(Circulation. 2000;101:366.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Cost-Effectiveness of Platelet Glycoprotein IIb/IIIa Inhibition With Eptifibatide in Patients With Non–ST-Elevation Acute Coronary Syndromes
From The Duke Clinical Research Institute, Duke University Medical Center (D.B.M., R.A.H., R.M.C., C.L.N., A.A.T., H.B., K.W.M., L.D.-R.), Durham, NC; The Cleveland Clinic Foundation (A.M.L., E.J.T.), Cleveland, Ohio; and The Department of Statistics, North Carolina State University (A.A.T.), Durham, NC.
Correspondence to Daniel B. Mark, MD, MPH, Professor of Medicine, Duke University Medical Center, Box 3485, Durham, NC 27710. E-mail daniel.mark{at}duke.edu
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Abstract |
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Background—In the PURSUIT trial, eptifibatide significantly reduced the 30-day incidence of death and myocardial infarction relative to placebo in 9461 patients with an acute coronary syndrome (unstable angina or non–Q-wave myocardial infarction).
Methods and Results—We conducted a 2-part prospective economic substudy of the 3522 US patients enrolled in PURSUIT: (1) an empirical intention-to-treat comparison of medical costs (hospital plus physician) up to 6 months after hospitalization and (2) a lifetime cost-effectiveness analysis. The base-case cost-effectiveness ratio was expressed as the 1996 US dollars required to add 1 life-year with eptifibatide therapy. The 2 treatment arms had equivalent resource consumption and medical costs (exclusive of the cost of the eptifibatide regimen) during the index (enrollment) hospitalization (P=0.78) and up to 6 months afterward (P=0.60). The average wholesale price of the eptifibatide regimen was $1217, but a typical hospital discounted price was $1014. The estimated life expectancy from randomization in the US patients was 15.96 years for eptifibatide and 15.85 years for placebo, an incremental difference of 0.111. The incremental cost-effectiveness ratio for eptifibatide therapy in US PURSUIT patients was $16 491 per year of life saved. This result was robust through a wide range of sensitivity analyses. The cost-utility ratio for eptifibatide (using time trade-off defined utilities) was $19 693 per added quality-adjusted life-year.
Conclusions—Based on the results observed in the US PURSUIT patients, the routine addition of eptifibatide to standard care for non–ST-elevation acute coronary syndrome patients is economically attractive by conventional standards.
Key Words: coronary disease • cost-benefit analysis • glycoproteins • eptifibatide
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Introduction |
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Recently, the US Food and Drug Administration approved 2 new intravenous antiplatelet agents for clinical use in acute coronary syndromes. Both agents block the final common pathway for platelet aggregation, which involves the platelet surface membrane glycoprotein (GP) IIb/IIIa receptor, thereby providing much more complete inhibition of platelet aggregation than is achieved with aspirin. This more aggressive antiplatelet effect offers the potential to further reduce ischemic events in acute coronary syndrome patients.
Eptifibatide (Integrilin) is the GP IIb/IIIa receptor antagonist that has been studied in the largest number of acute coronary syndrome patients. The PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial randomized 10 948 patients with acute coronary syndrome and found a statistically significant 1.5% absolute reduction in the 30-day incidence of death or myocardial infarction (MI) with eptifibatide relative to placebo.1 As part of the prospective PURSUIT research efforts, we conducted an economic analysis of the US PURSUIT results.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Patient Population
Between November 1995 and January 1997, 10 948 patients with acute coronary syndrome were enrolled in PURSUIT at 726 hospitals in 28 countries.1 Eligible patients met the following criteria: (1) ischemic chest discomfort of
10
minutes’ duration within the previous 24 hours and (2) transient
ST-segment elevation >0.5 mm or transient or persistent
ST-segment depression >0.5 mm or T-wave inversion >1 mm
within 12 hours of symptoms or (3) an elevated creatine kinase–MB
fraction. Exclusion criteria included persistent ST-segment elevation
>1 mm, contraindications to anticoagulation, severe hypertension,
or renal failure.
Overview of Major Clinical Outcomes in PURSUIT
PURSUIT was designed to reflect current practices in the care of
patients with acute coronary syndrome, and protocol-specified
care was minimal.1 The primary study end point, a
composite of death of any cause or nonfatal (re)infarction at 30 days,
occurred in 15.7% of the placebo patients and 14.2% of the
eptifibatide patients, a 1.5% absolute reduction (P=0.042).
In the US patients, the primary study end point occurred in 15.4% of
placebo and 11.9% of eptifibatide patients at 30 days
(P=0.002). The benefit of study drug was fully established
by 96 hours and was maintained without attenuation or amplification
through 30 days.1 The use of investigator-reported
infarctions as part of the primary end point rather than the Clinical
Events Committee–adjudicated events yielded a 30-day event rate in the
overall trial of 10.0% for placebo versus 8.1% for eptifibatide
(P=0.001). In the US subset, the corresponding figures were
9.4% for placebo and 7.1% for eptifibatide (P=0.012).
Bleeding was more common in the eptifibatide arm: major bleeding (TIMI
criteria) occurred in 10.6% versus 9.1% of placebo patients
(P=0.02). Neither strokes nor intracranial
hemorrhage rates increased with eptifibatide, and most of the
excess bleeding was mild.
Overview of PURSUIT US Economic Substudy
As part of the PURSUIT research effort, we conducted a
prospective economic substudy of trial patients randomized in the
United States. This substudy had 2 major components: an
intention-to-treat analysis of empirical resource use and costs
and a cost-effectiveness analysis. All costs were expressed in
1996 US dollars. The perspective of the analyses was societal,
although some societal costs (eg, nonmedical costs, outpatient care,
and productivity costs) were omitted.
Descriptive and Intention-to-Treat Analyses
We measured medical resource use and costs starting with the
index (enrollment) hospitalization and extending through the 6-month
follow-up period. To have at least 80% power to detect a $1000 cost
difference between the best eptifibatide arm and placebo for the index
hospitalization, we planned to collect costs data on 1000 patients
per treatment group. Of the final 3522-patient US enrollment, we
collected hospital bills related to 2464 (70%) selected at random. For
the 4562 baseline and follow-up hospitalizations that these patients
had, we obtained >99% of collectable bills. In the analysis,
hospital charges were converted to costs by use of the
department-specific correction factors contained in each hospital’s
annual Medicare Cost Report.2 Physician fees were assigned
from the 1996 Medicare Fee Schedule for the following activities: daily
examination/evaluation (intensive care unit [ICU] and non-ICU),
cardiac catheterization, coronary angioplasty,
and coronary bypass surgery. Inpatient consultations were not
recorded, and follow-up outpatient care (other than cardiac
catheterization) was not assessed.
Because eptifibatide was provided without cost, we used the average wholesale price of the drug and the actual weight-based dose administered to each patient to estimate the cost of eptifibatide therapy.3 If only some of a vial of the drug was used, the remainder was assumed to be wasted. Because many hospitals obtain pharmaceuticals at a discounted cost, we also used the cost of eptifibatide at Duke Hospital to provide a second estimate of drug cost.
To impute hospital costs for the 1055 US patients without hospital billing data, including patients at centers such as Veterans Administration hospitals that do not produce bills and patients who were not in the random subset selected for bill collection, we used the available resource data from the clinical case-report form to develop 2 linear-regression imputation models (baseline [R2=0.80] and follow-up [R2=0.83]) on the patients who had complete billing data. For the primary US intention-to-treat cost comparisons, the total US cohort (measured costs plus imputed costs) was used. Similar results (not presented) were obtained when only patients with complete billing data were used.
Descriptive statistics are presented as percentages for
discrete variables and mean±SDs for continuous variables.
Treatment groups were compared by intention to treat for index
hospitalization costs (hospital plus physician costs) and for
cumulative 6-month costs. Statistical testing was performed with either
the Wilcoxon rank sum test (for continuous variables) or
the 
2 test (for discrete variables).
Cost-Effectiveness Analysis
Base-Case Overview
For the base-case analysis, we estimated the
cost-effectiveness ratio as the additional lifetime costs required to
add 1 extra life-year with eptifibatide therapy plus standard care
versus standard care alone. The analysis was based on 6-month
survival and infarction-free survival among the 3522 US PURSUIT
patients enrolled in the study, along with their resource use and cost
data. Life expectancy was estimated with long-term follow-up data from
the Duke Cardiovascular Disease Database on
PURSUIT-eligible patients. Discounting was performed at
3%.4
Major Assumptions
Our cost-effectiveness analysis made 3 important
assumptions in designing the base-case scenario. First, we assumed that
the best available estimate of the effectiveness of eptifibatide for
the United States was provided by the empirical results observed in the
US PURSUIT cohort. Second, we assumed that the Clinical Events
Committee’s adjudicated primary end point (death plus nonfatal MI) was
the most reliable clinical efficacy end point to use in our
life-expectancy extrapolations. Finally, in estimating the adverse
prognostic impact of an end-point nonfatal MI beyond the 6-month
PURSUIT follow-up, we assumed that we did not need to account for
infarct size.5
Lifetime Costs
Because there were no empirical data on costs after 6 months and
because there was no evidence of higher incremental costs in the
eptifibatide arm between hospital discharge and 6 months (exclusive of
drug costs), the base-case analysis assumed no incremental cost
difference between the treatment groups after 6 months.
Life-Expectancy Modeling
PURSUIT was designed to detect a significant difference in the
primary end point but not a mortality benefit from treatment with
eptifibatide. Because the prevention of nonfatal MI is an important
therapeutic goal with presumptive long-term survival effects beyond
those measured empirically in PURSUIT, we developed a method to
extrapolate the composite primary end point into life expectancy for
each treatment cohort. This was done in 2 parts: estimation of lifetime
survival from 6-month PURSUIT survival data and estimation of the
additional lifetime prognostic effects of PURSUIT nonfatal end-point
MIs.
The basic life-expectancy projection, exclusive of the MI effect, is composed of 2 primary components: (1) the observed 6-month survival and (2) the lifetime survival projection beyond the 6-month study follow-up period. However, 2 supplementary models were required to incorporate the effect of a nonfatal MI on subsequent survival. Thus, a total of 4 models (2 survival models and 2 MI models) were used to extrapolate life expectancy for the PURSUIT study population.
Model 1: Initial Observed 6-Month Follow-Up Period
The observed 6-month survival in the PURSUIT population was
modeled with the Cox proportional hazards regression model. We chose to
model the initial 6 months rather than use the observed survival data
to ensure that overall differences in life expectancy were based on
treatment-effect differences only and not on any covariate imbalances
that may have existed between the 6-month survivors in each treatment
group. This survival model was stratified on the basis of treatment and
was adjusted for age, history of MI, and history of diabetes. The
6-month predicted survival estimates from this model were essentially
identical to those observed for US eptifibatide patients (observed
survival 0.9501; predicted survival 0.9501) and for US placebo patients
(observed survival 0.9452; predicted survival 0.9454).
Model 2: Survival Projection Beyond 6 Months
For projected survival beyond 6 months, we used the Cox
proportional hazards regression model with left-truncated and
right-censored data to model the hazard of death as a function of age,
conditional on surviving the initial 6-month period, and adjusted for
additional prognostic factors through covariates. This model was
developed with 8169 patients from the Duke database with acute MI or
unstable angina who presented for cardiac
catheterization between 1971 and 1994 and then survived
6 months. There were a total of 887 deaths among these patients during
follow-up. The model "adjusts" for age as the metric over which the
hazard is computed and treats additional prognostic factors available
in both the Duke and PURSUIT databases (sex, history of cerebrovascular
disease, history of MI, history of hypertension, history of diabetes,
history of smoking, and year of presentation) as
covariates. The hazard relationship, which under proportional hazards
is well estimated through the age range represented in our
data, is used for prediction on a patient-by-patient basis. By
estimating the hazard over the age metric (rather than over the
traditional time metric), we produced data-based survival predictions
through a much longer time period owing to the broad
representation of ages in our database. Thus, the need for
parametric extrapolation of the data was
eliminated.6
Model 3: Modeling the Effect of Nonfatal End-Point MIs
To estimate the long-term survival effect of a nonfatal
end-point MI, we modeled the independent effect of an MI occurring
within the first 30 days in our Duke population. There were 3234 such
MI events available in the Duke data. MI in the Duke database is
defined by the presence of a consistent clinical
presentation with either diagnostic ST-segment
elevation or elevated serum cardiac markers. We chose the effect of any
acute MI occurring within this time frame to represent the base
case. Such a model provides the increased relative risk in the
mortality rate attributable to an MI. The base-case hazard ratio
assigned to a nonfatal MI was 1.33.
Model 4: Estimating the Probability of an End-Point MI
We used logistic regression to develop a model to predict the
probability of a 30-day end-point MI to incorporate the patient- and
treatment-specific risk associated with an end-point MI into our
lifetime projections. This model adjusted for age, sex, and
treatment.
Integration of Models
Using the above models, we predicted lifetime survival for each
individual PURSUIT patient as a function of (1) their covariates,
(2) their probability of surviving the first 6 months, (3) their
treatment- and covariate-specific likelihood of experiencing an
end-point MI, and (4) their probability of surviving beyond 6 months,
conditional on surviving the initial 6-month study period,
incorporating the effect of a nonfatal end-point MI on lifetime
survival. When the laws of conditional probability were applied, these
4 models were linked together to obtain an individual
covariate-specific lifetime survival prediction for each patient. The
individual predicted survival estimates were then averaged over all the
patients for both treatment groups to produce a mean predicted survival
estimate for each treatment group. To obtain mean life expectancy for
each treatment group, the estimated mean survival curves were
integrated over a lifetime. Finally, differences between the area under
each survival curve were computed to obtain the incremental life
expectancy due to eptifibatide. The survival curve for the eptifibatide
arm is shown in the Figure
.
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Sensitivity Analyses
Extensive sensitivity analyses were conducted on the
main starting parameters in the base-case model. We varied
the prognostic effects of nonfatal MIs, the definition of MI used in
the primary end point, and the size of the absolute 30-day treatment
benefit used to generate life-expectancy estimates. Costs were varied
according to the 95% confidence limits around the cumulative 6-month
cost difference observed in the US cohort. Cost utility ratios were
calculated with the utility values measured at 6 months for the US
patients who completed a time trade-off interview (n=1978). These
patients were asked to trade 10 years in their current health against
less time in excellent health.6 Alternative discount rates
for the base case of 0%, 5%, and 7% were calculated.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Baseline Characteristics
The baseline characteristics of the entire PURSUIT cohort have been reported previously.1 The US cohort had a mean age of 62 years, with 65% male enrollment (Table 1
). ST-segment depression was present
on the qualifying ECG in 39%, transient ST-segment elevation in 16%,
and T-wave inversion in 50% of patients. Compared with the non-US
PURSUIT cohort, the US patients were a year younger, 7 kg heavier, and
more likely to be current smokers and to have hypertension,
hypercholesterolemia, and diabetes. US patients
also had a substantially higher prevalence of prior
revascularization.
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Medical Resource Consumption and Costs
During the index (enrollment) hospitalization, there was no
evidence of a difference in major resource consumption among US
patients randomized to eptifibatide versus placebo (Table 2). Eighty-five percent of patients in
both groups had a diagnostic
catheterization, 
33% had a
percutaneous coronary intervention, and 20%
underwent coronary bypass surgery. Medical costs (exclusive of
the cost of the eptifibatide regimen) were therefore equivalent in the
2 arms (Table 2): $14 729 for eptifibatide versus $14 957 for
placebo (P=0.78).
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Follow-up resource consumption was also equivalent in the 2 treatment
groups (Table 3). Diagnostic
catheterization was performed in 14%,
percutaneous coronary intervention in 7%, and
coronary bypass surgery in 4% of patients. Follow-up medical
costs (hospital plus physician) were $3727 for patients in the
eptifibatide group and $3871 for those given placebo
(P=0.60). Thus, the cumulative 6-month costs observed in the
PURSUIT US cohort were $18 456 for the eptifibatide arm and $18 828
for the placebo arm (P=0.78).
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Cost-Effectiveness Analysis: Base Case
Costs
At the end of the 6-month follow-up for PURSUIT, there was a $372
cost advantage for eptifibatide (exclusive of the drug cost). Because
this difference was not statistically distinguishable from a $0 cost
difference, we chose not to count this in calculating the incremental
lifetime treatment costs for eptifibatide. The Red Book
average wholesale price for the bolus-and-infusion regimen of
eptifibatide based on actual drug administered was $1217±574.
Life Expectancy
In the US cohort, the 6-month death or MI rate was 15.2% in
the eptifibatide arm and 18.9% in the placebo arm
(P=0.004). The corresponding 6-month mortality rates were
4.99% and 5.48%, respectively (P=0.52). Using the
empirical US PURSUIT primary end-point results, we projected a
life expectancy from the time of randomization in PURSUIT of 15.96
years for patients treated with eptifibatide and 15.85 years for
patients receiving placebo, yielding an undiscounted incremental life
expectancy of 0.111 (ie, 11.1 additional life-years per 100 patients
treated with eptifibatide).
Cost-Effectiveness
With an incremental life expectancy of 0.111 years of life per
patient, an incremental cost of $1217 per patient, and a discount rate
of 3%, the incremental cost-effectiveness ratio for eptifibatide
versus placebo was $16 491 per year of life saved.
Cost-Effectiveness Analysis: Sensitivity Analyses
Major Assumptions
Each of the 3 major assumptions that defined key
parameters of the base-case analysis was subjected
to sensitivity analysis. The magnitude of reduction in the
combined incidence of death or nonfatal MI with eptifibatide was larger
in the US cohort than in the overall PURSUIT Trial. When the
more conservative effectiveness produced by eptifibatide in the overall
PURSUIT cohort was substituted in the base-case analysis (with
other factors remaining unchanged), the cost-effectiveness ratio
increased to $33 619.
The second major assumption was that the Clinical Events Committee’s adjudicated primary end point was the most reliable estimate of the effectiveness of eptifibatide. When the base-case analysis was recalculated with investigator-defined MIs included in the primary end point (with other parameters unchanged), the cost-effectiveness ratio increased to $20 839. The use of both of the above changes in base-case analysis (ie, investigator-defined end-point MIs and the outcomes of the overall PURSUIT cohort) yielded a cost-effectiveness ratio of $31 942 per added life-year.
The third major assumption was that we did not need to account for
end-point MI size. When incremental life expectancy was calculated from
the observed 6-month difference in survival in US PURSUIT patients,
with nonfatal end-point MIs assumed to exert no long-term prognostic
effects beyond the 6-month follow-up, the incremental
cost-effectiveness ratio rose to $34 771. If the long-term prognostic
weight given to end-point nonfatal MIs is adjusted to give greater
weight to large MIs (ie, creatine kinase–MB 5 times the upper limit
of normal) and no prognostic weight to smaller MIs, the incremental
undiscounted life expectancy is essentially unchanged from the base
case at 0.124 life-years, yielding a cost-effectiveness ratio of
$15 308 per added life-year. If long-term prognostic weight is given
only to the largest end-point MIs (ie, creatine kinase–MB 10 times
the upper limit of normal), the corresponding cost-effectiveness ratio
is $18 986.
Discount Rate
With a discount rate of 5%, the cost-effectiveness ratio
increased to $20 768 per year of life saved. The corresponding ratios
with 0% and 7% discount rates were $10 954 and $25 460 per
life-year saved, respectively.
Incremental Costs
When the price of eptifibatide at Duke Hospital was substituted
for the average wholesale price of the drug, the result was an
incremental cost of $1014 and a cost-effectiveness ratio of $13 740
per year of life saved. A bootstrap 95% CI around the observed US
cumulative 6-month cost difference (excluding drug costs) was -$1399
to $652. The addition of these costs to the cost of the eptifibatide
regimen yielded corresponding cost-effectiveness ratios ranging from
dominance (better outcomes and lower net costs) to $25 325 per
life-year added.
Cost Utility Analysis
At 6 months, the US eptifibatide patients reported a mean time
trade-off value of 0.84, whereas the placebo patients reported a value
of 0.83 (P=0.45). The corresponding rating scale (0 to 100)
measures were 69.5 and 70.3 (P=0.19). Weighting of the
increased survival in the eptifibatide group by the observed 6-month
utility weight yielded a cost utility ratio of $19 693 per
quality-adjusted life-year added. When the rating scale weights were
used as more conservative utility substitutes, a cost per
quality-adjusted life-year of $23 449 resulted.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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We provide the first detailed economic analysis of an intravenous GP IIb/IIIa platelet inhibitor in non–ST-elevation acute coronary syndromes. Although the threshold for defining when a therapy does not provide enough medical benefit relative to its incremental costs is controversial, many agree that a cost-effectiveness ratio of <$50 000 per life-year added is economically attractive, whereas a ratio of
$100 000 per life-year
added is too high.2 On the basis of extensive empirical
data, our study shows that the cost per life-year added with
eptifibatide therapy in the PURSUIT trial falls in the economically
attractive range over a wide spectrum of starting
parameters and assumptions. Our base-case analysis used empirical data from US PURSUIT patients to estimate incremental lifetime effectiveness and costs. Because the US cohort had the largest absolute benefit with eptifibatide and because a higher proportion of US patients underwent early revascularization, our results are most relevant to similar cohorts of acute coronary syndrome patients. However, 2 points are worth noting. First, the benefit of eptifibatide over placebo at 30 days in the United States alone was statistically significant.1 The benefit in Canada and Western Europe was more modest in magnitude, whereas in Latin America and Eastern Europe, small adverse effects on the primary end point were noted for eptifibatide. The reason for this apparent geographic variation remains unclear, but multivariate analyses have shown that it is not primarily a function of different revascularization rates (R.A.H., oral communication, 1999). Other, unmeasured aspects of patient selection or care may be responsible. Second, the larger benefit of eptifibatide in the US patients was not a result of the greater number of patients who underwent percutaneous revascularization. As reported previously,1 the absolute benefit for eptifibatide in patients who underwent intervention within 72 hours of randomization was 3.8% before the procedure, 2.8% at 96 hours, and 2.2% at 30 days. Thus, the benefit of eptifibatide was actually attenuated after percutaneous revascularization rather than amplified by it.
The Prognostic Importance of Preventing Nonfatal MIs
Like all current large-scale trials of new therapies for acute
non–ST-elevation coronary syndromes, PURSUIT was not designed
to detect a mortality difference.1 A recent overview of
>33 000 acute coronary syndrome patients randomized in trials
of GP IIb/IIIa inhibitors showed that prevention of
infarction was the primary benefit evident from these agents at up to 6
months of follow-up.7 The central tenet of the PURSUIT and
other GP IIb/IIIa trials, therefore, is that preventing a nonfatal MI
is a worthwhile clinical accomplishment with important prognostic
benefits. The absence of a statistically significant mortality
difference, however, poses unique challenges to a cost-effectiveness
analysis. Specifically, to convert 6-month infarction-free
survival data into life-expectancy estimates, the quantitative effect
that a nonfatal MI (with survival to 6 months) has on life expectancy
must be established. Because no modern clinical trial has a
sufficiently long follow-up to answer this question empirically, we
used the extensive follow-up experience in the Duke
Cardiovascular Disease Database to estimate this
effect. These analyses showed that an acute MI was associated
with a long-term hazard ratio of between 0.33 and 0.75, depending on
how the MI was defined. A 33% increase in long-term hazard for MI
survivors translates into an 2-year reduction in life expectancy.
Thus, the prevention of a nonfatal MI in a cohort with a life
expectancy of 16 years has only one eighth the prognostic value of
preventing a death. Even with this conservative weighting of MIs
relative to death, our analyses showed that the relationship of
incremental life expectancy to incremental costs of eptifibatide in
PURSUIT made it "cost-effective" or economically attractive.
Because some of the end-point MIs in PURSUIT were diagnosed by the Clinical Events Committee but not the clinician who cared for the patient, and because these MIs tended to be smaller, with little discernible short-term effect on left ventricular function, we considered that our base-case incremental life-expectancy calculations might be too optimistic. Substitution of the investigator-defined MIs in the base-case analysis raised the cost-effectiveness ratio very modestly to $20 839. Hence, the elimination of "enzyme bump" MIs from the primary end point did not materially alter our results.
The other dimension of end-point MIs to be considered is size. In the present study, crediting all nonfatal end-point MIs with an intermediate long-term prognostic weight was quantitatively equivalent to giving larger MIs a bigger prognostic weight and smaller MIs no prognostic weight. The conclusions of our analysis, therefore, were not sensitive to differential prognostic weighting of end-point MIs on the basis of size. The GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto miocardico) investigators5 recently demonstrated in the GISSI-1 database that infarct size is important for short-term (eg, 30 day) prognosis but not for long-term (eg, 5 to 10 years) prognosis.
Study Limitations
Several caveats should be considered in the interpretation of our
study. First, our study was not powered to detect a significant
difference in life expectancy. A statistical comparison of life
expectancy would require a significantly larger sample than even the
entire PURSUIT cohort. Second, we did not calculate a within-trial
cost-effectiveness ratio because we felt that the 6-month empirical
follow-up was insufficient to give an interpretable result. Finally,
the finding that a therapy is economically attractive does not
guarantee that it will be adopted. Cost-effectiveness helps to define
the most efficient ways to produce health benefits within a given
healthcare budget. It does not address the more fundamental policy
question of how much money society should spend on health care.
Conclusions
Based on the results of the PURSUIT trial in US patients, the
routine addition of eptifibatide to the usual care for
non–ST-elevation acute coronary syndrome patients is
economically attractive by conventional standards.
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Acknowledgments |
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This study was supported in part by a research grant from Cor Therapeutics Inc and Schering-Plough Research Institute, which are worldwide development partners for Integrilin). The authors acknowledge the editorial support of Tracey Simons, MA, and Melanie R. Daniels.
Received June 11, 1999; revision received August 18, 1999; accepted August 26, 1999.
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1. The PURSUIT Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes without persistent ST-segment elevation. N Engl J Med. 1998;339:436–443.
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