A Systematic Review of the Economic Burden of Chronic Angina

October 1, 2004
Matthew W. Reynolds, PhD

,
Diana Frame, MEM

,
Rachel Scheye, BA

,
M. Evelyn Rose, PharmD

,
Samuel George, MD

,
Jennifer B. Watson, PhD

,
Mark A. Hlatky, MD

Supplements and Featured Publications, Chronic Angina: Clinical Management and Cost of Care, Volume 10, Issue 11 Suppl

Background: Chronic angina carries an economicburden because of symptom management, the riskof major cardiovascular events, and lost productivity.The level of these costs has not been systematicallyquantified.

Objective: This study sought to assemble bestevidence on the economic burden of chronic angina,including both the direct costs of healthcare andthe indirect costs of lost productivity.

Methods: Studies published in English fromJanuary 1990 to June 2003 were located via electronicand manual searches and systematically reviewed.Eligible studies included those with information oncost of illness, cost of treatment, employment status,and/or work productivity and/or limitations for a populationof patients with chronic angina.

Results: Seventeen studies assessed the healthcarecost of managing chronic angina. Cost estimates variedwidely because of differing patient populations,healthcare settings, countries of origin, and year(s) ofdata collection. The most critical determinant ofhealthcare costs appeared to be the use of revascularizationprocedures. Twenty studies reported worklimitations, 5 of which quantified productivity loss inmonetary terms. Interventions for chronic anginaresulted in some improvement in employment andwork limitations over the short term. However, thepositive effect of revascularization procedures tendedto erode over the long term (3 years and beyond) ina substantial number of patients.

Conclusions: Chronic angina carries substantialhealthcare costs caused by frequent medical visits,medications, and expensive revascularization procedures.Workplace productivity loss because of anginais also substantial, but lasting long-term improvementin work status has been difficult to achieve.

(Am J Manag Care. 2004;10:S347-S357)

Chronic angina is a cardinal manifestationof ischemic heart disease, one ofthe most common medical conditionsin the United States today.1 The treatment ofchronic angina has 2 main goals: first, to preventmore serious cardiovascular events,such as myocardial infarction or death, andsecond, to improve patients' quality of life byreducing symptoms caused by ischemia.There are many pharmacologic and proceduralinterventions available for the managementof chronic angina. Despite treatment,many patients continue to have angina painor discomfort that requires frequent medicalevaluations, polypharmacy, hospitalization,and/or revascularization. Angina may alsolimit patients' ability to work and engage innormal daily activities.2,3 All of these factorslead to substantial direct and indirect costsassociated with chronic angina.

The present study aimed to review theavailable published evidence regarding thecosts of chronic angina, specifically directmedical costs, interventional costs, and theeffects of employment and work limitationson indirect costs.

Study Designs and Methods

angina pectoris

The intent of the systematic review was togather data from the published literature thatsummarized or estimated costs of care relatedspecifically to patients with chronic angina,and to assess this data including identificationof any gaps in the literature. In general, thepurpose of a systematic review is to assemblean evidence base in as unbiased a manner aspossible, by using prospective inclusion criteriaand an explicit, reproducible plan for literaturesearch and synthesis. The first step ofthe systematic review was to identify andretrieve all potentially relevant literature thatdescribes patients with chronic angina,including quantitative information on costs orwork limitations. A MEDLINE search was conducted(via PubMed) using the medical subjectheading and was limitedto English language and human subjects. Inaddition, a supplemental search was performedfocusing on healthcare economicterms (costs and cost analysis, economics,pharmaceutical, absenteeism, work, or efficiency)crossed with the keyword "angina."Current Contents was searched using analogousapproaches for the past year to identifyrecent publications not yet indexed in MEDLINE.Finally, references from all acceptedpapers and recent reviews, and relevant citationsprovided by an information scientist,were manually checked to supplement theabove electronic searches. The search windowfor all sources was January 1990 to June 2003.

Articles were screened on 2 levels byusing a prospectively defined protocol. First,abstracts of all articles identified during theliterature searches described above werescreened. Abstracts were excluded if they fitany of the preidentified exclusion criteria:case reports, letters, comments, editorials,reviews, animal or in vitro studies, pharmacodynamicor pharmacokinetic studies,were published in languages other thanEnglish, or were not from an eligible geographiclocation (North America, Europe,Australia, or New Zealand). In addition, studieswith fewer than 10 patients with chronicangina were excluded.

The full text of all papers determined tobe possibly eligible after the first level ofscreening was reviewed to assure that it metinclusion criteria for population and outcomesof interest. Studies were excluded ifthey did not report a separable population ofpatients with chronic angina. For instance,studies of unstable angina or acute coronarysyndromes, ischemic heart disease or coronaryartery disease (CAD), in general, wereexcluded from the review unless they hadseparately extractable outcomes for a groupof patients with chronic angina, the conditionof interest. If details of the study populationwere not reported, ongoing medicaltherapy and elective revascularization proceduresto relieve angina/ischemia causedby CAD were presumed to represent nonurgentinterventions, and therefore qualifiedthe population as having chronic angina.Syndrome X and silent ischemia populationswere also of interest as long as other inclusioncriteria were met.

For each eligible study that passed bothlevels of screening, data elements of interestwere extracted and agreed upon by 2 reviewersto form an analyzable evidence base. Allcost information for patients with chronicangina (including costs of inpatient, outpatient,emergency room, medication, and surgicalcosts) was recorded, as was allinformation on loss of productivity (days ofwork missed, disability, and employmentstatus) for the population of interest. Forease of comparison, costs were extracted inthe currency reported and also converted toUS dollars per patient per year using thereported observation window and historicalexchange rates (average within year rangestudied).4,5 No attempt was made to adjustfor inflation, accounting methods, or variationin healthcare systems; however, cost-of-illnessstudies were stratified by the costcomponents evaluated (inpatient only vsinpatient plus outpatient costs), the populationstudied ("typical" angina patients vsadvanced/refractory patients with CADundergoing revascularization procedures),and the type of source data (observed datafrom enrolled patients vs claims data vsdecision models).

Results

A total of 6928 abstracts were reviewed, alarge majority of which were excluded for 1or more reasons. Nine hundred nineteenstudies were retrieved for full review of thetext, of which 82 publications (47 distinctstudies because of multiple publication of thesame patient population) reported 1 or moreof the prespecified outcomes of interest.

Of the 47 primary studies accepted, 17studies6-22 examined the overall healthcarecost of chronic angina, whereas 10 studies23-32 focused on the cost of specific treatmentsused to manage patients with chronicangina. Seven of the cost-of-illness studiesalso contained cost-of-treatment information.8,10,14,17,20-22Twenty studies addressedother societal cost dimensions including lossof productivity, work limitations, and effectson the employment status of patients withchronic angina.3,9,27,33-49

Costs of Chronic Angina

Ten studies addressed costs of chronicangina based on primary data collectedfrom clinical trials, medical records, or surveys(Table 1a). Five were based in Europeand 5 were based in the United States.Studies that included both inpatient andoutpatient healthcare costs reported annualdirect costs ranging from £3613 UK perpatient per 3 years (approximately $1937[1998-1999] per patient per year) for patientsin the medical management arm of a largerandomized trial, to almost 10 times thatamount for patients with advanced CAD($33 695 per patient per year, 1997) orundergoing transmyocardial laser revascularizationfor refractory angina (£11 470UK per patient per year, or approximately$18 467 per patient per year, 1998-1999).6,7,9,10,12,15,16,18,19,22

Six cost-of-illness studies used decisiontree modeling to estimate the healthcarecost of a typical patient with angina (Table1b).8,13,14,17,20,21 Generally, these studies combinedliterature data and expert determinationsof event risk with cost per eventestimates from public or institutional sources.Four of these studies were based on USdata and estimated that annual direct costsof treating a patient with chronic anginaranged from $2569 (1995) to $7207(1992).14,17,20,21 Estimated costs were lowerin the 2 non-US studies.8,13

One recent US study examined medicalclaims data based on episodes of care fromthe perspective of the employer and/orpayer.11 The study showed that angina pectoriswas the most costly condition becauseof both its prevalence and the expense oftreatment. Deriving the reported cost estimateon a per-angina-patient basis for purposesof comparison with othercost-of-illness studies yields an annual costper patient of $4949 (1999), within therange of the decision analysis studies andcomparable to the observed data forpatients with angina not selected for severityof condition or for undergoing revascularizationprocedures during the 1990s.

Costs of Chronic Angina Treatment

Seventeen studies contain informationon the cost of treatments and interventions,including nearly all of the decisionmodeling cost-of-illness studies. Thesestudies often reported the cost assumptionsused in their model for events such asrevascularization.

The majority of the studies were based ondata collected as early as the late 1980sthrough the mid-1990s. Twelve studies werebased on medical records or billing data.10,22-32The studies based on US cost data showedthat the cost of coronary artery bypass grafting(CABG) was approximately $20 000(1986-1987 observations, not adjusted forinflation)21,24,29 and the cost of percutaneoustransluminal coronary angioplasty (PTCA)ranged from $490031 to $955629 per episode,with the cost rising to $12 574 for PTCA withstenting (1986-1991 observations, not adjustedfor inflation).25 Several studies estimatedthe cost of all medical therapy used for controlof angina symptoms, with costs for USstudies ranging from $102 (1992) to $863(1986) per patient per year.14,20 No studieswere found that provided cost-of-care estimatesspecifically for patients with chronicangina by using data from the past 5 years.

Employment Status and Work Limitations

Five cost-of-illness studies attempted toquantify productivity loss (indirect cost) ofchronic angina in dollar terms, and, in mostcases, these estimates were nearly as largeas (or larger than) the estimates of directhealthcare costs.6,8,9,11,22 One exception wasthe study by Goetzel and colleagues, whichfocused on claims data from an employerperspective and was, by definition, enrichedwith patients who retained their employmentstatus throughout the window of dataobservation.11

A number of other studies reported productivityloss or work status of patients withchronic angina without translating theseresults into dollar amounts.3,9,27,33-49 Fourteenstudies9,27,33-38,41,43,46-49 included informationon the percentage of patients withchronic angina currently employed, rangingfrom 11% (patients with chronic angina at aVeterans Affairs medical center, mean age of68 years)35 to more than 70% in 2 trials ofCABG versus medical therapy. The meanage of patients undergoing CABG was 52years in the US study33 and 61 years in theItalian study.48

A substantial proportion of patients withchronic angina reported work limitationsbecause of illness (Figure). Most were interviewedat baseline before revascularizationprocedures. For the studies with longitudinalfollow-up, revascularization enabled somepatients who had been able to work beforetheir illness to return to work as their anginasymptoms abated.34,38,44,45,49 A study ofpatients awaiting CABG showed that in theabsence of the procedure, the proportion ofpatients unemployed because of illnessincreased over time.36

However, the evidence is that revascularizationhas only a transient effect on improvingwork status. Repeat CABG may improveemployment status, but the gain was moremodest than for initial procedures, with only15% of the patients who had been unable towork before surgery returning to work at amean of 3.7 years of follow up.27 Caine andcolleagues tracked employment status over5 years post-CABG. At 1-year post-CABG, a23% increase in the percentage of patientsemployed was reported. However, at 5 years,the percentage increase had declined to14%.34 Similarly, Herlitz and colleaguesreported unemployment caused by illness in40% of patients awaiting revascularization,of which 24% continued to report work limitations caused by illness at 5 years.39 Thelongest-term CABG study (10 years),33 aswell as 2 observational studies of approximately3.5 years duration,40,48 all reported adecrease in the number of patients continuingto work at follow-up (whether because ofwork limitations or retirement), regardlessof treatment.

Discussion

Chronic angina is associated with enormoushealthcare expenditures that includeboth direct costs in the form of hospitalizations,surgery, and medications, and indirectcosts in the form of unemployment and angina-related work limitations. In this review,the most critical determinant of healthcarecosts appears to be the use of revascularizationprocedures. Studies of patients withrevascularization or advanced CAD, or both,showed costs of up to $33 000 per patientper year (1997).12 Additionally, typical patientswith chronic angina have reporteddirect healthcare costs (including the riskof revascularization procedures and hospitalizations)ranging from $2500 to $7200per patient per year (1986-1995) in USstudies.9,11,14,15,17,20,21

The American Heart Association estimatesthat 6.8 million patients have chronic anginain the United States.50 Therefore, based onthe cost estimates extracted from the literatureand the prevalence of chronic angina,the associated costs in the United States mayrange from $17 billion to $49 billion annually.A recent United Kingdom estimate byStewart and colleagues51 showed that 1.3% ofall healthcare expenditures in the year 2000could be attributed to angina pectoris. In theUnited States in 2002, total healthcare expenditureswere $1550 billion,52 1.3% ($20 billion)of which may be associated with thedirect cost of angina.

These cost figures may be conservativebecause the majority of the studies in thepresent review were based on data collectedas early as the late 1980s through the late1990s. These estimates may not reflect currentchanges in healthcare cost and practice,particularly with the advent of morecomplex and costly revascularization proceduresand technologies (For instance, datafrom the 2001 National Healthcare Cost andUtilization Project estimate mean charges at$28 558 for PTCA and $60 853 for CABG).50Inflation, increased medical costs, andchanges in treatment patterns for chronicangina may all drive the cost of chronic angina higher. Although not the purpose of thisreview, all costs must be compared withchanges in the quality of associated patientoutcomes.

In addition to the direct medical effects,chronic angina reduces productivity andemployment. Analyses of the cost burden ofchronic angina that only include healthcareexpenditures may substantially underestimatethe true burden of this disease.

Unfortunately, indirect costs were rarelyreported in the studies that examined thecost of chronic angina. The studies that didinclude estimates of indirect costs showedthat the total costs of chronic anginaincreased 2 to 3 times compared with theestimates of direct chronic angina costsalone. Even patients with chronic anginawho were employed were likely to report significantwork limitations caused by their illness.Studies that reported the change inwork status over time in patients whoreceived revascularization showed improvementover a 1- to 2-year time frame. However,not all patients benefited from theprocedures, and little evidence was found ofa lasting improvement in employment status.

The present review includes a comprehensivesearch, prospective inclusion andexclusion criteria, and dual review of includedpapers, all of which reduce potential biasin the resulting dataset. The limitations ofthe review include the sparseness and variabilityof the data found in some areas, makinga formal meta-analysis of cost dataimpossible. Furthermore, the data are limitedby the time frame in which it was collectedand changes in practice patterns thatmay have occurred. There was wide variationin the cost-of-illness studies, meaningthat important variables, such as patientpopulation, healthcare setting, country oforigin, and year(s) of data collection, werenot able to be analyzed.

There appears to be many gaps in thepublished literature regarding the burdenand cost of chronic angina to patients. Oneof the largest limitations of the literature isthe long-term estimate of costs and workproductivity of chronic angina. Most studiesof costs included only estimates of patientsover 1 year, based on short-term follow-upthrough medical records and billing datathat primarily only addressed the directcosts of hospitalization. Several studies thatutilized decision trees attempted to estimatecosts up to 3 and 5 years. These modelingstudies utilized disparate data sources andoften only modeled these costs for a typical45- to 55-year-old male patient, makingmany assumptions of long-term treatmentpatterns and symptom resolution for bothmen and women that are not necessarilysupported by long-term evidence. Directionsof future research should also considerextended studies of patients with chronicangina in real-life settings that includeexamination of short- and long-term directand indirect costs in the current era of medicaltreatment, revascularization, genderbias, and ethnic diversity.

Conclusion

The current guidelines for the managementof chronic angina by the AmericanCollege of Cardiology/American Heart Associationstate that the associated annual costsof chronic angina can be measured in thetens of billions of dollars.1 Even without thebenefit of reflecting current treatment practicesand costs, the present review supportsthis estimation. Chronic angina not onlycauses pain or discomfort to patients, but isalso associated with a high cost to society,both in terms of healthcare expenditure andlost productivity. Further study is neededwith more recent, real-world data to identifythe primary determinants of both direct andindirect costs of chronic angina and thelong-term effects of surgical and medicalinterventions.

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