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Previous Volume 332:1418-1424 May 25, 1995 Number 21 Next

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ABSTRACT

Background Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 11/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective.

Methods Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment.

Results One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio — with both future costs and benefits discounted at 5 percent per year — was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study.

Conclusions The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.

We conducted a cost-effectiveness analysis to compare the value of t-PA treatment with that of streptokinase treatment on the basis of the information on mortality and use of resources from the GUSTO study and detailed data on the use of medical resources and the quality of life of a random subgroup of the GUSTO cohort residing in the United States.

Methods

Our analysis comparing accelerated t-PA with streptokinase used data from the GUSTO study: data on 1-year survival for all 41,021 patients enrolled in the study, data on the use of medical resources during the initial hospitalization for all 23,105 U.S. patients, and data on a prospective random sample of 2600 U.S. patients who underwent structured interviews by telephone 30 days, 6 months, and 12 months after enrollment on their use of medical resources and quality of life.^1,2 The particular costs and benefits examined in a cost-effectiveness analysis vary with the perspective of the study.^3,4 In medical economics, the analysis can be constructed to reflect the viewpoint of society as a whole, payers, health care providers, or patients. In the present study, we used a social perspective to identify relevant costs, although indirect costs (e.g., time lost from work) and nonmedical costs were not included. Effectiveness was measured in terms of additional life expectancy, and the effects of the treatments on the patients' quality of life were examined in a sensitivity analysis.^5,6 Both survival and costs were discounted continuously at an annual rate of 5 percent, as is consistent with conventional practice.^6,7 Extensive sensitivity analyses were performed. Cost-effectiveness ratios were expressed as the additional lifetime costs required to add one extra year of life with t-PA treatment as compared with streptokinase therapy. Higher cost-effectiveness ratios indicate lower cost effectiveness.

Determining Costs

The costs of initial hospitalization (including charges for any transfers between hospitals) were calculated in two ways: from total cost estimates (variable costs plus fixed costs) from the Duke Transition One cost-accounting system, and from Medicare diagnosis-related-group (DRG) reimbursement rates (Table 1). The Transition One system estimates hospital costs using a bottom-up approach that is based on resources consumed and unit prices for those resources.³ Costs of the thrombolytic agents were also calculated in two ways: from the Drug Topics Red Book average of 1993 wholesale prices,⁸ and from the average costs of the drugs in 16 randomly selected GUSTO hospitals (2 hospitals in each GUSTO geographic region).¹ The Red Book average wholesale price of 1.5 million units of streptokinase was $320; the price of 100 mg of t-PA was $2,750. The average cost to the 16 GUSTO hospitals was $270 for 1.5 million units of streptokinase and $2,216 for 100 mg of t-PA. We assumed that pharmacy handling and preparation costs and drug-administration costs would be equivalent for the two regimens. For follow-up hospitalization costs, we used Medicare DRG reimbursement rates for North Carolina (Table 1). Reported hospitalizations and revascularization procedures were verified with the relevant institution. Physicians' fees for both initial and follow-up hospitalizations were drawn from the Medicare fee schedule for North Carolina (Table 1).

View this table: [in this window] [in a new window]   Table 1. Costs Used in the Analysis.

 
For the primary analysis, incremental costs included only cumulative hospital and physicians' costs for the first year after treatment. Because there were no empirical data on costs after one year, the primary analysis assumed no cost differences between the treatment groups after one year. All costs were expressed in 1993 dollars.

Estimating Survival

To estimate survival rates after the end of follow-up in the GUSTO study, the primary analysis assumed that the hazard of death after one year did not depend on the thrombolytic agent received (i.e., that the survival curves of the two treatment groups were parallel) and that the patients' pattern of long-term survival was typical of the chronic, stable phase of coronary heart disease. To represent that pattern, we constructed a Cox proportional-hazards model based on the experience of 4379 patients in the Duke Cardiovascular Disease Database^9,10,11,12 with myocardial infarction between 1971 and 1992 who had either pathologic Q waves on a resting 12-lead electrocardiogram or a marked focal wall-motion abnormality seen on a left ventriculogram and who survived at least one year. This survival model was used to extend the 1-year survival data by an additional 14 years. For the model, we selected covariates that were available in the GUSTO data base, including age, sex, and location of infarction. Because, in the Duke data, approximately 20 percent of patients were alive at the last follow-up, we used a Gompertz function to extrapolate the tail of the survival curve.¹³

Using this composite modeling approach, we generated lifetime survival curves for both treatment groups and calculated life expectancy as the area under each curve. The increase in life expectancy for the t-PA group was thus represented by the difference between the areas under the two curves. The survival curve for the t-PA group is presented in Figure 1.

View larger version (2K): [in this window] [in a new window]   Figure 1. Probability of Survival among Patients Treated with t-PA. A survival function of this type was used to estimate life expectancy for each treatment group. The curve consists of three parts: the survival pattern in the first year after treatment in the GUSTO study, data for an additional 14 years on survivors of myocardial infarction in the Duke Cardiovascular Disease Database, and a Gompertz parametric survival function adjusted to agree with the empirical survival data at the 10-year and 15-year follow-up points.

 
Sensitivity Analyses

Extensive sensitivity analyses were performed in order to find threshold values for variables in the model that would result in a cost-effectiveness ratio of more than $50,000 per year of life saved. We varied survival and costs in both the short and the long term for the t-PA group, the costs and adverse health consequences of the increased risk of disabling stroke associated with t-PA, and the utility weights we used to reflect the attitude of patients toward their current state of health.

Utility

Utility (a number from 0 to 100 that summarizes the value patients attach to their current state of health) was measured in structured telephone interviews one year after treatment. Patients were asked, in a series of questions, how much of their current life expectancy — assumed to be 10 years in their present state of health — they would be willing to give up in order to live their remaining years in excellent health.^14,15

Subgroup Analysis

We calculated the comparative cost-effectiveness value for treatment with t-PA instead of streptokinase for eight clinical subgroups defined by the patient's age (up to 40 years, 41 to 60 years, 61 to 75 years, or more than 75 years) and the location of the infarction (anterior or inferior). In a linear regression analysis, neither age nor the location of the infarction had an identifiable association with costs in the first year after treatment. Consequently, we used the cost differences from our primary analysis in calculating the cost-effectiveness values for the eight subgroups.

Statistical Analysis

Descriptive data are presented as percentages for discrete variables and as medians with 25th and 75th percentiles for continuous variables (Table 2). Intention-to-treat analyses of base-line, six-month, and one-year data were performed with a chi-square test for discrete variables and by the Wilcoxon rank-sum test for continuous variables.

View this table: [in this window] [in a new window]   Table 2. Use of Medical Resources during the Initial Hospitalization and up to One Year after Discharge, According to Treatment.

 
Results

Primary Analysis

            Costs

Resource consumption within the first year was generally similar in the streptokinase and t-PA groups (Table 2). There was a slightly higher use of pulmonary-artery catheters in the patients who received streptokinase during the initial hospitalization (20 percent, vs. 18 percent in the t-PA group; P = 0.002). There was a trend toward more percutaneous transluminal coronary angioplasty in the t-PA group (3 percent vs. 2 percent, P = 0.03) and more rehospitalization (19 percent vs. 15 percent, P = 0.06) from six months to one year after enrollment (Table 2). At the time of initial hospital discharge, there was no difference between the two treatment groups in the rates of use of any of the major classes of cardiac medications. The estimated cumulative medical costs (hospital costs plus physicians' fees) at one year, exclusive of the cost of the thrombolytic agent, averaged $24,575 for patients treated with streptokinase and $24,990 for patients treated with t-PA. When the Red Book drug costs for the thrombolytic agent were added, the incremental, undiscounted costs for each patient who received t-PA were $2,845. The primary analysis assumed no increased costs for the t-PA group after the first year.

            Life Expectancy

Survival at 30 days was 92.7 percent in the streptokinase group and 93.7 percent in the t-PA group (P = 0.001), and 89.9 percent and 91.0 percent, respectively, after one year (P = 0.006). We projected a life expectancy from the time of enrollment in the GUSTO study of 15.27 years for patients treated with streptokinase and 15.41 years for patients treated with t-PA, or an undiscounted increase in life expectancy for the t-PA group of 0.14 year per patient (i.e., 14 additional years of life per 100 patients treated with t-PA).

            Cost Effectiveness

With an increased life expectancy in the t-PA group of 0.14 year of life per patient, an increased cost of $2,845 per patient, and a discount rate of 5 percent, the comparative primary cost-effectiveness ratio for the use of t-PA instead of streptokinase was $32,678 per year of life saved. Substituting the average thrombolytic-drug costs to the hospitals in the GUSTO study for the Red Book wholesale prices in our primary analysis yielded a cost-effectiveness value of $27,115 per year of life saved. If we used Medicare DRG reimbursement rates for the initial hospitalization rather than the Duke Transition One costs, kept the Red Book prices for the thrombolytic agents, and left all other factors unchanged, the increase in costs for patients treated with t-PA was $3,154 and the cost-effectiveness ratio became $36,218 per year of life saved. Substituting the GUSTO prices for thrombolytic agents into this latter calculation reduced the additional cost of t-PA treatment to $2,670 and lowered the cost-effectiveness value to $30,655 per year of life saved.

Sensitivity Analyses

            Differences in One-Year Survival

The 95 percent confidence interval for the 1.1 percent increase in one-year survival among patients in the t-PA group was 0.46 percent to 1.74 percent, a range that would produce cost-effectiveness ratios of $71,039 to $18,781 per year of life saved.

            Differences in Long-Term Survival

The true life expectancy of the subjects could differ from the value predicted in our model of approximately 15 years. In addition, the survival curves may actually converge or diverge after one year. Either reducing the life expectancy or causing the survival curves to converge would reduce the additional years of life saved by t-PA treatment (Figure 2). With a 5 percent discount rate, the cost-effectiveness ratio would rise above $50,000 if the number of years of life saved by t-PA treatment fell below 7 undiscounted years per 100 patients, and it would rise above $100,000 per year of life saved if the number of undiscounted years of life saved per 100 patients fell below 3.

View larger version (2K): [in this window] [in a new window]   Figure 2. Sensitivity Analysis of the Long-Term Increase in Survival in the t-PA Group as Compared with the Streptokinase Group. The y axis shows cost-effectiveness ratios expressed as dollars per additional year of life saved (all values are discounted). The x axis shows undiscounted years of life saved by the use of t-PA per 100 patients treated. In the primary analysis, t-PA saved 14 additional years of life per 100 patients treated and had a cost-effectiveness ratio of $32,678. If the t-PA and streptokinase survival curves converged over time, or if the life expectancy of the GUSTO cohort was less than that projected in our analysis, then the cost-effectiveness value would be greater and, therefore, less favorable.

 
Discounting the value of future costs and benefits reduces their present value. If costs and increased years of life were not discounted at all, the primary cost-effectiveness ratio in our study would be $20,468 per year of life saved; if a discount rate of 10 percent was used, however, the cost-effectiveness ratio would rise to $47,337 per year of life saved.

            Cost Differences in the First Year

Although the difference in associated costs between streptokinase and t-PA (exclusive of the cost of the drugs themselves) was not statistically significant, variations in the increased costs associated with t-PA treatment did affect the cost-effectiveness ratio (Figure 3). A cost-effectiveness value of $50,000 is reached when the additional cost of t-PA treatment, including the cost of the thrombolytic agents, exceeds $4,350 per patient (53 percent higher than the cost calculated in the primary analysis). If the additional cost of t-PA use were $2,000, the cost-effectiveness ratio would be $27,736 per year of life saved. If the drug costs were those typical in Europe (approximately $1,000 for 100 mg of t-PA and $200 for 1.5 million units of streptokinase), the cost-effectiveness ratio would be $13,943 per year of life saved.

View larger version (2K): [in this window] [in a new window]   Figure 3. Sensitivity Analysis of the Cost Difference between Treatment with t-PA and Treatment with Streptokinase, Assuming No Cost Differences beyond the First Year after Treatment. The y axis shows cost-effectiveness ratios expressed as dollars per additional year of life saved. The x axis shows the increased cost per patient associated with treatment with t-PA. In the primary analysis, the increased cost per patient was $2,845.

 
            Cost Differences after One Year

In the primary analysis, we assumed no cost difference between t-PA and streptokinase beyond the first year after treatment. In a random subgroup of U.S. patients, we observed a mean increased cost per patient for the t-PA group between six months and one year of $508 (P = 0.38). Although it was not statistically significant, we used this figure to estimate the possible increase in long-term costs for subjects who survived one year after treatment. If we annualize this figure to $1,016 per year, discount future costs at 5 percent per year, and calculate on the basis of the average GUSTO patient's life expectancy (15 years), an additional $9,975 is added to the costs associated with t-PA, yielding an incremental cost-effectiveness ratio of $147,333 per year of life saved. If the increased level of cost continues for only the second year after treatment, then the cost-effectiveness ratio would be approximately $44,000. If the higher costs continue through the third year of follow-up, the cost-effectiveness ratio would be approximately $55,300 per year of life saved.

            Quality of Life

At one year, the mean utility weights measured in our interviews were 0.90 for both treatment groups. That is, patients were hypothetically willing to trade 10 years of life at their present state of health for 9 years of excellent health. Weighting increased survival in both groups by this factor yielded a cost-effectiveness ratio of $36,402 per quality-adjusted year of life saved.

            Increased Risk of Stroke

In the first 30 days after treatment in the GUSTO study, t-PA produced a net increase of one disabling nonfatal stroke per 1000 patients treated, as compared with the rate with streptokinase.¹ If disabling nonfatal stroke is considered an end point equivalent to death in the hospital, then the increase in life expectancy estimated for the t-PA group in our model is reduced to 0.13 undiscounted year per patient, and the primary cost-effectiveness ratio increases to $35,538.

Costs for the care of survivors of stroke in the first year after treatment were included in our primary analysis. In a sensitivity analysis, we assumed that patients with stroke who were in a rehabilitation hospital or nursing home one year after treatment (12 percent of the stroke survivors) would incur the costs of such care (an average daily cost of $1,212 for care in a rehabilitation hospital and $155 for nursing home care) for the remainder of their life expectancy. Allocating these extra costs to the t-PA group on the basis of one additional disabling nonfatal stroke per 1000 patients, and counting disabling stroke as an end point equivalent to death in the hospital, produce a cost-effectiveness ratio of $36,238. If each additional disabling stroke in the t-PA group required nursing home care for an average of 15 years, then the cost-effectiveness ratio would be $42,400.

Subgroup Analyses

We calculated incremental cost-effectiveness ratios for eight clinical subgroups defined by age and location of the infarction (Table 3). The number of years of life added by treatment with t-PA was greater for older patients than for younger patients and greater for anterior than for inferior infarction. For patients with anterior myocardial infarction, cost-effectiveness ratios were above $50,000 only for subjects 40 years of age or younger. For patients with inferior myocardial infarction, values were above $50,000 for subjects up to 60 years of age.

View this table: [in this window] [in a new window]   Table 3. Cost-Effectiveness Ratios for t-PA as Compared with Streptokinase in the Primary Analysis and for Selected Subgroups of Patients.

 
Discussion

The substitution of accelerated t-PA for streptokinase in the treatment of acute myocardial infarction yields increased health benefits at a cost comparable to those of other expensive therapies routinely considered worthwhile. Benchmarks against which the average comparative cost-effectiveness ratio of t-PA ($32,678 per year of life saved) can be measured include that of coronary bypass surgery as compared with medical therapy for left main coronary artery disease ($7,000 per year of life saved), that of medical therapy as compared with no therapy for severe hypertension ($20,000 per year of life saved), and that of hemodialysis as compared with no dialysis for chronic renal failure ($35,000 per year of life saved).¹⁶ The upper limit for an acceptable cost-effectiveness ratio remains controversial, but values of more than $100,000 per year of life saved are generally considered too high. Most previous economic analyses of thrombolytic therapy have compared therapy with no therapy rather than comparing different agents.^16,17,18 Several earlier attempts to examine the incremental cost effectiveness of t-PA relative to streptokinase have made assumptions that are inappropriate in the light of the findings of the GUSTO study.^1,19,20 However, Naylor et al. found that treatment with t-PA was cost effective, providing that the drug's beneficial effect on survival, as compared with streptokinase, was sustained for five years.²¹

Sensitivity Analyses

Our sensitivity analysis examined the effects of altering the key assumptions of the cost-effectiveness analysis, such as our estimate of 14 years of life saved per 100 patients treated with t-PA. This estimate was based on our survival model, on the increase in one-year survival observed in patients treated with t-PA as compared with those treated with streptokinase, and on an assumption that the survival curves for the two treatment groups would remain parallel after one year. The assumption that the survival curves will remain parallel is supported by the findings of other studies indicating that the benefit of thrombolysis is sustained through five years of follow-up.^22,23,24,25 In our sensitivity analysis of the assumed increase in survival, a threshold cost-effectiveness ratio of $50,000 per year of life saved was not exceeded until the increased survival for the t-PA group fell below 7 years of life added per 100 patients treated; a threshold value of $100,000 per year of life saved was not reached until the added years of life per 100 patients treated fell below 3.

Our results were not sensitive to changes in our estimates of costs. Only when the assumed increase in costs attributable to treatment with t-PA during the first year was 1.5 times greater than the value used in our study did the resulting cost-effectiveness ratio exceed $50,000 per year of life saved. If the patients who received t-PA were assumed to have continuing additional costs of about $1,100 per year (a figure projected from the nonsignificant cost difference observed in the second six months of follow-up) past the second follow-up year, the cost-effectiveness ratio became greater than $50,000. However, there is no basis in the empirical data from the GUSTO study for expecting such long-term cost differences between the two treatments.

Importance of Disabling Strokes

One important question is the extent to which the additional hemorrhagic strokes produced by t-PA may cancel out some of the observed increase in survival, thereby making t-PA less attractive and less cost effective.¹ However, even the most unfavorable assumptions about nonfatal disabling stroke — that patients with stroke had no increase in survival due to t-PA and that each patient would require 15 years of institutional care — increased the cost-effectiveness ratio only moderately (to $42,400), because these costs were incurred by only 1 patient per 1000 receiving t-PA.

Subgroup Analyses

As is true of the main GUSTO study, our subgroup analyses should be interpreted cautiously.¹ For most of the eight subgroups we studied, defined on the basis of age and location of the infarction, the cost-effectiveness ratio was below our benchmark figure of $50,000 per year of life saved. The cost-effectiveness ratios were least favorable for patients 40 years of age or younger and for patients 60 years of age or younger with inferior-wall infarctions, since these groups had the lowest one-year mortality rates and the smallest increases in survival due to treatment with t-PA.²⁶ In our study, we calculated the life expectancies of treated subgroups on the basis of our survival model, rather than on short-term empirical data for each subgroup. This technique provided more stable and consistent estimates than the alternative approach and also allowed us to control for the fact that anterior myocardial infarction was more frequent in older patients.

Conclusions

The routine substitution of accelerated t-PA for streptokinase in the treatment of the approximately 250,000 eligible patients who have acute myocardial infarction in the United States each year would be cost effective by customary criteria. It would cost the nation approximately $500 million each year but would also provide 3.5 million additional years of life for patients after myocardial infarction. Our analysis can inform the decision about whether this should become the standard of care in the United States, but society itself must make the choice.

Supported in part by grants from the Agency for Health Care Policy and Research (HS-05635 and HS-06503), Genentech, the National Heart, Lung, and Blood Institute (HL-36587 and HL-17670), and the Robert Wood Johnson Foundation.

We are indebted to the international GUSTO investigators at 1081 hospitals in 15 countries, without whose hard work and commitment the present study would not have been possible; to Dr. Stephen Pauker for his editorial assistance; to Julia Burchett and Celia Hybels for data-collection support; to Linda Davidson-Ray for assistance in developing the cost data; to the GUSTO Steering Committee for their review of the manuscript and their useful suggestions; and to Maria Lee and Serena Smith for assistance in the preparation of the manuscript.

Source Information

From the Economic and Quality of Life Coordinating Center (D.B.M., C.L.N., N.C.-C., J.D.K.) and the Clinical Trials Coordinating Center (R.M.C., K.L.L.), Division of Cardiology, Department of Medicine, and the Division of Biometry, Department of Community and Family Medicine (K.L.L., F.E.H.), Duke University Medical Center, Durham, N.C.; the Division of Health Services Research, Department of Health Research and Policy, Stanford University School of Medicine, Palo Alto, Calif. (M.A.H.); the Department of Medicine, University of Toronto, and the Institute for Clinical Evaluative Sciences, Toronto (C.D.N.); the Department of Medicine, University of Alberta, Edmonton (P.W.A.); Tel Aviv Sorasky University Medical Center, Tel Aviv, Israel (G.B.); the Cardiology Department, Green Lane Hospital, Auckland, New Zealand (H.W.); Erasmus University, Rotterdam, the Netherlands (M.L.S.); the National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia (J.S.); and the Department of Cardiology, Cleveland Clinic, Cleveland (E.J.T.).

Address reprint requests to Dr. Mark at P.O. Box 3485, Duke University Medical Center, Durham, NC 27710.

References

1. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673-682. [Free Full Text]
2. Mark DB, Naylor CD, Hlatky MA, et al. Use of medical resources and quality of life after acute myocardial infarction in Canada and the United States. N Engl J Med 1994;331:1130-1135. [Free Full Text]
3. Mark DB. Medical economics and health policy issues for interventional cardiology. In: Topol EJ, ed. Textbook of interventional cardiology. 2nd ed. Philadelphia: W.B. Saunders, 1994:1323-53.
4. Eisenberg JM. Clinical economics: a guide to the economic analysis of clinical practices. JAMA 1989;262:2879-2886. [CrossRef][Medline]
5. Detsky AS, Naglie IG. A clinician's guide to cost-effectiveness analysis. Ann Intern Med 1990;113:147-154.
6. Weinstein MC, Fineberg HV, Elstein AS, et al. Clinical decision analysis. Philadelphia: W.B. Saunders, 1980.
7. Drummond MF, Stoddart GL, Torrance GW. Methods for the economic evaluation of health care programmes. Oxford, England: Oxford University Press, 1987.
8. Sifton DW. 1993 Red book: pharmacy's fundamental reference. Montvale, N.J.: Medical Economics Data, 1993.
9. Rosati RA, McNeer JF, Starmer CF, Mittler BS, Morris JJ Jr, Wallace AG. A new information system for medical practice. Arch Intern Med 1975;135:1017-1024. [Abstract]
10. Hlatky MA, Lee KL, Harrell FE Jr, et al. Tying clinical research to patient care by use of an observational database. Stat Med 1984;3:375-387. [Medline]
11. Pryor DB, Harrell FE Jr, Rankin JS, et al. Trends in the presentation, management, and survival of patients with coronary artery disease: the Duke database for cardiovascular disease. In: Higgins MW, Luepker RV, eds. Trends in coronary heart disease mortality: the influence of medical care. New York: Oxford University Press, 1988:76-87.
12. Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
13. Lee ET. Statistical methods for survival data analysis. Belmont, Calif.: Lifetime Learning, 1980.
14. Torrance GW, Feeny D. Utilities and quality-adjusted life years. Int J Technol Assess Health Care 1989;5:559-575. [Medline]
15. Tsevat J, Dawson NV, Matchar DB. Assessing quality of life and preferences in the seriously ill using utility theory. J Clin Epidemiol 1990;43:Suppl:73S-77S.
16. Mark DB. Economic analysis methods and endpoints. In: Califf RM, Mark DB, Wagner GS, eds. Acute coronary care in the thrombolytic era. 2nd ed. St. Louis: Mosby–Year Book, 1995:167-82.
17. Vermeer F, Simoons ML, de Zwaan C, et al. Cost benefit analysis of early thrombolytic treatment with intracoronary streptokinase: twelve month follow up report of the randomised multicentre trial conducted by the Interuniversity Cardiology Institute of the Netherlands. Br Heart J 1988;59:527-534. [Free Full Text]
18. Simoons ML, Vos J, Martens LL. Cost-utility analysis of thrombolytic therapy. Eur Heart J 1991;12:694-699.
19. Laffel GL, Fineberg HV, Braunwald E. A cost-effectiveness model for coronary thrombolysis/reperfusion therapy. J Am Coll Cardiol 1987;10:Suppl B:79B-90B.
20. Steinberg EP, Topol EJ, Sakin JW, et al. Cost and procedure implications of thrombolytic therapy for acute myocardial infarction. J Am Coll Cardiol 1988;12:Suppl A:58A-68A.
21. Naylor CD, Bronskill S, Goel V. Cost-effectiveness of intravenous thrombolytic drugs for acute myocardial infarction. Can J Cardiol 1993;9:553-558. [Medline]
22. Cerqueira MD, Maynard C, Ritchie JL, Davis KB, Kennedy JW. Long-term survival in 618 patients from the Western Washington Streptokinase in Myocardial Infarction trials. J Am Coll Cardiol 1992;20:1452-1459. [Abstract]
23. Simoons ML, Vos J, Tijssen JGP, et al. Long-term benefit of early thrombolytic therapy in patients with acute myocardial infarction: 5 year follow-up of a trial conducted by the Interuniversity Cardiology Institute of the Netherlands. J Am Coll Cardiol 1989;14:1609-1615. [Abstract]
24. Balgent C, Collins R. ISIS-2: 4-year mortality follow-up of 17,187 patients after fibrinolytic and antiplatelet therapy in suspected acute myocardial infarction. Circulation 1993;88:Suppl II:I-290.abstract 
25. Taylor GJ, Moses HW, Katholi RE, et al. Six-year survival after coronary thrombolysis and early revascularization for acute myocardial infarction. Am J Cardiol 1992;70:26-30. [Medline]
26. Lee KL, Woodlief LH, Topol EJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41,021 patients. Circulation 1995;91:1659-1668. [Free Full Text]

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Is the Use of t-PA as Compared with Streptokinase Cost Effective?
Rose E. A., Armentano R., Favaloro R. G., Mark D. B.
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N Engl J Med 1995; 333:1009-1010, Oct 12, 1995. Correspondence

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• Mark, D. B., Nelson, C. L., Anstrom, K. J., Al-Khatib, S. M., Tsiatis, A. A., Cowper, P. A., Clapp-Channing, N. E., Davidson-Ray, L., Poole, J. E., Johnson, G., Anderson, J., Lee, K. L., Bardy, G. H., for the SCD-HeFT Investigators, (2006). Cost-Effectiveness of Defibrillator Therapy or Amiodarone in Chronic Stable Heart Failure: Results From the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Circulation 114: 135-142 [Abstract] [Full Text]  
• Singaroyan, R., Seed, C. A., Egdell, R. M. (2006). Is a target culture in health care always compatible with efficient use of resources? A cost-effectiveness analysis of an intervention to achieve thrombolysis targets. J Public Health (Oxf) 28: 31-34 [Abstract] [Full Text]  
• Feldman, A. M., de Lissovoy, G., Bristow, M. R., Saxon, L. A., De Marco, T., Kass, D. A., Boehmer, J., Singh, S., Whellan, D. J., Carson, P., Boscoe, A., Baker, T. M., Gunderman, M. R. (2005). Cost Effectiveness of Cardiac Resynchronization Therapy in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Trial. J Am Coll Cardiol 46: 2311-2321 [Abstract] [Full Text]  
• King, J. T. Jr., Tsevat, J., Lave, J. R., Roberts, M. S. (2005). Willingness to Pay for a Quality-Adjusted Life Year: Implications for Societal Health Care Resource Allocation. Med Decis Making 25: 667-677 [Abstract]  
• Rinfret, S., Cohen, D. J., Lamas, G. A., Fleischmann, K. E., Weinstein, M. C., Orav, J., Schron, E., Lee, K. L., Goldman, L. (2005). Cost-Effectiveness of Dual-Chamber Pacing Compared With Ventricular Pacing for Sinus Node Dysfunction. Circulation 111: 165-172 [Abstract] [Full Text]  
• Cohen, D. J., Murphy, S. A., Baim, D. S., Lavelle, T. A., Berezin, R. H., Cutlip, D. E., Ho, K. K.L., Kuntz, R. E., the SAFER Trial Investigators, (2004). Cost-effectiveness of distal embolic protection for patients undergoing percutaneous intervention of saphenous vein bypass grafts: Results from the SAFER trial. J Am Coll Cardiol 44: 1801-1808 [Abstract] [Full Text]  
• Qureshi, A. I., Suri, M. F. K., Kirmani, J. F., Divani, A. A. (2004). The Relative Impact of Inadequate Primary and Secondary Prevention on Cardiovascular Mortality in the United States. Stroke 35: 2346-2350 [Abstract] [Full Text]  
• Menon, V., Harrington, R. A., Hochman, J. S., Cannon, C. P., Goodman, S. D., Wilcox, R. G., Schunemann, H. J., Ohman, E. M. (2004). Thrombolysis and Adjunctive Therapy in Acute Myocardial Infarction: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 549S-575S [Abstract] [Full Text]  
• Prystowsky, E. N. (2004). Primary Prevention of Sudden Cardiac Death: The Time of Your Life. Circulation 109: 1073-1075 [Full Text]  
• Le May, M. R., Davies, R. F., Labinaz, M., Sherrard, H., Marquis, J.-F., Laramee, L. A., O'Brien, E. R., Williams, W. L., Beanlands, R. S., Nichol, G., Higginson, L. A. (2003). Hospitalization Costs of Primary Stenting Versus Thrombolysis in Acute Myocardial Infarction: Cost Analysis of the Canadian STAT Study. Circulation 108: 2624-2630 [Abstract] [Full Text]  
• Stahl, J. E., Furie, K. L., Gleason, S., Gazelle, G. S. (2003). Stroke: Effect of Implementing an Evaluation and Treatment Protocol Compliant with NINDS Recommendations. Radiology 228: 659-668 [Abstract] [Full Text]  
• Donaldson, C., Currie, G., Mitton, C. (2002). Cost effectiveness analysis in health care: contraindications. BMJ 325: 891-894 [Full Text]  
• Mahoney, E. M., Jurkovitz, C. T., Chu, H., Becker, E. R., Culler, S., Kosinski, A. S., Robertson, D. H., Alexander, C., Nag, S., Cook, J. R., Demopoulos, L. A., DiBattiste, P. M., Cannon, C. P., Weintraub, W. S., for the TACTICS-TIMI 18 Investigators, (2002). Cost and Cost-effectiveness of an Early Invasive vs Conservative Strategy for the Treatment of Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction. JAMA 288: 1851-1858 [Abstract] [Full Text]  
• Baker, W. F. Jr (2002). Thrombolytic Therapy. CLIN APPL THROMB HEMOST 8: 291-314  
• (2002). Understanding Costs and Cost-Effectiveness in Critical Care . Report from the Second American Thoracic Society Workshop on Outcomes Research. Am. J. Respir. Crit. Care Med. 165: 540-550 [Abstract] [Full Text]  
• Mark, D. B., Lee, T. H. (2002). Conservative Management of Acute Coronary Syndrome: Cheaper and Better for You?. Circulation 105: 666-668 [Full Text]  
• Brown, R.E., Henderson, R.A., Koster, D., Hutton, J., Simoons, M.L. (2002). Cost effectiveness of eptifibatide in acute coronary syndromes. An economic analysis of Western European patients enrolled in the PURSUIT trial. Eur Heart J 23: 50-58 [Abstract] [Full Text]  
• Giri, S., Shaw, L. J., Murthy, D. R., Travin, M. I., Miller, D. D., Hachamovitch, R., Borges-Neto, S., Berman, D. S., Waters, D. D., Heller, G. V. (2002). Impact of Diabetes on the Risk Stratification Using Stress Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging in Patients With Symptoms Suggestive of Coronary Artery Disease. Circulation 105: 32-40 [Abstract] [Full Text]  
• Cannon, C. P., Battler, A., Brindis, R. G., Cox, J. L., Ellis, S. G., Every, N. R., Flaherty, J. T., Harrington, R. A., Krumholz, H. M., Simoons, M. L., Van De Werf, F. J. J., Weintraub, W. S., Mitchell, K. R., Morrisson, S. L., Brindis, R. G., Anderson, H. V., Cannom, D. S., Chitwood, W. R. Jr, Cigarroa, J. E., Collins-Nakai, R. L., Ellis, S. G., Gibbons, R. J., Grover, F. L., Heidenreich, P. A., Khandheria, B. K., Knoebel, S. B., Krumholz, H. L., Malenka, D. J., Mark, D. B., Mckay, C. R., Passamani, E. R., Radford, M. J., Riner, R. N., Schwartz, J. B., Shaw, R. E., Shemin, R. J., Van Fossen, D. B., Verrier, E. D., Watkins, M. W., Phoubandith, D. R., Furnelli, T. (2001). American College of Cardiology key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes: A report of the American College of Cardiology Task Force on Clinical Data Standards (Acute Coronary Syndromes Writing Committee) Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, American College of Emergency Physicians, American Heart Association, Cardiac Society of Australia & New Zealand, National Heart Foundation of Australia, Society for Cardiac Angiography and Interventions, and the Taiwan Society of Cardiology. J Am Coll Cardiol 38: 2114-2130 [Full Text]  
• Simon, G. E., Katon, W. J., VonKorff, M., Unutzer, J., Lin, E. H.B., Walker, E. A., Bush, T., Rutter, C., Ludman, E. (2001). Cost-Effectiveness of a Collaborative Care Program for Primary Care Patients With Persistent Depression. Am. J. Psychiatry 158: 1638-1644 [Abstract] [Full Text]  
• Lee, G. M., Fleisher, G. R., Harper, M. B. (2001). Management of Febrile Children in the Age of the Conjugate Pneumococcal Vaccine: A Cost-Effectiveness Analysis. Pediatrics 108: 835-844 [Abstract] [Full Text]  
• McMahon, P. M., Bosch, J. L., Gleason, S., Halpern, E. F., Lester, J. S., Gazelle, G. S. (2001). Cost-Effectiveness of Colorectal Cancer Screening. Radiology 219: 44-50 [Abstract] [Full Text]  
• Simon, G. E., Manning, W. G., Katzelnick, D. J., Pearson, S. D., Henk, H. J., Helstad, C. P. (2001). Cost-effectiveness of Systematic Depression Treatment for High Utilizers of General Medical Care. Arch Gen Psychiatry 58: 181-187 [Abstract] [Full Text]  
• Ohman, E. M., Harrington, R. A., Cannon, C. P., Agnelli, G., Cairns, J. A., Kennedy, J.W. (2001). Intravenous Thrombolysis in Acute Myocardial Infarction. Chest 119: 253S-277S [Full Text]  
• Mayer, S. A., Copeland, D., Bernardini, G. L., Boden-Albala, B., Lennihan, L., Kossoff, S., Sacco, R. L. (2000). Cost and Outcome of Mechanical Ventilation for Life-Threatening Stroke. Stroke 31: 2346-2353 [Abstract] [Full Text]  
• Hirth, R. A., Chernew, M. E., Miller, E., Fendrick, A. M., Weissert, W. G. (2000). Willingness to Pay for a Quality-adjusted Life Year: In Search of a Standard. Med Decis Making 20: 332-342 [Abstract]  
• Smith, K. J., Roberts, M. S. (2000). The Cost-Effectiveness of Sildenafil. ANN INTERN MED 132: 933-937 [Abstract] [Full Text]  
• McGarvey, M. R. (2000). Tough Choices: The Cost-Effectiveness of Sildenafil. ANN INTERN MED 132: 994-995 [Full Text]  
• Elliott, W. J., Weir, D. R., Black, H. R. (2000). Cost-effectiveness of the Lower Treatment Goal (of JNC VI) for Diabetic Hypertensive Patients. Arch Intern Med 160: 1277-1283 [Abstract] [Full Text]  
• Harrington, R.A., Simoons, M.L. (2000). What have we learned from the recent large trials in acute coronary syndromes without ST-segment elevation?. Eur Heart J 21: 702-704  
• Newby, L. K., Eisenstein, E. L., Califf, R. M., Thompson, T. D., Nelson, C. L., Peterson, E. D., Armstrong, P. W., Van de Werf, F., White, H. D., Topol, E. J., Mark, D. B. (2000). Cost Effectiveness of Early Discharge after Uncomplicated Acute Myocardial Infarction. NEJM 342: 749-755 [Abstract] [Full Text]  
• Tanne, D., Gorman, M. J., Bates, V. E., Kasner, S. E., Scott, P., Verro, P., Binder, J. R., Dayno, J. M., Schultz, L. R., Levine, S. R. (2000). Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke in Patients Aged 80 Years and Older : The tPA Stroke Survey Experience. Stroke 31: 370-375 [Abstract] [Full Text]  
• Mark, D. B., Harrington, R. A., Lincoff, A. M., Califf, R. M., Nelson, C. L., Tsiatis, A. A., Buell, H., Mahaffey, K. W., Davidson-Ray, L., Topol, E. J. (2000). Cost-Effectiveness of Platelet Glycoprotein IIb/IIIa Inhibition With Eptifibatide in Patients With Non-ST-Elevation Acute Coronary Syndromes. Circulation 101: 366-371 [Abstract] [Full Text]  
• O'Brien, B., Levine, M., Willan, A., Goeree, R., Haley, S., Blackhouse, G., Gent, M. (1999). Economic Evaluation of Outpatient Treatment With Low-Molecular-Weight Heparin for Proximal Vein Thrombosis. Arch Intern Med 159: 2298-2304 [Abstract] [Full Text]  
• Reed, G. L., Houng, A. K., Liu, L., Parhami-Seren, B., Matsueda, L. H., Wang, S., Hedstrom, L. (1999). A catalytic switch and the conversion of streptokinase to a fibrin-targeted plasminogen activator. Proc. Natl. Acad. Sci. USA 96: 8879-8883 [Abstract] [Full Text]  
• Weinstein, M. C. (1999). High-Priced Technology Can Be Good Value for Money. ANN INTERN MED 130: 857-858 [Full Text]  
• Neumann, P. J., Hermann, R. C., Kuntz, K. M., Araki, S. S., Duff, S. B., Leon, J., Berenbaum, P. A., Goldman, P. A., Williams, L. W., Weinstein, M. C. (1999). Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer's disease. Neurology 52: 1138-1138 [Abstract] [Full Text]  
• Shaw, L. J., Hachamovitch, R., Berman, D. S., Marwick, T. H., Lauer, M. S., Heller, G. V., Iskandrian, A. E., Kesler, K. L., Travin, M. I., Lewin, H. C., Hendel, R. C., Borges-Neto, S., Miller, D. D., for the Economics of Noninvasive Diagnosis (END) M, (1999). The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients: an observational assessment of the value of precatheterization ischemia. J Am Coll Cardiol 33: 661-669 [Abstract] [Full Text]  
• Tung, C. Y., Granger, C. B., Sloan, M. A., Topol, E. J., Knight, J. D., Weaver, W. D., Mahaffey, K. W., White, H., Clapp-Channing, N., Simoons, M. L., Gore, J. M., Califf, R. M., Mark, D. B. (1999). Effects of Stroke on Medical Resource Use and Costs in Acute Myocardial Infarction. Circulation 99: 370-376 [Abstract] [Full Text]  
• Waugh, J. M., Yuksel, E., Li, J., Kuo, M. D., Kattash, M., Saxena, R., Geske, R., Thung, S. N., Shenaq, S. M., Woo, S. L. C. (1999). Local Overexpression of Thrombomodulin for In Vivo Prevention of Arterial Thrombosis in a Rabbit Model. Circ. Res. 84: 84-92 [Abstract] [Full Text]  
• Cohen, A. B. (1998). Commentary. Med Care Res Rev 55: 289-297  
• Wright, J. C., Weinstein, M. C. (1998). Gains in Life Expectancy from Medical Interventions -- Standardizing Data on Outcomes. NEJM 339: 380-386 [Abstract] [Full Text]  
• (1998). Integrating Economic Analysis Into Cancer Clinical Trials: the National Cancer Institute-American Society of Clinical Oncology Economics Workbook. J Natl Cancer Inst Monogr 1998: 1-28 [Full Text]  
• White, H. D., Van de Werf, F. J. J. (1998). Thrombolysis for Acute Myocardial Infarction. Circulation 97: 1632-1646 [Abstract] [Full Text]  
• Drummond, M. F. (1998). Experimental versus Observational Data in the Economic Evaluation of Pharmaceuticals. Med Decis Making 18: S12-S18  
• Lipscomb, J., Ancukiewicz, M., Parmigiani, G., Hasselblad, V., Samsa, G., Matchar, D. B. (1998). Predicting the Cost of Illness: A Comparison of Alternative Models Applied to Stroke. Med Decis Making 18: S39-S56 [Abstract]  
• Hachamovitch, R., Berman, D. S., Shaw, L. J., Kiat, H., Cohen, I., Cabico, J. A., Friedman, J., Diamond, G. A. (1998). Incremental Prognostic Value of Myocardial Perfusion Single Photon Emission Computed Tomography for the Prediction of Cardiac Death : Differential Stratification for Risk of Cardiac Death and Myocardial Infarction. Circulation 97: 535-543 [Abstract] [Full Text]  
• GLASZIOU, P. (1998). Using cost-effectiveness for subsidy decisions. Heart 79: 7-8 [Full Text]  
• Scharfstein, J. A., Paltiel, A. D., Freedberg, K. A. (1997). The Cost-Effectiveness of Fluconazole Prophylaxis against Primary Systemic Fungal Infections in AIDS Patients. Med Decis Making 17: 373-381 [Abstract]  
• Stanek, E. J., Cheng, J. W.M., Peeples, P. J., Simko, R. J., Spinler, S. A. (1997). Patient Preferences for Thrombolytic Therapy in Acute Myocardial Infarction. Med Decis Making 17: 464-471 [Abstract]  
• Fryback, D. G., Lawrence, W. F. JR (1997). Dollars May Not Buy as Many QALYs as We Think:: A Problem with Defining Quality-of-life Adjustments. Med Decis Making 17: 276-284 [Abstract]  
• Collins, R., Peto, R., Baigent, C., Sleight, P. (1997). Aspirin, Heparin, and Fibrinolytic Therapy in Suspected Acute Myocardial Infarction. NEJM 336: 847-860 [Full Text]  
• Topol, E. J., Califf, R. M., Van de Werf, F., Simoons, M., Hampton, J., Lee, K. L., White, H., Simes, J., Armstrong, P. W. (1997). Perspectives on Large-Scale Cardiovascular Clinical Trials for the New Millennium. Circulation 95: 1072-1082 [Full Text]  
• Johannesson, M., Jonsson, B., Kjekshus, J., Olsson, A. G., Pedersen, T. R., Wedel, H., The Scandinavian Simvastatin Survival Study Group, (1997). Cost Effectiveness of Simvastatin Treatment to Lower Cholesterol Levels in Patients with Coronary Heart Disease. NEJM 336: 332-336 [Abstract] [Full Text]  
• Derdeyn, C. P., Powers, W. J. (1996). Cost-Effectiveness of Screening for Asymptomatic Carotid Atherosclerotic Disease. Stroke 27: 1944-1950 [Abstract] [Full Text]  
• White, H. D., Barbash, G. I., Califf, R. M., Simes, R. J., Granger, C. B., Weaver, W. D., Kleiman, N. S., Aylward, P. E., Gore, J. M., Vahanian, A., Lee, K. L., Ross, A. M., Topol, E. J. (1996). Age and Outcome With Contemporary Thrombolytic Therapy: Results From the GUSTO-I Trial. Circulation 94: 1826-1833 [Abstract] [Full Text]  
• Califf, R. M., White, H. D., Van de Werf, F., Sadowski, Z., Armstrong, P. W., Vahanian, A., Simoons, M. L., Simes, R. J., Lee, K. L., Topol, E. J. (1996). One-Year Results From the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) Trial. Circulation 94: 1233-1238 [Abstract] [Full Text]  
• Rose, E. A., Armentano, R., Favaloro, R. G., Mark, D. B. (1995). Is the Use of t-PA as Compared with Streptokinase Cost Effective?. NEJM 333: 1009-1010 [Full Text]  
• (1995). Cost Effectiveness of t-PA, Streptokinase. Journal Watch Cardiology 1995: 7-7 [Full Text]  
• Lee, T. H. (1995). Cost Effectiveness of Tissue Plasminogen Activator. NEJM 332: 1443-1444 [Full Text]