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Short- and long-term cost-effectiveness analysis of adding clopidogrel to standard therapy in acute coronary syndrome patients in Spain |
Badia X, Bueno H, Gonzalez Juanatey J R, Valentin V, Rubio M |
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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 Treatment with clopidogrel (clop) in combination with standard therapy (STh) was compared with STh alone (with acetylsalicylic acid) in patients with non-ST-elevation acute coronary syndrome (NSTEACS).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a hypothetical cohort of 1,000 patients with NSTEACS with a risk of suffering a cardiovascular event. A cardiovascular event was defined as a stroke, nonfatal acute myocardial infarction (AMI) or cardiovascular death.
Setting The study setting was secondary care. The economic study was conducted in Spain.
Dates to which data relate The effectiveness data were derived from studies published between 1999 and 2001. The price year was 2003.
Source of effectiveness data The effectiveness data were derived from a review of published studies.
Modelling No modelling was required for the short-term analysis, in which the costs and outcomes of both treatments were analysed at the end of the first year of the clinical CURE study (see 'Other Publications of Related Interest' below for bibliographic details). For the long-term analysis (i.e. lifetime of the patient with a maximum extrapolation of 30 years), a Markov model covering different health states reflecting clinical progress was adapted to the Spanish setting. The model consisted of six different health states:
the NSTEACS starting health state;
suffering an AMI in the first year;
suffering an AMI in the second and subsequent years;
suffering a stroke in the first year;
suffering a stroke in the second and subsequent years; and
death.
The cycle duration appears to have been one year. The model assumed that both groups received STh alone after the first year.
Outcomes assessed in the review The outcomes assessed were the relative risk of suffering an event in patients treated with clop+STh with respect to the STh group, and the probability of transition between the health states defined in the model.
Study designs and other criteria for inclusion in the review The authors did not clearly report the designs of the studies included in the review. Data on the effects of the treatment regimens on health were obtained from the CURE trial. To estimate the probability of transition between health states, empirical epidemiological data for the Swedish population were used. These data were derived from two registries, one recording hospital admissions and the other recording causes of death.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Three primary studies were included in the review.
Methods of combining primary studies Investigation of differences between primary studies Results of the review During the first year, the use of clop+STh in patients with NSTEACS was associated with a relative risk of suffering a cardiovascular event, with respect to the STh group, of 0.80 (95% confidence interval: 0.72 to 0.89).
The authors did not report the transition probabilities derived from the two registries.
Measure of benefits used in the economic analysis In the short-term model, the measure of benefits used in the economic analysis was the number of events avoided (i.e. AMI, stroke or cardiovascular death). Long-term effectiveness was measured as the number of life-years gained (LYGs). The health benefits were discounted at an annual rate of 3%.
Direct costs The direct costs included in the analysis were those to the health care system. For the short-term analysis, the costs associated with pharmacological treatment and patient management were obtained from the CURE study results. The resources directly associated with the management and treatment of patients in each health state were obtained from a review of the literature. Resource use associated with hospital stay, medication, and the tests and procedures required by patients with AMI were obtained from two registries of Spanish patients with acute coronary syndrome, with and without ST segment elevation. A group of three expert cardiologists was assembled to validate and to estimate the resource use not available from the literature. The unit costs were derived from a Spanish costs database, with those related to medications being taken from a pharmaceutical catalogue. Since the costs could be incurred over a long time period, future costs were appropriately discounted at an annual rate of 3%, as recommended by guides for the economic assessment of health care interventions. The study reported the average costs. The price year was 2003.
Statistical analysis of costs The costs were treated as point estimates (i.e. the data were deterministic).
Indirect Costs The indirect costs were not included.
Sensitivity analysis A series of one-way sensitivity analyses was performed on some of the variables used in the long-term model by:
varying the relative risk of suffering an event with clopidogrel compared with the control treatment;
not discounting the health benefits;
varying the number of patients using resources associated with each cost category by +/- 10%;
varying patient age;
varying the total health costs and the pharmaceutical cost of clopidogrel by +/- 10%; and
varying the time horizon.
Estimated benefits used in the economic analysis Over the first year, the mean number of events was 0.114 in the STh group and 0.093 in the clop+STh group. Therefore, the number of events avoided with clop+STh was 0.021.
After 30 years, the mean survival was 9.6526 years in the STh group and 9.7698 years in the clop+STh group. Therefore, the number of LYG with clop+STh was 0.1172.
Cost results Over the first year, the average cost per patient was EUR 6,712 in the STh group and EUR 7,073 in the clop+STh group. The incremental cost with clop+STh was EUR 361.
After 30 years, the average cost per patient was EUR 3,062 in the STh group and EUR 4,015 in the clop+STh group. The incremental cost with clop+STh was EUR 953.
Synthesis of costs and benefits The costs and benefits were combined using an incremental cost-effectiveness ratio (ICER). The additional cost per event avoided was estimated in the short-term model, whereas the additional cost per LYG was estimated in the long-term model. In the short term, the additional cost per event avoided when patients were treated with clop+STh over STh was EUR 17,190. In the long term, the additional cost per LYG was EUR 8,132.
The results of the sensitivity analysis showed that clop+STh became less cost-effective as the time horizon shortened, such that when the time horizon was 5 years the ICER increased to EUR 18,652. The results also showed that patient age and the relative risk of suffering an event when clop+STh was compared with STh were the variables with the greatest impact on the results.
Authors' conclusions The addition of clopidogrel (clop) to standard therapy (STh) during the first year of treatment is cost-effective, both in the short and long term.
CRD COMMENTARY - Selection of comparators The authors appropriately compared clop+STh with STh alone. However, they did not explicitly report what standard therapy entailed. You should decide if the comparator used represents current practice in your own setting.
Validity of estimate of measure of effectiveness The authors did not report that a systematic review of the literature had been undertaken to identify all relevant research and minimise biases. They used effectiveness data from three published studies. Data for the short-term model were obtained from the CURE study, whilst data for the long-term model were obtained from two Swedish studies. The authors did not provide details of the two Swedish studies, nor did they investigate whether the data were generalisable to a Spanish setting. The authors undertook a limited sensitivity analysis of the effectiveness data.
Validity of estimate of measure of benefit The estimation of benefits was modelled using a Markov model, which was appropriate for the study question. The use of LYG permits comparison with the results of other studies.
Validity of estimate of costs All the categories of cost relevant to the perspective adopted were included in the analysis. No major relevant costs appear to have been omitted. The authors reported the costs and the quantities separately, which will increase the generalisability of the results to other settings. Resource use was obtained from published sources, which were then supplemented and verified by a panel of cardiologists. A limited sensitivity analysis of resource use was carried out. The unit costs were derived from published sources, and an appropriate sensitivity analysis of the unit costs was conducted. Since the costs were accrued during a long time, discounting was necessary and was appropriately performed. The price year was reported, which will aid any possible inflation exercises.
Other issues The authors reported that their results were consistent with those from economic assessments of clopidogrel use in other countries, which had found that, during the first year of treatment, clop+STh was not only an effective but also a cost-effective treatment. The issue of generalisability to other settings was partly addressed through the sensitivity analysis. The authors do not appear to have presented their results selectively and their conclusions reflected the scope of the analysis.
The authors acknowledged several further limitations to their study. First, the data on the duration of the benefits of clop+STh treatment only referred to the first year. Second, the epidemiological data used to estimate the probability of transition between health states were obtained from a Swedish population since no such information was available for Spain. Third, the Markov model used did not take the possibility of transit between the health states pertaining to AMI and stroke into account. Finally, the study only included the direct health care costs.
Implications of the study The authors reported that the present study could be considered sufficiently robust to support the contention that clop+STh administration during the first year of treatment is cost-effective.
Source of funding Project was funded by Sanofi-Aventis and Bristol-Myers Squibb.
Bibliographic details Badia X, Bueno H, Gonzalez Juanatey J R, Valentin V, Rubio M. Short- and long-term cost-effectiveness analysis of adding clopidogrel to standard therapy in acute coronary syndrome patients in Spain. Revista Espanola de Cardiologia 2005; 58(12): 1385-1395 Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information
The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502.
Lamy A, Jonsson B, Weintraub W, et al. The cost-effectiveness of the use of clopidogrel in acute coronary syndromes in five countries based upon the CURE study. Eur J Cardiovasc Prev Rehabil 2004;11:460-5.
Annemans L, Lindgren P, Frei A, et al. Cost-effectiveness analysis of clopidogrel in acute coronary syndromes without ST-segment elevation: a five European countries analysis. Eur Heart J 2003;24:586.
Indexing Status Subject indexing assigned by NLM MeSH Cardiovascular Agents /economics /therapeutic use; Cost-Benefit Analysis; Humans; Models, Economic; Myocardial Ischemia /drug therapy /economics; Platelet Aggregation Inhibitors /economics /therapeutic use; Spain; Ticlopidine /analogs & Treatment Outcome; derivatives /economics /therapeutic use AccessionNumber 22006006504 Date bibliographic record published 28/02/2007 Date abstract record published 28/02/2007 |
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