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Economic evaluation of ezetimibe combined with simvastatin for the treatment of primary hypercholesterolaemia |
van Nooten F, Davies GM, Jukema JW, Liem AH, Yap E, Hu XH |
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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. CRD summary This study aimed to assess the cost-effectiveness of ezetimibe in combination with simvastatin, for the treatment of patients with primary hypercholesterolaemia. The authors concluded that ezetimibe plus simvastatin appeared to be cost-effective for these patients who had not achieved their low-density lipoprotein cholesterol targets on statin monotherapy, in the Netherlands. It appeared to be cost saving and more effective than atorvastatin. The methods were satisfactory, and they and the results were reported sufficiently. The authors’ conclusions appear to be appropriate. Type of economic evaluation Cost-effectiveness analysis, cost-utility analysis Study objective The objective was to assess the cost-effectiveness of ezetimibe in combination with simvastatin for the treatment of patients with primary hypercholesterolaemia. Interventions Two treatment scenarios were investigated, one based on Dutch Guidelines and the other on the EASEGO study. The Dutch Guidelines were that patients not achieving their goal of a low-density lipoprotein (LDL) cholesterol level of less than 2.5 millimoles per litre (mmol/L) while on simvastatin 40mg were given either ezetimibe 10mg plus simvastatin 40mg, or atorvastatin 40mg. The EASEGO scenario was that patients not achieving their goal of LDL cholesterol level of less than 2.5mmol/L, while on simvastatin 20mg or atorvastatin 10mg were given either ezetimibe 10mg plus simvastatin 20mg, or atorvastatin 20mg or simvastatin 40mg. Location/setting Netherlands/primary care. Methods Analytical approach:A published state-transition Markov model (Cook, et al. 2004, see 'Other Publications of Related Interest' below for bibliographic details) was used to combine the clinical and economic evidence from published literature to evaluate the cost-effectiveness of the treatment options. A lifetime horizon was adopted. The authors stated that the perspective was societal.
Effectiveness data:The clinical data came from published clinical and epidemiological studies, relevant to the Dutch setting, including the Dutch EASEGO study, the Dutch Guideline on Cardiovascular Risk Management 2006, and the Dutch Healthcare Performance Report 2008. The key clinical parameters were the change in LDL cholesterol level and the risk of cardiovascular disease events.
Monetary benefit and utility valuations:The utility estimates were from published age-specific Dutch values for the European Quality of life (EQ-5D) questionnaire.
Measure of benefit:The benefit measure was the number of quality-adjusted life-years (QALYs), which were discounted at an annual rate of 1.5%. Life-years were reported.
Cost data:The analysis included the direct medical costs of statin treatment. These included the costs of statin monotherapy and combination therapy, which were from Dutch medication prices (the Z-index), and those of cardiovascular events and monitoring, which were from a range of published sources. All costs were presented in Euros (EUR). Future costs were discounted at an annual rate of 4%.
Analysis of uncertainty:A univariate sensitivity analysis was performed by varying the key parameters across wide ranges. A probabilistic sensitivity analysis was carried out and the results were presented in a cost-effectiveness acceptability curve. Results In the EASEGO scenario, the discounted cost was EUR 18,941 for ezetimibe plus simvastatin, EUR 18,220 for atorvastatin, and EUR 13,495 for simvastatin. In the Dutch Guideline scenario the discounted cost was EUR 18,983 for ezetimibe plus simvastatin, and EUR 19,741 for atorvastatin.
Combination therapy was associated with more QALYs in both scenarios; ezetimibe plus simvastatin produced 12.06 QALYs, atorvastatin and simvastatin produced 11.85 QALYs, in each scenario.
In the EASEGO scenario, the cost-effectiveness ratio of combination therapy was EUR 3,497 per QALY gained compared with atorvastatin and EUR 26,417 per QALY gained compared with simvastatin. In the Dutch Guideline scenario, ezetimibe plus simvastatin was dominant, as it was more effective and less costly, compared with atorvastatin.
The sensitivity analysis showed that changing the assumptions had little impact on the results. Probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of EUR 30,000 QALY, ezetimibe plus simvastatin was cost-effective in 50% of simulations, compared with simvastatin, for the EASEGO scenario, it was cost-effective compared with atorvastatin, and in the Dutch Guideline scenario, it was dominant, compared with atorvastatin. Authors' conclusions The authors concluded that ezetimibe plus simvastatin appeared to be cost-effective for patients with primary hypercholesterolaemia, who had not achieved their LDL cholesterol target on statin monotherapy, in the Netherlands. It appeared to be cost saving and more effective than atorvastatin. CRD commentary Interventions:The interventions were clearly defined and they were appropriate comparators, as they included Dutch guidelines, which were the usual practice, and an alternative, which was relevant to the Netherlands. These strategies are likely to be relevant in other settings.
Effectiveness/benefits:The use of Dutch sources for the clinical estimates was appropriate, due to their relevance to the Dutch health care system. Some details of these studies and their references were provided. The literature review methods were not reported, making it impossible to ascertain if the best available evidence was used. The source for the utility data and the instrument used to elicit them were reported. QALYs and life-years were appropriate benefit measures, given the impact of the treatment on quality of life and survival.
Costs:The perspective was clearly defined as societal, but the authors excluded the indirect costs. It appears that all the relevant costs for a health care provider perspective were considered. The cost estimates were given in a table and referenced, and the discount rate was provided. The price year was not reported, which may hamper future inflationary exercises.
Analysis and results:The selected evidence on costs and outcomes was synthesised in a decision-analytic model. The analytic approach was satisfactorily reported, with a description of the model structure and diagrams. The results were reported clearly and in full. Appropriate one-way sensitivity analyses were performed and reported, and probabilistic sensitivity analysis was used to fully capture the parameter uncertainty. In general, the reporting was good, including the base-case estimates of the effectiveness and costs. The authors acknowledged and highlighted some limitations to their study.
Concluding remarks:: The methods were satisfactory, and they and the results were reported sufficiently. The authors’ conclusions appear to be appropriate. Funding Funded by Merck Sharpe and Dohme/Schering-Plough Pharmaceuticals, the Netherlands, manufacturers of ezetimibe and simvastatin. Bibliographic details van Nooten F, Davies GM, Jukema JW, Liem AH, Yap E, Hu XH. Economic evaluation of ezetimibe combined with simvastatin for the treatment of primary hypercholesterolaemia. Netherlands Heart Journal 2011; 19(2): 61-67 Other publications of related interest Cook JR, Yin D, Alemao E, et al. Development and validation of a model to project the long-term benefit and cost of alternative lipid-lowering strategies in patients with hypercholesterolaemia. Pharmacoeconomics 2004; 22(Supplement 3): 37-48. Indexing Status Subject indexing assigned by CRD MeSH Azetidines; Cost-Benefit Analysis; Drug Therapy, Combination; Humans; Hypercholesterolemia; Markov Chains; Netherlands; Quality-Adjusted Life Years; Simvastatin AccessionNumber 22011000916 Date bibliographic record published 06/07/2011 Date abstract record published 21/12/2011 |
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