Original Article
Cost Effectiveness of Thrombolytic Therapy with Streptokinase in Elderly Patients with Suspected Acute Myocardial Infarction
N Engl J Med 1992; 327:7-13July 2, 1992
- Abstract
- Abstract
Background.
There is a lack of consensus among cardiologists about the potential benefit of thrombolytic therapy for suspected acute myocardial infarction in older patients. To investigate this issue, we constructed a decision-analytic model for patients 75 years of age or older who present with ST-segment elevation within six hours of the onset of symptoms suggesting acute myocardial infarction.
Methods.
The variables incorporated in this model were the probability that the patient has an acute myocardial infarction, the probability of in-hospital death among patients with acute myocardial infarction who do not receive thrombolytic therapy, the probability of a fatal or incapacitating complication resulting from thrombolytic therapy, and the expected relative reduction in the risk of death associated with thrombolytic therapy in patients with acute myocardial infarction. Our analyses were based primarily on the use of streptokinase as the thrombolytic agent.
Results.
Given our base-line assumptions, the probability of dying in the hospital was 21.4 percent if thrombolytic therapy was given and 24.4 percent if it was not given. In one-way sensitivity analyses, thrombolytic therapy decreased the risk of dying if the probability that the patient had an acute myocardial infarction was assumed to be greater than 9 percent, if the probability of dying in the hospital after an acute myocardial infarction without thrombolytic therapy was assumed to be greater than 3 percent, if the rate of fatal or incapacitating complications due to thrombolytic therapy was assumed to be 4 percent or less, or if the relative reduction in the risk of death associated with thrombolytic therapy was assumed to be greater than 1 percent. On the basis of our base-line assumptions, our estimate of the cost effectiveness of streptokinase therapy (the cost per year of life saved) for an 80-year-old patient with suspected acute myocardial infarction was $21,200. For a wide range of assumptions about risks, benefits, and costs, the cost per year of life saved remained less than $55,000.
Conclusions.
Within the limitations imposed by the assumptions used in our analysis, thrombolytic therapy with streptokinase was found to be a beneficial and cost-effective treatment for suspected acute myocardial infarction in elderly patients in a wide variety of clinical circumstances. (N Engl J Med 1992;327:7–13.)
Media in This Article
Figure 1
Plot of a Two-Way Sensitivity Analysis in Which the Variables Are the Probability of Myocardial Infarction and the Relative Reduction in Mortality with Thrombolytic Therapy.Figure 2
Plot of a Two-Way Sensitivity Analysis in Which the Variables Are the Probability of a Fatal or Incapacitating Complication and the Relative Reduction in Mortality with Thrombolytic Therapy.Article Activity
- Article
PHYSICIANS must often decide whether to administer thrombolytic therapy to older patients who present with signs and symptoms of an acute myocardial infarction. Although some authorities believe that age should not be a contraindication to treatment with these agents,1 2 3 4 5 a joint task force of the American Heart Association and the American College of Cardiology recently stated that the efficacy of thrombolytic therapy in patients over 75 years of age is "uncertain" and "not well established by the evidence."6 Furthermore, recent studies show that older age is a factor that independently predicts that a patient will not receive thrombolytic therapy for suspected acute myocardial infarction.7 , 8
The decision whether to administer any medical therapy must often be based on incomplete information, since evidence from a clinical trial may not be available for a given patient group. Because no large trial has specifically addressed the use of thrombolytic therapy in the elderly, we constructed a decision-analytic model that incorporated estimates of the benefits and risks of treatment in various clinical situations and allowed these factors to be varied to determine their relative importance.
Methods
The Model
We developed a model to evaluate the benefit, risks, and cost of thrombolytic treatment of suspected myocardial infarction with streptokinase. The benefit was expressed in terms of the number of lives saved as a result of the expected reduction of in-hospital mortality among patients with acute myocardial infarction. It was assumed in our model that patients without a myocardial infarction would not benefit from thrombolytic therapy. The risks of thrombolytic therapy were defined as all complications associated with treatment that led to death, disability, or added cost.
The model was used to evaluate two strategies: treatment with a thrombolytic agent (streptokinase) and no treatment. According to the no-treatment strategy, patients with a suspected acute myocardial infarction were admitted to the hospital and received standard care. The survival rate among these patients was calculated as the product of the probability of an acute myocardial infarction and the probability of survival after an acute myocardial infarction plus the product of the probability of not having an acute myocardial infarction and the probability of survival if no myocardial infarction was present. The values for the probabilities were varied in order to assess outcome in a number of different clinical situations.
According to the thrombolytic-therapy strategy, patients received the same standard care plus an intravenous infusion of streptokinase. The risk of a complication of thrombolytic therapy was incurred by all the patients who received the treatment, whereas only the patients who actually had a myocardial infarction benefited from therapy. The expected survival in the treatment strategy was calculated as the product of the probability of having a myocardial infarction and the probability of survival after a myocardial infarction with thrombolytic therapy plus the product of the probability of not having a myocardial infarction and the probability of survival if no myocardial infarction was present, multiplied by the probability of not having a fatal or incapacitating complication. The values for these probabilities were also varied in our analysis.
The costs of thrombolytic therapy were calculated by considering the costs of administering a thrombolytic agent, the costs of treating major complications of thrombolytic therapy, the costs of treating hemorrhagic strokes caused by thrombolytic therapy, the increased incidence of reinfarction associated with thrombolytic therapy, and the costs of medical care required during the years of life gained by the patients who survived the myocardial infarction as a result of thrombolysis. Incremental costs were expressed in 1990 dollars. Both costs and life-years were discounted to present value at a rate of 5 percent per year.
Data and Assumptions
The probability of acute myocardial infarction in a hypothetical patient who presented to the emergency room with chest pain was estimated on the basis of data from the multicenter Chest Pain Study (Table 1Table 1
Rates of Acute Myocardial Infarction (MI) among Patients Who Presented to the Emergency Room within Six Hours of the Onset of Chest Pain and Who Had ST-Segment Elevation or Pathologic Q Waves Not Known to Be Old.*).9 The in-hospital mortality rate among patients over 75 years of age who presented with chest pain and were not given a diagnosis of myocardial infarction was estimated to be 2 percent (Chest Pain Study: unpublished data).The in-hospital mortality rate among patients with myocardial infarction was estimated by pooling data from the control groups of the two large trials of thrombolytic therapy with streptokinase that did not have an age restriction for entry, those by the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI)10 and the Second International Study of Infarct Survival (ISIS-2).11 The overall mortality rate for the 623 patients older than 75 years of age in the first GISSI study who did not receive thrombolytic therapy was 33 percent,10 and the rate of death from vascular causes (defined as all deaths attributed to cardiac, cerebral, hemorrhagic, other vascular, or unknown causes) for the 745 patients 75 years of age or older in the ISIS-2 study who did not receive thrombolytic therapy was 25 percent.12 The pooled mortality rate in these two studies was estimated to be 29 percent (Table 2Table 2
Benefit of Thrombolytic Therapy in Patients with Suspected Myocardial Infarction, Stratified According to Age, in the GISSI and ISIS-2 Studies.*).The efficacy of thrombolytic therapy in the model was restricted to patients who actually had an acute myocardial infarction and did not suffer a serious complication of therapy. Therefore, the relative reduction in the risk of death attributed to thrombolytic therapy was defined as the percent difference between the in-hospital survival rate among patients who had an acute myocardial infarction, were treated with thrombolytic therapy, and did not have a fatal or incapacitating complication and the in-hospital survival rate among patients who had a myocardial infarction but were not treated with thrombolytic therapy. These estimates were also obtained from data from the first GISSI trial and ISIS-2. Among the 1215 patients older than 75 years of age in the GISSI study,10 the net benefit from thrombolytic therapy was a 13 percent reduction in mortality. Among the 1463 patients 75 years of age or older in the ISIS-2 trial,11 the net benefit was a 14 percent reduction in mortality. Pooling the results for these elderly patients yielded a net reduction of 14 percent in mortality (Table 2). By comparison, the pooled reduction in mortality with thrombolytic therapy among patients younger than 65 years of age in the first GISSI trial and the ISIS-2 trial was 29 percent and that in patients 65 to 74 years of age was 14 percent (Table 2).
In the GISSI and ISIS-2 trials, no excess strokes were associated with thrombolytic therapy, even among older patients,10 11 12 but more of the strokes may have been hemorrhagic than would otherwise have been the case. In our model, all strokes in patients who did not receive thrombolytic therapy were considered to be nonhemorrhagic. To simplify the survival estimates in the model, all hemorrhagic strokes associated with thrombolytic therapy were considered equivalent to death. The number of excess hemorrhagic strokes, based on a series of 13 strokes in 708 patients treated with tissue plasminogen activator in the Thrombolysis and Angioplasty in Myocardial Infarction trials, was estimated as 31 percent of the total rate of stroke.13 Since the rate of stroke among patients 75 years of age or older who received thrombolytic therapy in the ISIS-2 trial was 1.3 percent (9 of 718; ISIS Collaborative Group: personal communication), the rate of excess hemorrhagic stroke was estimated to be 0.40 percent. Given stroke rates of 0.53 percent among patients under 65 years of age and 0.94 percent among patients 65 to 74 years of age (ISIS Collaborative Group: personal communication), the rates of excess hemorrhagic stroke in these age groups were estimated to be 0.16 percent and 0.29 percent, respectively.
Other complications considered in our analysis included hemorrhage requiring transfusion and an increased incidence of reinfarction. In the ISIS-2 trial, the rate of major bleeding in patients 75 years of age or older was 0.42 percent (3 of 718) in the streptokinase group and 0.13 percent (1 of 745) in the placebo group, resulting in an excess rate of major bleeding of 0.29 percent (ISIS Collaborative Group: personal communication). For comparison, the rate was 0.30 percent among patients under 65 years of age and 0.41 percent for those 65 to 74 years of age (ISIS Collaborative Group: personal communication). In the first GISSI trial,10 , 14 there were approximately three additional reinfarctions during hospitalization and in the subsequent six months for every 100 patients treated with streptokinase, as compared with placebo.
Costs
The cost at Beth Israel Hospital of administering streptokinase, including the drug and materials, was estimated to be $200 per patient. The costs of treatment for bleeding complications included the hospital costs for a transfusion of two units of packed red cells at Beth Israel Hospital (laboratory tests, materials, labor, administration, and hospital overhead) and the cost of two additional days in the cardiac care unit; these costs were estimated to be approximately $1,600. Bleeding complications requiring more intervention occur rarely,10 , 11 and the associated costs were considered to be offset by savings from the complications of the myocardial infarction, such as cardiac arrest,11 that were avoided as a result of thrombolytic therapy.
Although all hemorrhagic strokes were considered equivalent to death in the survival analysis, we included their long-term costs. We assumed that 50 percent of the hemorrhagic strokes would cause a persistent neurologic deficit, as compared with 22 percent of the nonhemorrhagic strokes.13 We further assumed that for every 100 strokes after thrombolytic therapy, 31 patients would have severe neurologic deficits requiring long-term care, as compared with 22 patients per 100 strokes in patients who did not receive thrombolytic therapy. On the basis of informal information from one Boston rehabilitation hospital, we considered the cost of caring for a patient with a severe neurologic deficit to be approximately $200,000 per year.
Average annual medical costs related to coronary heart disease after infarction were estimated as $2,100 a year; this estimate was calculated on the basis of the Coronary Heart Disease Policy Model15 and included costs associated with subsequent myocardial infarctions ($10,000 for fatal myocardial infarctions and $7,700 for nonfatal infarctions) and major procedures. Medical costs unrelated to coronary heart disease were considered to be $4,400 annually, on the basis of 1980 estimates,16 adjusted for inflation. The cost of a reinfarction attributable to thrombolysis was estimated to be $10,000.
Life Expectancy
Life expectancy after myocardial infarction was calculated with use of the Coronary Heart Disease Policy Model15 as 5.5 years (4.6 discounted years) for a 70-year-old patient and 2.7 years (2.4 discounted years) for an 80-year-old patient.
Base-Line Assumptions
Values for the base-line survival analysis (Table 3Table 3
Base-Line Assumptions for a Patient 75 Years of Age or Older Who Arrives at the Emergency Room within Six Hours of the Onset of Chest Pain with Electrocardiographic Evidence of ST-Segment Elevation.) were assigned by assuming that a patient more than 75 years of age presented to the emergency room within six hours of the onset of persistent chest pain with electrocardiographic evidence of ST-segment elevation. To compare the benefits of therapy in elderly and younger patients, the rate of in-hospital death due to myocardial infarction without thrombolytic therapy was assumed to be 8 percent for patients younger than 65 years and 18 percent for patients between 65 and 74 years of age (Table 2). The relative reduction in mortality due to thrombolytic therapy was estimated to be 29 percent among patients younger than 65 years of age and 14 percent among those 65 to 74 years of age (Table 2). The rate of fatal or incapacitating complications was assumed to be 0.16 percent for patients younger than 65 years of age and 0.29 percent for those 65 to 74 years of age, as noted above. We assumed that the probability of a myocardial infarction was the same among younger and older patients with the same electrocardiographic findings.We calculated the cost effectiveness of thrombolytic therapy for patients 70, 75, and 80 years old. For an 80-year-old patient, the cost-effectiveness ratio (the cost per year of life saved) was based on the survival benefit for patients 75 years of age or older and the life expectancy after myocardial infarction for an 80-year-old patient. Estimates for the 70-year-old patient were based on the survival benefit for patients 65 to 74 years of age and the life expectancy after myocardial infarction for a 70-year-old patient. Estimates for the 75-year-old patient were made by averaging the assumptions in the model for the patients 65 to 74 years of age and those 75 years of age or older and averaging the life-expectancy estimates for patients 70 and 80 years of age.
Results
Survival
When calculated according to the base-line assumptions, the probability of in-hospital death (after admission) for a patient more than 75 years of age with a suspected acute myocardial infarction was 21.4 percent when thrombolytic therapy was given and 24.4 percent without such therapy. For every 33 patients treated, 1 additional life would be saved (24.4 - 21.4 = 3.0 lives saved per 100 patients treated or 1 life saved per 33 patients treated). By comparison, 1 life would be saved for every 56 patients under 65 years of age who were treated and 1 for every 54 patients 65 to 74 years of age.
Sensitivity Analyses
As the estimate of the probability of myocardial infarction was decreased, the survival advantage associated with thrombolytic therapy for a suspected myocardial infarction decreased. Nevertheless, the probability of survival for a patient over 75 years of age improved with thrombolytic therapy if the risk of myocardial infarction was more than 9 percent. As the estimate of the relative reduction in mortality associated with thrombolytic therapy was decreased from the base-line assumption of 14 percent, the benefit of the treatment decreased. The expected survival rate remained higher with thrombolytic therapy, however, until the relative reduction in mortality associated with treatment was decreased to 1 percent. As the probability of myocardial infarction was decreased to below 9 percent, thrombolytic therapy was beneficial only if there was an increase in the assumed relative reduction in mortality associated with therapy to more than 14 percent (Fig. 1Figure 1
Plot of a Two-Way Sensitivity Analysis in Which the Variables Are the Probability of Myocardial Infarction and the Relative Reduction in Mortality with Thrombolytic Therapy.).As the estimate of the probability of in-hospital death among patients with acute myocardial infarctions who were not treated with thrombolytic therapy was decreased, the value of thrombolytic therapy diminished. Given our other base-line assumptions, treatment increased the probability of survival if the mortality rate associated with a myocardial infarction without thrombolytic therapy was higher than 3 percent.
Finally, as the estimate of the probability of a fatal or incapacitating complication of thrombolytic therapy was increased, the advantage of thrombolytic treatment decreased. According to our other base-line assumptions, the probability of survival was higher with thrombolytic therapy until the rate of fatal or incapacitating complications exceeded 4 percent. If the probability of a fatal or incapacitating complication was increased further, the survival advantage with treatment persisted only if there was also an increase in the efficacy of the treatment (Fig. 2Figure 2
Plot of a Two-Way Sensitivity Analysis in Which the Variables Are the Probability of a Fatal or Incapacitating Complication and the Relative Reduction in Mortality with Thrombolytic Therapy.), in the estimated in-hospital mortality rate (Fig. 3Figure 3
Plot of a Two-Way Sensitivity Analysis in Which the Variables Are the Probability of In-Hospital Death among Patients with Myocardial Infarction Who Do Not Receive Thrombolytic Therapy and the Probability of a Fatal or Incapacitating Complication after Thrombolytic Therapy.), or in the probability that the patient had a myocardial infarction. For example, if the rate of fatal or incapacitating complications was 5 percent, as could be true for some high-risk patients, and if the other base-line assumptions were considered separately, a survival advantage would be associated with treatment if any one of the base-line assumptions was changed as follows: if the probability of in-hospital death without thrombolytic therapy was greater than 35 percent, if the probability of myocardial infarction was greater than 99 percent, or if thrombolytic therapy caused a relative reduction in mortality of more than 17 percent.Cost Effectiveness
According to our base-line estimates for an 80-year-old patient, the cost of thrombolytic therapy with streptokinase was estimated to be $21,200 per year of life saved. Our analysis suggested that the cost-effectiveness ratio varied little for a patient who was 75 years of age ($22,400 per year of life saved) or 70 years of age ($21,600 per year of life saved).
Despite a wide range of assumptions about the cost of the thrombolytic agent, the cost of treatment for a major bleeding complication, the rate of major bleeding complications, the cost of caring for a stroke victim, and the number of years gained per life saved, the cost of streptokinase remained less than $55,000 per year of life saved (Table 4Table 4
Costs of Thrombolytic Therapy for Suspected Myocardial Infarction (MI) and Its Complications in an 80-Year-Old Patient.*). If all strokes in patients who received thrombolytic therapy were considered to be hemorrhagic, then the benefit of therapy decreased and the cost per year of life saved increased to $37,500 for an 80-year-old patient. If the costs of medical care for patients treated with thrombolysis increased because as many as 10 percent of the patients who received thrombolytic therapy had an additional $15,000 worth of cardiovascular procedures that they otherwise would not have required, then the cost per year of life saved increased to approximately $42,000 for an 80-year-old patient.Discussion
Heart disease is the most common cause of morbidity and mortality among the elderly.17 Among persons 75 years of age or older, acute myocardial infarction occurs twice as frequently as in younger persons,18 , 19 and nearly 50 percent of deaths among patients hospitalized for acute myocardial infarction occur in those 75 years of age or older.20 Despite the capacity of thrombolytic therapy to decrease the mortality rate from acute myocardial infarction,10 , 11 , 21 , 22 few elderly patients have been treated with these agents.7 , 8
The reluctance to use thrombolytic therapy in older patients results from concerns about its relative risks and benefits and from the paucity of data. Our analysis suggests that over a wide range of reasonable estimates of risk and benefit, thrombolytic therapy with streptokinase is associated with a survival advantage for patients over 75 years of age who meet traditional criteria for an acute myocardial infarction at presentation (onset of chest pain within six hours and ST-segment elevation). Furthermore, in these patients thrombolytic therapy is as cost effective as many other accepted practices, such as the screening of younger patients for moderate hypertension.23
Our analysis also addressed the rates of complications among elderly patients. Thrombolytic therapy with streptokinase was associated with a survival advantage even when the rate of major complications was estimated to be as high as 4 percent. We also calculated that thrombolytic therapy was associated with a survival benefit if the probability of myocardial infarction was set as low as 10 percent — an estimate far below that expected for patients presenting with chest pain and ST-segment elevation. Although patients with atypical symptoms and ST-segment elevation merit consideration for treatment, such a recommendation cannot be extended to the approximately 85 percent of elderly patients with myocardial infarction who present more than six hours after the onset of symptoms or with other electrocardiographic patterns,24 since the efficacy of thrombolytic therapy in such patients has not been demonstrated.11
Because of the high mortality rate among elderly patients, even a small relative reduction in mortality due to thrombolytic therapy will save lives and offset the risks of therapy. If the expected mortality rate were lower, as with inferior myocardial infarction, the expected benefit of therapy would decrease, but our analysis indicated that thrombolytic therapy was associated with a survival benefit as long as the mortality rate was estimated to be above 4 percent. Since inferior myocardial infarctions in the elderly are associated with a mortality rate far higher than 4 percent (Chest Pain Study: unpublished data), our analysis suggests that thrombolytic therapy would be beneficial for any elderly patient with acute myocardial infarction who presents with ST-segment elevation.
Although all our analyses are based on empirical data, none of the randomized trials have proved the efficacy of thrombolytic therapy in the elderly. These trials, however, have studied too few elderly patients to be conclusive. For instance, a trial with the power to detect a survival advantage given our base-line assumptions would require more than 10,000 patients. Nevertheless, the ISIS Collaborative Group recently reported, on the basis of pooled results for 2678 patients enrolled in the first GISSI trial and the ISIS-2 trial, that a statistically significant reduction in mortality is associated with thrombolytic therapy in patients 75 years of age and older.12
For a broad range of clinical assumptions and cost estimates, our analysis suggested that the cost per year of life saved with streptokinase was less than $55,000. At the substantially higher current costs of the other commonly used thrombolytic agents, tissue plasminogen activator and anisoylated plasminogen—streptokinase activator complex, however, the cost-effectiveness ratio more than doubled in the base-line analysis.
Our model contained many assumptions that tended to bias the analysis against the use of thrombolytic therapy. We overestimated the potential harm caused by thrombolytic therapy by assuming in the survival analysis that all hemorrhagic strokes led to death. We assumed that only patients with myocardial infarction benefited from thrombolytic therapy. We underestimated the true mortality rate among elderly patients with acute myocardial infarction by basing our estimates on the overall mortality rate for all patients in the first GISSI trial and the rate of death from vascular causes for all patients in the ISIS-2 trial, even though some patients did not have infarctions. Furthermore, patients well enough to be enrolled in a clinical trial may have had lower mortality rates than would be expected in the general population, and mortality from vascular causes in the ISIS-2 trial was therefore an underestimate of the overall mortality. We also underestimated the efficacy of therapy, because the net reduction in mortality reported from the thrombolytic trials was based on data for all patients treated, not just patients with myocardial infarctions in whom thrombolytic therapy did not result in a major complication. Although our base-line analysis did not explicitly consider the increased use of cardiovascular procedures after thrombolysis, since the use of thrombolysis does not require their use and since there is no evidence that they are beneficial in the short term in this age group,25 we did test the effect of this assumption in the sensitivity analyses.
Our analysis has some important limitations. First, we combined data from the first GISSI trial and the ISIS-2 trial, which did not use exactly equivalent definitions of mortality (mortality from all causes vs. mortality from vascular causes), stratification of age groups (e.g., >75 years vs. ≥75 years), or lengths of follow-up (events occurring during hospitalization vs. events occurring within five weeks). We relied on unpublished empirical data from well-known studies, a procedure we thought was preferable to relying on the consensus of expert opinion. We also assumed that there was no decrease in benefit after the initial observation period among survivors of an acute myocardial infarction who received thrombolytic therapy. This assumption was supported by evidence that thrombolytic therapy exerts its most important effect on survival in the hospital.14 , 26 An additional limitation was that we presented data for patients over 75 years of age as if they were a homogeneous group. Unfortunately, there is a dearth of age-specific information on the effect of thrombolytic therapy in patients more than 80 years old. Therefore, the sensitivity analysis was designed to consider various estimates for patients who do not seem to fit the base-line assumptions. Sufficient empirical data were not available for us to analyze patients older than 80 years as a separate group.
Finally, because we based our estimates on data from the first GISSI trial10 and the ISIS-2 trial,11 , 12 we did not explicitly consider the use of aspirin, which is now an accepted treatment for acute myocardial infarction. The effects of aspirin and thrombolytic therapy are additive.11 If we had assumed all the patients in our model (with and without thrombolytic therapy) had received aspirin, then our estimate of base-line mortality without thrombolytic therapy would have been lower, but the relative reduction in mortality associated with thrombolytic therapy would not have been very different. Our sensitivity analysis showed that even if in-hospital mortality were 50 percent lower than our estimate, which is a greater reduction than would be expected from aspirin alone, thrombolytic therapy would remain a cost-effective intervention for an 80-year-old patient.
Our analysis extends the data from large thrombolytic trials that have suggested that thrombolysis has a net benefit for patients in the older age groups. We conclude that age alone should not contraindicate the use of streptokinase, and we suggest that thrombolytic therapy is cost effective and has a survival benefit in elderly patients. This was the case in our analysis even when a wide range of assumptions about the benefits and risks of therapy were used. Furthermore, our results emphasize that concern about the risk of complications should be balanced by the fact that the high rate of mortality due to acute myocardial infarction among elderly patients means that even a small relative reduction in mortality will save many lives and offset even relatively high rates of expected complications.
Supported by grants from the Agency for Health Care Policy and Research (1R01HS06452, 1R01HS06258, and 1P01HS06341) and the National Heart, Lung, and Blood Institute (HL07374–12).
We are indebted to Drs. E. Francis Cook and J. Anthony Parker, Ms. Karen Keaney, and the ISIS Collaborative Group for their assistance.
Source Information
From the Cardiovascular Division (H.M.K., R.C.P., P.M.R., L.G.) and the Division of Clinical Epidemiology (M.C.W., G.C.F., L.G., A.N.A.T.), Departments of Medicine, Beth Israel Hospital (H.M.K., R.C.P., L.G., A.N.A.T.) and Brigham and Women's Hospital (M.C.W., G.C.F., P.M.R., A.N.A.T., L.G.), Harvard Medical School, Boston, and the Department of Health Policy and Management, Harvard School of Public Health (M.C.W., A.N.A.T.), all in Boston; and the Cardiovascular Division, Vanderbilt University Medical Center, Nashville (G.C.F.). Address reprint requests to Dr. Krumholz at the Section of Cardiovascular Medicine, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510.
- References
References
1
Muller
Web of Science | Medline2
Grines
CrossRef | Web of Science | Medline3
Gurwitz
CrossRef | Web of Science | Medline4
Pasternak RC, Braunwald E, Sobel BE. Acute myocardial infarction. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 4th ed. Philadelphia: W.B. Saunders, 1992:1232.
5
Sherry
CrossRef | Web of Science | Medline6
Gunnar
CrossRef | Web of Science | Medline7
Pfeffer
CrossRef | Web of Science | Medline8
Cragg
Web of Science | Medline9
Goldman
Full Text | Web of Science | Medline10
Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI)
Web of Science | Medline11
ISIS-2 (Second International Study of Infarct Survival) Collaborative Group
Web of Science | Medline12
ISIS Collaborative Group 13
O'Connor
CrossRef | Web of Science | Medline14
Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI)
Web of Science | Medline15
Weinstein
CrossRef | Web of Science | Medline16
Hodgson
Medline17
U.S. Senate Special Committee on Aging. Aging America: trends and projections. Washington. D.C.: Department of Health and Human Services, 1988.
18
Goldberg
CrossRef | Web of Science | Medline19
Goldberg
CrossRef | Web of Science | Medline20
Roig
CrossRef | Web of Science | Medline21
AIMS Trial Study Group
Web of Science | Medline22
Wilcox
CrossRef | Web of Science | Medline23
Littenberg
Web of Science | Medline24
Weaver
CrossRef | Web of Science | Medline25
The TIMI Study Group
Full Text | Web of Science | Medline26
AIMS Trial Study Group
CrossRef | Web of Science | Medline
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CrossRef12
Gottlieb C Friesinger, Raphael F Smith. (2000) Old age, left bundle branch block and acute myocardial infarction: a vexing and lethal combination. Journal of the American College of Cardiology 36:3, 713-716
CrossRef13
Ivan T. Straznicky, Harvey D. White. (2000) Thrombolytic therapy for acute myocardial infarction in the elderly. Coronary Artery Disease 11:4, 299-304
CrossRef14
Gary E. Lane, David R. Holmes. (2000) Primary angioplasty for acute myocardial infarction in the elderly. Coronary Artery Disease 11:4, 305-313
CrossRef15
Marie F. Johnson, Michael Lin, Saurabh Mangalik, Donald J. Murphy, Andrew M. Kramer. (2000) Patients' Perceptions of Physicians' Recommendations for Comfort Care Differ by Patient Age and Gender. Journal of General Internal Medicine 15:4, 248-255
CrossRef16
Manuel Dj Arbo, David R Snydman, John B Wong, Howard S Goldberg, Christopher H Schmid, Stephen G Pauker. (2000) Cytomegalovirus immune globulin after liver transplantation: a cost-effectiveness analysis 1. Clinical Transplantation 14:1, 19-27
CrossRef17
T. Michael Kashner, A. John Rush, Kenneth Z. Altshuler. (1999) Measuring costs of guideline-driven mental health care: the Texas Medication Algorithm Project. The Journal of Mental Health Policy and Economics 2:3, 111-121
CrossRef18
David L. Edbrooke, Clare L. Hibbert. (1999) Cost determinants and economic assessment in the critical care setting. Current Opinion in Critical Care 5:4, 316
CrossRef19
Todd B. Seto, Deborah A. Taira, Warren J. Manning. (1999) Cardioversion in Patients with Atrial Fibrillation and Left Atrial Thrombi on Initial Transesophageal Echocardiography: Should Transesophageal Echocardiography Be Repeated Before Elective Cardioversion? A Cost-Effectiveness Analysis. Journal of the American Society of Echocardiography 12:6, 508-516
CrossRef20
Steven B Gollub. (1999) Is intensive drug therapy appropriate for older patients?. The Lancet 353:9157, 940-941
CrossRef21
Francesco Di Costanzo, Andrea Sdrobolini, Luigi Manzione, Domenico Bilancia, Luigi Acito, Silvia Gasperoni, Lanfranco Valenti, Lorella Fioriti, Sabrina Angiona, Lucio Giustini. (1999) Dose intensification of mitoxantrone in combination with paclitaxel in advanced breast cancer: a phase II study. Breast Cancer Research and Treatment 54:2, 165-171
CrossRef22
David R Holmes, Harvey D White, Karen S Pieper, Stephen G Ellis, Robert M Califf, Eric J Topol. (1999) Effect of age on outcome with primary angioplasty versus thrombolysis. Journal of the American College of Cardiology 33:2, 412-419
CrossRef23
Christopher J. Ellis, John K. French, Harvey D. White. (1998) Thrombolytic eligibility. Australian and New Zealand Journal of Medicine 28:4, 518-524
CrossRef24
Richard Parsons, Peter Thompson, Mark Nidorf, Michael Hobbs, Konrad Jamrozik. (1998) Refining the risk-benefit equation for thrombolysis: How to identify the low risk patient before administering thrombolytic therapy. Australian and New Zealand Journal of Medicine 28:4, 525-528
CrossRef25
Tracy A Lieu, R.Jan Gurley, Robert J Lundstrom, G.Thomas Ray, Bruce H Fireman, Milton C Weinstein, William W Parmley. (1997) Projected Cost-Effectiveness of Primary Angioplasty for Acute Myocardial Infarction. Journal of the American College of Cardiology 30:7, 1741-1750
CrossRef26
Bengt Jönsson, Milton C. Weinstein. (1997) Economic Evaluation Alongside Multinational Clinical Trials: Study Considerations for GUSTO iib. International Journal of Technology Assessment in Health Care 13:01, 49
CrossRef27
Neil M Resnick, Edward R Marcantonio. (1997) How should clinical care of the aged differ?. The Lancet 350:9085, 1157-1158
CrossRef28
Ivana T. Croghan, Kenneth P. Offord, Roger W. Evans, Silke Schmidt, Leigh C. Gomez-Dahl, Darrell R. Schroeder, Christi A. Patten, Richard D. Hurt. (1997) Cost-Effectiveness of Treating Nicotine Dependence: The Mayo Clinic Experience. Mayo Clinic Proceedings 72:10, 917-924
CrossRef29
Kumanan Wilson, Deborah J. Cook. (1997) Economics and the intensive care unit: A conflict of interests?. Journal of Critical Care 12:3, 147-151
CrossRef30
Kenneth A. Freedberg, Calvin J. Cohen, Thomas W. Barber. (1997) Prophylaxis for Disseminated Mycobacterium avium Complex(MAC) Infection in Patients With AIDS. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 15:4, 275-282
CrossRef31
M Gisselbrecht, JL Diehl, G Meyer, H Sors. (1997) Comparaison de l'efficacité et de la tolérance d'un traitement thrombolytique par rt-PA dans l'embolie pulmonaire aiguë massive chez le sujet âgé et chez les moins de 75 ans. La Revue de Médecine Interne 18:7, 521-527
CrossRef32
Richard J. Sperry. (1997) Principles of Economic Analysis. Anesthesiology 86:5, 1197-1205
CrossRef33
Gary Kynman. (1997) Thrombolysis: the development of unit guidelines. Intensive and Critical Care Nursing 13:1, 30-41
CrossRef34
Todd B Seto, Deborah A Taira, Joel Tsevat, Warren J Manning. (1997) Cost-Effectiveness of Transesophageal Echocardiographic-Guided Cardioversion: A Decision Analytic Model for Patients Admitted to the Hospital With Atrial Fibrillation. Journal of the American College of Cardiology 29:1, 122-130
CrossRef35
TRACY A. LIEU, ROBERT J. LUNDSTROM, G.THOMAS RAY, BRUCE H. FIREMAN, R.JAN GURLEY, WILLIAM W. PARMLEY. (1996) Initial Cost of Primary Angioplasty for Acute Myocardial Infarction. Journal of the American College of Cardiology 28:4, 882-889
CrossRef36
D. B. Chalfin, I. L. Cohen, J. Lambrinos. (1995) The economics and cost-effectiveness of critical care medicine. Intensive Care Medicine 21:11, 952-961
CrossRef37
Joel Tsevat, Daniella Duke, Lee Goldman, Marc A. Pfeffer, Gervasio A. Lamas, Jane R. Soukup, Karen M. Kuntz, Thomas H. Lee. (1995) Cost-effectiveness of captopril therapy after myocardial infarction. Journal of the American College of Cardiology 26:4, 914-919
CrossRef38
Steven Crowley, David Dunt, Neil Day. (1995) Cost-effectiveness of alternative interventions for the prevention and treatment of coronary heart disease. Australian Journal of Public Health 19:4, 336-346
CrossRef39
Susan C. Kalish, Jerry H. Gurwitz, Harlan M. Krumholz, Jerry Avorn. (1995) A cost-effectiveness model of thrombolytic therapy for acute myocardial infarction. Journal of General Internal Medicine 10:6, 321-330
CrossRef40
Lee Goldman. (1995) Cost and quality of life: Thrombolysis and primary angioplasty. Journal of the American College of Cardiology 25:7, S38-S41
CrossRef41
Michael A Horan, Neil Pendleton. (1995) The relationship between aging and disease. Reviews in Clinical Gerontology 5:02, 125
CrossRef42
J KUPERSMITH, M HOLMESROVNER, A HOGAN, D ROVNER, J GARDINER. (1995) Cost-effectiveness analysis in heart disease, part III: Ischemia, congestive heart failure, and arrhythmias. Progress in Cardiovascular Diseases 37:5, 307-346
CrossRef43
Chris L. Pashos, Sharon-Lise T. Normand, Jeffrey B. Garfinkle, Joseph P. Newhouse, Arnold M. Epstein, Barbara J. McNeil. (1994) Trends in the use of drag therapies in patients with acute myocardial infarction: 1988 to 1992. Journal of the American College of Cardiology 23:5, 1023-1030
CrossRef44
William B. Hillegass, James G. Jollis, Christopher B. Granger, E.Magnus Ohman, Robert M. Califf, Daniel B. Mark. (1994) Intracranial hemorrhage risk and new thrombolytic therapies in acute myocardial infarction. The American Journal of Cardiology 73:7, 444-449
CrossRef45
BARBARA J. McNEIL. (1993) Use of Claims Data to Monitor Patients over Time: Acute Myocardial Infarction as a Case Study. Annals of the New York Academy of Sciences 703:1 Doing More Go, 63-73
CrossRef46
Joseph Herman, Jack Froom. (1993) Thrombolytic therapy in acute myocardial infarction: Some reservations. Journal of Clinical Epidemiology 46:11, 1237-1241
CrossRef47
Harlan M. Krumholz, Brian J. Cohen, Joel Tsevat, Richard C. Pasternak, Milton C. Weinstein. (1993) Cost-effectiveness of a smoking cessation program after myocardial infarction. Journal of the American College of Cardiology 22:6, 1697-1702
CrossRef48
Topol, Eric J., , Califf, Robert M., . (1992) Thrombolytic Therapy for Elderly Patients. New England Journal of Medicine 327:1, 45-47
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