratio of 5 but no other risk factors ranged from $5424 to $9548 per year of life saved for men and $8389 to $13 747 per year of life saved for women. In high-risk subjects (hypertensive smokers) with an LDL/HDL ratio of 5, the estimated costs ranged from $4487 to $8532 per year of life saved in men and $5138 to $8389 per year of life saved in women. Assuming that lipid modification h as n o e ffect o n t he r isk o f s troke, c osteffectiveness increased by as much as 100%. Conclusions: These long-term cost estimates are consistent with the short-term economic analyses of the published 4S results. The long-term treatment of hyperlipidemia in secondary prevention is forecasted to be cost-effective across a broad range of patients between 40 and 70 years of age. Recognizing the additional effects of lipid changes on cerebrovascular events can substantially improve the cost-effectiveness of treating hyperlipidemia.

Background —The objective of this study was to estimate the long-term costs and benefits of treating hyperlipidemia among diabetic patients with and without known cardiovascular disease after validating the Cardiovascular Life Expectancy Model. Methods and Results —The model estimates were compared with the Scandinavian Simvastatin Survival Study (4S) and used to estimate the long-term costs and benefits of treatment with simvastatin. Simulations were performed for men and women, 40 to 70 years of age, having pretreatment LDL cholesterol values of 5.46, 4.34, and 3.85 mmol/L (211, 168, and 149 mg/dL). We forecasted the long-term risk of cardiovascular events, the need for medical and surgical interventions, and the associated costs in 1996 US dollars. The model validated well against the observed results of the of the 4S diabetic patients. In this validation, the model estimates fell within the 95% confidence interval of the observed results for 7 of the 8 available end points (coronary deaths, total deaths, and so forth). Treatment with simvastatin for patients with cardiovascular disease is cost-effective for men and women, with or without diabetes. Among diabetic individuals without cardiovascular disease, the benefits of primary prevention were also substantial and the cost-effectiveness ratios attractive across a wide range of assumptions (≈$4000 to $40 000 per year of life saved). These conclusions were robust even among diabetics with lower baseline LDL values and smaller LDL reductions as observed in the Cholesterol and Recruitment Events (CARE) trial. Conclusions —Among adults with hyperlipidemia, the presence of diabetes identifies men and women among whom lipid therapy is likely to be effective and cost-effective even in the absence of other risk factors or known cardiovascular disease.

Background: The losses in productivity due to cardiovascular disease (CVD) are substantial but rarely considered in health economic analyses. We compared the costeffectiveness of lipid level modification in the primary prevention of CVD with and without these indirect costs. Methods: We used the Cardiovascular Life Expectancy Model to estimate the long-term benefits and costeffectiveness of lipid level modification with atorvastatin calcium, including 28% and 38% reductions in total cholesterol and low-density lipoprotein cholesterol levels, respectively, and a 5.5% increase in high-density lipoprotein cholesterol level. The direct costs included all medical care costs associated with CVD. The indirect costs represented the loss of employment income and the decreased value of housekeeping services after different manifestations of CVD. All costs were expressed in 2000 Canadian dollars. Results: When only direct medical care costs were considered, the incremental cost-effectiveness ratios for lifelong therapy with atorvastatin calcium, 10 mg/d, were generally positive, ranging from a few thousand to nearly $20000 per year of life saved. When the societal point of view was adopted and indirect costs were included, the total costs were generally negative, representing substantial cost savings (up to $50000) and increased life expectancy for most groups of individuals. Conclusions: Lipid therapy with statins can reduce CVD morbidity and mortality as demonstrated in a number of clinical trials. Adding the indirect CVD costs associated with productivity losses at work and home can result in forecasted cost savings to society as a whole such that lipid therapy could potentially save lives and money. Arch Intern Med. 2003;163:333-339