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Cost-effectiveness analysis of enoxaparin versus unfractionated heparin in the secondary prevention of acute coronary syndrome |
Brosa M, Rubio-Terres C, Farr I, Nadipelli V, Froufe J |
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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 Enoxaparin, a low molecular weight heparin (LMWH), was compared with unfractionated heparin (UFH) in the treatment of patients with acute coronary syndrome (ACS).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients with ACS. No further details of the population were provided. The study relied on data from two randomised controlled trials (RCTs), which were synthesised using a meta-analysis.
Setting The setting was secondary care. The economic study was conducted in Spain.
Dates to which data relate The dates to which the effectiveness and resource use data related were not stated. The price year was 2001.
Source of effectiveness data The effectiveness data were derived from two published RCTs (see Other Publications of Related Interest).
Modelling A model was constructed to incorporate the available information on the clinical and economic consequences (resource use) of treating patients with ACS. The purpose of the model was to calculate the average cost per proportion of patients without complications in each arm of the study. The total costs were obtained by applying local unit costs to the different medical resources utilised in each treatment group, while the number of patients free of ACS and unstable angina at the end of the study was estimated using a composite measure of the end points in the RCTs.
Outcomes assessed in the review The main outcomes assessed were death, myocardial infarction and unstable angina, for both the short- and long-term analyses.
Study designs and other criteria for inclusion in the review RCTs offering comparative data on the efficacy of enoxaparin and UHF were included.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Only two studies were included. Both were very large intention to treat (ITT) RCTs.
Methods used to judge relevance and validity, and for extracting data The methods were described elsewhere (see Other Publications of Related Interest).
Number of primary studies included Two RCTs and one meta-analysis of these RCTs were included.
Methods of combining primary studies The meta-analysis techniques used were reported elsewhere (see Other Publications of Related Interest). The main variables of effectiveness were patients surviving and patients surviving without cardiovascular complications (reinfarction and/or unstable angina). These were calculated from the results of the ITT analysis of both RCTs. Two sub-analyses with different time horizons were performed, at 30 days (ESSENCE) and 43 days (TIMI 11B) and at 1 year (ESSENCE) from initial treatment.
Investigation of differences between primary studies Results of the review ITT analysis (30 and 43 days):
death occurred in 3.8% of the UFH group and 3.4% of the enoxaparin group, (95% confidence interval, CI: 2.5 - 4.3);
myocardial infarction occurred in 5.5% of the UFH group and 4.5% of the enoxaparin group, (95% CI: 3.5 - 5.5); and
unstable angina occurred in 13.9% of the UFH group and 12.0% of the enoxaparin group, (95% CI: 10.4 - 13.5).
ITT analysis (1 year):
death occurred in 5.9% (UFH) and 5.4% (enoxaparin) of the patients (95% CI: 3.9 - 6.5);
myocardial infarction occurred in 8.4% (UFH) and 7.4% (enoxaparin) of the patients (95% CI: 5.4 - 8.4); and
unstable angina occurred in 21.3% (UFH) and 19.4% (enoxaparin) of the patients (95% CI: 16.0 - 20.7);
Measure of benefits used in the economic analysis The measure of benefits used in the economic analysis was the percentage of patients surviving and those surviving without cardiovascular complications.
Direct costs The direct costs to the hospital were included in the analysis. The quantities and the costs were analysed separately. The quantities were estimated using actual data from the two RCTs. The treatment costs and follow-up costs were also measured. The treatment costs were for UFH, enoxaparin and nursing time, whereas the follow-up costs were for diagnostic catheterisation, revascularisation procedures (CABG and PTCA) and hospitalisations (intensive care unit and ward). The costs reported appear to have been the average unit costs. The 95% CIs were also reported. No discounting was carried out since the resource use data were for one year. The price year was 2001.
Statistical analysis of costs The unit costs were treated stochastically and 95% CIs were reported.
Indirect Costs No indirect costs were reported
Sensitivity analysis A one-way sensitivity analysis was carried out on all variables. In addition, a number of scenarios were constructed on the basis of the minimum and maximum values of the health resource variables.
Estimated benefits used in the economic analysis Incremental benefits were calculated for the short term and one-year follow-up. In the short-term analysis, 80.1% of the patients in the enxaparin group survived free from cardiovascular complications versus 76.8% of those in the UFH group. The corresponding figures for the one-year follow-up were 67.7% (enoxaparin) and 64.4% (UFH), respectively. The incremental effectiveness was -3.3 for the short-term analysis and -3.4 for the long-term analysis.
Cost results In the short-term analysis, the total costs were Euro 6,678 in the enoxaparin group and Euro 7,126 in the UFH group. The incremental cost was Euro 448 per patient treated.
At the one-year follow-up, the total costs were Euro 10,020 (enoxaparin) and Euro 10,680 (UFH), respectively. The incremental cost was Euro 660 per patient treated.
Synthesis of costs and benefits The cost and benefits were combined by average cost-effectiveness ratios (CERs) and incremental cost-effectiveness ratios (ICERs).
In the short-term analysis, the CER was Euro 8,340 for enoxaparin and Euro 9,283 for UFH. The ICER "dominated" as the difference in effectiveness was less than 0 (-3.3% of patients without complications). In all one-way sensitivity analyses, enoxaparin resulted in a negative net cost, that is, a saving in comparison with the cost of UFH. In the scenario analysis, when a less favourable to enoxaparin scenario was tested, (i.e. the minimum values of the CI for the absolute risk of diagnostic catheterisations, revascularisation procedures and hospitalisations were considered simultaneously), the total costs of enoxaparin were higher than those of UFH.
At the one-year follow-up, the CER was Euro 14,794 for enoxaparin and Euro 16,594 for UFH. The ICER "dominated" as the difference in effectiveness was less than 0 (-3.4% of patients without complications).
Authors' conclusions The results of this study revealed that enoxaparin was less expensive and more effective than unfractionated heparin (UFH) in the treatment of patients with acute coronary syndrome (ACS).
CRD COMMENTARY - Selection of comparators A justification was given for the comparator used. Standard anticoagulation treatment for ACS involves the intravenous administration of UFH. You should decide if this is a widely used health technology in your own setting.
Validity of estimate of measure of effectiveness The authors did not state that a systematic review of the literature had been undertaken. However, the effectiveness data were obtained from two very large IIT RCTs (more than 7,000 patients in total). The effectiveness estimates were combined using meta-analysis techniques for the short-term effectiveness results, while the results from only one RCT were used for long-term effectiveness. The methods used to combine the studies, although reported elsewhere, seem to have been valid. On this basis, the effectiveness results appear valid and are unlikely to be biased. However, the authors recognised the low number of Spanish participants in the RCTs and the problem of generalising these international RCTs to Spain.
Validity of estimate of measure of benefit The estimation of benefit was obtained directly from the effectiveness analysis.
Validity of estimate of costs All the categories of costs relevant to the perspective adopted seem to have been included in the analysis, as this was based on the resource use in the RCTs. The costs and resource use were reported separately, which facilitates generalising to other settings. Moreover, the price year was reported, which will aid adjustments (i.e. inflation) in the future. The authors recognised that the observed results could be biased by differences in the care pattern of patients with ACS in Spain. This is because their study estimated the differences in revascularisation procedure rates, rehospitalisation and the average hospital stay (intensive care unit and ward) from the rates of the control group and the absolute risk reduction in these RCTs. However, the authors compared the data used with those from other Spanish studies and there appears to have been little difference.
Other issues The authors made appropriate comparisons of their findings with those from other studies for other countries. Differences in the results may have arisen from different practice patterns in each country. The issue of generalisability to other settings was addressed. A one-way sensitivity analysis and an extreme value (95% CI from RCT) scenario analysis were performed. The latter could provide a sense of the effect of variation in joint variables on the results. However, if primary data from RCTs were available, a probabilistic sensitivity analysis might be developed and a complete picture with ICERs and CIs could be presented. The study population comprised patients with ACS and the authors' conclusions were justified when applied to this population. The authors do not appear to have presented their results selectively.
Implications of the study Although the use of LMWH to treat patients with acute myocardial infarction and unstable angina is not yet widespread in Spain, the findings of this study reinforce the recommendations of recent Spanish guidelines on the care of patients and the use of antithrombolitic therapy in cardiology.
Source of funding Financed by a research grant from Aventis Pharma SA.
Bibliographic details Brosa M, Rubio-Terres C, Farr I, Nadipelli V, Froufe J. Cost-effectiveness analysis of enoxaparin versus unfractionated heparin in the secondary prevention of acute coronary syndrome. PharmacoEconomics 2002; 20(14): 979-987 Other publications of related interest Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractioned heparin for unstable coronary artery disease. New England Journal of Medicine 1997;337;447-52.
Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results from the Thrombolysis In Myocardial Infarction (TIMI) 11B trial. Circulation 1999;100:1593-1601.
Antman EM, Cohen M, Radley D, et al. Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction. TIMI 11B ESSENCE meta-analysis. Circulation 1999;100:1602-8.
Indexing Status Subject indexing assigned by NLM MeSH Acute Disease; Angioplasty, Balloon, Coronary /economics; Anticoagulants /economics /therapeutic use; Coronary Artery Bypass /economics; Coronary Disease /economics /prevention & Coronary Thrombosis /economics /prevention & Cost-Benefit Analysis; Enoxaparin /economics /therapeutic use; Heparin /economics /therapeutic use; Hospital Costs; Humans; Models, Economic; Randomized Controlled Trials as Topic; Spain; control; control /therapy AccessionNumber 22002008279 Date bibliographic record published 31/03/2004 Date abstract record published 31/03/2004 |
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