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Circulation. 1996;94:957-965

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(Circulation. 1996;94:957-965.)
© 1996 American Heart Association, Inc.

Articles

Cost-effectiveness of Routine Coronary Angiography After Acute Myocardial Infarction

Karen M. Kuntz, ScD; Joel Tsevat, MD, MPH; Lee Goldman, MD, MPH; Milton C. Weinstein, PhD

the Section for Clinical Epidemiology (K.M.K., L.G., M.C.W.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and the Departments of Biostatistics (M.C.W), Health Policy and Management (K.M.K., M.C.W.), and Epidemiology (L.G.), Harvard School of Public Health, Boston, Mass; Section of Outcomes Research (J.T.), Division of General Internal Medicine, University of Cincinnati Medical Center (Ohio); and Department of Medicine (L.G.), University of California, San Francisco School of Medicine.

Correspondence to Karen M. Kuntz, ScD, Section for Clinical Epidemiology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail keaney@hsph.harvard.edu.


*    Abstract
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 *Abstract
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Background Coronary angiography is indicated for many patients after acute myocardial infarction (AMI). There are a number of subgroups of AMI patients, however, for whom the indication for coronary angiography is not well established.

Methods and Results We developed a decision-analytic model for AMI in representative patient subgroups based on relevant clinical characteristics. The model estimates quality-adjusted life expectancy and direct lifetime costs for two strategies: coronary angiography and treatment guided by its results versus initial medical therapy without angiography. Decision tree chance node probabilities were estimated with the use of pooled data from randomized clinical trials and other relevant literature, costs were estimated with the use of the Medicare Part A database, and quality of life adjustments were derived from a survey of 1051 patients who had had a recent AMI. In our analysis, incremental cost-effectiveness ratios for coronary angiography and treatment guided by its result, compared with initial medical therapy without angiography, ranged between $17 000 and >$1 million per quality-adjusted year of life gained. Patient subgroups with severe postinfarction angina or a strongly positive exercise tolerance test (ETT) typically had cost-effectiveness ratios of <$50 000 per quality-adjusted year of life gained. In addition, most patient subgroups with a prior AMI had cost-effectiveness ratios of <$50 000 per quality-adjusted year of life gained, even with a negative ETT result.

Conclusions In many patient subgroups after AMI, the cost-effectiveness of routine coronary angiography and treatment guided by its results compares favorably with other treatment strategies for coronary heart disease.


Key Words: angiography • coronary disease • cost-effectiveness analysis


*    Introduction
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 *Introduction
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An estimated 600 000 Americans are hospitalized each year for AMI.1 Patients who survive the first 3 days of hospitalization remain at risk for subsequent myocardial events, including sudden death, recurrent nonfatal AMI, angina, and CHF. The need for routine coronary angiography for patients in the convalescent phase of AMI remains controversial.2 3 Guidelines developed by the Joint Task Force of the American Heart Association and the American College of Cardiology2 and appropriateness ratings developed by the RAND Corporation3 identify a number of clinical conditions for which the indication for coronary angiography in this setting remains uncertain. For example, coronary angiography in patients with mild angina who do not test positive on ETT, in asymptomatic patients <50 years old, or in patients with a history of prior AMI is controversial. In two studies designed to evaluate routine versus symptom-driven coronary angiography in patients after AMI, the TIMI Phase II Trial4 and the TIMI IIIB Trial5 found no significant difference in 1-year death and reinfarction rates. Nevertheless, there is a trend toward the increasing use of coronary angiography for patients who survive uncomplicated AMI.6

Few studies have evaluated the cost-effectiveness of routine coronary angiography after AMI. Dittus et al7 compared strategies for the management of clinically asymptomatic AMI patients in terms of their expected 6-month cardiovascular mortality and cost. However, their model did not incorporate events that occurred >6 months after the AMI and did not incorporate quality-of-life adjustments. Patterson et al8 compared the costs and benefits of screening patients for left main or three-vessel CAD with ETT. However, their results were presented in terms of cost per case of multivessel disease avoided. Accordingly, we sought to evaluate the cost-effectiveness of routine coronary angiography in patients after AMI and treatment guided by its results in terms of the extra cost per quality-adjusted year of life gained.


*    Methods
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 *Methods
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The Model
We developed a model to compare the costs and quality-adjusted life expectancy of performing routine coronary angiography during the convalescent phase of AMI versus initial MEDS without angiography. Because we expected the cost-effectiveness for coronary angiography to vary with clinical characteristics, we grouped patients by relevant variables known at the time of the decision. A schematic diagram of the decision tree (Fig 1Down) illustrates the two basic options: angiography versus no angiography. Our model quantifies angiographic results in terms of number of stenosed vessels (none to three), with a separate category for left main disease. If angiography is successfully performed, knowledge of coronary anatomy leads to a choice among three treatment modalities: CABG, PTCA, or MEDS. For patients with LVEF >=0.20, we considered 13 possible treatment strategies after successful coronary angiography: we specified CABG for patients with left main disease; we allowed for the possibility of any of the three treatments for patients with multivessel (two or three) disease; we allowed for either PTCA or MEDS for patients with one-vessel disease, unless the patient was ineligible for PTCA, in which case we allowed for CABG; and we always designated MEDS alone for patients with no anatomically confirmed CAD. In patients not undergoing angiography, coronary anatomy is unknown, and patients are treated medically.



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  		Figure 1. Schematic of the coronary angiography decision tree. Decisions are represented by squares, and uncertain events are represented by circles.

Decision tree probabilities for number of stenosed vessels, procedure-related mortality, long-term survival, and subsequent AMI and revascularization were modeled conditionally on patient characteristics that are usually known before angiography: age (35 to 84 years, in decades); gender; presence/absence of comorbidity; and clinical factors, including postinfarction angina (none, mild, severe), ETT result (not determined; negative; equivocal; positive, defined as >=1-mm ST-segment depression; strongly positive, defined as >=2-mm ST-segment depression), presence/absence of CHF, LVEF (not determined, >=0.50, 0.20 to 0.49, <0.20), and presence/absence of prior AMI.

To model long-term costs and health status associated with subsequent cardiac events, angina level, and presence/absence of CHF for patients surviving the first 30 days after AMI, we used a Markov cycle tree,9 which updates a patient's clinical status and costs annually. Long-term adjustments for the quality of life associated with angina and CHF were made by multiplying each year of life by a coefficient, ranging from 0 to 1, representing the relative quality during that year of life. Short-term quality adjustments for AMI, coronary angiography, PTCA, and CABG were approximated by decrementing a person's life expectancy by a certain number of days.

Some Key Assumptions
Because of the lack of or conflicting data, we had to specify which patient characteristics influenced coronary anatomy and/or long-term survival (Fig 2Down). We assumed that age, gender, and LVEF influenced both coronary anatomy and long-term survival; history of prior AMI, ETT result, and postinfarction angina influenced only coronary anatomy, which, in turn, affected long-term survival; and CHF and comorbidity influenced only long-term survival.



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  		Figure 2. Correlates of coronary anatomy and long-term survival. Ovals and rectangles represent variables that are known or unknown, respectively, before the decision is made to perform coronary angiography. The direction of the arrows describes the manner in which these variables were modeled. Merging lines indicate dependence between variables.

For a hypothetical patient in the model who was designated to undergo PTCA, we assumed that a certain percentage would be ineligible and would therefore either undergo CABG or receive MEDS. We also assumed that 30% of PTCA patients would undergo a repeat procedure as warranted by clinical symptoms within the year and 5% would undergo emergency CABG.10 11 12 13 For our baseline analysis, we assumed no survival benefit for PTCA but assessed the impact of different assumptions in sensitivity analyses. During the first year after revascularization, we assumed that PTCA was 50% as effective as CABG in terms of angina relief but thereafter assumed they were equivalent.12 We also assumed that the quality-of-life benefits (relief of angina) from PTCA or CABG persisted for 8 years. The long-term survival benefit of CABG depended on a patient's coronary anatomy14 and was assumed to persist for 12 years.

The Data
To estimate the probabilities for our model, we used pooled data from the literature with an emphasis on randomized clinical trials and large population-based studies. For variables such as CABG-related survival, in which there were no adequate studies involving survivors of AMI, we used studies of patients with CAD and assumed that the data were applicable to patients with AMI.

Coronary Anatomy
Since the advent of thrombolytic therapy, angiographic studies have shown a decrease in the number of stenosed vessels in survivors of AMI. For example, the incidence of three-vessel disease ranged from 23% to 50% in prethrombolytic angiographic studies compared with 7% to 20% in thrombolytic trials.15 16 As a conservative estimate, we used data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) angiographic substudy (Robert M. Califf, MD, personal communication, September 25, 1995) to estimate coronary artery stenosis probabilities adjusted for age, gender, and recent AMI. In that substudy, 2271 patients with AMI who were candidates for thrombolytic therapy systematically underwent coronary angiography according to protocol, and significant disease was defined as >75% stenosis. The proportion of post-AMI patients who fell into each of the various ETT result categories, stratified by their coronary anatomy, was estimated from a number of studies performed in patients surviving AMI.17 18 19 20 21 The interrelationships among LVEF, prior AMI, and coronary anatomy were estimated from three angiographic studies (Table 1Down).22 23 24


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  		Table 1. Model Estimates

Short-term Mortality
In-hospital mortality was estimated for coronary angiography, PTCA, and CABG based on relevant patient characteristics. Because no large studies specifically reported angiography-related mortality in patients after AMI, we used two population-based sources: the Society for Cardiac Angiography and Interventions Registry (n=222 553),25 26 and the Collaborative Study of Coronary Artery Surgery (CASS; n=7553).27 Angiographic mortality estimates were 0.018%, 0.051%, 0.071%, 0.119%, and 0.550% for no, one-vessel, two-vessel, three-vessel, and left main CAD, respectively. These mortality rates were then adjusted for the presence or absence of CHF and LVEF.

In-hospital mortality associated with PTCA was estimated from the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry (n=1801).28 29 Mortality associated with PTCA was 0.2%, 0.9%, and 2.2% for patients with one-, two-, and three-vessel disease, respectively. These mortality rates were then adjusted based on age, gender, and the presence or absence of CHF.

To estimate the operative mortality associated with CABG, we used data from the New York State Cardiac Surgery Reporting System,30 the Northern New England Cardiovascular Disease Study Group,31 and Brigham and Women's Hospital.32 The mortality estimates for surgical patients were 1.9%, 2.3%, 3.3%, 4.1%, and 6.1% for ages 35 to 44, 45 to 54, 55 to 64, 65 to 74, and 75 to 84 years, respectively. These mortality rates were then adjusted for gender and the presence or absence of CHF or LVEF.

Long-term Survival
Long-term survival after the first 30 days was modeled on "intention to treat"; although the model allowed for subsequent revascularization procedures and AMI (to include the costs and quality of life associated with these events), prognosis was determined only by the initial patient characteristics and treatment, similar to the manner in which randomized clinical trials are analyzed. Gender- and age-specific baseline survival curves for patients after AMI were derived from the Coronary Heart Disease Policy Model,33 which incorporates data from US life tables34 and a number of epidemiological and population studies to simulate prognosis of patients with coronary heart disease. Unique survival curves were estimated for each gender/age group and were adjusted with the use of risk ratios associated with relevant patient characteristics. We used a proportional hazards assumption to incorporate the long-term prognostic effects of LVEF, CHF, and comorbidity, as well as coronary anatomy, treatment, and their interaction.

To estimate the effectiveness of CABG, we used a systematic review of seven trials that randomized patients with stable coronary heart disease to CABG or MEDS.14 Long-term mortality risk ratios were estimated for (1) two-vessel, three-vessel, and left main disease relative to one-vessel disease; (2) CABG relative to MEDS for one-vessel, two-vessel, three-vessel, and left main disease; and (3) LVEF between 0.20 and 0.49 relative to LVEF of >=0.50. Mortality risk ratios were approximated by the reported 5-year odds ratios, increased or decreased (toward 1) by 10% to reflect 7-year estimates. The long-term mortality risk ratio for CHF was estimated from the 4-year survival experience from the Multicenter Investigation of the Limitation of Infarct Size (MILIS) Study Group35 in patients after AMI (see Table 1Up).

Annual Rates of Subsequent Myocardial Events and Revascularization Procedures
Subsequent nonfatal AMIs and revascularization procedures occurring after the initial treatment decision were modeled to capture their effects on cost and quality of life. For example, if CABG was performed in the second year after the index AMI, then the discounted cost of the operation was included in the lifetime cost of the patient, and the disutility associated with CABG was incorporated into the quality adjustments. However, neither the operative mortality nor the survival benefit associated with the subsequent revascularization was modeled separately because they were already incorporated in the "intention to treat" survival curves.

Estimates of annual probabilities of subsequent nonfatal AMIs for men <65 years old were .021, .058, and .074 for patients initially having one-, two-, and three-vessel disease, respectively.36 These were adjusted upward or downward with the use of risk ratios based on age,35 gender,37 and initial treatment.38 Annual revascularization probabilities were .010, .042, and .075 for patients initially having one-, two-, and three-vessel disease, respectively, and treated medically, based on the annual crossover rates in the medical arm of CASS.39 Sixty-nine percent of these revascularizations were assumed to be CABGs based on the experience of the Medicare AMI population (unpublished data, AMI Patient Outcomes Research Team). For patients with two- and three-vessel disease initially treated with CABG, the annual revascularization probabilities were .036 and .064,10 39 respectively, with 7% of these revascularizations being CABGs. Because we incorporated the revascularizations that occur in the first year after PTCA into its cost, we estimated subsequent revascularizations after the first year. Annual revascularization rates for patients initially treated with PTCA were estimated to be the same as those for CABG with 30% of revascularizations being CABGs. We allowed differences in revascularization probabilities among initial treatments to last for 8 years.

Annual Changes in Angina and CHF Status
We estimated the annual probabilities of changing from one level of angina (none, mild, or severe) to another with the use of the CASS quality-of-life study,40 which reported the proportion of patients in each angina group over time, stratified by coronary anatomy and initial treatment. The annual probability that a patient without CHF would develop CHF was estimated to be 5%.41 We assumed that once a patient developed CHF, he or she remained in that condition.

Costs
Direct treatment costs were primarily estimated with the use of the Medicare Provider Analysis and Review (MEDPAR) files for Medicare beneficiaries admitted to a hospital in 1987 with a primary diagnosis of AMI (n=218 427). Costs were obtained by applying cost-to-charge ratios provided in the Medicare Cost Report. Costs were available for ages >=65 in 5-year age groups. We assumed that the costs for patients less than age 65 were equal to those of the 65- to 69-year-old age group, based in part on a study that found no cost difference in patients less than age 60 but an increasing trend in costs for patients more than age 60.42

Estimates of hospital costs in the first 30 days after AMI were stratified on the basis of cardiac procedures performed within the 30-day period (ie, no procedure, coronary angiography only, coronary angiography and PTCA, or coronary angiography and CABG). Thirty-day costs for subsequent AMI were assumed to be the same as the 30-day costs estimated for an index AMI in which the same procedure, if any, was performed. Hospital costs for revascularization interventions without AMI were estimated from 30-day costs for procedures that were not performed within 30 days of AMI. Professional costs associated with AMI and cardiac interventions were estimated from the Medicare Fee Schedule published in the Federal Register and were included in the total 30-day, age-adjusted costs (see Table 1Up).

We assigned an annual cost associated with medications, tests, and outpatient follow-up visits based on whether the initial treatment assignment was MEDS or revascularization. The annual hospitalization cost for the first year for patients who survive the first 30 days was estimated from the 1987 MEDPAR cohort for two patient groups: those who underwent revascularization within the first 30 days after AMI ($2060) and those who did not undergo revascularization during this 30-day period ($2350). We used the relative cost relation between the first and subsequent years found in an earlier study by Hemenway et al43 (54% decrease in annual cost in subsequent years) for both the revascularization and MEDS groups. In addition, we assumed that the differences in annual costs between the revascularization and MEDS groups remained constant for 12 years, after which those two costs were equivalent. When a 30-day cost was used in a subsequent year, it was added to 11/12 of the annual cost in that year. All costs were adjusted to 1994 dollars with the use of the medical care component of the Consumer Price Index and were discounted at an annual rate of 3%.

Quality Adjustments for Health States
Utilities (health values) for health states were assessed through the use of a telephone survey of a sample of 1051 survivors of AMI from New York and Texas with the use of the time-trade-off method.44 In this survey, patients were classified as having no angina, mild angina, or severe angina based on a series of questions regarding their history of chest pain. Patients were also classified according to the presence or absence of dyspnea, which we used as a proxy for CHF for the purpose of our model (see Table 1Up).

Sensitivity Analyses
Sensitivity analyses were used to assess whether variations in our estimates or assumptions, alone or in combination, significantly altered the results.


*    Results
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 up arrowMethods
 *Results
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Baseline Analyses
In analyses in which we varied age, gender, postinfarction angina level, ETT result, LVEF, and presence/absence of prior AMI and CHF, the performance of routine coronary angiography increased quality-adjusted life expectancy in all post-AMI patient subgroups except one: women who were 35 to 44 years old and had no postinfarction angina, a negative ETT, LVEF of >=0.50, no history of prior AMI, and CHF.

We identified two clinical factors that were especially influential in determining favorable cost-effectiveness ratios for coronary angiography in patients of all ages after AMI: inducible myocardial ischemia (whether defined as severe postinfarction angina or strongly positive ETT) and history of AMI before the current infarction. In general, the incremental cost-effectiveness ratio for coronary angiography and treatment guided by its results versus no angiography for patients in whom both of these factors were present was between $17 000 and $44 000 per quality-adjusted year of life gained (Table 2Down). The one major exception to this range was the subgroup of patients 75 to 84 years old who had both an LVEF between 0.20 and 0.49 and CHF, because their relative gain in life expectancy translated into a small absolute gain.


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  		Table 2. Incremental Quality-Adjusted Life Expectancy, Cost, and Cost-effectiveness Ratios for Routine Coronary Angiography Compared With Initial MEDS: Strongly Positive ETT Result and Prior AMI

For a majority of the patient subgroups with a negative ETT, the incremental cost-effectiveness ratios for coronary angiography were >$50 000 per quality-adjusted year of life gained. However, for certain patient subgroups with a history of prior AMI, coronary angiography was associated with favorable cost-effectiveness ratios, even with a negative ETT (Table 3Down). For example, male patients 45 to 74 years old who had a prior AMI and an LVEF of >=0.50 had incremental cost-effectiveness ratios of <$50 000 per quality-adjusted year of life gained, regardless of the ETT result.


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  		Table 3. Incremental Quality-Adjusted Life Expectancy, Cost, and Cost-effectiveness Ratios for Routine Coronary Angiography Compared With Initial MEDS: Negative ETT Result and LVEF of >=0.50

For patients with an ETT result, the incremental cost-effectiveness ratio for patient subgroups with mild postinfarction angina was only slightly less than that for patients with no postinfarction angina, all other factors being equal. The difference between mild and no postinfarction angina was greater, however, for patients who did not have ETT results, especially for subgroups at moderate risk. For example, male patients 45 to 54 years old without an ETT result and with an LVEF of >=0.50 had incremental cost-effectiveness ratios of <$50 000 per quality-adjusted year of life gained if mild postinfarction angina was present and >$70 000 per quality-adjusted year of life gained if no postinfarction angina was present, raising the question as to whether alternative tests should be considered in asymptomatic patients who cannot exercise.

With the use of a threshold of $50 000 per quality-adjusted year of life gained, we constructed a flow diagram that synthesizes our findings and provides recommendations for routine coronary angiography in patients after AMI (Fig 3Down). There are a few discrepancies between these generalizations and our analysis. For example, there were some patient subgroups with inducible myocardial ischemia for whom the cost-effectiveness ratio of coronary angiography was >$50 000 per quality-adjusted year of life gained. These tended to be older patients who had shortened life expectancies (eg, CHF and an LVEF between 0.20 and 0.49).



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  		Figure 3. Flow diagram for performing routine coronary angiography in patients after AMI based on a cost-effectiveness threshold of $50 000 per quality-adjusted year of life gained. Angio indicates coronary angiography; M, male patients; F, female patients; ETT, exercise tolerance test; and ++, ETT with >=2-mm ST-segment depression.

The morbidity variable had little effect on the incremental cost-effectiveness ratios for coronary anatomy at small magnitudes. However, when we assumed that a patient subgroup had an acute disease that greatly affects life expectancy (eg, mortality risk ratio of 5), the cost-effectiveness ratios increased markedly.

Sensitivity Analysis
Results were not sensitive to short-term mortality rates associated with coronary angiography, PTCA, or CABG. A doubling of the mortality associated with coronary angiography resulted in only minimal increases in the incremental cost-effectiveness ratios. The results were somewhat sensitive to the risk ratio associated with the reduction in late mortality of CABG versus MEDS for patients with three-vessel disease. Assuming a reduction in mortality that was two thirds of our baseline estimate, we found an increase in cost per quality-adjusted year of life saved of {approx}50%.

If we assumed that PTCA had equivalent, 80%, and 50% mortality reductions of CABG for one-, two-, and three-vessel disease, respectively (base case=0%), then the incremental cost-effectiveness ratios for angiographically detected treatment were more favorable than in the base case analysis, as expected. The overall conclusions regarding the cost-effectiveness of coronary angiography were not altered substantially, but the optimal postcatheterization treatment strategy was altered substantially. Under the assumption of no PTCA survival advantage, the optimal postcatheterization treatment strategy was to perform CABG if a patient has left main or three-vessel disease and to provide MEDS otherwise. Under the assumption of a small survival benefit for PTCA, the optimal postcatheterization strategy was to perform CABG if a patient has left main or three-vessel disease, to perform PTCA if a patient has one- or two-vessel disease (MEDS if the patient is ineligible for PTCA), and to prescribe MEDS if the patient has no angiographically confirmed CAD.

Our results were not sensitive to the assumption that the probability of a subsequent AMI was different for patients who initially received MEDS than for those who received a revascularization procedure. For example, the incremental cost-effectiveness ratio for the high-risk patient increased by {approx}$2000 per quality-adjusted year of life gained when we assumed that this probability was equal for all initial treatment groups. Our results were also not sensitive to changes in the utilities for health states. The incremental cost-effectiveness ratios in terms of cost per life-year saved were very similar to the corresponding ratios in which cost per quality-adjusted year of life gained was calculated. Under the assumption that there is no difference in downstream annual costs between patients who were initially treated with MEDS versus those undergoing revascularization, we found only small changes in our base case results: the incremental cost-effectiveness ratios increased {approx}$4000 per quality-adjusted year of life gained.


*    Discussion
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 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 *Discussion
down arrowReferences
 
There is little debate regarding the need to identify patients with jeopardized myocardium during the convalescent phase of AMI. Although the most direct approach for evaluating patients who are stable after AMI is coronary angiography,24 45 routine angiography may result in a large number of unnecessary procedures and has a mortality risk associated with it. Initial evaluation with the use of ETT, followed by coronary angiography if positive, is often advocated as the appropriate strategy for the evaluation of patients after AMI2 46 47 ; however, certain patients who are at high risk before undergoing an ETT may remain at a sufficiently high risk to warrant coronary angiography, even with a negative ETT result. Our analysis emphasizes that history of prior AMI and, in some cases, LVEF is also important in stratifying patients after AMI to undergo further evaluation. For example, many patient subgroups with a history of prior AMI had relatively favorable incremental cost-effectiveness ratios, regardless of their ETT result (Table 3Up).

We used the methods of decision and cost-effectiveness analysis to combine the available data on the potential benefits of coronary angiography and treatment guided by its results in a structured model with our assumptions explicitly stated. We incorporated costs and quality-of-life measures, aspects that were not explicitly included in recently published guidelines for coronary angiography in AMI patients.2 3 In addition, we were able to identify the variables that most influenced the cost-effectiveness results. Based on our model, we found that incremental cost-effectiveness ratios for coronary angiography and treatment guided by its result, compared with initial MEDS without angiography, ranged between $17 000 and >$1 million per quality-adjusted year of life gained. Patient subgroups with severe postinfarction angina or a strongly positive ETT typically had incremental cost-effectiveness ratios of <$50 000 per quality-adjusted year of life gained. Exceptions to this were patients who had markedly reduced life expectancies who are not expected to live long enough for the benefits of revascularization to justify the up-front cost of the procedure. For most patients with no postinfarction angina, no prior AMI, and a negative ETT, there was modest gain in quality-adjusted life expectancy, but the incremental cost-effectiveness ratios were usually >$100 000 per quality-adjusted year of life gained (in one patient subgroup, coronary angiography was both more costly and less effective than initial MEDS).

For many patient subgroups, the cost-effectiveness ratios of routine coronary angiography after AMI compared reasonably well with those of other medical interventions. For example, ß-adrenergic antagonist therapy after AMI costs $2000 to $14 000 per year of life saved (1987 dollars)48 ; captopril therapy after AMI costs $3600 to $60 800 per quality-adjusted year of life saved (1991 dollars)49 ; the use of cholesterol-lowering agents for 50-year-old men with cholesterol levels of >300 mg/dL costs $13 000 to $110 000 per year of life saved (1989 dollars)50 ; and various antihypertensive therapies cost $10 900 to $72 100 per year of life saved (1987 dollars).51

Although the TIMI Phase II and the TIMI IIIB studies did not show a significant difference in 1-year mortality between patients who were randomized to either routine or symptom-driven coronary angiography,4 5 both trials reported a trend toward lower 1-year mortality in the former group compared with the latter. The reported decrease in 1-year mortality was 0.005 in TIMI Phase II and 0.003 in TIMI IIIB. With the use of comparable patients, our model predicted a 1-year mortality difference of {approx}0.004 and {approx}0.002 for TIMI Phase II and TIMI IIIB patients, respectively. Although these differences were not shown to be statistically significant in the trials, the best estimates of mortality differences provided by the trials were comparable to our model predictions for the first year after AMI. However, our model considers the patient's entire lifetime and assumes that the benefits of revascularization, in terms of reducing mortality, nonfatal AMIs, improving angina severity, and decreasing subsequent revascularizations, persists for 8 to 12 years after the initial coronary angiogram.

Ross et al52 recommended coronary angiography after AMI for patients with severe resting ischemia, a previous AMI, an LVEF between 0.20 and 0.44, or age of <75 years based on a moderate to high risk of death during the first year after infarction (average 1-year mortality, 16%; range, 6% to 25%). Overall, our cost-effectiveness analysis corroborates their recommendations. However, we found that older patients who have an LVEF between 0.20 and 0.49 have higher cost-effectiveness ratios than patients with an LVEF of >=0.50, all else being equal, as a result of the shortened life expectancy in the patients with low LVEF.

The optimal postcatheterization treatment strategy involved only CABG or MEDS in our baseline analysis. This was due to the fact that we did not assume any survival benefit for PTCA. However, the use of conservative assumptions regarding the effect of PTCA on long-term survival resulted in postcatheterization strategies that involved PTCA for the treatment of one- and two-vessel disease. Although the primary goal of our analysis was not to evaluate postcatheterization strategies, their inclusion into our analysis was implicit. Our conclusions assume, however, that "cost-effective" care will be undertaken after coronary angiography. Recently published clinical trials that randomized patients to receive either CABG or PTCA found no significant mortality difference between these two groups.10 11 12 13 However, because the mortality differences are estimated to be fairly small, the question of whether there is a statistically significant difference between CABG and PTCA or between PTCA and MEDS can only be answered with a very large trial.

A limitation of our analysis is that we calculated the short- and long-term mortality estimates with the use of clinical trials or large population-based studies of patients with documented CAD, but not necessarily AMI. It has been shown, however, that patients with documented CAD may progress to an advanced stage of disease in the absence of symptoms.53 In fact, left ventricular function and the extent of anatomic disease have been shown to be of greater prognostic importance than the severity of symptoms in patients with known CAD,54 although not necessarily after AMI. Data regarding the efficacy of CABG specifically for symptomatic or asymptomatic patients after AMI with three-vessel or left main disease would be important additions to our model.

A concise number of clinical variables was used in our model. Although we initially considered a number of prognostic factors such as echocardiography and arrhythmia, we sought to identify a tractable number of variables that captured the most relevant independent predictors of outcomes. Thus, some potentially important variables were not included in our analysis. The addition of each clinical variable, however, adds considerably to the complexity of the model and to the underlying assumptions.

Although coronary angiography is often viewed as a costly, invasive procedure, its results are important in evaluating patients with suspected CAD. Even in cases where the probability of three-vessel disease is small, the benefits that revascularization provides more than offset the small risk associated with coronary angiography in the majority of patients. In many patient subgroups, the cost associated with coronary angiography and possible revascularization results in favorable cost-effectiveness ratios compared with other acceptable medical interventions. We believe that data regarding patients' histories of prior AMI and their LVEFs should be incorporated into the decision to recommend routine coronary angiography after AMI. In addition, ETT should be performed in selected patients for whom the information is most influential.


*    Selected Abbreviations and Acronyms
 
AMI = acute myocardial infarction
CABG = coronary artery bypass graft surgery
CAD = coronary artery disease
CHF = congestive heart failure
ETT = exercise tolerance test
LVEF = left ventricular ejection fraction
MEDS = medical therapy
PTCA = percutaneous transluminal coronary angioplasty
TIMI = Thrombolysis in Myocardial Infarction


*    Acknowledgments
 
This study was supported by grant HS-06341 from the Agency for Health Care Policy and Research, Rockville, Md. The authors would like to thank the members of the Acute Myocardial Infarction Patient Outcomes Research Team (PORT), in particular, Drs Barbara McNeil, Chris Pashos, Paul Cleary, and Edward Guadagnoli, Karen Fung, and Alison Eastwood. We would also like to thank the members of the Ischemic Heart Disease PORT for helpful conversations.

Received February 12, 1996; revision received April 29, 1996; accepted May 1, 1996.


*    References
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 *References
 

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