doi: 10.1161/CIRCOUTCOMES.108.775247
Original Articles |
One-Year Costs in Patients With a History of or at Risk for Atherothrombosis in the United States
From the From Saint Luke’s Mid America Heart Institute (E.M.M., K.W., D.J.C.), Kansas City, Mo; Division of Epidemiology and Community Health, University of Minnesota School of Public Health, and Minneapolis Heart Institute Foundation (A.T.H.), Minneapolis, Minn; Northwestern University Medical School (M.J.A.), Chicago, Ill; University of Michigan Medical School (K.E.), Ann Arbor, Mich; Sanofi-Aventis (F.M.), Paris, France; Bristol-Myers Squibb (J.D.J.), Princeton, NJ; AP-HP Hôpital Bichat-Claude Bernard (P.G.S.), Paris, France; and VA Boston Healthcare System and Brigham and Women’s Hospital (D.L.B.), Boston, Mass.
Correspondence to Elizabeth M. Mahoney, ScD, Director, Health Economics and Technology Assessment, Mid America Heart Institute of Saint Luke’s Hospital, 4401 Wornall Rd, Kansas City, MO 64111. E-mail emahoney1{at}saint-lukes.org
Received June 30, 2008; accepted July 10, 2008.
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Abstract |
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Background— Atherothrombosis is the underlying cause of cardiovascular, cerebrovascular, and peripheral arterial disease and is the leading cause of death in the industrialized world. The objectives of the present study are (1) to examine the annual costs associated with vascular events and interventions that require hospitalization, as well as long-term medication use for the management of associated risk factors, in a US population of outpatients with multiple atherothrombotic risk factors or a history of symptomatic disease and (2) to compare costs across patient subgroups defined according to specific arterial bed(s) affected and the number of affected arterial beds.
Methods and Results— The international REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled outpatients 
45 years of age who had established coronary artery, cerebrovascular, or peripheral artery disease or 3 atherothrombotic risk factors. Data on risk factors, associated medications, and vascular hospitalizations and interventions were collected. Of the total 68 236-patient REACH cohort, 25 763 were enrolled from US sites. Complete 1-year data were available for 23 974 (93%) of the US patients. Annualized medication costs ranged from $2401 to $3481. Mean annual hospitalization costs per patient were $1344, $2864, $4824, and $8155 for patients with 0 (n=6145), 1 (n=14 353), 2 (n=3106), and 3 (n=370) affected arterial beds at baseline (P<0.0001 for trend). Among patients with 1 affected arterial bed, mean hospitalization costs were $2999, $2010, and $3911 for patients with coronary artery disease (n=11 063), cerebrovascular disease (n=2613), and peripheral arterial disease (n=677), respectively. Annualized medication costs ranged from $2401 to $3481.
Conclusions— These results reveal the high economic burden of atherothrombosis-related clinical events and procedures and the especially high economic burden associated with polyvascular disease.
Key Words: costs • coronary disease • cerebrovascular disorders • peripheral vascular disease • thrombosis
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Introduction |
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Atherothrombosis is the underlying cause of cardiovascular, cerebrovascular, and peripheral arterial disease. Ultimately resulting in acute coronary syndromes, stroke, or the development of critical limb ischemia, it is the leading cause of morbidity and mortality in the industrialized world.1 Cardiovascular disease affects 1 in 3 Americans and was the underlying cause of death in 36.3% of all deaths in the United States in 2004.2 US death rates in young and middle-aged adults after acute cardiovascular events have been decreasing, primarily because of improvements in both acute treatment and secondary prevention; however, the population at risk of cardiovascular events has been increasing because of the overall increase in life expectancy.3,4 In fact, the actual number of people dying of cardiovascular diseases has not changed substantially over the past 20 years because of both increased life expectancy and sustained death rates from chronic manifestations of cardiovascular disease.2
Clinical Perspective p 45
Atherosclerosis is a diffuse disease that can affect multiple arterial territories, and atherothrombotic ischemic events may occur in >1 arterial bed in an individual patient. Patients who have had an initial atherothrombotic event are at high risk for both a subsequent ischemic event in the same arterial bed and ischemic events at other arterial sites.5 The clinical management of patients with atherothrombosis exerts a huge economic burden on the US healthcare system, and this burden is projected to increase as the population ages and as risk factors such as obesity and diabetes mellitus become increasingly prevalent. The estimated direct and indirect costs associated with cardiovascular disease in the United States for 2008 are $448.5 billion.6
The REduction of Atherothrombosis for Continued Health (REACH) Registry is a large, international, prospective study of a stable outpatient population with either established symptomatic atherothrombosis (coronary artery disease [CAD], cerebrovascular disease [CVD], or peripheral artery disease [PAD]) or 3 risk factors for atherothrombotic events.7 One-year results from REACH showed that among patients with established vascular disease at baseline, 1 in 7 experienced a major cardiovascular event (death, myocardial infarction [MI], or stroke) or were hospitalized for revascularization or a cardiovascular event.8 In addition, 1-year results from REACH revealed a clear additive risk of major cardiovascular events associated with each additional symptomatic arterial disease location, which ranged from 2.2% for patients enrolled with multiple risk factors to 9.2% for patients with symptomatic disease in all 3 arterial locations.8
Although current data exist that describe the economic costs associated with specific acute ischemic events, no study has yet examined and compared costs associated with the treatment of atherothrombotic events and management of associated risk factors in a population of outpatients with multiple atherothrombotic risk factors or a history of symptomatic disease. Using 1-year follow-up data from US patients enrolled in REACH, we examined 1-year costs associated with related hospitalizations and long-term medication use across patient subgroups defined according to specific arterial bed(s) affected and number of affected arterial beds.
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Methods |
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The design,7 baseline characteristics,9 and 1-year clinical outcomes8 for the REACH Registry have been published previously. The present analysis focuses on the 25 763 patients enrolled from 1686 sites in the United States between December 2003 and June 2004.
Healthcare Resource Use
Medication use was recorded as chronic therapy (yes/no) at baseline, 6 months, and 1 year and included antiplatelet agents; oral anticoagulants; nonsteroidal antiinflammatory drugs; lipid-lowering agents; cardiovascular agents, including calcium channel blockers, β-blockers, nitrates, and other antianginal agents; diuretics; angiotensin-converting enzyme inhibitors; angiotensin II receptor antagonists and other antihypertensive drugs; claudication medications; and antidiabetic agents. Follow-up data relating to clinical events and hospitalizations were collected at 6 months and 1 year.
Medication Costs
Patient-level reported medication use for each medication class was assigned to the most commonly prescribed drug and dose on the basis of expert opinion of 2 clinical cardiologists, and costs were assigned according to the 2004 Red Book average wholesale costs.10 Whenever possible, a generic alternative for the drug class was selected.
Hospitalization Costs
Each reported hospitalization was assigned to one or more diagnosis-related groups (DRGs) on the basis of the primary reason for hospitalization and procedures (if any) performed. Hospital costs from the provider (ie, hospital) perspective were assigned using 2004 average costs, by DRG, obtained from the Medicare Provider Analysis and Review (MedPAR) database.11 These MedPAR-based hospital cost estimates are derived from individual hospital charges that were submitted to Medicare in 2004 and were converted to costs with 2004 hospital-level cost-to-charge ratios from the Medicare Cost Report. A weighted average of DRG-specific costs, with weights determined by the relative number of hospitalization records within MedPAR with each DRG, was used for hospitalizations for which more than one DRG may apply. Physician costs associated with hospitalizations were estimated as a percentage of hospital costs according to DRG and corresponding Medicare physician cost to hospital cost percentages.12 This approach to the estimation of physician costs has been used in several recent health economic studies.13–15 Details about unit costs for medications and hospitalizations are presented in the Appendix in the online-only Data Supplement.
Statistical Analysis
Costs associated with medications and hospitalizations were estimated for the 93% of patients for whom data were available for both the 6- and 12-month follow-up time points. Baseline clinical and demographic characteristics did not differ between patients with and without complete follow-up data. Although neither resource use nor cost data were imputed for patients completely missing one or both follow-up visits, to retain as many patients as possible in the analysis, missing information related to use of individual medications at baseline or follow-up was multiply imputed by a stepwise approach. The percentage of patients with missing data for any given medication at any time point ranged from 3% to 8%. Missing observations at baseline were first multiply imputed with baseline characteristics used as predictors; missing observations at the 6-month follow-up were multiply imputed with 6-month follow-up vascular events and baseline medication use used as predictors; and missing observations at the 12-month follow-up were multiply imputed with 12-month follow-up events and 6-month medication use as predictors. For the purpose of estimating the cost of medication use for surviving patients who completed both follow-up visits, baseline medication use was assumed to persist throughout the period from baseline through 3 months, 6-month medication use was assumed to persist from 3 through 9 months, and 12-month medication use was assumed from 9 to 12 months. Patients who were reported to have died during follow-up were included in all cost analyses, with all costs after death assumed to be zero.
ANOVA was used to test the relationship between both risk group and number of diseased arterial beds and costs. Regression models were used to evaluate potential demographic and clinical predictors of costs, from which mean predicted hospitalization and total costs for various risk groups, adjusted for age and sex, were obtained. Eighty-seven percent of REACH patients enrolled in the United States reported no hospitalizations during the 1-year follow-up period and therefore had zero hospitalization costs. To accommodate this empirical cost distribution, a 2-part model was used that split the distribution and analysis into 2 parts, allowing the impact of covariates on the probability of any hospitalization to be independent of the impact on hospitalization costs for patients with one or more hospitalization events. For this analysis, logistic regression was used for part 1, and a generalized linear model,16 which assumed a 
-error distribution and log link function, was used for part 2. Predicted mean hospitalization costs and associated 95% confidence limits for different risk groups, adjusted for age and sex, were computed via simulation based on 2-part model results. Predictors of total annual costs were examined using generalized linear models, and predicted mean total costs by risk group, adjusted for age and sex, were computed via simulation based on the generalized linear model results.
The authors had full access to the data and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
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Results |
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The distribution of US REACH patients according to risk factor group is shown in Figure 1. Forty-three percent of these patients were women, and the patients’ mean age was 70 years. At baseline, 52% of patients had diagnosed diabetes mellitus, 87% had diagnosed hypertension, and 83% had diagnosed hypercholesterolemia (Table 1). Overall, 76% were receiving some form of antiplatelet therapy, and 77% were receiving statins. Use of multiple medications was high, with the majority of patients in each risk group (55% of patients overall) prescribed between 4 and 6 medications.
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Medication Costs
Annualized medication costs for patients enrolled on the basis of multiple risk factors only were $2588; 75% of these patients had diabetes mellitus (compared with 44% of symptomatic patients), and diabetes medications accounted for 27% of these costs. Annualized medication costs ranged from $2401 for patients with CVD only to $3481 for patients with disease in all 3 arterial sites (Figure 2).
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Hospitalization Rates, Hospitalization Costs, and Total Costs
Rates of cardiovascular death, the composite of cardiovascular death/MI/stroke, and the composite of cardiovascular death/MI/stroke or cardiovascular hospitalization at 1 year for each of the risk groups are presented in Table 2. For each of these 3 clinical end points, rates were lowest for patients with risk factors only and tended to increase as the number of symptomatic arterial beds at baseline increased. The rate of cardiovascular hospitalizations for reasons other than cardiovascular death, MI, or stroke was considerable, especially for patients with CAD and PAD, because of high intervention rates.
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One-year rates of hospitalizations, classified for the purpose of DRG assignment into those involving and those not involving vascular procedures, are presented in Table 2. Some of the hospitalizations that involved revascularization (eg, percutaneous coronary intervention/stenting) also involved a reported clinical event (eg, unstable angina or MI); the 19 categories of hospitalizations presented in Table 2 correspond to the characteristics of the hospitalization that determined the DRG assignment. These hospitalization rate results corroborate that secondary ischemic events were most likely to occur in the arterial segments that defined the initial enrollment cohort. For example, the highest rates of nonfatal MI, unstable angina, coronary artery bypass graft surgery, and percutaneous coronary intervention/stenting occurred in patients with CAD; similarly, the highest rates of nonfatal stroke and transient ischemic attack occurred in patients with CVD, and the highest rates of worsening of claudication, peripheral angioplasty/stenting, peripheral bypass surgery, and lower-limb amputation occurred in patients with PAD. The rate of lower-limb amputation (25 per 1000 patients) was particularly high among patients with PAD alone at enrollment.
Mean 1-year costs associated with hospitalizations for atherosclerotic ischemic events and associated procedures ranged from $1344 per patient for patients with multiple risk factors only to $8155 per patient for patients with atherosclerotic disease in all 3 arterial sites (Figure 3). Annual costs associated with vascular procedures were especially high for patients with CAD (hospitalizations that involved coronary artery bypass graft surgery and percutaneous coronary intervention/stenting accounted for 50% of total annual hospitalization costs for patients with CAD only) and PAD (hospitalizations that involved peripheral angioplasty/stenting, peripheral bypass graft, and lower-limb amputation accounted for 57% of total annual hospitalization costs for patients with PAD only). There was a consistent increase in costs with each additional diseased arterial bed (Figure 4; P<0.0001, test for overall linear trend, and tests comparing 0 versus 1 and 1 versus 2 beds; P=0.03 for test comparing 2 versus 3 beds).
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Model-based predictions of mean hospitalization costs and total costs and associated 95% confidence limits, adjusted for age and sex, for each of the risk groups are presented in Figures 5 and 6
, respectively. These adjusted results also reveal the especially high costs associated with PAD and the significant incremental cost associated with each additional involved arterial bed.
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Discussion |
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Clinical outcome rates over a 1-year period from the international REACH Registry cohort revealed high rates of cardiovascular death, MI, and stroke that increased considerably with the number of symptomatic disease locations. Results from the 25 763-patient US subset show similarly high clinical outcome rates and parallel trends with number of symptomatic arterial sites. The present US economic analysis revealed an extremely high economic burden of atherothrombosis-related hospitalizations in this stable outpatient population, with statistically significant increases in the magnitude of both hospitalization costs and total (hospitalization plus long-term medication) costs with each additional symptomatic arterial bed. Age- and sex-adjusted average annual hospitalization costs for patients with 0, 1, 2, and 3 symptomatic sites were $1370, $2862, $4828, and $8162, respectively. Inclusion of long-term medication costs increased these values to $3969, $5609, $8153, and $11 482, respectively. Because the REACH population consisted of relatively stable outpatients (as opposed to hospitalized patients), these costs can be considered as estimates of the annual long-term economic burden of hospitalizations and medication use associated with atherothrombosis in the United States. These results highlight the especially high economic burden associated with symptomatic polyvascular disease.
To put these costs in perspective, in 2004, average healthcare expenses (including inpatient and outpatient care, prescription drugs, and out-of-pocket expenses) per civilian, noninstitutionalized person in the United States were $6280.17,18 In 2002, people 65 years of age made up 13% of the US population but consumed 36% of total US personal healthcare expenses; the average healthcare expense in 2002 was $11 089 for people 65 years of age and $3352 per year for people of working age (19 to 64 years of age).19 Cost estimates from the present study demonstrate how healthcare expenses associated with the treatment of atherothrombosis in an identifiable at-risk outpatient population account for a large proportion of healthcare expenditures at the national level.
In 2004 in the United States, there were approximately 15.8 million individuals with coronary heart disease and 5.6 million with a history of stroke.2 If we assume that our cost estimates are broadly applicable to these overall populations at risk, the estimated total annual costs associated with vascular hospitalizations for outpatients with a history of CAD and CVD events are more than $47 billion and $11 billion, respectively. Total hospital costs related to cardiovascular disease are estimated to have been $101.7 billion in the United States in 2004.20 Total direct costs associated with cardiovascular disease (including hospital costs, physician/professional costs, nursing home care, medications, home health care, and other medical durables) are estimated to have been $226.7 billion; by comparison, in 2003, total direct cancer-related costs for the United States are estimated to have been $64 billion.20
Results from the present study demonstrate that symptomatic PAD was associated with the greatest cost relative to CAD and CVD, largely because of costs associated with the high rate of peripheral vascular procedures. As for the overall international REACH population,8 patients with PAD enrolled from the United States had the highest rate of fatal MI (8.9% for PAD versus 4.9% and 1.5% for CAD and CVD, respectively). Although PAD tends to be underdiagnosed, it has been estimated that in 2000, there were approximately 5 million adults 40 years of age with PAD.21 On the basis of our results and 2004 US census data, total annual costs associated with vascular hospitalizations in patients with PAD are in excess of $21 billion.
The US population 65 years of age is expected to double in size by 2030, when nearly 1 in 5 Americans are expected to be 65.22 This rapid growth in the number of older persons may be expected to result in a tremendous increase in healthcare spending and a challenge for public health in the United States. The high costs associated with the treatment of atherothrombosis will contribute significantly to this upward pressure on public healthcare resources.
A previous analysis of baseline data from REACH reported a substantial proportion of patients throughout all geographic regions who did not meet established risk factor targets for cholesterol reduction, blood pressure, glucose, body weight, and tobacco nonuse.9 Although more aggressive treatment of these core risk factors early in the disease process may be associated with increased up-front costs because of increased outpatient visits and medication use, the present data suggest that these additional costs might be offset by considerable savings due to the reduced need for costly hospitalizations and vascular procedures downstream.
Study Limitations
The REACH Registry did not collect outpatient and long-term healthcare resource use, such as nursing home and rehabilitation stays following stroke or amputation. Because these missing cost components may affect some risk groups more than others, the overall relative economic burden of the risk groups may differ somewhat from our estimates. In addition, we did not collect data on hospitalizations for noncardiovascular conditions. If noncardiovascular hospitalizations correlate with cardiovascular events, our cost estimates may systematically underestimate the true economic burden in the US population.
Also not included in the present study are indirect costs associated with lost productivity on the part of the patient and other informal caregivers. Although the REACH Registry collected data relating to employment status and number of sick leave days taken due to reported vascular outcomes that occurred during follow-up, information relating to informal caregiver time was not collected. Only 26% of the US REACH population overall was working full or part time at baseline (66% reported being retired, and the remaining 8% reported being incapacitated or not working for other reasons), and this number decreased with the number of symptomatic arterial locations (only 10% of patients with 3 involved arterial sites were working at baseline). The annual number of sick leave days taken among the subset of employed patients increased with the number of symptomatic locations, ranging from 2 days for patients with multiple risk factors only to 10 days for patients with 3 symptomatic arterial sites. Averaging across all patients within each risk group yielded estimates of annual costs due to lost productivity on the part of the patient, based on average national daily gross income,23 that varied by subgroup from $69 for patients with multiple risk factors only to $203 for patients with CAD plus PAD. These lost productivity costs were not included in the formal analysis presented here because they account for only a small fraction of the actual overall indirect costs of atherothrombotic disease in this patient population. The application of average DRG-specific Medicare costs to reported hospitalizations and procedures, due to the limited resource use data collected in REACH, is another limitation of this cost study, as is the use of estimated physician cost percentages, which were derived from 1992 Medicare data.
Conclusions
Stable outpatients in the United States with a history of established vascular disease have very high hospitalization rates for atherothrombotic events, and associated costs for acute medical care and pharmacological disease management are extremely high. The significant increase in cost with each additional affected arterial disease site illustrates the especially high economic burden associated with symptomatic polyvascular disease. With the steady increase in the number of older persons in the United States expected over the next quarter-century, atherothrombosis likely will continue to exert tremendous pressure on public healthcare resources, especially given that a very low proportion of patients at high risk are working and contributing through employment taxes to the pool of available healthcare funds. An increased focus on aggressive, guidelines-based risk factor modification and prevention efforts is needed to lessen the burden of atherothrombotic disease for both patients and society.
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Acknowledgments |
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Sources of Funding
This study was supported by a grant from Sanofi-Aventis and Bristol-Myers Squibb.
Disclosures
Dr Mahoney has received grant support from Sanofi-Aventis, Bristol-Myers Squibb, and Eli Lilly and has received honoraria from Sanofi-Aventis and Bristol-Myers Squibb. Dr Cohen has received grant support from Sanofi-Aventis, Bristol-Myers Squibb, Eli Lilly, Schering-Plough, The Medicines Company, Accumetrics, Cordis, and Boston Scientific. Dr Hirsch has received research grant support from Kos Pharmaceuticals, Bristol-Myers Squibb, Sanofi-Aventis, AstraZeneca, and SonoSite and consulting fees/honoraria from Bristol-Myers Squibb, Sanofi-Aventis, and Vasogen and has been on the speakers’ bureau for Bristol-Myers Squibb and Sanofi-Aventis. Dr Alberts has received grant support from, has been a member of the speakers’ bureau and advisory board for, and has received honoraria from Bristol-Myers Squibb and Sanofi-Aventis. Dr Eagle has received grant support from Biosite, Bristol-Myers Squibb, Cardiac Sciences, Blue Cross Blue Shield of Michigan, Hewlett Foundation, Mardigian Fund, Pfizer, Sanofi-Aventis, and the Varbedian Fund. Dr Mosse is an employee of Sanofi-Aventis. Dr Jackson is an employee of and owns stock in Bristol-Myers Squibb. Dr Steg has served as a member of the speakers’ bureau for Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sharp & Dohme, Novartis, Nycomed, Sanofi-Aventis, Sankyo, Servier, and ZLB-Behring and has received consulting fees/honoraria from Sanofi-Aventis, Servier, Bristol-Myers Squibb, AstraZeneca, and Novartis. Dr Bhatt has received research grants from Heartscape, The Medicines Company, Bristol-Myers Squibb, Sanofi-Aventis, Eisai, and Ethicon and consulting fees/honoraria from AstraZeneca, Bristol-Myers Squibb, Cardax Pharmaceuticals, Centocor, Daiichi-Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Millennium, Otsuka Pharmaceuticals, ParinGenix, PDL, Sanofi-Aventis, Schering Plough, The Medicines Company, and TNS Healthcare and has been on the speakers’ bureau for Bristol-Myers Squibb, Sanofi-Aventis, and The Medicines Company. Dr Wang reports no conflicts.
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Footnotes |
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The online-only Data Supplement is available with this article at http://circoutcomes.ahajournals.org/cgi/content/full/1/1/38/DC1.
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