|Long-term cost-effectiveness of clopidogrel in patients with acute coronary syndrome without ST-segment elevation in Germany
|Bruggenjurgen B, Lindgren P, Ehlken B, Rupprecht H J, Willich S N
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.
The study examined 1-year of clopidogrel added to acetylsalicylic acid (ASA) in patients with acute coronary syndrome without ST-segment elevation. Clopidogrel plus ASA was compared with ASA monotherapy.
Economic study type
The study population comprised a hypothetical cohort of patients with acute coronary syndrome without ST-segment elevation, who were at risk of cardiovascular events.
The setting was secondary care. The economic study was carried out in Germany.
Dates to which data relate
The effectiveness data were derived from studies published between 2000 and 2004. The costs were mainly derived from a German study published in 2005. Resource use is presumed to have referred to 2004. The price year was unclear, but it might have been 2005.
Source of effectiveness data
The clinical and epidemiological data used in the analysis were:
the probabilities of cardiovascular events including myocardial infarction (MI), ischaemic stroke (IS) and cardiovascular death with ASA;
the effectiveness of clopidogrel (cardiovascular event risk reduction for clopidogrel plus ASA with respect to ASA alone);
demographic data for patients with MI and IS;
mortality due to cardiovascular events; and
A published Markov model was adapted to the authors' context to assess the cost-effectiveness of the two approaches. The structure of the model was reported. The time horizon of the analysis was lifetime, and the model had annual cycles. Patients entered the Markov model in the at-risk state and moved across six possible health states. A description of transition pathways across the model health states was illustrated. The starting age in the model was 66 years.
Sources searched to identify primary studies
The probabilities of cardiovascular events were derived from the Swedish modelling study, which involved more than 4,000 patients admitted to Swedish hospitals between 1992 and 2000. The effectiveness of clopidogrel was obtained from the CURE trial, which showed a 20% relative reduction in cardiovascular events with respect to ASA alone. Overall mortality, life expectancy and mortality due to cardiovascular events were taken from Swedish hospital discharge records. Demographic data for German patients with MI and IS were obtained from German registries to adapt the previous Swedish data to the German setting.
Methods used to judge relevance and validity, and for extracting data
The primary studies were identified selectively in order to choose the more appropriate sources of data. For example, treatment effect was taken from a randomised controlled trial to ensure high internal validity. Epidemiological data, on the other hand, were taken from large registries and then validated to the German context.
Measure of benefits used in the economic analysis
The summary benefit measure was survival. This was estimated using the decision model. The life-years were discounted at an annual rate of 3%.
The analysis of the costs was carried out from the perspective of the health care payer. It included the costs of drugs, physician visits, hospitalisation, rehabilitation, reintegration, and nursing. The unit costs were presented for some events (MI and IS), but there was little information on other items or resource consumption. The cost of clopidogrel was estimated using average wholesale prices from the Rote Liste. Other direct medical costs were mainly derived from a German study published in 2005. Data on resource use were mainly obtained from a Delphi panel updated to 2004. Discounting was relevant, as the long-term costs were evaluated, and an annual rate of 3% was used. The price year was unclear, but it might have been 2005.
Statistical analysis of costs
The costs were treated deterministically.
Productivity costs were not considered.
A deterministic one-way sensitivity analysis was carried out to investigate the robustness of the base-case findings to variations in clinical and economic inputs, such as risk reduction (varied around the published confidence interval), drug prices including rebates and co-payments, follow-up treatment costs (-50% to +100% of base-case estimates), and discount rates for both the costs and benefits.
Estimated benefits used in the economic analysis
The long-term benefit of 1-year of treatment was 9.02 years with clopidogrel added to ASA and 8.89 years with ASA monotherapy. The difference in survival was 0.13 years.
The long-term cost of 1-year of treatment was EUR 8,953 with clopidogrel added to ASA and EUR 8,548 with ASA monotherapy. The difference in cost was EUR 405.
Synthesis of costs and benefits
Incremental cost-effectiveness ratios (ICERs) were calculated in order to combine the costs and benefits of the two treatment strategies.
Under base-case assumptions, the ICER with clopidogrel added to ASA over ASA alone was EUR 3,113.
The sensitivity analysis corroborated the main conclusions, showing that the ICER ranged from EUR 1,338 (28% risk reduction) to EUR 9,322 (only 10% risk reduction). Variations in other clinical and economic inputs did not alter the base-case findings.
One-year treatment with clopidogrel added to acetylsalicylic acid (ASA) in patients with acute coronary syndrome without ST-segment elevation was cost-effective in comparison with ASA monotherapy in Germany.
CRD COMMENTARY - Selection of comparators
The rationale for the choice of the comparators was clear. The new drug was compared with ASA monotherapy, which is likely to have represented the current pattern of care for this specific patient population in the authors' context. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness
The clinical data were derived from published studies. No systematic search for data was reported. In effect, the primary studies appear to have been selected ad hoc from among those available, in order to identify clinical sources useful to the current study. Swedish data, which were presumably considered as the most reliable, were adapted to the German setting. The authors demonstrated that the epidemiological characteristics of the two countries were similar. Treatment effectiveness was derived from a clinical trial, which usually represents a robust source of data. The impact of the variability in this key parameter on the final cost-effectiveness results was analysed in a univariate sensitivity analysis.
Validity of estimate of measure of benefit
The estimation of health benefits (survival) was modelled using the Markov model. An appropriate discount rate was used and the impact of using alternative rates was investigated in the sensitivity analysis.
Validity of estimate of costs
The analysis of the costs was consistent with the authors' stated perspective. The costs associated with productivity losses were not included as the starting age of the patient population was 66 years and, in Germany, people of 65 years of age and older are retired. Data on resource consumption came mainly from a panel of experts, but details on the process used to derive these data were not given. The costs came from different German sources, which might be appropriate. The impact of changes in key cost-drivers was investigated in the sensitivity analysis. Statistical analyses were not performed. The costs were discounted at an annual rate of 3%, which would appear to be appropriate given the German health care setting. The price year was not explicitly stated.
The authors stated that their findings were similar to those from other European countries (Scandinavian countries, Switzerland and Austria) and the USA. The issue of the generalisability of the study results to other settings was partially addressed in the sensitivity analysis, which enhances the external validity of the study. The authors' conclusions would appear to be an adequate reflection of the scope of the analysis. A potential limitation of the analysis was the use of Swedish clinical data. However, the authors stated that the two epidemiological settings were comparable in terms of the characteristics of patients with cardiovascular disease. It was also highlighted that the duration of clopidogrel treatment might be an uncertain issue. The patient population considered in the current economic evaluation represented those patients enrolled in the CURE trial, thus caution will be required when extrapolating the results of the analysis to other patient groups, such as patients with severe heart failure or patients on long-term anticoagulant therapy.
Implications of the study
The study results support the use of clopidogrel added to ASA for the treatment of patients with acute coronary syndrome without ST-segment elevation.
Source of funding
Supported by Aventis Pharma Deutschland.
Bruggenjurgen B, Lindgren P, Ehlken B, Rupprecht H J, Willich S N. Long-term cost-effectiveness of clopidogrel in patients with acute coronary syndrome without ST-segment elevation in Germany. European Journal of Health Economics 2007; 8: 51-57
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 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.
Weintraub WS, Mahoney EM, Lamy A, et al. Long-term cost-effectiveness of clopidogrel given for up to one year in patients with acute coronary syndromes without ST-segment elevation. JACC 2005;45:838-45.
Lindgren P, Jonsson B, Yusuf S. Cost-effectiveness of clopidogrel in acute coronary syndrome in Sweden: a longterm model based on the CURE trial. J Intern Med 2004;255:562-70.
Subject indexing assigned by CRD
Coronary Disease; Cost-Benefit Analysis; Germany; Markov Chains; Myocardial Infarction; Ticlopidine; Treatment Outcome
Date bibliographic record published
Date abstract record published