Health technology Abciximab use in high-risk patients undergoing percutaneous transluminal coronary angioplasty.

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1 Costs and effects in therapy for acute coronary syndromes: the case of abciximab in highrisk patients undergoing percutaneous transluminal coronary angioplasty in the EPIC study van Hout B A, Bowman L, Zelinger D J, Simoons M L Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Abciximab use in high-risk patients undergoing percutaneous transluminal coronary angioplasty. Type of intervention Treatment. Economic study type Cost-effectiveness analysis. Study population Patients scheduled to undergo coronary angioplasty or artherectomy in high-risk situations involving severe unstable angina, evolving acute myocardial infarction (MI), or high-risk coronary morphologic characteristics. Setting Secondary care. The economic study was conducted in the Netherlands and the USA. Dates to which data relate Effectiveness data were taken from the EPIC trial (Evaluation of 7E3 for the Prevention of Ischemic Complications), the first results of which were published in 1994, with 1-year results published in Cost estimates were derived from a previous analysis published by the authors in The price year was Source of effectiveness data The bulk of the effectiveness data came from the EPIC trial, with 1-year results published in Estimates of life expectancy were taken from the GUSTO trial, published in Link between effectiveness and cost data Costing was undertaken retrospectively on the same patient sample as that used in the effectiveness analysis, using previously published unit costs. Study sample The study included 2,099 patients scheduled to undergo coronary angioplasty or artherectomy in high-risk situations involving severe unstable angina, evolving acute MI, or high-risk coronary morphologic characteristics. Patients were allocated to 3 treatment arms: abciximab bolus plus abciximab 12-hour infusion (n=708); Page: 1 / 5

2 abciximab bolus plus placebo infusion (n=695); and placebo bolus plus placebo infusion (n=696). Details of power calculations relating to the sample size and comparability of groups are published elsewhere. The present analysis was based on 1-year findings. Study design The EPIC study was a prospective, randomised, double-blind, placebo-controlled United States multicentre trial. Analysis of effectiveness The analysis was based on intention to treat. The main health outcomes used in the analysis at primary end point were: death from any cause, non-fatal MI, emergency coronary artery bypass grafting (CABG), emergency PTCA, stent placement because of treatment failure and balloon-pump insertion to relieve refractory ischaemia. Secondary end points included non-emergency revascularisation. Bleeding risk was analysed by distinguishing among major, minor and insignificant bleeding. Effectiveness results The volume of events was as follows for all patients for placebo versus abciximab groups: initial PTCA 682 (689), c7e3 0(678), death 31(30), MI 68(46), CABG 89(76), PTCA 196(144), major bleeding 23(75). For unstable angina patients results were as follows for the placebo versus abciximab groups: initial PTCA 154(160), c7e3 0(156), death 10(3), MI 16(6), CABG 22(16), PTCA 38(36) and major bleeding 7(16). Clinical conclusions Compared with placebo treatment, abciximab treatment was associated with a significant reduction in incidence of MI and revascularisation after 1 year, with a trend towards increased survival being observed. An excessive risk of bleeding in patients who received abciximab was also observed. Estimates of effectiveness and key assumptions It was assumed that each survivor had a life expectancy of 15 years, the life expectancy estimate used by Mark et al. for patients in the Global Use of Strategy to Open Occluded Arteries (GUSTO) study. Measure of benefits used in the economic analysis The short-term benefits used in the economic analysis were survival, MI-free survival and event-free survival, with events being defined as death, MI and revascularisation. Life-years gained were used for the long-term analysis. Direct costs Direct health service costs were considered in the analysis. Costs during the first year after study treatment were calculated per patient by multiplying the number of events per patient by unit costs per event, where event was defined as any of the following: initial procedure, major bleeding, MI, PTCA or CABG. Unit cost estimates were derived by a study published by the authors in 1994, which included the distinction between Q-wave MI and costs for non-q-wave MI. All costs were expressed in 1994 Dutch guilders and were discounted at 5% per year. Statistical analysis of costs Not detailed as such in this paper. Uncertainties relating to incremental cost-effectiveness ratios were presented in the form of probability ellipses on the cost-effectiveness plane. Page: 2 / 5

3 Indirect Costs Indirect costs were not included. Currency Dutch guilders (Dfl). For 1994, US$1.00 = Dfl 1.81 and for 1997, US$1.00 = Dfl Estimated benefits used in the economic analysis For all patients, benefits were as follows, for placebo versus abciximab groups: 1-year survival, placebo 95.55% versus abciximab 95.76%, 1-year MI-free survival, placebo 86.78% versus abciximab 90.68% and 1-year event free survival, placebo 61.35% versus abciximab 68.08%. For unstable angina patients the results were: 1-year survival, placebo 93.59% versus abciximab 98.18%, 1-year MIfree survival, placebo 86.42% versus abciximab 95.76% and 1-year event free survival, placebo 60.26% versus abciximab Based on the life-expectancy of 15 years for patients with MI used in the GUSTO trial, average life-years gained in the EPIC patients were estimated at 0.03 years per patient for all patients and 0.69 years per patient for patients with unstable angina. Cost results Total costs of events after 1 year were as follows (Dfl): all patients, placebo Dfl 22,432 versus abciximab Dfl 22,681; unstable angina patients, placebo Dfl 22,604 versus abciximab Dfl 22,132. Synthesis of costs and benefits For all patients, costs were as follows for placebo versus abciximab groups: cost per additional survivor, placebo Dfl 23,477 versus abciximab Dfl 23,684, cost per MI-free survivor, placebo Dfl 25,849 versus abciximab Dfl 25,012, and cost per-event free survivor, placebo Dfl 36,563 versus abciximab Dfl 33,315 For unstable angina patients: cost per additional survivor, placebo Dfl 24,152 versus abciximab Dfl 22,541, cost per MI-free survivor, placebo Dfl 26,714 versus abciximab Dfl 23,112, and cost per-event free survivor, placebo Dfl 37,513 versus abciximab Dfl 31,211. Costs per life-year gained were Dfl 16,493 for all patients and Dfl 3,971 for patients with unstable angina. Authors' conclusions A comprehensive cost-effectiveness evaluation of abciximab use would require careful consideration of use, outcomes and costs of other large-scale trials, in addition to EPIC, that have been performed with this agent. Page: 3 / 5

4 CRD COMMENTARY - Selection of comparators The reason for the choice of the placebo-controlled treatment alternative was clear, as this is widely used for assessing the cost-effectiveness of new drugs. You, as a database user should consider if the same applies to your own environment. Validity of estimate of measure of benefit The prospective and randomised character of the study reinforces the validity of benefit measures used. Validity of estimate of costs The statistical analysis of costs was not detailed in this paper; costs were discounted at 5% per annum and the numbers of events as well as costs/event were detailed. The authors illustrated and utilised the cost-effectiveness plane and ellipse curves to show treatment effects and average and incremental cost-effectiveness ratios, and their use in addressing uncertainty. Other issues The authors acknowledged the fact that a certain degree of uncertainty was present in every clinical trial, linked mainly to the short time span of the analysis and the difficulty of identifying relevant analysis subgroups. Implications of the study The results of other large-scale trials of this agent should be considered by health care decision-makers. The present study was perhaps primarily focussed on the methodology of economic evaluations but did undertake a credible analysis to illustrate the issues around the use of abciximab in high-risk patients undergoing percutaneous transluminal coronary angioplasty. Source of funding None stated. Bibliographic details van Hout B A, Bowman L, Zelinger D J, Simoons M L. Costs and effects in therapy for acute coronary syndromes: the case of abciximab in high-risk patients undergoing percutaneous transluminal coronary angioplasty in the EPIC study. American Heart Journal 1998; 135(4): S98-S106 PubMedID Other publications of related interest Topol E J, Califf R M, Weisman H F et al. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis; results at six months. Lancet 1994;343: The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in highrisk coronary angioplasty. New England Journal of Medicine 1994;330: Topol E J, Ferguson J J, Weisman H F et al. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin B3 blockade with percutaneous coronary intervention. JAMA 1997;278: Van Hout B A, Al M, Gordon G S, Rutten F F H. Costs, effects and C/E-ratios alongside a clinical trial. Health Economics 1994;3: Mark D B, Hlatky M A, Califf R M et al. Cost effectiveness of thrombolytic therapy with tissue plasminogen activator Page: 4 / 5

5 Powered by TCPDF ( as compared with streptokinase for acute myocardial infarction. New England Journal of Medicine 1995;332: Indexing Status Subject indexing assigned by NLM MeSH Acute Disease; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal /economics /therapeutic use; Coronary Disease /economics /therapy; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Humans; Immunoglobulin Fab Fragments /economics /therapeutic use; Infusions, Intravenous; Platelet Aggregation Inhibitors /economics /therapeutic use; Prospective Studies; Risk Factors; Treatment Outcome; United States AccessionNumber Date bibliographic record published 31/05/2001 Date abstract record published 31/05/2001 Page: 5 / 5