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Costs associated with cardiovascular events in patients with hypertension in US managed care settings
Journal of the American Society of Hypertension 3(6) (2009) 403–415
Research Article
Costs associated with cardiovascular events in patients with hypertension in US managed care settings Mei Sheng Duh, MPH, ScDa,*, Nicole M. Fulcher, MAa, Leigh Ann White, PhDa, Sujata S. Jayawant, PhDa, Priyanka Ramamurthy, BAa, Erick Moyneur, MAa, and Siew Hwa Ong, MScb a Analysis Group, Inc., Boston, Massachusetts, USA; and Global Health Economics & Outcomes Research, Novartis Pharma AG, Basel, Switzerland Manuscript received June 12, 2009 and accepted September 8, 2009
b
Abstract Study quantified incremental cost of cardiovascular (CV) events in 6 high-risk and compelling indication subgroups: postmyocardial infarction (MI), diabetes, diabetic nephropathy, elderly, chronic kidney disease, and prior stroke. Based on claims data from privately insured individuals with 2þ hypertension (HTN) diagnoses in 2004–2006, we estimated regression-adjusted per-member-per-month healthcare costs after CVE. Costs were compared between patients with and without a CV events, and before and after CVevents in each subgroup. The following CVevents were studied: acute MI, acute coronary syndrome, angina, ventricular arrhythmia, atrial arrhythmia, heart failure, coronary artery disease, left ventricular hypertrophy, stroke, and sinus tachycardia. Of 1,598,890 HTN patients, 510,118 had 1 CV event. Compared with controls, healthcare costs among patients with events were significantly greater across all cost components (inpatient, outpatient, and prescription drug). Acute MI and congestive heart failure generally had the largest incremental total healthcare costs. First-quarter post-event costs were attributable to inpatient costs. CV events are costly sequelae of hypertension in high-risk and CI subgroups. J Am Soc Hypertens 2009;3(6):403–415. Ó 2009 American Society of Hypertension. All rights reserved. Keywords: Healthcare costs; outcome assessment (healthcare); hypertension; cardiovascular diseases.
Introduction Hypertension, a risk factor for cardiovascular (CV) and cerebrovascular disease, is a substantial public health problem affecting more than 70 million people in the United States and has a wide spectrum of symptom manifestations, ranging from asymptomatic high blood pressures to stroke, heart failure, heart attack, kidney failure, and vision impairment.1–3 Although its exact causes are unknown, several factors and conditions including age, physical inactivity, dyslipidemia, glucose intolerance, left ventricular hypertrophy, obesity, alcohol consumption,
This study was funded by Novartis Pharma AG, Basel, Switzerland. The results of the study were not contingent on the funding. Conflict of interest: none. *Corresponding author: Mei Sheng Duh, MPH, ScD, Analysis Group, Inc., 111 Huntington Avenue, 10th Floor, Boston, Massachusetts 02199. Tel: 617-425-8131; fax: 617-425-8001. E-mail: [email protected]
and cigarette smoking play a role in the development of hypertension.4–7 Healthcare costs for the treatment of hypertension and its complications are substantial, with estimates ranging from $15 billion to approximately $60 billion.8,9 Hodgson and colleagues estimated hypertension-related CV complications accounting for approximately $30 billion.10 Despite the high costs, it is still one of the most poorly controlled conditions, and approximately 30% of individuals remain undiagnosed.11,12 It is estimated that the cumulative lifetime risk of developing hypertension (140/90 mm Hg) is approximately 90% in patients ages 55–85.13 Guidelines from the Joint National Committee (JNC 7) on Detection, Evaluation, and Treatment of Hypertension contain a clearly defined treatment goal for management of hypertension involving combination of lifestyle modifications, such as modifications in diet, exercise, and alcohol consumption, and pharmacotherapy. Treatment with antihypertensive medications has been shown to significantly reduce CV morbidity and mortality, with efficacy demonstrated for the majority of CV diseases.14,15 According to the JNC 7,
1933-1711/09/$ – see front matter Ó 2009 American Society of Hypertension. All rights reserved. doi:10.1016/j.jash.2009.09.001
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presence of compelling indications, such as myocardial infarction (MI), coronary diseases, diabetes, chronic kidney disease (CKD), and stroke as well as older age, in patients with hypertension is considered high-risk for development of CV disease.13 Estimating the cost of CV events in hypertensive patients and in those with compelling indications or at high-risk of CV events (eg, elderly) provides a more accurate assessment of potential savings to payers that may accrue from prevention and treatment of hypertension. Few studies have provided estimates of the cost of CV events in samples of hypertension patients. In studies that have included estimates of CV event costs, researchers have focused on specific conditions such as chronic angina16 and acute coronary syndrome (ACS)17 without limiting the study population to hypertension patients or providing a broad set of estimates on CV events in hypertensive patients. Etemad and colleagues analyzed 12-month healthcare costs after onset of ACS and found that total medical and pharmacy costs incurred by the health plan and patients was $2,312 per patient per month of follow-up, with 72% of the total cost attributable to hospitalizations.17 Studies with a broader focus have included cost estimates for CV diseases such as hypertension, coronary heart disease, stroke, and congestive heart failure; however, as in the Hodgson Study, most authors have relied on survey data (ie, self-reports) rather than administrative data, which are more likely to reflect real-world clinical practice.18,19 No studies, to the authors’ knowledge, have included cost estimates for individual CV events based on multiple JNC 7 indications, nor have any studies included time trends in costs surrounding the occurrence of a CV event. The objective of this study is to quantify direct incremental CV event–specific costs in patients with hypertension, particularly those patients with increased risk of developing a CV event. Data on the incremental costs of CV events in hypertensive patients are valuable both to understand the importance of preventing these events and to assess their impacts on healthcare costs. In this article, we present estimates of direct healthcare costs associated with 10 CV events in a cohort of hypertension patients, based on analysis of a large healthcare claims database. We present estimates of incremental costs of CV events in specific subgroups for which aggressive treatment of hypertension is indicated: the elderly and patients with comorbidities of diabetes, diabetic nephropathy, CKD, prior myocardial infarction, or prior stroke. In addition, we present time trend analyses of pre-event and post-event costs, of each of the 10 CV events.
Methods Data Source This study used administrative claims data from the Thomson MedStat MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination
of Benefits (Medicare) databases for the period January 1, 2004 to December 31, 2006. The MedStat MarketScan databases contain the inpatient medical service claims, outpatient medical service claims, and outpatient prescription drug claims of more than 10 million employees, dependents, and retirees covered through a variety of privately insured employer-based health plans. The Medicare Supplemental database includes approximately 1 million individuals with employer-funded coverage. For the Medicare population, both the Medicare-paid and employer-paid amounts for services are included. The databases include patient demographics and health plan enrollment information, inpatient and outpatient diagnoses and procedures, and outpatient prescription drug dispensing claims for all patients. Diastolic and systolic blood pressure readings were not available. Diagnosis-specific claims were identified by International Classification of Diseases, 9th Revision (ICD-9) codes and prescription drugs claims by National Drug Codes. Medical procedures were coded using Current Procedural Terminology codes, Healthcare Common Procedure Coding System codes, and ICD-9 procedure codes.
Study Population The base case population for this study was comprised of all hypertension patients that met sample selection criteria. To be included in the base case population, patients had to have at least two medical claims carrying the following essential or secondary hypertension diagnosis codes: essential hypertension (ICD-9 codes: 401.xx), hypertensive heart disease (ICD-9 codes: 402.xx), hypertensive CKD (ICD-9 codes: 403.xx), hypertensive heart and CKD (ICD-9 codes: 404.xx), and secondary hypertension (ICD-9 codes: 405.xx). We included other hypertension diagnosis codes, such as hypertension secondary to renovascular disorders or to endocrine disorders, because preliminary examination of the claims data suggested that coding misclassifications between essential and secondary hypertension ICD-9 codes were likely to occur in favor of the later; thus, exclusion of 405.xx would not necessarily exclude secondary cases. In other studies using claims data to examine hypertensionrelated CV outcomes, selection criteria for hypertensive patients have included ICD-9 codes for secondary hypertension.20,21 The observation period for the base case population began on the service date of the first hypertension claim (the index event), then continued until the date of disenrollment, the defined study end date (December 31, 2006), or progression to end-stage renal disease (ESRD), whichever occurred first. We imposed additional criteria to select a population aged 18 years or older at the time of the index event and that was continuously enrolled 6 months before and 6 months after the date of index event. Progression to ESRD was indicated when a claim contained
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dialysis-related procedures: (Current Procedural Terminology codes: 90919–90998, 99512, 99559; ICD-9 procedure codes: 39.95, 54.98; Healthcare Common Procedure Coding System codes A4690, A4820, A4900, A4901, A4905, E1510, E1590, E1592, E1594, E1632, E1635) or ESRD-related or dialysis-related diagnosis codes (ICD-9 codes: V451, V56, V560, V561, V562, V5631, V5632, V568, E8702, E8712, E8722, E8742, E8791, 996.56, 996.73, 58.56). There were 1,599,549 patients who met the inclusion criteria for the study population. From the hypertension or base case population, we created 6 mutually nonexclusive subgroups of patients with CV events based on JNC’s recommendations regarding compelling indications or high-risk groups. The 6 groups were elderly patients and patients with the following conditions: diabetes, diabetic nephropathy, CKD, prior MI, and prior stroke. The 6 subgroups were defined as: 1. Elderly patients were 65 years or older at the time of initial diagnosis for hypertension. 2. Diabetes patients had at least two medical claims carrying a diabetes diagnosis code (ICD-9 codes: 250.0, 250.x0, 250.x2). 3. Diabetic nephropathy patients had at least two medical claims carrying a diabetic nephropathy diagnosis code (ICD-9 codes: 250.40, 250.42, 580.xx, 581.xx, 582.xx, 583.xx). 4. CKD patients had at least two medical claims carrying a CKD diagnosis (ICD-9 codes: 585.xx, 586.xx). These codes exclude ESRD and diabetic nephropathy. 5. Prior MI patients had at least two medical claims carrying a diagnosis of acute MI (AMI; ICD-9 codes: 410.xx). 6. Prior stroke patients had at least two medical claims carrying a diagnosis of stroke (ICD-9 codes: 430.xx, 431.xx, 432.xx, 433.xx, 434.xx, 435.xx, 436.xx, 437.xx). The observation period for each subgroup population began on the service date of the first hypertension claim or the service date of the first subgroup qualifying claim, whichever occurred later. The observation ended at the disenrollment date.
Definition of CV Event Outcomes To quantify the incremental costs of CV event occurrence, we identified 10 CV events in the sample of hypertension patients described previously. Patients with at least one medical claim after their observation start date for any of the 10 CV events constituted the pool of patients with at least one of the 10 CV events (Table 1). Based on the literature review of CV events, the events most common in patients with hypertension were chosen for this study. The CV events are acute myocardial infarction (AMI), ACS, angina, serious ventricular arrhythmia, serious atrial
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arrhythmia, congestive heart failure (CHF), coronary artery disease (CAD), left ventricular hypertrophy (LVH), stroke or transient ischemic attack, and sinus tachycardia (ST). We initially considered the CV events sudden death and cardiac arrest, but because of insufficient numbers of cases and the likelihood that we would not be able to observe costs after death, these events were excluded from the analysis. Exclusion of these events reduced the sample from 510,624 to 510,118 patients with hypertension. Table 1 contains the list of CV events and corresponding diagnosis codes used to identify each event. Patients with multiple CV events were classified based on their first (index) CV event. Patients in the prior stroke and prior MI subgroups were classified in the 10 CV event groups based on the second (index) CV event (ie, the event after stroke or MI). Patients who died within the 6 months from the index date were excluded. Deaths are not comprehensively captured in claims data, because disenrollment reason is not listed. We were able to identify only deaths occurred in a healthcare facility based on the ICD-9 codes of sudden death. The person-time of observation stopped when the patient is disenrolled. We assigned patients to a CV event group based on their observed CV event, termed index event. The index date was defined as the earlier date of first outpatient visit, inpatient hospitalization, or emergency room visit associated with that CV event. CV events were identified based on principal diagnosis (first ICD-9 code field). For patients in the prior MI and prior stroke subgroups, we assigned an index CV event based on the first CV event after the AMI or stroke event. That is, for the prior MI (or prior stroke) subgroup, their index date was the service date of their second event. At least 60 days between the claims for the first and second MI (or stroke) must have passed for assignment of an index CV event in the prior MI (prior stroke) subgroup. We imposed this additional criterion to ensure that any subsequent claims for MI (or stroke) within 60 days for the first MI (or stroke) event constituted follow-up or treatment related to the initial MI (or stroke) and that the patient did, indeed, suffer a second event. Remaining hypertension patients who had no claims for CV events after their first hypertension claim composed the no-CV event group, or the control group. For the control group, we imputed a faux index date to compare the cost of CV-event groups. The faux index date was defined as the service date of the first hypertension claim plus an imputed measure of a faux pre-CV event period that matched the distribution of the patient-months between the first hypertension claim date and the first CV event claim date of the CV event group. This index date ensured that the control group would not be systematically observed for a longer period of time compared to the CV event group. For subgroups, comparisons were made with patients having the risk (older age) or conditions (eg, diabetes), but no index CV event.
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Table 1 ICD-9 diagnosis codes used to identify cardiovascular events Cardiovascular event
ICD-9 codes
Description
Acute myocardial infarction Acute coronary syndrome
410.xx 411.0x 411.81 411.89 411.1x 413.xx 427.1x 427.4x 427.3x 428.xx 414.0x 414.1x 414.8x 414.9x 429.3x 430.xx 431.xx 432.xx 433.xx 434.xx 435.xx 436.xx 437.xx 427.89
Acute myocardial infarction Postmyocardial infarction syndrome Acute coronary occlusion without myocardial infarction Other Intermediate coronary syndrome (unstable angina) Angina pectoris (stable angina) Paroxysmal ventricular tachycardia Ventricular fibrillation and flutter Atrial fibrillation and flutter Heart failure Coronary atherosclerosis Aneurysm and dissection of heart AHA Other specified forms of chronic ischemic heart disease Chronic ischemic heart disease, unspecified Cardiomegaly Subarachnoid hemorrhage Intracerebral hemorrhage Other and unspecified intracranial hemorrhage Occlusion and stenosis of precerebral arteries Occlusion of cerebral arteries Transient cerebral ischemia Acute, but ill-defined, cerebrovascular disease Other and ill-defined cerebrovascular disease Sinus tachycardia
Angina Ventricular arrhythmia Atrial arrhythmia Congestive heart failure Coronary artery disease
Left ventricular hypertrophy Stroke and transient ischemic attack
Sinus tachycardia
AHA, American Heart Association; ICD-9, International Classification of Disease, 9th Revision.
Pre-Event and Post-Event Periods The pre-event period for all groups consisted of the 6month period preceding the index date. The post-event period for all groups began on the index date and continued to the date of disenrollment, the defined study end date (December 31, 2006) or progression to ESRD, whichever occurred first. For all analyses, we imposed the criterion that patients have a minimum of 6 months continuous enrollment in both the pre-event and post-event periods. Patients not meeting these minimum observation time criteria were excluded from the study. Baseline characteristics reported for the sample reflect the 6-month period preceding the index date.
Cost Measurement We calculated per member per month (PMPM) direct healthcare costs (inpatient, outpatient, and pharmacy) over the post-event period for each patient in the study cohort. Direct healthcare costs considered in this study were the total paid amounts to providers for medical services, as recorded at the claims level. To analyze trends in the cost burden of patients before and after the CV event as well as the extent of cost escalation before the onset of an event, quarterly univariate cost estimates were calculated for two-quarters before the CV event (6-month
baseline period) and up to four-quarters after the index date. This quarterly breakdown of costs made it possible to compute the first-year costs after CV event for hypertension patients with each type of event. A person-time approach was used to account for different lengths of observation among study subjects due to the nonexperimental study setting. PMPM costs were calculated separately for each patient as the total cost during the follow-up period divided by the patient-months of observation. Therefore, if a patient has a longer observation period than 6 months, all months are considered in the calculation. We required a minimum of 6 months to allow stable estimates of costs; the observation did not truncate at 6 months. In the persontime approach, the costs are aggregated over time without explicit modeling of time patterns. That is why we further conducted trend analysis to examine the cost variability over time. This measurement has the advantages of smoothing cost fluctuations over time, and enabling comparisons across different populations. However, it is also subject to volatility from patients with short duration of observation.
Statistical Analysis A multivariate Tobit regression model was used to evaluate the incremental direct costs attributable to CV events.
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Because healthcare costs are typically continuous over positive values and zero for a nontrivial portion of the data, the error term of estimated models will not be normally distributed. The non-normality of costs is corrected by the employment of Tobit statistical estimation procedures which use all dependent variable observations (costs), including those including those clustered at zero, to obtain efficient parameters describing the relationship between the costs and the explanatory variables. The Tobit analyses estimated average monthly post-event incremental costs by adjusting for factors that were potentially unevenly distributed between the CV event and noCV event control groups. Covariates factors included in the regression model were the patient’s age, age squared, gender, geographic region of residence, health plan type (ie, health maintenance organization, preferred provider organization, and point of service), disease penetration assessed through the number of months from the first hypertension claim, and selected individual comorbidity indicators (chronic diabetes, dementia, hemiplegia, chronic liver disease, mild to moderate liver disease, peptic ulcer disease, rheumatologic disease, HIV/AIDS, peripheral vascular disease, and malignancy/metastatic solid tumors). Comorbidity covariates included in the model represent selected individual components of the Charlson Comorbidity Index.22 The multivariate analyses also adjusted for the costs incurred during the pre-event period for the CV event group, controlling for the baseline costs in estimations of the incremental costs of each CV event. Each cost category (ie, inpatient cost, outpatient cost, prescription drug cost, and total direct cost) was estimated in a separate regression model; because of the non-linearity of the Tobit model, regression results for total direct healthcare costs are not equal to the sum of the individual components (inpatient, outpatient, and prescription drug costs).
Results Patient Baseline Characteristics Of the 1,598,980 patients who met the inclusion criteria for the study population, 510,118 patients (32%) had at least one CV event, and 1,088,862 (68%) patients served as no-CV event controls. There were differences in patient demographic and health characteristics between the CV group and the no-CV event controls (Table 2). CV event patients were older (mean, 67 13 years of age vs. mean, 57 13 years of age) and a larger percentage were male (50.7% vs. 45.7%; P < .0001). Compared with patients with no CV events, patients with CV events were more likely to be enrolled in indemnity plans (22.6% in the no-CV event group vs. 39.1% in the CV event group) than in other types of plans. Conditions commonly present in hypertensive patients, such as diabetes, benign prostatic
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Table 2 Baseline characteristics of hypertension patients with and without cardiovascular events Patients with hypertension No cardiovascular event
Cardiovascular event
Baseline characteristics
n ¼ 1,088,862
n ¼ 510,118
Demographics Age (year), mean SD Male, %
57 13a 45.7a
67 13 50.7
Health plan type (%)b Indemnity HMO POS PPO POS with capitation Other
22.6 19.7 9.0 42.4 1.7 4.6
39.1 19.2 4.8 33.3 0.9 2.7
Geographic region (%)b Northeast North Central South West Unknown
7.1 27.4 45.2 19.8 0.5
7.2 35.5 36.8 19.9 0.7
Selected baseline health conditions (%) Benign prostatic 4.1a hyperplasia Chronic kidney disease 0.3 Diabetes 17.4a Diabetic nephropathy 0.4 Edema and angioedema 3.4a End-stage renal disease 0.3
5.9 0.1 25.3 0.6 5.5 0.1
HMO, health maintenance organization; POS, point of service; PPO, preferred provider organization; SD, standard deviation. a All P < .05 for a test of between-group differences in means or proportions. b Chi-squared test; P < .05 for test of independence.
hyperplasia, and edema/angioedema were more common in CV-event patients than no-CV event controls.
Healthcare Costs Healthcare costs across all cost components were significantly greater for CV event patients compared with no-CV event controls (Table 3). For the base population of all hypertension patients, the direct incremental PMPM costs for specific CV events ranged from $502 (95% CI, $487– $518) for ACS to $1,688 (95% CI, $1,647–$1,729) for CHF. AMI ($1,350; 95% CI, $1,341–$1,358) and CHF events ($1,688; 95% CI, $1,647–$1,729) were associated with the highest incremental monthly total healthcare cost compared with incremental total healthcare costs of other CV events in the $500 to $700 range. Inpatient costs were the largest component of healthcare costs, ranging from
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Table 3 Incremental average monthly healthcare cost of cardiovascular events in a hypertension population Regression-adjusteda healthcare costs
All hypertension patients (n ¼ 510,118) CV event Acute myocardial infarction Inpatient Outpatient Drugs Total healthcare Acute coronary syndrome Inpatient Outpatient Drugs Total healthcare Angina Inpatient Outpatient Drugs Total healthcare Ventricular arrhythmia Inpatient Outpatient Drugs Total healthcare Atrial arrhythmia Inpatient Outpatient Drugs Total healthcare Congestive heart failure Inpatient Outpatient Drugs Total healthcare Coronary artery disease Inpatient Outpatient Drugs Total healthcare Left ventricular hypertrophy Inpatient Outpatient Drugs Total healthcare Stroke and transient ischemic attack Inpatient Outpatient Drugs Total healthcare Sinus tachycardia Inpatient Outpatient Drugs Total healthcare
$PMPMb
Lower 95% CI
Upper 95% CI
1,203 365 81 1,350
1,199 362 80 1,341
1,207 369 82 1,358
325 268 46 502
316 260 44 487
333 275 48 518
413 262 50 504
500 411 260 49
509 416 264 51
438 349 68 714
431 343 66 701
445 355 70 727
395 323 55 578
392 321 55 574
397 325 56 583
1,112 445 23 1,688
1,094 427 17 1,647
1,129 464 29 1,729
323 251 66 507
321 250 65 504
326 253 66 510
436 323 32 617
432 321 32 611
439 325 33 622
427 273 54 541
425 271 53 537
429 274 54 544
400 272 32 503
396 269 31 497
403 274 32 509
CI, confidence interval; CV, cardiovascular; PMPM, per-member per-month. Based on Tobit specification with covariates for age, gender, insurance plan type, geographic region, comorbidity, and months between hypertension diagnosis and CV event. Each cost category was estimated separately, thus total direct costs are not equal to the sum of cost categories. b All P < .05 for the test of the null hypothesis of incremental costs being equal to 0. a
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$323 (95% CI, 321–326; P < .0001) for CAD to $1,203 (95% CI, $1,199–$1,207; P < .0001) for AMI. Outpatient costs across all CV events ranged from $251 (95% CI, 250–253; P < .0001) for CAD to $445 (95% CI, $427– $464; P < .0001) for CHF. A review of the chronic disease and high-risk subgroups revealed that the CV events AMI, CHF, and LVH had the largest incremental total healthcare costs within each subgroup (Table 4). Incremental total healthcare costs ranged from $578 PMPM (95% CI, $537–$618) for ACS to $1,574 PMPM (95% CI, $1,553–$1,595) for AMI in the diabetes subgroup, $406 PMPM (95% CI, $169–$643) for ACS to $1,356 PMPM (95% CI, $1,260–$1,452) for AMI in the CKD subgroup and $387 PMPM (95% CI, $24–$750) for ACS to $1,617 PMPM (95% CI, $1,460– $1,775) for AMI in the diabetic nephropathy subgroup. Consistent with the overall hypertension population, inpatients costs were the largest component of healthcare costs for all CV events. Outpatient costs were the second largest contributor to incremental healthcare costs and were significantly different than no-CV event controls with the exception of ACS in the diabetic nephropathy subgroup. Prescription drug costs were the smallest incremental component for all CV events, and were not significantly different from no-CV event controls for the ACS in the CKD and diabetic nephropathy subgroups. Table 5 contains results for the subgroups of elderly, prior stroke, and prior MI. As with the chronic disease subgroups, inpatient healthcare costs were the largest component, with incremental costs ranging from $263 (95% CI, $259–$266) for CAD to $895 (95% CI, $888– $901) for AMI in the elderly subgroup, from $130 (95% CI, $119–$141) for stroke or transient ischemic attack to $1,315 (95% CI, $1,283–$1,348) for AMI in prior stroke patients, and $48 (95% CI, $5–$92) for CAD to 1299 (95% CI, $1,136–$1,463) for serious ventricular arrhythmia in prior MI patients. Outpatient healthcare costs were the second largest incremental cost component for all CV events within the subgroups of elderly, prior stroke, and prior MI. Among the prior MI patients, incremental drug costs were negative ($19) (95% CI, 27 to 11) for AMI patients, and not statistically significant from no-CV event controls for the CV events of ACS and LVH. Incremental drug costs for ACS in the prior stroke subgroup were also not significant.
Trends in Incremental Costs Average quarterly direct costs (inpatient, outpatient, and pharmacy) are reported in Table 6 for each of the 10 CV events. For all CV conditions, healthcare costs were highest surrounding and immediately following the event. In the pre-event period, quarterly costs were observed to increase from the second-quarter before the event to the first-quarter before the event. After each CV event, quarterly healthcare
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costs peaked in the first-quarter post-event followed by declining costs throughout the next three- quarters, and costs in the fourth-quarter post-event declined to levels near those present in the second-quarter pre-event. Total direct costs in the first-quarter post-event were largely driven by inpatient costs, however in the following threequarters, outpatient costs accounted for the largest part of total direct costs. The three most expensive CV events in the first year after the event were acute MI ($39,041), CHF ($26,614), and ventricular arrhythmia ($22,806). The 3 CV events with the lowest first year total direct costs were CAD ($17,483), atrial arrhythmia ($17,803), and angina ($18,503).
Discussion Hypertensive patients who are at high-risk of experiencing CV events are potentially expensive. Moreover, certain compelling indications and high-risk groups— advanced age, diabetes, CKD, diabetic neuropathy, prior stroke, and prior MI—require greater attention and care.13 New information on the cost of a broad set of CV events in such subgroups can help inform clinicians and payers about the populations at greatest risk of incurring downstream costs from CV events. Targeted prevention efforts and disease management strategies hold opportunities for improving clinical management of hypertension in populations at greatest risk of such high-cost events, and may potentially reduce costs from CV events that are more likely to occur in at-risk populations. In this study, we conducted a retrospective claims-based analysis to assess the incremental direct healthcare costs from CV events in hypertensive patients who were diagnosed and treated for any of 10 CV events, with a focus on certain high-risk subgroups. Patients with CV events on an average were 10 years older and had a higher percentage of patients with agerelated baseline comorbidities than patients without a CV event. Although the Tobit regressions controlled for age as a confounding variable, the age-related cost differences in certain CV event subgroups may not have been adequately controlled. Interestingly, patients enrolled in an indemnity plan were more likely to have an event than other insurance coverage groups potentially reflecting ‘‘adverse selection’’ into indemnity policies. Indemnity plans are the most expensive healthcare insurance options that offer flexibility regarding provider selection and service utilization. People who need extensive treatment tend to stay in the plan because it is undesirable to change physicians interrupting the treatment. Inpatient costs for CV events are an important contributor to incremental increases in direct healthcare costs among patients with hypertension. For the base population of all hypertension patients, inpatient costs accounted for more than 50% of incremental direct costs in all CV events. Outpatient costs ranged from 22% to 42% of total
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Table 4 Incremental average monthly healthcare costa of CV events for chronic disease subgroups of hypertension patients CV event
Diabetes n ¼ 262,423 $PMPM
Acute myocardial infarction Inpatient 1,455 Outpatient 451 Drugs 69 Total healthcare 1,574 Acute coronary syndrome Inpatient 396 Outpatient 307 Drugs 33 Total healthcare 578 Angina Inpatient 576 Outpatient 297 Drugs 59 Total healthcare 608 Ventricular arrhythmia Inpatient 612 Outpatient 483 Drugs 82 Total healthcare 979 Atrial arrhythmia Inpatient 537 Outpatient 351 Drugs 58 Total healthcare 666 Congestive heart failure Inpatient 990 Outpatient 480 Drugs 76 Total Healthcare 1,071 Coronary artery disease Inpatient 472 Outpatient 304 Drugs 74 Total healthcare 618 Left ventricular hypertrophy Inpatient 715 Outpatient 481 Drugs 46 Total healthcare 955 Stroke and transient ischemic attack Inpatient 611 Outpatient 331 Drugs 56 Total healthcare 658 Sinus tachycardia Inpatient 598 Outpatient 319 Drugs 34 Total healthcare 643
CKD n ¼ 9,874
Diabetic nephropathy n ¼ 7,893
95% CI
$PMPM
95% CI
$PMPM
95% CI
1,445–1,466 442–460 66–72 1,553–1,595
2,285 337 58 1,356
2,227–2,343 293–382 47–68 1,260–1,452
2,115 429 41 1,617
2,022–2,209 367–491 10–71 1,460–1,775
372–421 290–325 28–39 537–618
660 280 3b 406
497–822 161–399 24–31 169–643
712 101b 19b 387
479–946 45–248 28–65 24–750
569–583 292–303 57–60 596–620
1,051 259 88 613
1,002–1,101 224–294 80–96 541–686
1,120 272 73 961
1,046–1,195 229–315 60–86 852–1,070
593–631 468–497 77–86 945–1,012
1,069 387 99 792
979–1,159 319–456 83–115 652–933
1,037 261 14b 745
883–1,192 159–364 16–45 496–994
530–545 346–356 57–60 655–678
1,221 423 78 922
1,177–1,264 396–450 72–84 864–980
1,123 389 45 821
1,052–1,194 349–430 33–57 718–923
984–997 476–485 74–77 1,059–1,082
1,734 489 68 1,201
1,692–1,776 468–511 64–73 1,150–1,253
1,656 540 55 1,344
1,605–1,706 510–569 48–63 1,274–1,413
467–478 301–307 73–75 611–625
969 294 102 772
932–1005 276–311 97–107 731–814
707 329 66 729
707–724 475–487 44–48 941–969
1,603 454 57 1,169
1,554–1,653 420–488 49–65 1,095–1,244
1,621 644 22 1,406
1,552–1,690 601–688 9–34 1,298–1,515
605–616 327–335 55–57 649–666
1,183 319 66 825
1,144–1,222 297–341 61–72 775–875
1,040 413 42 841
985–1,094 384–443 34–51 768–915
588–607 312–326 31–36 626–659
1,335 240 70 699
1,282–1,388 203–278 61–79 618–779
922 594 43 918
822–1,022 533–656 24–61 766–1,070
661–754 307–351 59–72 674–784
CI, confidence interval; CKD, chronic kidney disease; CV, cardiovascular; PMPM, per-member per-month. Regression-adjusted costs based on Tobit specification with covariates for age, gender, insurance plan type, geographic region, comorbidity, and months between hypertension diagnosis and CV event. Each cost category was estimated separately, thus total direct costs are not equal to the sum of cost categories. b All P < .05 for the test of the null hypothesis of incremental costs being equal to 0 unless marked with b. a
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Table 5 Incremental average monthly healthcare costsa of CV events for elderly, prior stroke, and prior myocardial infarction subgroups of hypertension patients CV event
Elderly n ¼ 318,861 $PMPM
Acute myocardial infarction Inpatient 895 Outpatient 311 Drugs 91 Total healthcare 990 Acute coronary syndrome Inpatient 272 Outpatient 236 Drugs 59 Total healthcare 432 Angina Inpatient 332 Outpatient 207 Drugs 64 Total healthcare 419 Ventricular arrhythmia Inpatient 337 Outpatient 266 Drugs 84 Total healthcare 516 Atrial arrhythmia Inpatient 338 Outpatient 260 Drugs 59 Total healthcare 475 Congestive heart failure Inpatient 535 Outpatient 306 Drugs 78 Total healthcare 644 Coronary artery disease Inpatient 263 Outpatient 203 Drugs 73 Total healthcare 413 Left ventricular hypertrophy Inpatient 387 Outpatient 263 Drugs 50 Total healthcare 521 Stroke and transient ischemic attack Inpatient 328 Outpatient 219 Drugs 58 Total healthcare 420 Sinus tachycardia Inpatient 328 Outpatient 200 Drugs 38 Total healthcare 388
Prior stroke n ¼ 61,385
Prior MI n ¼ 9,723
95% CI
$PMPM
95% CI
$PMPM
888–901 306–316 89–93 978–1,002
1,315 362 42 1,297
1,283–1,348 344–380 38–47 1,250–1,345
1,035 211 19 631
95% CI 920–1,150 172–250 27–11 505–757
259–285 227–245 55–62 411–453
341 215 7b 410
271–411 180–249 2–16 321–498
709 247 1b 631
551–867 190–305 11–13 445–817
328–336 204–209 63–65 412–426
497 245 44 476
473–521 234–257 41–47 446–506
636 142 19 555
579–694 121–163 14–23 487–622
327–348 258–273 81–87 498–534
684 323 51 782
632–735 295–350 44–58 712–852
1,299 554 35 1,636
1,136–1,463 493–615 23–48 1,436–1,837
334–341 258–262 58–59 469–480
499 290 29 539
480–518 281–299 27–31 515–562
970 285 15 879
880–1,059 256–315 9–22 776–982
531–539 303–308 77–79 638–651
971 394 53 879
951–992 384–404 51–56 852–906
1,278 397 40 1,139
1,205–1,350 372–421 34–45 1,059–1,218
259–266 201–205 73–74 409–417
334 208 51 446
320–348 202–214 50–53 431–462
48 64 6 108
5–92 50–78 2–10 61–154
382–392 260–266 49–51 514–529
721 329 19 758
697–746 316–342 16–22 726–791
1,098 332 2b 992
986–1,210 291–373 10–7 855–1,128
325–331 217–221 58–59 415–424
130 91 16 153
119–141 86–97 15–18 140–165
1,240 356 6 1,013
1,157–1,324 327–384 0–12 917–1,108
323–333 197–203 37–39 380–396
614 246 29 532
589–639 233–259 25–32 499–565
1,122 251 20 910
1,012–1,231 210–291 11–28 778–1,043
CI, confidence interval; CV, cardiovascular; MI, myocardial infarction; PMPM, per-member per-month. Regression-adjusted costs based on Tobit specification with covariates for age, gender, insurance plan type, geographic region, comorbidity, and months between hypertension diagnosis, and CV event. Each cost category was estimated separately, thus total direct costs are not equal to the sum of cost categories. b All P < .05 for the test of the null hypothesis of incremental costs being equal to 0 unless marked with b. a
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Table 6 Trend in average quarterly direct healthcare costs surrounding cardiovascular events in a hypertension population CV event
Acute myocardial infarction Inpatient Outpatient Drugs Total healthcare Acute coronary syndrome Inpatient Outpatient Drugs Total healthcare Angina Inpatient Outpatient Drugs Total healthcare Ventricular arrhythmia Inpatient Outpatient Drugs Total healthcare Atrial arrhythmia Inpatient Outpatient Drugs Total healthcare Congestive heart failure Inpatient Outpatient Drugs Total healthcare Coronary artery disease Inpatient Outpatient Drugs Total healthcare Left ventricular hypertrophy Inpatient Outpatient Drugs Total healthcare Stroke/transient ischemic attack Inpatient Outpatient Drugs Total healthcare Sinus tachycardia Inpatient Outpatient Drugs Total healthcare
PMPM quarterly healthcare costs Q2 Pre-event
Q1 Pre-event
Q1 Post-event
Q2 Post-event
Q3 Post-event
Q4 Post-event
12,369 668 1,063 538 2,268 2,938 488 1,200 639 2,327 43,505 406 1,022 581 2,008 4,368 1,294 1,475 674 3,442 50,645 2,447 1,100 617 546 50,105 1,064 1,570 768 3,402 175,680 680 1,109 698 2,488 31,867 582 1,390 599 2,570 110,827 625 1,162 642 2,429 27,814 592 1,252 580 2,424
12,369 1,624 1,311 563 3,497 2,938 762 1,391 670 2,823 43,505 529 1,210 593 2,332 4,368 1,810 1,756 713 4,279 50,645 3,259 1,382 638 632 50,105 1,872 1,889 796 4,558 175,680 907 1,316 711 2,933 31,867 1,211 1,693 627 3,530 110,827 997 1,335 660 2,992 27,814 1,117 1,583 593 3,293
12,369 20,896 4,338 925 26,160 2,938 4,449 3,508 778 8,735 43,505 4,765 3,959 716 9,439 4,368 6,117 3,746 764 10,627 50,645 7,119 2,631 714 1,071 50,105 6,145 3,517 889 10,550 175,680 3,669 2,926 798 7,393 31,867 5,450 3,857 707 10,015 110,827 4,182 3,184 758 8,124 27,814 4,945 3,523 684 9,152
1,2,369 1,876 2,195 852 4,923 2,938 1,139 1,823 766 3,727 43,505 991 1,491 704 3,186 4,368 1,684 2,079 781 4,545 50,645 3,721 1,724 708 714 50,105 2,191 2,562 886 5,639 175,680 1,122 1,515 792 3,429 31,867 1,570 2,336 708 4,614 110,827 1,260 1,750 763 3,773 27,814 1,171 1,885 671 3,727
1,2,369 1,542 1,815 818 4,175 2,938 1,209 1,523 764 3,496 43,505 817 1,419 694 2,930 4,368 1,127 1,903 766 3,796 50,645 3,464 1,557 696 692 50,105 2,118 2,374 866 5,358 175,680 1,039 1,474 788 3,301 31,867 1,344 2,060 692 4,096 110,827 171 1,577 755 3,403 27,814 987 1,629 663 3,279
11,189 1,311 1,640 833 3,783 2,742 959 1,324 774 3,057 40,157 839 1,388 721 2,948 4,032 1,211 1,825 803 3,839 46,396 3,499 1,541 719 647 44,861 1,881 2,296 890 5,068 163,845 1,098 1,455 808 3,361 29,206 1,179 1,940 718 3,838 101,244 1,019 1,538 774 3,331 25,605 983 1,614 675 3,272
Q1 to Q4 Post-event 25,625 9,987 3,429 39,041 7,756 8,178 3,081 19,016 7,412 8,256 2,835 18,504 10,139 9,553 3,114 22,806 17,803 7,454 2,837 3,125 12,335 10,749 3,531 26,615 6,927 7,370 3,186 17,484 9,544 10,194 2,825 22,562 7,533 8,048 3,050 18,631 8,086 8,651 2,693 19,430
CI, confidence interval; CV, cardiovascular; PMPM, per-member per-month; Q1, first-quarter; Q2, second-quarter; Q3, third-quarter; Q4, fourth-quarter.
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healthcare costs, whereas prescription drugs generally accounted for less than 8% of total healthcare costs. Findings were consistent across subgroups and the importance of inpatient costs was most pronounced in patients with CKD, diabetic nephropathy, a prior MI, or prior stroke. On the whole, incremental costs of CV events across all subgroups were positive and statistically significant for direct healthcare costs in hypertension patients after the CV event. Although this result is not unexpected, we observed statistically insignificant, and in some cases negative incremental costs of prescription drugs. After controlling for confounding factors in the multivariate analysis, we observed no prescription drug cost increases for some event/subgroup combinations, particularly in patients suffering a second CV event of AMI, ACS, and LVH. This observation occurred more often among patients with prior MI subgroup. The finding that inpatient and outpatient costs were higher than in the control population after the second event is intuitive; however, the occurrence of a CV event may not necessarily dictate an increase in prescription drug costs, particularly with prior MI and prior stroke patients. Patients suffering a second CV event may simply have their prescription regimen modified, which may or may not result in additional costs. As is the case in many analyses of administrative cost data, between-group differences in costs may be due to potential unobservable and confounding variables, especially those variables that indicate disease severity. Nevertheless, there were important subgroup differences. For example, diabetic patients with hypertension had greater costs associated with acute MI than did any other subgroup; and those with CKD had greater costs associated with CHF, LVH, and ST than did any other subgroup. Our assessment of pre-event and post-event healthcare costs for 10 CV events indicates that costs of CV events in hypertension patients extend to pre- and post-event periods, with most of the costs immediately after the event being attributable to inpatient stays. The result that most immediate post-event costs were attributable to inpatient stays is consistent with another study, which focused on 12-month costs after a diagnosis of ACS.17 For each of the 10 CV events analyzed here, however, outpatient costs composed a substantial portion of total healthcare costs in the second-, third-, and fourth-quarters after event occurrence. Treatment of hypertension with antihypertensive medications, particularly in the pre-hypertension stage decreases CV morbidity and mortality.23 One implication of our study findings is that a reduction in CV events would result in significant cost savings across all subgroups, particularly for healthcare costs associated with hospitalization, but also potentially for outpatient costs incurred over a longer period after an event. The documented clinical and resource utilization benefits of antihypertensive treatments support the economic hypothesis that reduced CV events will translate into overall cost savings in both direct inpatient and outpatient costs.
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The study findings of substantial cost differences between CV and non-CV event groups and within subgroups among patients with hypertension are consistent with a limited number of studies addressing direct healthcare costs associated with CV complications of hypertension.2,16–19 These published studies include total or average costs of some CV events, but not incremental costs of a broad set of specific CV events or subgroup populations. However, they may provide a general frame of reference for the findings we present in this article. In terms of magnitude, our findings are consistent with the literature in that conditions such as CHF and stroke are associated with high disease-attributable costs in comparison to hypertension,18 which is likely to result in severe and costly conditions without aggressive treatment. Authors of one study reported hypertension-related costs associated with CV events. Using American Heart Association data, Flack and colleagues reported average per-patient hypertensionrelated healthcare costs of $26,000 in the first year after stroke: $19,100 for MI and $5,500 for CHF.2 Estimates for stroke and MI were drawn from the 1999 National Inpatient Profile and the opinions of a physician consultant on outpatient and pharmaceutical use in the year following an event. CHF estimates were drawn from data presented in the 2003 American Heart Association statistical update. In our study, acute MI and CHF were the CV events associated with the highest incremental healthcare costs among all hypertension patients. The estimates of Flack and colleagues are not directly comparable to the incremental cost estimates presented in our article because both the methods and data employed in each study. Moreover, the use of claims data in our study allowed cost estimates to be calculated from diagnoses recorded on administrative data and actual payments to providers at the patient level. Our estimates of the overall economic impact associated with CV events in hypertension patients are likely to conservatively reflect true incremental costs. One limitation of obtaining costs of severe medical events from administrative data is that death is unobservable in the data unless the event is recorded as a death on diagnosis. Residual claims after death from any one of the CV events may be included in our data, but because deceased patients will no longer incur additional charges, CV events that are more likely to result in death (compared with the control group) will appear to have lower incremental costs. In addition, in identifying certain subgroups like CKD and diabetes, we excluded patients with end-stage organ disease; patients such as those undergoing renal dialysis and patients with retinopathy are likely to have severe disease and high- costs. Thus, exclusion of more severely ill patients will also lead to conservative estimation of incremental costs. Limitations frequently encountered in the use of claims data apply to the findings reported in this article. As is typical in such studies, the data do not include information on patient race, ethnicity, or income. Lack of information
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on these unobservable characteristics reduces the ability to control for potentially important confounding variables in the multivariate analysis. Claims data also do not include information on duration and severity of hypertension, which further limits our analytical ability to control for or stratify by these factors. Furthermore, in this study, we included all patients with hypertension regardless of antihypertensive treatments, as we are interested in the economics of hypertension. However, because hypertensive patients receiving treatment may be different, probably clinically more severe, than patients not prescribed treatment, the costs in treated patients are probably higher. This effect modification by treatment has not been addressed in this article. Clinical coding variation may also be a limiting factor. CV events such as LVH do not typically have nearly as discrete an onset as an event-like CHF because of insensitivities of electrocardiogram. Thus, costs before and after the claim should be interpreted with caution. Costs presented in this study may vary from those of other private or public insurers. This study focused on the portion reimbursed by the employer, which included all discounts and was net of the following amounts: excluded expenses, deductible, coinsurance, copay, coordination of other benefits, and other adjustments. Although a large portion of hypertensive patients are elderly and are on Medicare, the present study focuses on costs from the employer payer perspective.
Conclusion A spectrum of CV events occurring in multiple high-risk subgroups results in substantial incremental direct healthcare costs. Incremental costs vary across CV events and are largely driven by increases in the cost of inpatient care; however, trends in healthcare costs incurred by hypertension patients before and after a CV event indicate that outpatient care is also a contributor to post-event costs over the longer term. Our findings may be set in the context of the knowledge base suggesting that use of antihypertensive medications reduces the incidence of CV events and associated costs. Improvements in the prevention and management of hypertension through the use of antihypertensive medications, especially those that are effective in specific subgroups (ie, patients with compelling indications) could result in significant savings in healthcare expenditures, particularly through avoidance of high-cost care in inpatient settings.
References 1. Agency for Healthcare Research and Quality. Effective healthcare. Available at: http://effectivehealthcare.ahrq. gov/getInvolved.cfm?involvetype¼rs&topicID¼93& source¼current. Accessed: July 21, 2009.
2. Flack JM, Casciano R, Casciano J, Doyle J, Arikian S, Tang S, et al. Cardiovascular disease costs associated with uncontrolled hypertension. Managed Care Interface 2002;15:28–36. 3. Kung HC, Hoyert DL, Xu JQ, Murphy SL. Deaths: final data for 2005. National Vital Statistics Reports (Vol. 56, No. 10). Hyattsville, Maryland: National Center for Health Statistics; 2008. 4. Vasan RS, Beiser A, Seshadri S, Larson MG, Kannel WB, D’Agustino RB, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: the Framingham Heart Study. JAMA 2002;287: 1003–10. 5. Kannel WB. Some lessons in cardiovascular epidemiology from Framingham. Am J Cardiol 1976;37: 269–85. 6. Selby JV, Peng T, Karter AJ, Alexander M, Sidney S, Lian J, et al. High rates of co-occurrence of hypertension, elevated low-density lipoprotein cholesterol, and diabetes mellitus in a large managed care population. Am J Managed Care 2004;10:163–70. 7. Dickey RA, Janick JJ. Lifestyle modifications in the prevention and treatment of hypertension. Endocrine Practice 2001;7:92–9. 8. Druss BG, Marcus SC, Olfson M, Tanielian T, Elinson L, Pincus HA. Comparing the national economic burden of five chronic conditions. Health Affairs 2001;20: 233–41. 9. Hodgson TA, Cohen AJ. Medical care expenditures for selected circulatory diseases: opportunities for reducing national health expenditures. Med Care 1999;37: 994–1012. 10. Hodgson TA, Cai L. Medical care expenditures for hypertension, its complications, and its comorbidities. Med Care 2001;39:599–615. 11. Hing E, Cherry DK, Woodwell DA. National Ambulatory Medical Care Survey: 2004 summary. Advance Data 2006;374:1–36. 12. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1205–52. 13. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560–72. 14. Mancia G. Treatment of hypertension and ischemic heart disease. J Cardiovasc Pharmacol 1989;14: S12–9. 15. Cutler DM, Long G, Berndt ER, Royer J, Fournier AA, Sasser A, et al. The value of antihypertensive drugs: a perspective on medical innovation. Health Affairs 2007;26:97–110.
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16. Javitz HS, Ward MM, Watson JB, Jaana M. Cost of illness of chronic angina. Am J Managed Care 2004; 10:S358–69. 17. Etemad LR, McCollam PL. Total first-year costs of acute coronary syndrome in a managed care setting. J Managed Care Pharm 2005;11:300–6. 18. Trogdon JG, Finkelstein EA, Nwaise IA, Tangka FK, Orenstein D. The economic burden of chronic cardiovascular disease for major insurers. Health Promotion Pract 2007;8:234–42. 19. Mensah GA, Brown DW. An overview of cardiovascular disease burden in the United States. Health Affairs 2007;26:38–48. 20. Jackson JH, Frech F, Ronen R, Mullany L, Lennert B, Jhaveri V. Assessment of drug therapy management
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and the prevalence of heart failure in a managed care population with hypertension. J Managed Care Pharm 2004;10:513–20. 21. Margolis KL, Piller LB, Ford CE, Henriquez MA, Cushman WC, Einhorn PT, et al. Blood pressure control in Hispanics in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Hypertension 2007;50:854–61. 22. Romano PS, Roos LL, Jollis JG. Adapting a clinical comorbidity index for use with ICD-9-CM administrative data: differing perspectives. J Clin Epidemiol 1993;46: 1075–9, discussion: 1081–90. 23. Palmer BF. Management of hypertension in patients with chronic kidney disease and diabetes mellitus. Am J Med 2008;121:S16–22.
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Research Article
Costs associated with cardiovascular events in patients with hypertension in US managed care settings Mei Sheng Duh, MPH, ScDa,*, Nicole M. Fulcher, MAa, Leigh Ann White, PhDa, Sujata S. Jayawant, PhDa, Priyanka Ramamurthy, BAa, Erick Moyneur, MAa, and Siew Hwa Ong, MScb a Analysis Group, Inc., Boston, Massachusetts, USA; and Global Health Economics & Outcomes Research, Novartis Pharma AG, Basel, Switzerland Manuscript received June 12, 2009 and accepted September 8, 2009
b
Abstract Study quantified incremental cost of cardiovascular (CV) events in 6 high-risk and compelling indication subgroups: postmyocardial infarction (MI), diabetes, diabetic nephropathy, elderly, chronic kidney disease, and prior stroke. Based on claims data from privately insured individuals with 2þ hypertension (HTN) diagnoses in 2004–2006, we estimated regression-adjusted per-member-per-month healthcare costs after CVE. Costs were compared between patients with and without a CV events, and before and after CVevents in each subgroup. The following CVevents were studied: acute MI, acute coronary syndrome, angina, ventricular arrhythmia, atrial arrhythmia, heart failure, coronary artery disease, left ventricular hypertrophy, stroke, and sinus tachycardia. Of 1,598,890 HTN patients, 510,118 had 1 CV event. Compared with controls, healthcare costs among patients with events were significantly greater across all cost components (inpatient, outpatient, and prescription drug). Acute MI and congestive heart failure generally had the largest incremental total healthcare costs. First-quarter post-event costs were attributable to inpatient costs. CV events are costly sequelae of hypertension in high-risk and CI subgroups. J Am Soc Hypertens 2009;3(6):403–415. Ó 2009 American Society of Hypertension. All rights reserved. Keywords: Healthcare costs; outcome assessment (healthcare); hypertension; cardiovascular diseases.
Introduction Hypertension, a risk factor for cardiovascular (CV) and cerebrovascular disease, is a substantial public health problem affecting more than 70 million people in the United States and has a wide spectrum of symptom manifestations, ranging from asymptomatic high blood pressures to stroke, heart failure, heart attack, kidney failure, and vision impairment.1–3 Although its exact causes are unknown, several factors and conditions including age, physical inactivity, dyslipidemia, glucose intolerance, left ventricular hypertrophy, obesity, alcohol consumption,
This study was funded by Novartis Pharma AG, Basel, Switzerland. The results of the study were not contingent on the funding. Conflict of interest: none. *Corresponding author: Mei Sheng Duh, MPH, ScD, Analysis Group, Inc., 111 Huntington Avenue, 10th Floor, Boston, Massachusetts 02199. Tel: 617-425-8131; fax: 617-425-8001. E-mail: [email protected]
and cigarette smoking play a role in the development of hypertension.4–7 Healthcare costs for the treatment of hypertension and its complications are substantial, with estimates ranging from $15 billion to approximately $60 billion.8,9 Hodgson and colleagues estimated hypertension-related CV complications accounting for approximately $30 billion.10 Despite the high costs, it is still one of the most poorly controlled conditions, and approximately 30% of individuals remain undiagnosed.11,12 It is estimated that the cumulative lifetime risk of developing hypertension (140/90 mm Hg) is approximately 90% in patients ages 55–85.13 Guidelines from the Joint National Committee (JNC 7) on Detection, Evaluation, and Treatment of Hypertension contain a clearly defined treatment goal for management of hypertension involving combination of lifestyle modifications, such as modifications in diet, exercise, and alcohol consumption, and pharmacotherapy. Treatment with antihypertensive medications has been shown to significantly reduce CV morbidity and mortality, with efficacy demonstrated for the majority of CV diseases.14,15 According to the JNC 7,
1933-1711/09/$ – see front matter Ó 2009 American Society of Hypertension. All rights reserved. doi:10.1016/j.jash.2009.09.001
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presence of compelling indications, such as myocardial infarction (MI), coronary diseases, diabetes, chronic kidney disease (CKD), and stroke as well as older age, in patients with hypertension is considered high-risk for development of CV disease.13 Estimating the cost of CV events in hypertensive patients and in those with compelling indications or at high-risk of CV events (eg, elderly) provides a more accurate assessment of potential savings to payers that may accrue from prevention and treatment of hypertension. Few studies have provided estimates of the cost of CV events in samples of hypertension patients. In studies that have included estimates of CV event costs, researchers have focused on specific conditions such as chronic angina16 and acute coronary syndrome (ACS)17 without limiting the study population to hypertension patients or providing a broad set of estimates on CV events in hypertensive patients. Etemad and colleagues analyzed 12-month healthcare costs after onset of ACS and found that total medical and pharmacy costs incurred by the health plan and patients was $2,312 per patient per month of follow-up, with 72% of the total cost attributable to hospitalizations.17 Studies with a broader focus have included cost estimates for CV diseases such as hypertension, coronary heart disease, stroke, and congestive heart failure; however, as in the Hodgson Study, most authors have relied on survey data (ie, self-reports) rather than administrative data, which are more likely to reflect real-world clinical practice.18,19 No studies, to the authors’ knowledge, have included cost estimates for individual CV events based on multiple JNC 7 indications, nor have any studies included time trends in costs surrounding the occurrence of a CV event. The objective of this study is to quantify direct incremental CV event–specific costs in patients with hypertension, particularly those patients with increased risk of developing a CV event. Data on the incremental costs of CV events in hypertensive patients are valuable both to understand the importance of preventing these events and to assess their impacts on healthcare costs. In this article, we present estimates of direct healthcare costs associated with 10 CV events in a cohort of hypertension patients, based on analysis of a large healthcare claims database. We present estimates of incremental costs of CV events in specific subgroups for which aggressive treatment of hypertension is indicated: the elderly and patients with comorbidities of diabetes, diabetic nephropathy, CKD, prior myocardial infarction, or prior stroke. In addition, we present time trend analyses of pre-event and post-event costs, of each of the 10 CV events.
Methods Data Source This study used administrative claims data from the Thomson MedStat MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination
of Benefits (Medicare) databases for the period January 1, 2004 to December 31, 2006. The MedStat MarketScan databases contain the inpatient medical service claims, outpatient medical service claims, and outpatient prescription drug claims of more than 10 million employees, dependents, and retirees covered through a variety of privately insured employer-based health plans. The Medicare Supplemental database includes approximately 1 million individuals with employer-funded coverage. For the Medicare population, both the Medicare-paid and employer-paid amounts for services are included. The databases include patient demographics and health plan enrollment information, inpatient and outpatient diagnoses and procedures, and outpatient prescription drug dispensing claims for all patients. Diastolic and systolic blood pressure readings were not available. Diagnosis-specific claims were identified by International Classification of Diseases, 9th Revision (ICD-9) codes and prescription drugs claims by National Drug Codes. Medical procedures were coded using Current Procedural Terminology codes, Healthcare Common Procedure Coding System codes, and ICD-9 procedure codes.
Study Population The base case population for this study was comprised of all hypertension patients that met sample selection criteria. To be included in the base case population, patients had to have at least two medical claims carrying the following essential or secondary hypertension diagnosis codes: essential hypertension (ICD-9 codes: 401.xx), hypertensive heart disease (ICD-9 codes: 402.xx), hypertensive CKD (ICD-9 codes: 403.xx), hypertensive heart and CKD (ICD-9 codes: 404.xx), and secondary hypertension (ICD-9 codes: 405.xx). We included other hypertension diagnosis codes, such as hypertension secondary to renovascular disorders or to endocrine disorders, because preliminary examination of the claims data suggested that coding misclassifications between essential and secondary hypertension ICD-9 codes were likely to occur in favor of the later; thus, exclusion of 405.xx would not necessarily exclude secondary cases. In other studies using claims data to examine hypertensionrelated CV outcomes, selection criteria for hypertensive patients have included ICD-9 codes for secondary hypertension.20,21 The observation period for the base case population began on the service date of the first hypertension claim (the index event), then continued until the date of disenrollment, the defined study end date (December 31, 2006), or progression to end-stage renal disease (ESRD), whichever occurred first. We imposed additional criteria to select a population aged 18 years or older at the time of the index event and that was continuously enrolled 6 months before and 6 months after the date of index event. Progression to ESRD was indicated when a claim contained
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dialysis-related procedures: (Current Procedural Terminology codes: 90919–90998, 99512, 99559; ICD-9 procedure codes: 39.95, 54.98; Healthcare Common Procedure Coding System codes A4690, A4820, A4900, A4901, A4905, E1510, E1590, E1592, E1594, E1632, E1635) or ESRD-related or dialysis-related diagnosis codes (ICD-9 codes: V451, V56, V560, V561, V562, V5631, V5632, V568, E8702, E8712, E8722, E8742, E8791, 996.56, 996.73, 58.56). There were 1,599,549 patients who met the inclusion criteria for the study population. From the hypertension or base case population, we created 6 mutually nonexclusive subgroups of patients with CV events based on JNC’s recommendations regarding compelling indications or high-risk groups. The 6 groups were elderly patients and patients with the following conditions: diabetes, diabetic nephropathy, CKD, prior MI, and prior stroke. The 6 subgroups were defined as: 1. Elderly patients were 65 years or older at the time of initial diagnosis for hypertension. 2. Diabetes patients had at least two medical claims carrying a diabetes diagnosis code (ICD-9 codes: 250.0, 250.x0, 250.x2). 3. Diabetic nephropathy patients had at least two medical claims carrying a diabetic nephropathy diagnosis code (ICD-9 codes: 250.40, 250.42, 580.xx, 581.xx, 582.xx, 583.xx). 4. CKD patients had at least two medical claims carrying a CKD diagnosis (ICD-9 codes: 585.xx, 586.xx). These codes exclude ESRD and diabetic nephropathy. 5. Prior MI patients had at least two medical claims carrying a diagnosis of acute MI (AMI; ICD-9 codes: 410.xx). 6. Prior stroke patients had at least two medical claims carrying a diagnosis of stroke (ICD-9 codes: 430.xx, 431.xx, 432.xx, 433.xx, 434.xx, 435.xx, 436.xx, 437.xx). The observation period for each subgroup population began on the service date of the first hypertension claim or the service date of the first subgroup qualifying claim, whichever occurred later. The observation ended at the disenrollment date.
Definition of CV Event Outcomes To quantify the incremental costs of CV event occurrence, we identified 10 CV events in the sample of hypertension patients described previously. Patients with at least one medical claim after their observation start date for any of the 10 CV events constituted the pool of patients with at least one of the 10 CV events (Table 1). Based on the literature review of CV events, the events most common in patients with hypertension were chosen for this study. The CV events are acute myocardial infarction (AMI), ACS, angina, serious ventricular arrhythmia, serious atrial
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arrhythmia, congestive heart failure (CHF), coronary artery disease (CAD), left ventricular hypertrophy (LVH), stroke or transient ischemic attack, and sinus tachycardia (ST). We initially considered the CV events sudden death and cardiac arrest, but because of insufficient numbers of cases and the likelihood that we would not be able to observe costs after death, these events were excluded from the analysis. Exclusion of these events reduced the sample from 510,624 to 510,118 patients with hypertension. Table 1 contains the list of CV events and corresponding diagnosis codes used to identify each event. Patients with multiple CV events were classified based on their first (index) CV event. Patients in the prior stroke and prior MI subgroups were classified in the 10 CV event groups based on the second (index) CV event (ie, the event after stroke or MI). Patients who died within the 6 months from the index date were excluded. Deaths are not comprehensively captured in claims data, because disenrollment reason is not listed. We were able to identify only deaths occurred in a healthcare facility based on the ICD-9 codes of sudden death. The person-time of observation stopped when the patient is disenrolled. We assigned patients to a CV event group based on their observed CV event, termed index event. The index date was defined as the earlier date of first outpatient visit, inpatient hospitalization, or emergency room visit associated with that CV event. CV events were identified based on principal diagnosis (first ICD-9 code field). For patients in the prior MI and prior stroke subgroups, we assigned an index CV event based on the first CV event after the AMI or stroke event. That is, for the prior MI (or prior stroke) subgroup, their index date was the service date of their second event. At least 60 days between the claims for the first and second MI (or stroke) must have passed for assignment of an index CV event in the prior MI (prior stroke) subgroup. We imposed this additional criterion to ensure that any subsequent claims for MI (or stroke) within 60 days for the first MI (or stroke) event constituted follow-up or treatment related to the initial MI (or stroke) and that the patient did, indeed, suffer a second event. Remaining hypertension patients who had no claims for CV events after their first hypertension claim composed the no-CV event group, or the control group. For the control group, we imputed a faux index date to compare the cost of CV-event groups. The faux index date was defined as the service date of the first hypertension claim plus an imputed measure of a faux pre-CV event period that matched the distribution of the patient-months between the first hypertension claim date and the first CV event claim date of the CV event group. This index date ensured that the control group would not be systematically observed for a longer period of time compared to the CV event group. For subgroups, comparisons were made with patients having the risk (older age) or conditions (eg, diabetes), but no index CV event.
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Table 1 ICD-9 diagnosis codes used to identify cardiovascular events Cardiovascular event
ICD-9 codes
Description
Acute myocardial infarction Acute coronary syndrome
410.xx 411.0x 411.81 411.89 411.1x 413.xx 427.1x 427.4x 427.3x 428.xx 414.0x 414.1x 414.8x 414.9x 429.3x 430.xx 431.xx 432.xx 433.xx 434.xx 435.xx 436.xx 437.xx 427.89
Acute myocardial infarction Postmyocardial infarction syndrome Acute coronary occlusion without myocardial infarction Other Intermediate coronary syndrome (unstable angina) Angina pectoris (stable angina) Paroxysmal ventricular tachycardia Ventricular fibrillation and flutter Atrial fibrillation and flutter Heart failure Coronary atherosclerosis Aneurysm and dissection of heart AHA Other specified forms of chronic ischemic heart disease Chronic ischemic heart disease, unspecified Cardiomegaly Subarachnoid hemorrhage Intracerebral hemorrhage Other and unspecified intracranial hemorrhage Occlusion and stenosis of precerebral arteries Occlusion of cerebral arteries Transient cerebral ischemia Acute, but ill-defined, cerebrovascular disease Other and ill-defined cerebrovascular disease Sinus tachycardia
Angina Ventricular arrhythmia Atrial arrhythmia Congestive heart failure Coronary artery disease
Left ventricular hypertrophy Stroke and transient ischemic attack
Sinus tachycardia
AHA, American Heart Association; ICD-9, International Classification of Disease, 9th Revision.
Pre-Event and Post-Event Periods The pre-event period for all groups consisted of the 6month period preceding the index date. The post-event period for all groups began on the index date and continued to the date of disenrollment, the defined study end date (December 31, 2006) or progression to ESRD, whichever occurred first. For all analyses, we imposed the criterion that patients have a minimum of 6 months continuous enrollment in both the pre-event and post-event periods. Patients not meeting these minimum observation time criteria were excluded from the study. Baseline characteristics reported for the sample reflect the 6-month period preceding the index date.
Cost Measurement We calculated per member per month (PMPM) direct healthcare costs (inpatient, outpatient, and pharmacy) over the post-event period for each patient in the study cohort. Direct healthcare costs considered in this study were the total paid amounts to providers for medical services, as recorded at the claims level. To analyze trends in the cost burden of patients before and after the CV event as well as the extent of cost escalation before the onset of an event, quarterly univariate cost estimates were calculated for two-quarters before the CV event (6-month
baseline period) and up to four-quarters after the index date. This quarterly breakdown of costs made it possible to compute the first-year costs after CV event for hypertension patients with each type of event. A person-time approach was used to account for different lengths of observation among study subjects due to the nonexperimental study setting. PMPM costs were calculated separately for each patient as the total cost during the follow-up period divided by the patient-months of observation. Therefore, if a patient has a longer observation period than 6 months, all months are considered in the calculation. We required a minimum of 6 months to allow stable estimates of costs; the observation did not truncate at 6 months. In the persontime approach, the costs are aggregated over time without explicit modeling of time patterns. That is why we further conducted trend analysis to examine the cost variability over time. This measurement has the advantages of smoothing cost fluctuations over time, and enabling comparisons across different populations. However, it is also subject to volatility from patients with short duration of observation.
Statistical Analysis A multivariate Tobit regression model was used to evaluate the incremental direct costs attributable to CV events.
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Because healthcare costs are typically continuous over positive values and zero for a nontrivial portion of the data, the error term of estimated models will not be normally distributed. The non-normality of costs is corrected by the employment of Tobit statistical estimation procedures which use all dependent variable observations (costs), including those including those clustered at zero, to obtain efficient parameters describing the relationship between the costs and the explanatory variables. The Tobit analyses estimated average monthly post-event incremental costs by adjusting for factors that were potentially unevenly distributed between the CV event and noCV event control groups. Covariates factors included in the regression model were the patient’s age, age squared, gender, geographic region of residence, health plan type (ie, health maintenance organization, preferred provider organization, and point of service), disease penetration assessed through the number of months from the first hypertension claim, and selected individual comorbidity indicators (chronic diabetes, dementia, hemiplegia, chronic liver disease, mild to moderate liver disease, peptic ulcer disease, rheumatologic disease, HIV/AIDS, peripheral vascular disease, and malignancy/metastatic solid tumors). Comorbidity covariates included in the model represent selected individual components of the Charlson Comorbidity Index.22 The multivariate analyses also adjusted for the costs incurred during the pre-event period for the CV event group, controlling for the baseline costs in estimations of the incremental costs of each CV event. Each cost category (ie, inpatient cost, outpatient cost, prescription drug cost, and total direct cost) was estimated in a separate regression model; because of the non-linearity of the Tobit model, regression results for total direct healthcare costs are not equal to the sum of the individual components (inpatient, outpatient, and prescription drug costs).
Results Patient Baseline Characteristics Of the 1,598,980 patients who met the inclusion criteria for the study population, 510,118 patients (32%) had at least one CV event, and 1,088,862 (68%) patients served as no-CV event controls. There were differences in patient demographic and health characteristics between the CV group and the no-CV event controls (Table 2). CV event patients were older (mean, 67 13 years of age vs. mean, 57 13 years of age) and a larger percentage were male (50.7% vs. 45.7%; P < .0001). Compared with patients with no CV events, patients with CV events were more likely to be enrolled in indemnity plans (22.6% in the no-CV event group vs. 39.1% in the CV event group) than in other types of plans. Conditions commonly present in hypertensive patients, such as diabetes, benign prostatic
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Table 2 Baseline characteristics of hypertension patients with and without cardiovascular events Patients with hypertension No cardiovascular event
Cardiovascular event
Baseline characteristics
n ¼ 1,088,862
n ¼ 510,118
Demographics Age (year), mean SD Male, %
57 13a 45.7a
67 13 50.7
Health plan type (%)b Indemnity HMO POS PPO POS with capitation Other
22.6 19.7 9.0 42.4 1.7 4.6
39.1 19.2 4.8 33.3 0.9 2.7
Geographic region (%)b Northeast North Central South West Unknown
7.1 27.4 45.2 19.8 0.5
7.2 35.5 36.8 19.9 0.7
Selected baseline health conditions (%) Benign prostatic 4.1a hyperplasia Chronic kidney disease 0.3 Diabetes 17.4a Diabetic nephropathy 0.4 Edema and angioedema 3.4a End-stage renal disease 0.3
5.9 0.1 25.3 0.6 5.5 0.1
HMO, health maintenance organization; POS, point of service; PPO, preferred provider organization; SD, standard deviation. a All P < .05 for a test of between-group differences in means or proportions. b Chi-squared test; P < .05 for test of independence.
hyperplasia, and edema/angioedema were more common in CV-event patients than no-CV event controls.
Healthcare Costs Healthcare costs across all cost components were significantly greater for CV event patients compared with no-CV event controls (Table 3). For the base population of all hypertension patients, the direct incremental PMPM costs for specific CV events ranged from $502 (95% CI, $487– $518) for ACS to $1,688 (95% CI, $1,647–$1,729) for CHF. AMI ($1,350; 95% CI, $1,341–$1,358) and CHF events ($1,688; 95% CI, $1,647–$1,729) were associated with the highest incremental monthly total healthcare cost compared with incremental total healthcare costs of other CV events in the $500 to $700 range. Inpatient costs were the largest component of healthcare costs, ranging from
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Table 3 Incremental average monthly healthcare cost of cardiovascular events in a hypertension population Regression-adjusteda healthcare costs
All hypertension patients (n ¼ 510,118) CV event Acute myocardial infarction Inpatient Outpatient Drugs Total healthcare Acute coronary syndrome Inpatient Outpatient Drugs Total healthcare Angina Inpatient Outpatient Drugs Total healthcare Ventricular arrhythmia Inpatient Outpatient Drugs Total healthcare Atrial arrhythmia Inpatient Outpatient Drugs Total healthcare Congestive heart failure Inpatient Outpatient Drugs Total healthcare Coronary artery disease Inpatient Outpatient Drugs Total healthcare Left ventricular hypertrophy Inpatient Outpatient Drugs Total healthcare Stroke and transient ischemic attack Inpatient Outpatient Drugs Total healthcare Sinus tachycardia Inpatient Outpatient Drugs Total healthcare
$PMPMb
Lower 95% CI
Upper 95% CI
1,203 365 81 1,350
1,199 362 80 1,341
1,207 369 82 1,358
325 268 46 502
316 260 44 487
333 275 48 518
413 262 50 504
500 411 260 49
509 416 264 51
438 349 68 714
431 343 66 701
445 355 70 727
395 323 55 578
392 321 55 574
397 325 56 583
1,112 445 23 1,688
1,094 427 17 1,647
1,129 464 29 1,729
323 251 66 507
321 250 65 504
326 253 66 510
436 323 32 617
432 321 32 611
439 325 33 622
427 273 54 541
425 271 53 537
429 274 54 544
400 272 32 503
396 269 31 497
403 274 32 509
CI, confidence interval; CV, cardiovascular; PMPM, per-member per-month. Based on Tobit specification with covariates for age, gender, insurance plan type, geographic region, comorbidity, and months between hypertension diagnosis and CV event. Each cost category was estimated separately, thus total direct costs are not equal to the sum of cost categories. b All P < .05 for the test of the null hypothesis of incremental costs being equal to 0. a
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$323 (95% CI, 321–326; P < .0001) for CAD to $1,203 (95% CI, $1,199–$1,207; P < .0001) for AMI. Outpatient costs across all CV events ranged from $251 (95% CI, 250–253; P < .0001) for CAD to $445 (95% CI, $427– $464; P < .0001) for CHF. A review of the chronic disease and high-risk subgroups revealed that the CV events AMI, CHF, and LVH had the largest incremental total healthcare costs within each subgroup (Table 4). Incremental total healthcare costs ranged from $578 PMPM (95% CI, $537–$618) for ACS to $1,574 PMPM (95% CI, $1,553–$1,595) for AMI in the diabetes subgroup, $406 PMPM (95% CI, $169–$643) for ACS to $1,356 PMPM (95% CI, $1,260–$1,452) for AMI in the CKD subgroup and $387 PMPM (95% CI, $24–$750) for ACS to $1,617 PMPM (95% CI, $1,460– $1,775) for AMI in the diabetic nephropathy subgroup. Consistent with the overall hypertension population, inpatients costs were the largest component of healthcare costs for all CV events. Outpatient costs were the second largest contributor to incremental healthcare costs and were significantly different than no-CV event controls with the exception of ACS in the diabetic nephropathy subgroup. Prescription drug costs were the smallest incremental component for all CV events, and were not significantly different from no-CV event controls for the ACS in the CKD and diabetic nephropathy subgroups. Table 5 contains results for the subgroups of elderly, prior stroke, and prior MI. As with the chronic disease subgroups, inpatient healthcare costs were the largest component, with incremental costs ranging from $263 (95% CI, $259–$266) for CAD to $895 (95% CI, $888– $901) for AMI in the elderly subgroup, from $130 (95% CI, $119–$141) for stroke or transient ischemic attack to $1,315 (95% CI, $1,283–$1,348) for AMI in prior stroke patients, and $48 (95% CI, $5–$92) for CAD to 1299 (95% CI, $1,136–$1,463) for serious ventricular arrhythmia in prior MI patients. Outpatient healthcare costs were the second largest incremental cost component for all CV events within the subgroups of elderly, prior stroke, and prior MI. Among the prior MI patients, incremental drug costs were negative ($19) (95% CI, 27 to 11) for AMI patients, and not statistically significant from no-CV event controls for the CV events of ACS and LVH. Incremental drug costs for ACS in the prior stroke subgroup were also not significant.
Trends in Incremental Costs Average quarterly direct costs (inpatient, outpatient, and pharmacy) are reported in Table 6 for each of the 10 CV events. For all CV conditions, healthcare costs were highest surrounding and immediately following the event. In the pre-event period, quarterly costs were observed to increase from the second-quarter before the event to the first-quarter before the event. After each CV event, quarterly healthcare
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costs peaked in the first-quarter post-event followed by declining costs throughout the next three- quarters, and costs in the fourth-quarter post-event declined to levels near those present in the second-quarter pre-event. Total direct costs in the first-quarter post-event were largely driven by inpatient costs, however in the following threequarters, outpatient costs accounted for the largest part of total direct costs. The three most expensive CV events in the first year after the event were acute MI ($39,041), CHF ($26,614), and ventricular arrhythmia ($22,806). The 3 CV events with the lowest first year total direct costs were CAD ($17,483), atrial arrhythmia ($17,803), and angina ($18,503).
Discussion Hypertensive patients who are at high-risk of experiencing CV events are potentially expensive. Moreover, certain compelling indications and high-risk groups— advanced age, diabetes, CKD, diabetic neuropathy, prior stroke, and prior MI—require greater attention and care.13 New information on the cost of a broad set of CV events in such subgroups can help inform clinicians and payers about the populations at greatest risk of incurring downstream costs from CV events. Targeted prevention efforts and disease management strategies hold opportunities for improving clinical management of hypertension in populations at greatest risk of such high-cost events, and may potentially reduce costs from CV events that are more likely to occur in at-risk populations. In this study, we conducted a retrospective claims-based analysis to assess the incremental direct healthcare costs from CV events in hypertensive patients who were diagnosed and treated for any of 10 CV events, with a focus on certain high-risk subgroups. Patients with CV events on an average were 10 years older and had a higher percentage of patients with agerelated baseline comorbidities than patients without a CV event. Although the Tobit regressions controlled for age as a confounding variable, the age-related cost differences in certain CV event subgroups may not have been adequately controlled. Interestingly, patients enrolled in an indemnity plan were more likely to have an event than other insurance coverage groups potentially reflecting ‘‘adverse selection’’ into indemnity policies. Indemnity plans are the most expensive healthcare insurance options that offer flexibility regarding provider selection and service utilization. People who need extensive treatment tend to stay in the plan because it is undesirable to change physicians interrupting the treatment. Inpatient costs for CV events are an important contributor to incremental increases in direct healthcare costs among patients with hypertension. For the base population of all hypertension patients, inpatient costs accounted for more than 50% of incremental direct costs in all CV events. Outpatient costs ranged from 22% to 42% of total
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Table 4 Incremental average monthly healthcare costa of CV events for chronic disease subgroups of hypertension patients CV event
Diabetes n ¼ 262,423 $PMPM
Acute myocardial infarction Inpatient 1,455 Outpatient 451 Drugs 69 Total healthcare 1,574 Acute coronary syndrome Inpatient 396 Outpatient 307 Drugs 33 Total healthcare 578 Angina Inpatient 576 Outpatient 297 Drugs 59 Total healthcare 608 Ventricular arrhythmia Inpatient 612 Outpatient 483 Drugs 82 Total healthcare 979 Atrial arrhythmia Inpatient 537 Outpatient 351 Drugs 58 Total healthcare 666 Congestive heart failure Inpatient 990 Outpatient 480 Drugs 76 Total Healthcare 1,071 Coronary artery disease Inpatient 472 Outpatient 304 Drugs 74 Total healthcare 618 Left ventricular hypertrophy Inpatient 715 Outpatient 481 Drugs 46 Total healthcare 955 Stroke and transient ischemic attack Inpatient 611 Outpatient 331 Drugs 56 Total healthcare 658 Sinus tachycardia Inpatient 598 Outpatient 319 Drugs 34 Total healthcare 643
CKD n ¼ 9,874
Diabetic nephropathy n ¼ 7,893
95% CI
$PMPM
95% CI
$PMPM
95% CI
1,445–1,466 442–460 66–72 1,553–1,595
2,285 337 58 1,356
2,227–2,343 293–382 47–68 1,260–1,452
2,115 429 41 1,617
2,022–2,209 367–491 10–71 1,460–1,775
372–421 290–325 28–39 537–618
660 280 3b 406
497–822 161–399 24–31 169–643
712 101b 19b 387
479–946 45–248 28–65 24–750
569–583 292–303 57–60 596–620
1,051 259 88 613
1,002–1,101 224–294 80–96 541–686
1,120 272 73 961
1,046–1,195 229–315 60–86 852–1,070
593–631 468–497 77–86 945–1,012
1,069 387 99 792
979–1,159 319–456 83–115 652–933
1,037 261 14b 745
883–1,192 159–364 16–45 496–994
530–545 346–356 57–60 655–678
1,221 423 78 922
1,177–1,264 396–450 72–84 864–980
1,123 389 45 821
1,052–1,194 349–430 33–57 718–923
984–997 476–485 74–77 1,059–1,082
1,734 489 68 1,201
1,692–1,776 468–511 64–73 1,150–1,253
1,656 540 55 1,344
1,605–1,706 510–569 48–63 1,274–1,413
467–478 301–307 73–75 611–625
969 294 102 772
932–1005 276–311 97–107 731–814
707 329 66 729
707–724 475–487 44–48 941–969
1,603 454 57 1,169
1,554–1,653 420–488 49–65 1,095–1,244
1,621 644 22 1,406
1,552–1,690 601–688 9–34 1,298–1,515
605–616 327–335 55–57 649–666
1,183 319 66 825
1,144–1,222 297–341 61–72 775–875
1,040 413 42 841
985–1,094 384–443 34–51 768–915
588–607 312–326 31–36 626–659
1,335 240 70 699
1,282–1,388 203–278 61–79 618–779
922 594 43 918
822–1,022 533–656 24–61 766–1,070
661–754 307–351 59–72 674–784
CI, confidence interval; CKD, chronic kidney disease; CV, cardiovascular; PMPM, per-member per-month. Regression-adjusted costs based on Tobit specification with covariates for age, gender, insurance plan type, geographic region, comorbidity, and months between hypertension diagnosis and CV event. Each cost category was estimated separately, thus total direct costs are not equal to the sum of cost categories. b All P < .05 for the test of the null hypothesis of incremental costs being equal to 0 unless marked with b. a
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Table 5 Incremental average monthly healthcare costsa of CV events for elderly, prior stroke, and prior myocardial infarction subgroups of hypertension patients CV event
Elderly n ¼ 318,861 $PMPM
Acute myocardial infarction Inpatient 895 Outpatient 311 Drugs 91 Total healthcare 990 Acute coronary syndrome Inpatient 272 Outpatient 236 Drugs 59 Total healthcare 432 Angina Inpatient 332 Outpatient 207 Drugs 64 Total healthcare 419 Ventricular arrhythmia Inpatient 337 Outpatient 266 Drugs 84 Total healthcare 516 Atrial arrhythmia Inpatient 338 Outpatient 260 Drugs 59 Total healthcare 475 Congestive heart failure Inpatient 535 Outpatient 306 Drugs 78 Total healthcare 644 Coronary artery disease Inpatient 263 Outpatient 203 Drugs 73 Total healthcare 413 Left ventricular hypertrophy Inpatient 387 Outpatient 263 Drugs 50 Total healthcare 521 Stroke and transient ischemic attack Inpatient 328 Outpatient 219 Drugs 58 Total healthcare 420 Sinus tachycardia Inpatient 328 Outpatient 200 Drugs 38 Total healthcare 388
Prior stroke n ¼ 61,385
Prior MI n ¼ 9,723
95% CI
$PMPM
95% CI
$PMPM
888–901 306–316 89–93 978–1,002
1,315 362 42 1,297
1,283–1,348 344–380 38–47 1,250–1,345
1,035 211 19 631
95% CI 920–1,150 172–250 27–11 505–757
259–285 227–245 55–62 411–453
341 215 7b 410
271–411 180–249 2–16 321–498
709 247 1b 631
551–867 190–305 11–13 445–817
328–336 204–209 63–65 412–426
497 245 44 476
473–521 234–257 41–47 446–506
636 142 19 555
579–694 121–163 14–23 487–622
327–348 258–273 81–87 498–534
684 323 51 782
632–735 295–350 44–58 712–852
1,299 554 35 1,636
1,136–1,463 493–615 23–48 1,436–1,837
334–341 258–262 58–59 469–480
499 290 29 539
480–518 281–299 27–31 515–562
970 285 15 879
880–1,059 256–315 9–22 776–982
531–539 303–308 77–79 638–651
971 394 53 879
951–992 384–404 51–56 852–906
1,278 397 40 1,139
1,205–1,350 372–421 34–45 1,059–1,218
259–266 201–205 73–74 409–417
334 208 51 446
320–348 202–214 50–53 431–462
48 64 6 108
5–92 50–78 2–10 61–154
382–392 260–266 49–51 514–529
721 329 19 758
697–746 316–342 16–22 726–791
1,098 332 2b 992
986–1,210 291–373 10–7 855–1,128
325–331 217–221 58–59 415–424
130 91 16 153
119–141 86–97 15–18 140–165
1,240 356 6 1,013
1,157–1,324 327–384 0–12 917–1,108
323–333 197–203 37–39 380–396
614 246 29 532
589–639 233–259 25–32 499–565
1,122 251 20 910
1,012–1,231 210–291 11–28 778–1,043
CI, confidence interval; CV, cardiovascular; MI, myocardial infarction; PMPM, per-member per-month. Regression-adjusted costs based on Tobit specification with covariates for age, gender, insurance plan type, geographic region, comorbidity, and months between hypertension diagnosis, and CV event. Each cost category was estimated separately, thus total direct costs are not equal to the sum of cost categories. b All P < .05 for the test of the null hypothesis of incremental costs being equal to 0 unless marked with b. a
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Table 6 Trend in average quarterly direct healthcare costs surrounding cardiovascular events in a hypertension population CV event
Acute myocardial infarction Inpatient Outpatient Drugs Total healthcare Acute coronary syndrome Inpatient Outpatient Drugs Total healthcare Angina Inpatient Outpatient Drugs Total healthcare Ventricular arrhythmia Inpatient Outpatient Drugs Total healthcare Atrial arrhythmia Inpatient Outpatient Drugs Total healthcare Congestive heart failure Inpatient Outpatient Drugs Total healthcare Coronary artery disease Inpatient Outpatient Drugs Total healthcare Left ventricular hypertrophy Inpatient Outpatient Drugs Total healthcare Stroke/transient ischemic attack Inpatient Outpatient Drugs Total healthcare Sinus tachycardia Inpatient Outpatient Drugs Total healthcare
PMPM quarterly healthcare costs Q2 Pre-event
Q1 Pre-event
Q1 Post-event
Q2 Post-event
Q3 Post-event
Q4 Post-event
12,369 668 1,063 538 2,268 2,938 488 1,200 639 2,327 43,505 406 1,022 581 2,008 4,368 1,294 1,475 674 3,442 50,645 2,447 1,100 617 546 50,105 1,064 1,570 768 3,402 175,680 680 1,109 698 2,488 31,867 582 1,390 599 2,570 110,827 625 1,162 642 2,429 27,814 592 1,252 580 2,424
12,369 1,624 1,311 563 3,497 2,938 762 1,391 670 2,823 43,505 529 1,210 593 2,332 4,368 1,810 1,756 713 4,279 50,645 3,259 1,382 638 632 50,105 1,872 1,889 796 4,558 175,680 907 1,316 711 2,933 31,867 1,211 1,693 627 3,530 110,827 997 1,335 660 2,992 27,814 1,117 1,583 593 3,293
12,369 20,896 4,338 925 26,160 2,938 4,449 3,508 778 8,735 43,505 4,765 3,959 716 9,439 4,368 6,117 3,746 764 10,627 50,645 7,119 2,631 714 1,071 50,105 6,145 3,517 889 10,550 175,680 3,669 2,926 798 7,393 31,867 5,450 3,857 707 10,015 110,827 4,182 3,184 758 8,124 27,814 4,945 3,523 684 9,152
1,2,369 1,876 2,195 852 4,923 2,938 1,139 1,823 766 3,727 43,505 991 1,491 704 3,186 4,368 1,684 2,079 781 4,545 50,645 3,721 1,724 708 714 50,105 2,191 2,562 886 5,639 175,680 1,122 1,515 792 3,429 31,867 1,570 2,336 708 4,614 110,827 1,260 1,750 763 3,773 27,814 1,171 1,885 671 3,727
1,2,369 1,542 1,815 818 4,175 2,938 1,209 1,523 764 3,496 43,505 817 1,419 694 2,930 4,368 1,127 1,903 766 3,796 50,645 3,464 1,557 696 692 50,105 2,118 2,374 866 5,358 175,680 1,039 1,474 788 3,301 31,867 1,344 2,060 692 4,096 110,827 171 1,577 755 3,403 27,814 987 1,629 663 3,279
11,189 1,311 1,640 833 3,783 2,742 959 1,324 774 3,057 40,157 839 1,388 721 2,948 4,032 1,211 1,825 803 3,839 46,396 3,499 1,541 719 647 44,861 1,881 2,296 890 5,068 163,845 1,098 1,455 808 3,361 29,206 1,179 1,940 718 3,838 101,244 1,019 1,538 774 3,331 25,605 983 1,614 675 3,272
Q1 to Q4 Post-event 25,625 9,987 3,429 39,041 7,756 8,178 3,081 19,016 7,412 8,256 2,835 18,504 10,139 9,553 3,114 22,806 17,803 7,454 2,837 3,125 12,335 10,749 3,531 26,615 6,927 7,370 3,186 17,484 9,544 10,194 2,825 22,562 7,533 8,048 3,050 18,631 8,086 8,651 2,693 19,430
CI, confidence interval; CV, cardiovascular; PMPM, per-member per-month; Q1, first-quarter; Q2, second-quarter; Q3, third-quarter; Q4, fourth-quarter.
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healthcare costs, whereas prescription drugs generally accounted for less than 8% of total healthcare costs. Findings were consistent across subgroups and the importance of inpatient costs was most pronounced in patients with CKD, diabetic nephropathy, a prior MI, or prior stroke. On the whole, incremental costs of CV events across all subgroups were positive and statistically significant for direct healthcare costs in hypertension patients after the CV event. Although this result is not unexpected, we observed statistically insignificant, and in some cases negative incremental costs of prescription drugs. After controlling for confounding factors in the multivariate analysis, we observed no prescription drug cost increases for some event/subgroup combinations, particularly in patients suffering a second CV event of AMI, ACS, and LVH. This observation occurred more often among patients with prior MI subgroup. The finding that inpatient and outpatient costs were higher than in the control population after the second event is intuitive; however, the occurrence of a CV event may not necessarily dictate an increase in prescription drug costs, particularly with prior MI and prior stroke patients. Patients suffering a second CV event may simply have their prescription regimen modified, which may or may not result in additional costs. As is the case in many analyses of administrative cost data, between-group differences in costs may be due to potential unobservable and confounding variables, especially those variables that indicate disease severity. Nevertheless, there were important subgroup differences. For example, diabetic patients with hypertension had greater costs associated with acute MI than did any other subgroup; and those with CKD had greater costs associated with CHF, LVH, and ST than did any other subgroup. Our assessment of pre-event and post-event healthcare costs for 10 CV events indicates that costs of CV events in hypertension patients extend to pre- and post-event periods, with most of the costs immediately after the event being attributable to inpatient stays. The result that most immediate post-event costs were attributable to inpatient stays is consistent with another study, which focused on 12-month costs after a diagnosis of ACS.17 For each of the 10 CV events analyzed here, however, outpatient costs composed a substantial portion of total healthcare costs in the second-, third-, and fourth-quarters after event occurrence. Treatment of hypertension with antihypertensive medications, particularly in the pre-hypertension stage decreases CV morbidity and mortality.23 One implication of our study findings is that a reduction in CV events would result in significant cost savings across all subgroups, particularly for healthcare costs associated with hospitalization, but also potentially for outpatient costs incurred over a longer period after an event. The documented clinical and resource utilization benefits of antihypertensive treatments support the economic hypothesis that reduced CV events will translate into overall cost savings in both direct inpatient and outpatient costs.
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The study findings of substantial cost differences between CV and non-CV event groups and within subgroups among patients with hypertension are consistent with a limited number of studies addressing direct healthcare costs associated with CV complications of hypertension.2,16–19 These published studies include total or average costs of some CV events, but not incremental costs of a broad set of specific CV events or subgroup populations. However, they may provide a general frame of reference for the findings we present in this article. In terms of magnitude, our findings are consistent with the literature in that conditions such as CHF and stroke are associated with high disease-attributable costs in comparison to hypertension,18 which is likely to result in severe and costly conditions without aggressive treatment. Authors of one study reported hypertension-related costs associated with CV events. Using American Heart Association data, Flack and colleagues reported average per-patient hypertensionrelated healthcare costs of $26,000 in the first year after stroke: $19,100 for MI and $5,500 for CHF.2 Estimates for stroke and MI were drawn from the 1999 National Inpatient Profile and the opinions of a physician consultant on outpatient and pharmaceutical use in the year following an event. CHF estimates were drawn from data presented in the 2003 American Heart Association statistical update. In our study, acute MI and CHF were the CV events associated with the highest incremental healthcare costs among all hypertension patients. The estimates of Flack and colleagues are not directly comparable to the incremental cost estimates presented in our article because both the methods and data employed in each study. Moreover, the use of claims data in our study allowed cost estimates to be calculated from diagnoses recorded on administrative data and actual payments to providers at the patient level. Our estimates of the overall economic impact associated with CV events in hypertension patients are likely to conservatively reflect true incremental costs. One limitation of obtaining costs of severe medical events from administrative data is that death is unobservable in the data unless the event is recorded as a death on diagnosis. Residual claims after death from any one of the CV events may be included in our data, but because deceased patients will no longer incur additional charges, CV events that are more likely to result in death (compared with the control group) will appear to have lower incremental costs. In addition, in identifying certain subgroups like CKD and diabetes, we excluded patients with end-stage organ disease; patients such as those undergoing renal dialysis and patients with retinopathy are likely to have severe disease and high- costs. Thus, exclusion of more severely ill patients will also lead to conservative estimation of incremental costs. Limitations frequently encountered in the use of claims data apply to the findings reported in this article. As is typical in such studies, the data do not include information on patient race, ethnicity, or income. Lack of information
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on these unobservable characteristics reduces the ability to control for potentially important confounding variables in the multivariate analysis. Claims data also do not include information on duration and severity of hypertension, which further limits our analytical ability to control for or stratify by these factors. Furthermore, in this study, we included all patients with hypertension regardless of antihypertensive treatments, as we are interested in the economics of hypertension. However, because hypertensive patients receiving treatment may be different, probably clinically more severe, than patients not prescribed treatment, the costs in treated patients are probably higher. This effect modification by treatment has not been addressed in this article. Clinical coding variation may also be a limiting factor. CV events such as LVH do not typically have nearly as discrete an onset as an event-like CHF because of insensitivities of electrocardiogram. Thus, costs before and after the claim should be interpreted with caution. Costs presented in this study may vary from those of other private or public insurers. This study focused on the portion reimbursed by the employer, which included all discounts and was net of the following amounts: excluded expenses, deductible, coinsurance, copay, coordination of other benefits, and other adjustments. Although a large portion of hypertensive patients are elderly and are on Medicare, the present study focuses on costs from the employer payer perspective.
Conclusion A spectrum of CV events occurring in multiple high-risk subgroups results in substantial incremental direct healthcare costs. Incremental costs vary across CV events and are largely driven by increases in the cost of inpatient care; however, trends in healthcare costs incurred by hypertension patients before and after a CV event indicate that outpatient care is also a contributor to post-event costs over the longer term. Our findings may be set in the context of the knowledge base suggesting that use of antihypertensive medications reduces the incidence of CV events and associated costs. Improvements in the prevention and management of hypertension through the use of antihypertensive medications, especially those that are effective in specific subgroups (ie, patients with compelling indications) could result in significant savings in healthcare expenditures, particularly through avoidance of high-cost care in inpatient settings.
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