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(Circulation. 1996;94:629-635.)
© 1996 American Heart Association, Inc.

Articles

Economic Assessment of Platelet Glycoprotein IIb/IIIa Inhibition for Prevention of Ischemic Complications of High-Risk Coronary Angioplasty

Daniel B. Mark, MD, MPH; J. David Talley, MD; Eric J. Topol, MD; Lee Bowman, PhD; Lai Choi Lam, MS; Keaven M. Anderson, PhD; James G. Jollis, MD; Michael W. Cleman, MD; Kerry L. Lee, PhD; Thomas Aversano, MD; William J. Untereker, MD; Linda Davidson-Ray, BA; Robert M. Califf, MD; for the EPIC Investigators

the Economics and Quality of Life Research Group (D.B.M., J.G.J., L.C.L., L.D.R.) and the Clinical Trials Coordinating Center (R.M.C., K.L.L.), Division of Cardiology, Department of Medicine, and the Division of Biometry (K.L.L.), Department of Community and Family Medicine, Duke University Medical Center, Durham, NC; the Cardiovascular Division (J.D.T.), University of Louisville (Ky); Yale University School of Medicine (M.W.C.), New Haven, Conn; Johns Hopkins Hospital (T.A.), Baltimore, Md; Cooper Hospital (W.J.U.), Camden, NJ; the Department of Cardiology (E.J.T.), Cleveland Clinic, Cleveland, Ohio; the Department of Biostatistics (K.M.A.), Centocor Inc, Malvern, Pa; and the Health Economics Research Group (L.B.), Eli Lilly and Co, Indianapolis, Ind.

Correspondence to Daniel B. Mark, MD, MPH, Cardiovascular Division, Duke University Medical Center, DUMC-3485, Durham, NC 27710.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background In the EPIC trial, c7E3 Fab, an antiplatelet IIb/IIIa receptor antibody, reduced 30-day ischemic end points after high-risk coronary angioplasty by 35% and 6-month ischemic events by 23% but increased in-hospital bleeding episodes.

Methods and Results Of the 2099 patients randomized in EPIC, data were collected on 2038 (97%) for prospective hospital cost and major resources. Physician fees were estimated from the Medicare Fee Schedule. Regression analysis was used to examine the economic tradeoff between reduced ischemic events and increased major bleeding during the initial hospitalization. A potential cost savings of $622 per patient during the initial hospitalization from reduced acute ischemic events with c7E3 Fab was offset by an equivalent rise ($521) in costs as the result of an increase in bleeding episodes. Baseline medical costs for the bolus and infusion c7E3 Fab arm averaged $13 577 (exclusive of drug cost) compared with $13 434 for placebo (P=.42). During the 6-month follow-up, c7E3 Fab decreased repeat hospitalization rates by 23% (P=.004) and repeat revascularization by 22% (P=.04), producing a mean $1270 savings per patient (exclusive of drug cost) (P=.018). With a cost of $1407 for the bolus and infusion c7E3 Fab regimen, the cumulative net 6-month cost to switch from standard care to routine c7E3 Fab averaged $293 per patient.

Conclusions In high-risk coronary angioplasty, aggressive platelet inhibition with c7E3 Fab, by significantly reducing ischemic events and repeat revascularization, recoups most of the cost of therapy and has the potential to pay for itself.

Key Words: angioplasty • trials • glycoproteins • cost-benefit analysis

	Introduction

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Although the use of coronary angioplasty has grown dramatically over the past decade, the two major limitations associated with the procedure, abrupt closure and restenosis, have not decreased significantly during that period.^{1 2 3 4} Abrupt closure occurs in approximately 4% to 9% of angioplasty procedures and frequently leads to acute myocardial infarction, emergency coronary bypass surgery, or both; it also is associated with an 10-fold increase in mortality relative to patients without this complication.^{5 6} Restenosis occurs in 35% to 45% of patients with initially successful angioplasty and frequently leads to repeat angioplasty or referral for bypass surgery.⁴ Before the present trial, restenosis had proved remarkably resistant to a wide array of preventive interventions.^{4 7} An early economic analysis of coronary angioplasty showed that its cost advantage over bypass surgery was largely lost at the end of the first follow-up year because of early crossover to surgery and because of later treatment of restenosis with repeat revascularization.⁸

The multicenter EPIC (Evaluation of 7E3 for the Prevention of Ischemic Complications) randomized, placebo-controlled trial recently reported the results of potent inhibition of platelet aggregation with c7E3 Fab (abciximab).^{2 3} This agent is a chimeric (human-mouse) monoclonal antibody fragment that blocks the final common pathway of platelet aggregation involving the platelet glycoprotein IIb/IIIa receptor. EPIC showed that a bolus plus 12-hour infusion regimen of c7E3 Fab reduced 30-day clinical events related to abrupt closure by 35% and reduced subsequent major ischemic events (death or myocardial infarction) or the need for revascularization up to 6 months by 23%.^{2 3} An integral part of the EPIC research effort involved a prospective, detailed analysis of the effects of c7E3 Fab on the cost of coronary angioplasty. The purpose of this report is to describe the principal findings from the EPIC economic substudy.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patient Population
Between November 1991 and November 1992, 2099 patients were randomized into the EPIC trial at 56 institutions in the United States. As described previously,² patients referred for coronary angioplasty at each participating site were eligible for enrollment if they were judged to be at high risk for ischemic complications. Study patients included those with acute myocardial infarction within 12 hours of symptom onset, early postinfarction angina or unstable rest angina, or high-risk angiographic lesion morphology as defined by the American Heart Association/American College of Cardiology criteria.⁹ Exclusions included age 80 years and high risk of bleeding.

Overview of EPIC Protocol
All study patients received 325 mg of oral aspirin (before angioplasty and once a day thereafter) and intravenous heparin (before angioplasty and for 12 hours after the procedure). Patients were randomized into three treatment groups in a double-blind design: bolus and infusion c7E3 Fab, bolus c7E3 Fab and placebo infusion, and placebo bolus and placebo infusion. Protocol-specified management was limited to a small number of selected laboratory tests. Other management decisions were made according to the usual practices at each site. The primary end point of the trial was a composite: occurrence during the first 30 days after randomization of death (any cause), nonfatal myocardial infarction, coronary artery bypass graft surgery for acute ischemia, repeat percutaneous intervention for acute ischemia, insertion of a coronary stent because of a procedural failure, or insertion of an intra-aortic balloon pump because of refractory ischemia.² A prespecified secondary end point of the trial was the composite at 6 months of death, nonfatal myocardial infarction, or need for repeat revascularization.³ As described previously, all major clinical events were reviewed by an independent events committee blinded to treatment group.² Major bleeding was defined as bleeding associated with a drop in hemoglobin >5 g/dL or an intracranial hemorrhage.

Summary of Principal EPIC Clinical Outcomes
As reported previously, the c7E3 Fab groups showed a dose-dependently reduced incidence of postprocedure ischemic complications.² At 30 days, the primary composite clinical end point occurred in 12.8% of the placebo group, 11.4% of the bolus c7E3 Fab only group, and 8.3% of the bolus and infusion c7E3 Fab group (dose-response P=.009, P=.43 for bolus only versus placebo, P=.008 for bolus and infusion versus placebo). The major end point components that differed between placebo and bolus and infusion c7E3 Fab were nonfatal myocardial infarction (8.6% for placebo versus 5.2% for bolus and infusion c7E3 Fab, P=.01), emergency percutaneous transluminal coronary angioplasty (PTCA) (4.5% versus 0.8%, P<.001), and emergency coronary artery bypass grafting (CABG) (3.6% versus 2.4%, P=.18). Major bleeding occurred in 14% of the bolus and infusion patients, 11% of the bolus only patients, and 7% of the placebo patients (P=.001 for bolus and infusion versus placebo). The most common type of major bleed (72%) in all three treatment groups for patients not receiving bypass surgery was access site bleeding followed by gastrointestinal (20%) and genitourinary (15%) bleeding.¹⁰ Two treated patients (one placebo, one bolus plus infusion) died after hemorrhagic stroke; one additional treated patient in each treatment group experienced a hemorrhagic stroke. Rates of major bleeding in patients undergoing bypass surgery did not differ among treatment groups.

At the 6-month follow-up point, c7E3 Fab bolus and infusion had produced a 23% reduction in major ischemic events and repeat revascularization (P=.001).³ Target vessel repeat revascularization in patients with an initially successful PTCA was reduced 26% by c7E3 Fab bolus and infusion relative to placebo (P=.007).

Design of Economic Substudy
Economic outcomes were assessed both in terms of medical costs and medical resource consumption.^{11 12} For 2038 of the 2099 patients (97%) enrolled in EPIC, we obtained copies of hospital bills covering the patients' medical care from the time of randomization through hospital discharge. We collected complete 6-month follow-up hospitalization cost data on 1923 (93%) of the 2072 patients who survived the initial hospitalization. Both itemized and summary ledger forms of hospital bills were obtained along with a UB 82 bill form. Hospital charges were converted to hospital costs with the use of the cost-to-charge ratios and per diems derived from the annual Medicare Cost Report of each hospital.¹¹ The importance of converting from charges to costs has been discussed previously.^{11 12 13} The cost of the c7E3 Fab was calculated from the weight-adjusted dose prescribed for each active treatment patient: 0.25 mg/kg bolus and 10 µg/min infusion for 12 hours. The cost assigned to each 10-mg vial of c7E3 Fab was $450. Our calculations assumed that any partial vial remaining at the end of the patient's treatment would be wasted. Patients who did not receive c7E3 Fab were not assigned a drug cost. Physician fees were assigned with use of the Medicare Fee schedule (North Carolina version) for the following activities: admission work-up, daily follow-up (intensive care unit [ICU], non-ICU), cardiac catheterization, coronary angioplasty, coronary bypass surgery, vascular repair, diagnostic procedures to evaluate major bleeding, and consultation for major bleeding complications. Costs for outpatient follow-up care (except for cardiac catheterization) were not assessed.

For the 61 patients with missing baseline hospital cost data, we imputed their hospital costs using a linear regression model developed on the patients with complete cost data that included major clinical outcomes as independent variables (model presented in Table 5). In follow-up, 44 patients were excluded from the cost analysis because they were lost to clinical follow-up. An additional 105 patients with incomplete follow-up hospital cost data had their follow-up costs imputed with the use of the average costs for patients who had complete cost data and a similar follow-up hospitalization (on the basis of the primary discharge diagnosis). Since the inclusion of imputed costs did not significantly alter the results of the study, we present the study results with imputed costs included.

View this table: [in this window] [in a new window]   Table 5. Multivariable Linear Regression Model

In addition to medical costs, counts were made of selected medical resources consumed during the study, including "big ticket" inpatient care items (such as total and ICU length of stay, repeat cardiac catheterization, coronary angioplasty, coronary bypass surgery) and follow-up hospitalization.

Data Analysis
Descriptive statistics are presented as percentages for discrete variables and medians and interquartile ranges (25th to 75th percentiles) or means and standard deviations for continuous variables. Because of the considerable skewness typically present in the distribution of cost data, description of such distributions tends to be problematic. Thus, we present both means (reflecting the cost of the program expressed on a per patient basis) and medians (reflecting the cost of the "typical" patient). Comparisons by intention-to-treat of total hospital costs at the end of the initial hospitalization and during the 6-month follow-up period were performed with the use of the Wilcoxon rank sum test. On the basis of the clinical findings of superior efficacy with bolus and infusion c7E3 Fab over bolus only,^{2 3} major statistical comparisons in this article emphasize comparison of bolus and infusion c7E3 Fab with placebo. A second set of analyses was performed with the use of data from the 2038 patients who were actually treated according to randomized assignment (c7E3 Fab or placebo). Since the decision not to treat for the remaining 61 patients was never based on knowledge of the treatment assigned (blinding preserved), comparison by treatment received preserves all the protections of an intention-to-treat analysis and provides a more precise estimate of treatment effect (undiluted by the random differences of patients who were not treated). All figures cited in this article are from the intention-to-treat analysis unless otherwise specified.

To explore the joint effects of decreased ischemic end points and increased major bleeding associated with bolus and infusion c7E3 Fab relative to placebo on total baseline medical cost, we performed multivariable linear regression analyses with and without log transformation of the dependent variable.¹⁴ Since the results of these two analyses were very similar, we present the model with the untransformed dependent variable.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Baseline Characteristics, Procedural Results, Hospital Outcomes
The baseline characteristics, procedural results, and hospital outcomes from EPIC have been reported previously.² The three treatment groups were well balanced at baseline, with a median age of 61 years (52 to 68), 72% men, 27% with an acute myocardial infarction (<8 days), and 13% with a recent myocardial infarction (8 to 30 days). Twenty-two percent had a prior angioplasty and 15% had prior bypass surgery. Single-vessel disease was present in 53%, two-vessel disease in 31%, and three-vessel disease in 14%. Ninety percent of patients had a balloon angioplasty as their index procedure, 5% had atherectomy, and 5% had both.

The resource consumption patterns for the index procedure did not differ among treatment groups, with a median procedure time in the catheterization laboratory of 53 minutes, a median of 200 mL of contrast used, and a 3% use of thrombolytics.

Baseline Resource Consumption and Medical Costs
Comparison of selected resource consumption items among treatment groups (Table 1) showed a reduced need for urgent repeat PTCA in the bolus and infusion c7E3 Fab group relative to placebo (0.7% versus 3.6%) but no difference in nonurgent repeat PTCA or use of coronary stents. Urgent CABG also was lower in the bolus and infusion c7E3 Fab group (2.4% versus 3.6% for placebo), but nonemergency CABG was slightly more frequent in these patients. The need for an intra-aortic balloon pump was similar in the three treatment groups.

View this table: [in this window] [in a new window]   Table 1. Major Baseline Hospital Resource Consumption and Hospital Costs

Total mean hospital costs (exclusive of costs of c7E3 Fab) were almost identical in the three treatment groups (P=.63) (Table 1). Hospital charge data showed a similar relationship (P=.65), as did physician fees (P=.26). Bolus and infusion c7E3 Fab costs exceeded those of the placebo arm by an average of $143 by intention-to-treat analysis, while the placebo arm was $66 more expensive by treatment-received analysis. Length of stay, either total (P=.26) or ICU (P=.64), was not significantly different among the treatment groups (Table 1).

Table 2 displays the breakdown of total hospital costs by individual cost centers. The overall parity in hospital costs among the treatment groups is maintained in each of the major cost centers.

View this table: [in this window] [in a new window]   Table 2. Baseline Hospital Cost Distribution by Cost Center

Follow-up Resource Consumption and Medical Costs
One or more follow-up hospitalizations were reported by 24.1% of the bolus and infusion c7E3 Fab group and 31.2% of the placebo group (P=.004) (Table 3). For all three groups, 84% to 86% of these hospitalizations were for cardiac reasons. The major differences in rehospitalizations among treatment groups were for the diagnoses of unstable angina, other ischemic heart disease, and heart failure (Table 4). Many of these patients underwent repeat cardiac procedures (cardiac catheterization, PTCA, and CABG) (Table 3). During the 6-month follow-up period, 15.6% of the bolus and infusion c7E3 Fab group required additional revascularization procedures compared with 19.9% of the placebo group (P=.04).

View this table: [in this window] [in a new window]   Table 3. Follow-up Medical Resource Consumption and Hospital Costs

View this table: [in this window] [in a new window]   Table 4. Primary Discharge Diagnosis (ICD-9) From Follow-up Hospitalizations

The average follow-up hospital costs were $2881 for the bolus and infusion c7E3 Fab group and $3988 for the placebo group (Table 3). The average follow-up physician fees were $451 for the bolus and infusion c7E3 Fab group and $614 for the placebo group. The medical cost difference (hospital plus physician fees) between these two groups, amounting to $1270, was significant (P=.018). The placebo group had a correspondingly higher number of follow-up hospital days (mean of 2.3 versus 1.7 days, P=.022).

Cumulative 6-Month Medical Costs
The average cumulative 6-month hospital and physician costs for the bolus and infusion c7E3 Fab arm (exclusive of the cost of c7E3 Fab and assigning $0 follow-up costs to patients who died during the initial hospitalization) was $16 862, while that for the placebo arm was $17 976. With a cost for the c7E3 Fab bolus and infusion regimen averaging $1407 per treated patient, the total 6-month cost of the bolus and infusion arm was $18 269. Thus, the net incremental 6-month cost of switching to a strategy of routine bolus and infusion c7E3 Fab relative to usual care was $293 (P for difference=.72, 95% CI, -$1300 to +$1886).

Multivariable Analysis
During the initial hospitalization for PTCA, treatment with bolus and infusion c7E3 Fab was associated with a significant decrease in major ischemic end points and a significant increase in major bleeding relative to placebo. To understand how these outcomes balanced to produce a net equivalence in total baseline medical costs, we constructed a multivariable linear regression model with total medical costs as the dependent variable (exclusive of the cost of c7E3 Fab). Candidate predictor variables considered included baseline demographic and clinical characteristics as well as major in-hospital clinical outcomes. The resulting model (Table 5) shows that total costs were significantly increased both by the need for repeat revascularization and by bleeding complications necessitating additional medical care. Furthermore, need for emergency repeat revascularization substantially increased costs relative to elective procedures. In contrast, the assigned treatment group did not affect hospital costs independent of these factors (coefficient for bolus and infusion group=$27, P=.95). This model predicts that by reducing urgent PTCA from 3.7% to 0.7% and urgent CABG from 3.7% to 2.4%, bolus and infusion c7E3 Fab saved an average of $444 per patient over placebo therapy during the initial hospitalization. (The corresponding estimate for the treatment-received analysis is $622 saved.) However, when the rate of major bleeding increased in nonsurgical patients from 3.3% to 10.6% and minor bleeding from 9.2% to 16.8%, the c7E3 Fab arm lost $531 of its potential cost advantage ($521 lost by treatment-received analysis) leaving a projected net cost of $77 per patient (observed=$143).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
EPIC is the first randomized trial to demonstrate that a potent antiplatelet agent can significantly reduce both the early and late ischemic complications of PTCA.^{2 3} In the present prospective economic substudy of EPIC, we demonstrated that both of these clinical benefits have important cost implications. While no net difference in medical costs was observed among treatment groups during the initial hospitalization for PTCA, regression analysis suggests that a mean cost savings of $400 to $600 per patient (exclusive of c7E3 Fab cost) was induced by the lower ischemic complication rate associated with bolus and infusion c7E3 Fab. This potential cost savings was lost, however, because of a concomitant increase in the rate of bleeding complications in that treatment arm. During the 6-month follow-up period of this study, the reduced clinical restenosis rate of bolus and infusion c7E3 Fab relative to placebo was associated with less need for rehospitalization and repeat revascularization and a mean medical cost savings of $1270 per patient. With a drug cost of $1407 per patient, the incremental 6-month cost of the bolus and infusion c7E3 Fab regimen in this study was $293. Thus, c7E3 Fab is the first pharmacological agent demonstrated to improve the clinical outcomes of PTCA while recouping most of the cost of therapy required to produce these benefits.

While the regression analysis presented in Table 5 provides a post hoc explanation of why no actual cost savings was observed during the index hospitalization for bolus and infusion c7E3 Fab in this study, it does not prove that this potential cost savings can ever be uncoupled from the offsetting effects of bleeding. Much of the excess bleeding seen with this regimen may be related to the use of full heparinization (target activated clotting times of 300 seconds) in conjunction with c7E3 Fab during the PTCA procedure. Patients who had lower degrees of anticoagulation had preserved efficacy, with much lower major bleeding rates.¹⁰ In addition, major bleeding rates varied significantly across participating institutions.¹⁵ These findings support the hypothesis that the reduction in ischemic events observed for bolus and infusion c7E3 Fab is not necessarily tied to the increased bleeding seen in this trial. Consequently, it is a reasonable supposition that at least some of the potential index hospitalization cost savings suggested by our analysis are recoverable. A second trial of c7E3 Fab with less intensive heparin therapy during the PTCA procedure (EPILOG) was stopped recently by its Data and Safety Monitoring Board because of significantly greater efficacy for active treatment in conjunction with lower rates of major bleeding. A prospective economic analysis is being conducted in that study.

During the 6-month follow-up period of EPIC, the bolus and infusion c7E3 Fab arm experienced a 22% reduction in the need for repeat revascularization (PTCA or CABG) and a 23% reduction in repeat hospitalization rates (Table 3). This was accompanied by a 28% reduction in follow-up hospitalization and physician costs (P=.018), amounting to a mean cost savings for the bolus and infusion c7E3 Fab regimen of $1270. The repeat revascularization figures in Table 3 differ slightly from the figures published in the recent clinical follow-up report from the EPIC trial.³ The clinical study described repeat revascularization in terms of post–48-hour and post–30-day end points, while the present economic analysis is framed in terms of the index hospitalization (during which the patient was enrolled in the trial) and follow-up hospitalizations/procedures.

The cost implications of bleeding complications were largely restricted to the initial hospitalization. Nonfatal intracranial hemorrhage occurred in one patient in each treatment group and thus did not affect the incremental costs of bolus and infusion c7E3 Fab relative to placebo. The majority of major bleeding events recorded in all three groups were access site bleeding in the femoral region and gastrointestinal bleeding, both of which occurred more commonly in the bolus and infusion c7E3 Fab group, and blood loss associated with coronary bypass surgery, which occurred with equal frequency in all three treatment groups.¹⁰ Major bleeding was associated with an increased need for transfusion and with a prolonged hospital stay. However, rates of surgical intervention (primarily femoral vascular repair) did not differ between bolus and infusion c7E3 Fab and placebo.¹⁰ Although we did not assess outpatient care in this study and therefore cannot rule out the possibility that additional outpatient visits were required by the bolus and infusion c7E3 Fab patients as sequelae to their femoral or other bleeding complication, a doubling or tripling of outpatient visits for the extra 7% of patients with a major bleed in this treatment group would have very little effect on the mean costs for the group.

Several caveats should be considered in the interpretation of this study. We did not consider outpatient costs (office visits, medications) or direct nonmedical costs. We also did not consider indirect costs, such as those related to time lost from work. It is possible that the reduced rehospitalization and repeat revascularization rates seen with bolus and infusion c7E3 Fab could have been associated with less time lost from work and decreased indirect costs. Finally, EPIC demonstrated the efficacy of c7E3 Fab in high-risk PTCA patients. The generalizability of the study to other types of PTCA patients and to stent patients is currently under study in the EPILOG trial.

Summary
Prospective economic analysis of the EPIC randomized trial demonstrates that the reduced clinical restenosis rate observed over a 6-month follow-up in high-risk PTCA patients treated with bolus and infusion c7E3 Fab was accompanied by a net cumulative 6-month medical cost of $293 per patient. During the index hospitalization, regression analysis suggested that an additional $400 to $600 in cost savings induced by lowering the acute ischemic complication rate was lost as the result of a concomitant rise in bleeding with c7E3 Fab, necessitating additional medical care.

	Acknowledgments

 
This study was supported in part by a grant from Centocor, Inc, Malvern, Pa; research grants HL-36587 and HL-17670 from the National Heart, Lung, and Blood Institute, Bethesda, Md; research grants HS-05636 and HS-06503 from the Agency for Health Care Policy and Research, Rockville, Md; and a grant from the Robert Wood Johnson Foundation, Princeton, NJ. The authors wish to acknowledge the study coordinators at each of the participating EPIC sites whose hard work made the present study possible. We also wish to recognize the participating investigators for their diligent efforts on EPIC and their support of this study. A complete list of the EPIC study group has recently been published.^{2 3} Finally, the authors thank Maria Lee, Serena Smith, Patricia Russell, and Tracey Simons for technical support in the preparation of the manuscript.

Received November 2, 1995; revision received February 6, 1996; accepted February 15, 1996.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Lincoff AM, Topol EJ. Abrupt vessel closure. In: Topol EJ, ed. Textbook of Interventional Cardiology. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1994:207-230.
   
2. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med. 1994;330:956-961.[Abstract/Free Full Text]
   
3. Topol EJ, Califf RM, Weisman HF, Ellis SG, Tcheng JE, Worley S, Ivanhoe R, George BS, Fintel D, Weston M, Sigmon K, Anderson KM, Lee KL, Willerson JT, on behalf of the EPIC Investigators. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. Lancet. 1994;343:881-886.[Medline] [Order article via Infotrieve]
   
4. Hillegass WB, Ohman EM, Califf RM. Restenosis: the clinical issues. In: Textbook of Interventional Cardiology. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1994:415-435.
   
5. Lincoff AM, Popma JJ, Ellis SG, Hacker JA, Topol EJ. Abrupt vessel closure complicating coronary angioplasty: clinical, angiographic and therapeutic profile. J Am Coll Cardiol. 1992;19:926-935.[Abstract]
   
6. Tenaglia AN, Fortin DF, Frid DJ, Gardner LH, Nelson CL, Tcheng JE, Stack RS, Califf RM. Long-term outcome following successful reopening of abrupt closure after coronary angioplasty. Am J Cardiol. 1993;72:21-25.[Medline] [Order article via Infotrieve]
   
7. Fortin DF, Tcheng JE, Hillegass WB, Phillips HR III. Clinical management of restenosis. In: Roubin GS, Califf RM, O'Neill WW, Phillips HR III, Stack RS, eds. Interventional Cardiovascular Medicine: Principles and Practice. New York, NY: Churchill-Livingstone; 1994:555-573.
   
8. Reeder GS, Krishan I, Nobrega FT, Naessens J, Kelly M, Christianson JB, McAffee MK. Is percutaneous coronary angioplasty less expensive than bypass surgery? N Engl J Med. 1984;311:1157-1162.[Abstract]
   
9. Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB III, Loop FD, Peterson KL, Reeves TJ, Williams DO, Winters WL Jr. Guidelines for percutaneous transluminal coronary angioplasty: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). Circulation. 1988;78:486-502.[Free Full Text]
   
10. Aguirre F, Topol EJ, Ferguson JJ, Anderson K, Blankenship JC, Heuser RR, Sigmon K, Taylor M, Gottlieb R, Hanovich G, Rosenberg M, Donohue TJ, Weisman HF, Califf RM. Bleeding complications with the chimeric antibody to platelet glycoprotein IIb/IIIa integrin in patients undergoing percutaneous coronary intervention. Circulation. 1995;91:2882-2890.[Abstract/Free Full Text]
    
11. Mark DB. Medical economics and health policy issues for interventional cardiology. In: Topol EJ, ed. Textbook of Interventional Cardiology. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1993:1323-1353.
    
12. Hlatky MA, Lipscomb J, Nelson C, Califf RM, Pryor DB, Wallace AG, Mark DB. Resource use and cost of initial coronary revascularization: coronary angioplasty versus coronary bypass surgery. Circulation. 1990;82(suppl IV):IV-208-IV-213.
    
13. Finkler SA. The distinction between costs and charges. Ann Intern Med. 1982;96:102-109.
    
14. Dudley RA, Harrell FE Jr, Smith LR, Mark DB, Califf RM, Pryor DB, Glower D, Lipscomb J, Hlatky MA. Comparison of analytic models for estimating the effect of clinical factors on the cost of coronary artery bypass graft surgery. J Clin Epidemiol. 1993;46:261-271.[Medline] [Order article via Infotrieve]
    
15. Shadoff N, Califf RM, for the EPIC Study Group. Impact of clinical site on ischemic events and bleeding complications: results from the EPIC trial. J Am Coll Cardiol. 1994;23:404A. Abstract.
    

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				C. P. Cannon, A. Battler, R. G. Brindis, J. L. Cox, S. G. Ellis, N. R. Every, J. T. Flaherty, R. A. Harrington, H. M. Krumholz, M. L. Simoons, et al. 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., December 1, 2001; 38(7): 2114 - 2130. [Full Text] [PDF]

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				A. M. Lincoff, D. B. Mark, J. E. Tcheng, R. M. Califf, M. V. Bala, K. M. Anderson, L. Davidson-Ray, J. D. Knight, C. F. Cabot, and E. J. Topol Economic Assessment of Platelet Glycoprotein IIb/IIIa Receptor Blockade With Abciximab and Low-Dose Heparin During Percutaneous Coronary Revascularization : Results From the EPILOG Randomized Trial Circulation, December 12, 2000; 102(24): 2923 - 2929. [Abstract] [Full Text] [PDF]

				W. W. O'Neill, P. Serruys, M. Knudtson, G.-A. van Es, G. C. Timmis, C. van der Zwaan, J. Kleiman, J. Gong, E. B. Roecker, R. Dreiling, et al. Long-Term Treatment with a Platelet Glycoprotein-Receptor Antagonist after Percutaneous Coronary Revascularization N. Engl. J. Med., May 4, 2000; 342(18): 1316 - 1324. [Abstract] [Full Text] [PDF]

				W. S. Weintraub, S. Culler, S. J. Boccuzzi, J. R. Cook, A. S. Kosinski, D. J. Cohen, J. Burnette, and for the RESTORE Trial Study Group Economic impact of GPIIB/IIIA blockade after high-risk angioplasty: Results from the restore trial J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1061 - 1066. [Abstract] [Full Text] [PDF]

				N Robinson, K Barakat, and D Dymond Platelet IIb/IIIa antagonists followed by delayed stent implantation. A new treatment for vein graft lesions containing massive thrombus Heart, April 1, 1999; 81(4): 434 - 437. [Abstract] [Full Text]

				D. R. Holmes Jr., J. Hirshfeld Jr., D. Faxon, R. Vlietstra, A. Jacobs, S. B. King III, T. M. Bashore, N. D. Bridges, C. B. Higgins, L. F. Hiratzka, et al. ACC expert consensus document on coronary artery stents: Document of the American College of Cardiology J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1471 - 1482. [Full Text] [PDF]

				T. Mann, G. Cubeddu, J. Bowen, J. E. Schneider, M. Arrowood, W. N. Newman, M. J. Zellinger, and G. C. Rose Stenting in acute coronary syndromes: a comparison of radial versus femoral access sites J. Am. Coll. Cardiol., September 1, 1998; 32(3): 572 - 576. [Abstract] [Full Text] [PDF]

				H. V. Anderson, R. E. Jordan, and H. F. Weisman Concept and Clinical Application of Platelet Glycoprotein IIb/IIIa Inhibition with Abciximab (c7E3 Fab; ReoPro) for the Prevention of Acute Ischemic Syndromes Clinical and Applied Thrombosis/Hemostasis, October 1, 1997; 3(4): 256 - 266. [Abstract] [PDF]

				T. R. Investigators Effects of Platelet Glycoprotein IIb/IIIa Blockade With Tirofiban on Adverse Cardiac Events in Patients With Unstable Angina or Acute Myocardial Infarction Undergoing Coronary Angioplasty Circulation, September 2, 1997; 96(5): 1445 - 1453. [Abstract] [Full Text]

				The EPILOG Investigators Platelet Glycoprotein IIb/IIIa Receptor Blockade and Low-Dose Heparin during Percutaneous Coronary Revascularization N. Engl. J. Med., June 12, 1997; 336(24): 1689 - 1697. [Abstract] [Full Text] [PDF]

				ANTIPLATELET THERAPY COST-EFFECTIVE AFTER HIGH-RISK PTCA Journal Watch (General), September 3, 1996; 1996(903): 5 - 5. [Full Text]

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