Diagnosis of suspected coronary artery disease in women: A cost-effectiveness analysis

Diagnosis of suspected coronary artery disease inwomen: A cost-effectiveness analysisCatherine Kim, MD, MPH,a Yeong S. Kwok, MD,a Somnath Saha, MD,a and Rita F. Redberg, MD, MSc, FACCa,b SanFrancisco, Calif

Background The optimal strategy for the diagnosis of coronary artery disease (CAD) in women is not well defined.We compared the cost-effectiveness of several strategies for diagnosing CAD in women with chest pain.

Methods We performed decision and cost-effectiveness analyses with simulations of 55-year-old ambulatory womenwith chest pain. With a Markov model, simulations of patients underwent exercise electrocardiography, exercise testing withthallium scintigraphy, exercise echocardiography, angiography, or no workup.

Results Diagnosis with angiography cost less than $17,000 per quality-adjusted life-year compared with exerciseechocardiography if the patient had definite angina and less than $76,000 per life-year if she had probable angina. If shehad nonspecific chest pain, diagnosis with exercise echocardiography increased life-years compared with no testing.

Conclusions Cost-effectiveness of first-line diagnostic strategy for diagnosis of CAD in women varies mostly accordingto pretest probability of CAD. Diagnosis of coronary artery disease with angiography is cost-effective in 55-year-old womenwith definite angina. In 55-year-old women with probable angina, diagnosis with angiography would increase quality-adjusted life-years but significantly increase costs. Use of exercise echocardiography as a first-line diagnosis for CAD is costeffective in 55-year-old women with probable angina and nonspecific chest pain. (Am Heart J 1999;137:1019-27.)

The optimal strategy for the diagnosis of coronary arterydisease (CAD) in women is not well defined.Previousanalyses in men have demonstrated that cost-effectivenessof a diagnostic strategy varied primarily with CAD preva-lence in the tested population.1-3 Application of thesestrategies to women is controversial because physiciansmay underdiagnose and undertreat CAD in women com-pared with men.4 Underdiagnosis may occur for severalreasons.Angina is less predictive of CAD in women than inmen.5 Also,noninvasive tests for CAD were developed andevaluated primarily in men and may be less accurate inwomen.6 Adverse outcomes for revascularization inwomen may be partially caused by referral bias and techni-cal difficulties in procedure performance.7,8

In an effort to use current and sex-specific data todetermine the most cost-effective approach to diagnosingCAD in women,we constructed a decision analysis modelto compare several diagnostic strategies for simulatedpatients.Decision analysis helps provide comparative

information on different diagnostic or therapeutic strate-gies.These strategies included workup with exercise elec-trocardiography (ECG),exercise testing with thalliumscintigraphy (exercise-thallium),exercise testing withechocardiogram,and cardiac catheterization or none ofthese tests.We included only exercise test data, and wedid not include pharmacologic stress testing in themodel.We compared the usefulness and costs of thesetests for varying pretest probabilities of CAD.

MethodsDecision analysis model

We constructed a cost-effectiveness model to project costsand coronary disease outcomes over a 35-year period using theDATA 2.5 program (TreeAge Software, Boston, Mass) (Figure1).9 Markov modeling was used to estimate annual transitionsto different health states.10 We considered 3 clinical scenarios:an ambulatory 55-year-old woman with definite angina, proba-ble angina, or nonspecific chest pain as defined by the Coro-nary Artery Surgery Study Trial (CASS) (Table I).11 Simulatedpatients underwent 1 of 4 tests currently accepted forworkups in the diagnosis of CAD: exercise ECG, exercise-thal-lium, exercise echocardiography, cardiac catheterization, or noworkup at all.There were not sufficient data on accuracy ofexercise-sestamibi to include it in the model. Each of the exer-cise tests had 4 possible outcomes: true-positive, false-positive,true-negative, or false-negative.

We used the following assumptions to construct theMarkov model.All assumptions are for simulations of patientsbased on data in the literature for modeling purposes; thesedata do not reflect actual patients.Whenever possible we

From the aDepartment of Medicine and the bDivision of Cardiology, University ofCalifornia.Dr Redberg is supported by National Institutes of Health grant RO1 HL 50772.Submitted January 5, 1998; accepted June 3, 1998.Reprint requests: Rita F. Redberg, MD, Division of Cardiology, University of California-San Francisco, 505 Parnassus Ave, San Francisco, CA 94131-0214.Copyright © 1999 by Mosby, Inc.0002-8703/99/$8.00 + 0 4/1/93208

See related Editorial on page 983.

used data from randomized controlled trials to construct themodel.We assumed that simulated patients with positiveexercise tests proceeded to cardiac catheterization. If car-diac catheterization showed CAD, patients underwent coro-nary artery bypass grafting (CABG), percutaneous translumi-nal coronary angioplasty (PTCA), or medical management.On the basis of medical literature, we assumed that womenwith CAD underwent CABG in the presence of triple-vesseldisease or left main vessel disease.11 Those with inoperabledisease underwent medical management. Simulated patientswith a lesser degree of CAD underwent PTCA or medicaltherapy. PTCA with stent was not included in the modelbecause data on stenting in women were not available.

Markov models were used to model survival for womenafter CABG, PTCA, and during medical management. If car-diac catheterization showed no CAD, a Markov process wasused to model survival without CAD.

Patients with negative exercise test results did not undergofurther workup in the model.We assumed that these resultsincluded true-negatives and false-negatives; the survival ofthese patients was modeled with Markov processes forpatients with and without coronary disease. Possible outcomestates included well, asymptomatic CAD, angina, myocardialinfarction (MI), and death.

We made several simplifying assumptions. Simulatedpatients did not undergo more than 1 noninvasive test, and

American Heart JournalJune 1999Kim et al1020

Coronary 1- To 2-vessel 3-Vessel or LMVdisease disease disease

Definite angina .71 .44 .27Probable angina .31 .23 .08Nonspecific chest pain .06 .06 .00

LMV, Left main vessel.

Table I, A. Model variables: Base-case values—pretest probability of coronary artery disease11

Figure 1

Decision model. Square at far left symbolizes choice among 5 diagnostic strategies: exercise ECG, exercise-thallium, exerciseechocardiogram, catheterization, or no test. M represents a Markov process with 4 health states. Circles on far right indicate whichhealth state patient enters.

they did not undergo more than 1 invasive therapy unlessabrupt coronary closure occurred after PTCA.

ProbabilitiesWe obtained pretest probabilities of CAD prevalence and

severity from sex-specific data from the CASS trial and the Fram-ingham study (Table I,A through H).11-13 We obtained exercisetest sensitivities and specificities from a meta-analysis of diagnos-tic testing in women.6 The majority of studies included in themeta-analysis excluded patients with abnormal baseline electro-cardiograms.However, this exclusion did not improve the sensi-tivity and specificity of treadmill testing.Using the pretest proba-bilities for disease and exercise-test sensitivity and specificity,wecalculated the posttest probabilities of CAD.We performed a sen-sitivity analysis of the exercise test sensitivity and specificityusing as range limits the 95% confidence intervals.

Because the indications for PTCA are controversial, and

practice does not necessarily reflect a standard guideline weassumed that not every patient with coronary disease receiv-ing cardiac catheterization would undergorevascularization.14-18 We performed a sensitivity analysis andvaried rate of PTCA between 5% and 95%. Rate of CABG oper-ability also varied; we estimated a 90% operability rate and var-ied this between 50% and 100% in a sensitivity analysis.

For patients without coronary disease,we obtained outcomesdata from the National Vital Statistics System.19 We obtained out-comes data for patients with CAD from the CASS trial and theFramingham study.12,20,21,23 The impact of angina on prevalenceof MI and death after surgery is not reported for the CASS trial,so we used the same probabilities for symptomatic and asymp-tomatic patients.We performed a sensitivity analysis on asymp-tomatic patients after CABG with CASS trial estimates of theincidences of MI and death as the upper limit.

For PTCA outcomes data,we referred to 4 large-scale random-

American Heart JournalVolume 137, Number 6 Kim et al 1021

Sensitivity (95% CI)* Specificity (95% CI)*

Exercise electrocardiogram 0.61 (0.37-0.86) 0.69 (0.48-0.91)Exercise thallium 0.78 (0.69-0.86) 0.64 (0.44-0.84)Exercise echocardiogram 0.86 (0.72-0.99) 0.79 (0.71-0.87)

CI, Confidence interval.

Table I, B. Model variables: Base-case values—test parameters6

Rate of angina Rate of MI Rate of deathState (range) (range) (range) Reference

Well 0.55 0.25 0.85 12,191- And 2-vessel disease –7.4 2.1 (2.1-2.5) 3.7 (3.7-10.5) 13,20,223- and LMV disease –5.6 2.5 (2.5-5.0) 10.5 (10.5-12.5) 13,20,22Status after PTCA –1.7 4.2 (1.6-4.2) 2.1 (0.9-2.7) 14-18,23-5Status after CABG 6.8 1.4 (1.4-2.5) 6.9 (2.0-10.5) 13,20,22,23,25


Table 1, E. Model variables: Base-case values—coronary artery disease parameters (% per year)

Percent (95% CI) Reference

Rate of PTCA performance for patients with 1- or 2-vessel disease 27 (5.0-95) 16Rate of CABG performance for patients with 3- or left main vessel disease 90 (50-100)

Table I, C. Model variables: Base-case values—procedure rates

Rate of angina Rate of MI Rate of deathState (range) (range) (range) Reference

Well 0 0 0 12,191- And 2-vessel disease 78.0 0 0 13,20,223- And LMV disease 78.0 0 0 13,20,22Status after PTCA 20.0 (20.0-29.0) 3.0 (2.1-4.6) 1.2 (0.3-2.6) 14-18,23-5Status after CABG 5.0 (2.0-8.0) 8.0 (5.8-8.0) 6.9 (1.3-6.9) 13,20,22,23,25Catheterization 0.2 (0.0-1.0)


Table I, D. Model variables: Base-case values—coronary artery disease parameters (% initially)

ized trials that listed varying outcomes.18,23-25 These trials didnot list data separately for women.Therefore we also referred todata from observational studies of PTCA that did list data sepa-rately for women.14,16 We performed sensitivity analyses withthe most extreme outcomes as sensitivity analysis limits.

Quality of life estimationsTo incorporate the inconvenience of undergoing a proce-

dure or experiencing an adverse event, we exacted a one-timetoll for cardiac catheterization, PTCA, CABG, and MI.Weobtained the tolls from a decision analysis model comparingtherapeutic interventions.26 We then varied these tolls in a sen-sitivity analysis by a factor of 0.1 to 10 (Table I,F and G).

Because the make the quality of life adjustments, we usedestimates from time trade-off interviews concerning the rel-ative worth of angina and MI from the Beaver Dam healthoutcomes study.27 In time trade-off assessment, patients areasked how many additional years of life with illness arefound to be the equivalent of years of life healthy.Weassumed that the use of CAD without symptoms was slightlyless than the use of not having CAD. Sensitivity analysis wasperformed on quality of life with asymptomatic CAD withthe value for symptomatic angina as the lowest limit and thevalue for healthy as the highest limit. Sensitivity analysis onquality of life with angina was done with the value forangina as the lower limit and the value for asymptomaticCAD as the upper limit. Sensitivity analysis was performedon value of MI with the value for congestive heart failure, asthe worst outcome for MI, as the lowest estimate and withthe value for angina as the highest estimate.We discountedat a rate of 5% per year.

CostWe estimated costs from a societal perspective in 1996 US

dollars (Table I,H).We obtained costs from 1996 records of anurban, academic, tertiary care medical center for exercise ECG,exercise-thallium, exercise echocardiography, CABG, PTCA, andacute MI.The medical center uses a bottom-up method Transi-tional System Incorporated (TSI, Boston, Mass) cost-accountingsystem to determine labor and equipment costs and physicianfees. Because several methods of cost estimation exist and theoptimal method is controversial,28,29 we repeated the analysiswith costs from a Northern California health maintenance orga-nization (HMO).The most significant difference was the HMO’slower cost for exercise-thallium and PTCA.These costs wereincorporated in a sensitivity analysis.The estimate for the costof medical management of CAD was obtained from relevant lit-erature and consisted of medication cost.30

ResultsBase case analyses

We used the time horizon of 35 years, which takesour simulated patient to age 90; after this amount oftime, there was no significant increase in quality of life-years (QALY) (Table II). Differences in survival betweendifferent diagnostic strategies were 6 months at most,and overall the differences decreased with decreasingpretest probability of CAD.

TSI costs Definite angina. For a 55-year-old woman with defi-

nite angina, cardiac catheterization improved survival by24 days (0.065 of a QALY) compared with exerciseechocardiography, 39 days (0.108 of a QALY) comparedwith exercise-thallium, 72 days (0.196 of a QALY) com-pared with exercise ECG, and 170 days (0.465 of aQALY) compared with no test at all.The cost of usingcardiac catheterization as a first-line procedure com-pared with exercise echocardiography was $21,000 foreach extra QALY.

Probable angina. For a 55-year-old woman with proba-


QALY (range)

Catheterization 0.0027 (0.0027-0.027)MI 0.0190 (0.00190-0.190)PTCA 0.00822 (0.00082-0.082)CABG 0.0822 (0.0822-0.822)

Table 1, F. Model variables: Base-case values—tolls26

QALY (range)

Catheterization 0.0027 (0.0027-0.027)MI 0.0190 (0.00190-0.190)PTCA 0.00822 (0.00082-0.082)CABG 0.0822 (0.0822-0.822)

Table 1, G. Model variables: Base-case values—tolls26

Figure 2

Sensitivity analysis of pretest probability for coronary disease.Sensitivity analysis in 55-year-old woman with chest pain show-ing effect of pretest probability for coronary disease on cost-effectiveness. For patients with probable angina, cardiaccatheterization provides more QALYs at cheaper cost than exer-cise-thallium. Note that cardiac catheterization is more cost-effective at higher pretest probabilities. At pretest probability of0.48, marginal cost-effectiveness of catheterization comparedwith exercise echocardiogram is roughly $50,000 per QALY.

ble angina,cardiac catheterization improved survival by 4days (0.012 of a QALY) compared with exercise echocar-diography,11 days (0.031 of a QALY) compared withexercise-thallium,23 days (0.063 of a QALY) comparedwith exercise ECG,and 116 days (0.319 of a QALY) com-pared with no test at all.Using cardiac catheterization asa first-line procedure compared with exercise echocar-diography cost more than $75,000 for each extra QALYbut less than $27,000 for each QALY compared withexercise ECG and no test strategy.

Nonspecific chest pain. For a 55-year-old womanwith nonspecific chest pain, exercise-echocardiographyimproved survival by 8 days (0.021 of a QALY) com-pared with cardiac catheterization, 3 days (0.007 of aQALY) compared with exercise-thallium, 3 days (0.009of a QALY) compared with exercise ECG, and 41 days(0.112 of a QALY) compared with no test at all. Usingexercise echocardiography as a first-line procedure pro-vided a slightly improvement in survival at a cost lessthan $10,000 for each extra QALY compared with exer-cise ECG and no test; exercise echocardiography domi-nated, or provided more survival and was cheaper than,cardiac catheterization and exercise-thallium.

HMO cost case. We repeated the analysis with costsfrom an HMO based in Northern California.The costsmost significantly changed were the cost for exercise-thallium and PTCA (Table I, H).Although exerciseechocardiography still provided more QALYs than exer-cise-thallium, initial diagnosis with exercise-thalliumbecame cheaper than initial diagnosis with exerciseechocardiography for patients with definite and proba-ble angina, presumably because exercise echocardiogra-phy led to more expensive interventions. However, itwas still more expensive than exercise echocardiogra-phy for patients with nonspecific chest pain, presum-ably because exercise-thallium’s slightly higher initialcost was not offset by the low procedure costs in thisgroup.As with costs obtained from the TSI system, exer-cise echocardiography still provided an extra QALY atcosts less than $25,000 compared with other noninva-

sive tests for all pretest probabilities of disease. Cardiaccatheterization still provided an extra QALY at costsless than $30,000 for patients with definite angina com-pared with other strategies and for greater than$60,000 for patients with probable angina comparedwith other strategies.

Sensitivity analysesBecause exercise echocardiography and cardiac

catheterization provided the most QALYs,we empha-sized the cost-effectiveness of exercise-echocardiographycompared with cardiac catheterization in the sensitivityanalyses.We examined the influence of different esti-mates in every variable throughout its range (Table I).

Pretest probability of coronary disease, as determinedby chest pain characterization, was the most importantvariable affecting cost-effectiveness.As long as patientshad definite angina or a pretest probability of 71%, car-diac catheterization increased QALYs at costs less than$17,000 per QALY compared with exercise echocardio-graphy.When pretest probability decreased to 48%, car-diac catheterization improved QALYs at costs equal to$50,000 per QALY gained compared with exerciseechocardiography (Figure 2). If the simulated womenhad probable angina, or a pretest probability of 31%, car-diac catheterization cost greater than $75,000 per QALYcompared with exercise echocardiography. If patientshad nonspecific chest pain, or a pretest probability of6%, exercise echocardiography improved QALYs at costsless than $10,000 per QALY compared with exerciseECG and no test at all.

Varying the time horizon affected the decision analysisoutcome.As time after testing increased, the cost perQALY saved by cardiac catheterization compared withexercise echocardiography decreased for patients withdefinite and probable angina (Figure 3).More specifically,at 1 year after testing,cardiac catheterization provided aQALY at a cost exceeding $1 million when comparedwith exercise echocardiography for patients with defi-nite angina.However, at 5 years after testing, additional


UCSF costs ($)(95% CI) HMO costs ($) Reference

Exercise ECG 282 (104-435) 247Exercise thallium 1379 (415-2,240) 415*Exercise echocardiogram 435 (278-1000) 297Cardiac catheterization 1672 (900-2000) 904PTCA 4333 (4000-12,000) 2,319CABG 21,131 (17,000-35,000) 20,391CAD, treatment per year 863 (500-2000) 30Acute MI 7797 (7000-20,000)MI, treatment per year 863 (500-2000)

*Includes only the cost of time spent in the nuclear medicine department.

Table I,H. Model variables: Base-case values—costs

cost for cardiac catheterization dropped drastically for anextra QALY when compared with exercise echocardiog-raphy.At 35 years after testing,cardiac catheterizationprovided an extra QALY at a cost of roughly $17,000when compared with exercise echocardiography.Simi-larly, as time after diagnosis increased, the cost per QALYsaved by exercise echocardiography compared with notest decreased (Figure 4).Most of the diagnostic test ben-efit accrued within the first 10 years after diagnosis.

Varying the sensitivity and the specificity of exercisetests within the 95% confidence interval (Table I) did notsignificantly influence the decision analysis outcomeexcept for patients with definite angina.When the sensi-tivity of exercise echocardiography was less than 0.78,exercise echocardiography saved fewer QALYs than exer-cise-thallium for patients with definite angina.

Varying PTCA and CABG rates did not significantlyinfluence the decision analysis outcome for patientswith definite angina or nonspecific chest pain.VaryingCABG rates did not significantly influence the decisionanalysis outcome for patients with probable angina; car-diac catheterization still provided a cost per QALYsaved at greater than $70,000 compared with exerciseechocardiography. However, varying PTCA rates didchange outcome for patients with probable angina. Car-diac catheterization provided a QALY for $27,000 com-pared with exercise echocardiography when PTCA per-formance rate was 95%; exercise echocardiography wascheaper and more effective than cardiac catheterizationwhen PTCA performance rate was 5%.

Varying the costs within the specified ranges (Table I)

did not significantly affect the marginal cost-effective-ness of procedures with the exception of exercise-thal-lium compared with exercise echocardiography.

Estimates of the quality of life with asymptomatic coro-nary disease, symptomatic coronary disease,or MI didnot significantly influence decision-analysis outcome. Inaddition,varying the tolls for procedures minimallyaffected the relative differences in diagnostic strategies.

DiscussionCommon screening strategies provide an extra QALY

for a wide range of costs.26 For example, screening adultsfor hypertension results in expenditures of $10,000 to$50,000 per QALY saved.31 Thus diagnosis with cardiaccatheterization in women with definite angina is compa-rable to other health interventions that are routinely per-formed.However, for women with probable angina, ini-tial diagnosis with cardiac catheterization increasesQALYs,but at costs exceeding $75,000 compared withexercise echocardiography.For women with nonspecificchest pain,diagnosis with initial exercise echocardiogra-phy is also comparable to interventions such as screen-ing for hypertension that are routinely performed.

Therefore we conclude that for a 55-year-old womanwith definite angina, cardiac catheterization is the pre-ferred initial diagnostic test. For a patient with probableangina, cardiac catheterization provides the most QALYsbut at a cost exceeding $75,000 per QALY comparedwith exercise echocardiography. For a patient with non-specific chest pain, exercise echocardiography is thepreferred initial diagnostic test (Table III).


Figure 3

Time elapsed after diagnostic test. Until roughly 10 years afterdiagnostic test, exercise echocardiogram provides moreQALYs and is cheaper than cardiac catheterization for patientswith probable angina. Note that marginal cost-effectiveness ofcatheterization improves as time elapsed after diagnostic testincreases; thus benefits of aggressive diagnostic interventionaccumulate over time.

Figure 4

Sensitivity analysis of time elapsed after diagnostic test. Sensi-tivity analysis in 55-year-old woman with nonspecific chest painshowing effect of time on cost-effectiveness of exerciseechocardiogram compared with no test. Note that marginalcost-effectiveness improves as time elapsed after diagnostic testincreases; thus benefits of diagnostic intervention accumulateover time.

Our findings are consistent with previous cost-effectiveanalyses performed in men.These analyses showed that ata high pretest probability, initial diagnosis with cardiaccatheterization provides more QALYs,albeit at an extraoverall cost compared with other strategies,and that non-invasive imaging at lower pretest probabilities is costeffective.Doubilet et al1 found that cardiac catheterizationwas justified in patients with typical angina at a cost com-parable with other accepted medical practices,and thatexercise ECG provided useful information in the presenceof nonspecific chest pain or probable angina.Similarly,Patterson et al2 found that in patients with prevalence ofCAD less than 80%,exercise-thallium was a more cost-effective initial test than exercise ECG alone,and at preva-lences greater than 80% proceeding to angiography as thefirst test was more cost-effective than initial noninvasivetesting with exercise ECG or exercise-thallium.Exerciseechocardiography was not included in these analyses.

Our results are generally consistent with previous rec-ommendations in women.Marwick et al32 examined theaccuracy and cost of exercise echocardiography in thediagnosis of CAD in women and found that exerciseechocardiography had accuracies exceeding exerciseECG and could limit cost. In a review of angina in women,

Douglas et al33 recommended that cardiac catheterizationbe the initial diagnostic test for women with a highpretest probability of CAD (defined as greater than 80%),noninvasive imaging for women with intermediatepretest probability (defined as 20% to 80%),and no testfor women with low pretest probability (defined as lessthan 20%).Our analyses primarily differed in our findingthat exercise echocardiography was cost effective forpatients with nonspecific chest pain and therefore a lowpretest probability of disease.

For women with definite angina in our analysis,cardiaccatheterization increased QALYs because the likelihoodof CAD was high.Therefore patients received benefitfrom aggressive diagnostic intervention.However,cardiaccatheterization was more expensive than exerciseechocardiography,exercise-thallium,exercise ECG,and notest because cardiac catheterization led to expensive ther-apeutic procedures, specifically revascularizations.Forwomen with probable angina,cardiac catheterizationincreased QALYs because the likelihood of CAD was stillsignificant and patients could still receive benefit fromaggressive diagnostic intervention.However, the cost perQALY increased because of the higher number of womenwithout CAD in this group who underwent cardiac


Marginal cost per QALY saved per year ($/y)

Cost ($) QALY vs Cath vs Echo vs Thallium vs ECG vs No test

Definite anginaNo test 6918 10.232ECG 13,268 10.501Thallium 15,823 10.589Echocardiography 15,404 10.632 Dominates 16,305 21,215Cardiac catheterization 16,487 10.697 16,662 6148 16,423 20,578

Probable anginaNo test 4031 12.610ECG 6951 13.296Thallium 8678 13.328Echocardiography 7742 13.347 Dominates 15,510 12,088Cardiac catheterization 8646 13.359 75,333 Dominates 26,904 14,524

Nonspecific chest painNo test 2128 14.785ECG 3124 14.897Thallium 4419 14.899Echocardiography 3201 14.906 Dominates Dominates 3555 9580Cardiac catheterization 4082 14.885

Table II. Cost-effectiveness of diagnostic strategies in a 55-year-old woman with chest pain stratified by chest pain characteristics

Chest pain type Pretest probability Initial diagnostic test

Definite angina 0.71 Cardiac catheterizationProbable angina 0.31 Cardiac catheterization or exercise echocardiographyNonspecific chest pain 0.06 Exercise echocardiography

Table III. Recommendations for diagnostic testing

catheterization that might have been avoided had theyundergone noninvasive testing initially.

Finally, for a woman with nonspecific chest pain, exer-cise echocardiography provided more QALYs than car-diac catheterization because the likelihood of CAD waslow. Exercise echocardiography minimized the numberof patients who received unnecessary angiography. Italso better identified the small number of patients withCAD who benefitted from diagnosis in this group com-pared with exercise ECG, exercise-thallium, or no test.Because there were relatively few cardiac eventexpenses to offset the cost of exercise echocardiogra-phy, the net cost of treatment with exercise echocardio-graphy was greater than diagnosis with exercise ECGand no test at all. However, enough cardiac events didoccur to make diagnostic testing worthwhile.

The fact that cardiac catheterization provided no sur-vival advantage at a low prevalence of disease drawsattention to the risk of the procedure.Even though risk isslight, it becomes relatively more significant in a low-riskpopulation.At higher prevalences of disease, the risks ofcatheterization are outweighed by the benefit of diagnos-ing a potentially treatable disease.However, at lowerprevalence of disease, the patient undergoes an invasiveprocedure to diagnose a disease that is highly unlikely.

Such risk can also be incurred by ordering an inaccu-rate diagnostic test because a false-positive test can leadto further invasive diagnostic testing.A positive exerciseECG in a low-risk patient presents a difficult situation.Unless the results of the exercise test were followed-up,there is no reason for performing the test; a positive testresult increases suspicion for coronary disease to anuncomfortable threshold for clinicians.Although thequestion of a false-positive result could be resolvedwith catheterization, this would expose the low-riskpatient to the morbidity risks of catheterization for adisease that is unlikely.

Similar assessment of disease prevalence is necessarywhen considering noninvasive diagnostic testing whenthe test result is negative as well.Although exercise test-ing has little morbidity risk as a procedure, a false-nega-tive test result can provide false reassurance and pre-vent the patient from receiving necessary aggressiveintervention. For patients with definite and probableangina, a false-negative exercise echocardiogram,although uncommon, can prevent the patient fromreceiving catheterization and therefore CABG or PTCA.

Although the cost of exercise-thallium was higher thanexpected, decreasing the cost of exercise-thalliumwithin the specified ranges did not make it more advan-tageous than the other strategies. Exercise-thallium had alower sensitivity and specificity than exercise echocar-diography and was still more expensive than other non-invasive strategies, even with the HMO data.This findingmay reflect operator bias; exercise echocardiography is anewer test than exercise-thallium and therefore the liter-

ature published on exercise echocardiography reflectsthe high accuracies of expert operators.

Most of the benefits of diagnostic testing occurredover the first 10 years after testing.The high initial costsof testing and subsequent procedures were offset bythe QALYs that accumulated over this time period.

Differences in QALYs saved between strategies weregenerally small. However, the differences we found arecomparable to the effect of diagnosis and treatment inother illnesses. For patients with high risk of stroke,treatment with warfarin provides roughly 5 addedmonths of QALY compared with no treatment at all.34

LimitationsOur analysis has several limitations. Our decision

model did not incorporate the prognostic or functionalinformation provided by noninvasive exercise testing.In actual practice a false-negative exercise test resultprobably carries better prognosis than a true-positivetest, but we were unable to incorporate this differencein our model because of insufficient data on prognosisof a false-negative result. In the absence of completedata, such an adjustment penalizes the test with ahigher number of true-positives; the adjustment wouldarbitrarily increase the number of patients with severedisease for the more accurate test result. In addition, notall positive exercise results are equivalent in actualpractice.Also, because they are reported as such in theliterature, we could not risk-stratify on the basis of earlyversus late positive exercise tests.

Our model did not have patients undergo repeat test-ing and repeat invasive procedures.Patients can undergoseveral diagnostic tests,but we did not have data forrepetitive test referral rates.Patients can also undergorepeated PTCA and CABG for persistent angina,but nodata indicate exactly when this should be done.Also,out-comes data after PTCA in women are only available inobservational studies.Assuming women are referred forcardiac catheterization at a later point in the evolution ofCAD, the symptom relief success rate may be significantlylower than in men,and the morbidity and mortality rateshigher than in men.

Our diagnostic accuracy for exercise tests in womenwas obtained from a meta-analysis.6 As noted in themeta-analysis, there were few studies of the diagnosticvalue of exercise-thallium and exercise echocardiogra-phy data in women. Higher energy agents such as tech-netium sestamibi may have higher specificity for thediagnosis of CAD in women, but this hypothesis awaitsconfirmatory studies.35 Finally, because our model waslargely based on CASS registry data, and medical and sur-gical therapies have evolved considerably since the initi-ation of that study, the accuracy of morbidity and mortal-ity rates for medical management and CABG may haveimproved. Unfortunately, there are no newer randomizedcontrolled trials available with separate data for women.


We believe cardiac catheterization should be used asthe initial diagnostic test for women with definiteangina. For female patients with an intermediate proba-bility of coronary disease, issues of costs and the lowermargin of benefit provided by invasive testing shouldbe considered in choosing a diagnostic strategy andexercise echocardiography may be optimal in thisgroup. For women with nonspecific chest pain, exerciseechocardiography may prolong QALYs at costs compa-rable to other acceptable medical practices.

We thank Ms Kathy Marks, Department of Medicine,Moffitt Hospital, for her assistance in obtaining finan-cial data.

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Diagnosis of suspected coronary artery disease in women: A cost-effectiveness analysis

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