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Cost-effectiveness of intensive atorvastatin therapy in secondary cardiovascular prevention in the United Kingdom, Spain, and Germany, based on the Treating to New Targets study |
Taylor DC, Pandya A, Thompson D, Chu P, Graff J, Shepherd J, Wenger N, Greten H, Carmena R, Drummond M, Weinstein MC |
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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 The study investigated the cost-utility of intensive (80mg) versus moderate (10mg) atorvastatin treatment to reduce cardiovascular events in patients with stable coronary heart disease in the UK, Spain, and Germany. The authors concluded that 80mg atorvastatin appeared to be a cost-effective approach for the secondary prevention of cardiovascular events across all three countries. The study methods were transparent and the analysis was comprehensive. The authors’ conclusions should be considered a fair assessment of their findings. Type of economic evaluation Cost-effectiveness analysis, cost-utility analysis Study objective The aim was to assess the cost-effectiveness of intensive versus moderate statin therapy that used atorvastatin to reduce cardiovascular events in patients with stable coronary heart disease in the UK, Spain, and Germany. Interventions The study compared daily intensive 80mg atorvastatin with moderate 10mg atorvastatin, a treatment that lowered low-density lipoprotein levels and consequently also reduced major cardiovascular events. Location/setting UK, Spain, and Germany/out-patient care. Methods Analytical approach:The analysis extrapolated outcome data beyond the end of a trial and used that data to populate a Markov model that evaluated the costs and outcomes over a lifetime horizon or maximum of 40 years. Data from other sources were used to inform mortalities beyond the end of the trial period. The study perspective was that of the payer in the respective countries.
Effectiveness data:The evidence for most clinical endpoints and model parameters was abstracted from a key randomised controlled trial; the Treating to New Targets (TNT) trial (LaRosa, et al. 2005, and Waters, et al. 2004, see 'Other Publications of Related Interest' below for bibliographic details). Survival probabilities were estimated from the published literature. The clinical estimates included first and second cardiovascular event rates, mortality and survival probabilities.
Monetary benefit and utility valuations:Utility valuations were derived from a US-based catalogue of preference-based scores (Sullivan, et al. 2005, see 'Other Publications of Related Interest' below for bibliographic details). The utility weight for revascularization was assumed to be equal to that of stable coronary heart disease.
Measure of benefit:The two measures of benefit used were life-years saved (LYS) and quality-adjusted life-years (QALYs), discounted at 3.5%.
Cost data:Direct medical costs were included in the analysis and involved the drug and event costs specific to each country. Full compliance with medication was assumed and acute event costs only (without follow-up) were used. Data on resources and valuations were abstracted from the literature. Annual drug and event costs for the respective countries were presented and referenced. Costs were provided in 2005 Euros (EUR) and discounted at an annual rate of 3.5%.
Analysis of uncertainty:Parameter uncertainty was addressed using one-way sensitivity analyses of the key variables (drug and event costs, event hazard ratios, mortality multipliers and utility weights). Results were illustrated in a tornado plot. Probabilistic sensitivity analyses were performed on all parameters and were illustrated in a cost-effectiveness acceptability curve. Results For all countries, costs, QALYs and LYS were higher for 80mg versus 10mg atorvastatin treatment. Discounted incremental mean QALYs were 0.18 (UK), 0.19 (Spain), and 0.20 (Germany). Discounted incremental mean costs were EUR 1,791 (UK), EUR 3,880 (Spain), and EUR 2,896 (Germany). The daily increased costs of atorvastatin treatment were offset by the treatment costs for cardiovascular events avoided.
The incremental cost-effectiveness ratios per QALY for atorvastatin 80mg compared with 10mg were: EUR 9,500 (UK); EUR 21,000 (Spain); and EUR 15,000 (Germany).
Sensitivity analyses showed that the base-case analysis results were most sensitive to daily drug costs of 10mg and 80mg atorvastatin and the hazard ratio of myocardial infarction events for patients who received 80mg atorvastatin. Atorvastatin 80mg was estimated to be cost-effective in 99.8% (UK), 86.0% (Spain), and 96.9% (Germany) of simulations at a threshold of EUR 30,000. Authors' conclusions The authors concluded that intensive lipid-lowering therapy using atorvastatin 80mg appeared to be a cost-effective approach for the secondary prevention of cardiovascular events in UK, Spain, and Germany. CRD commentary Interventions:The two strategies were clearly described. Database users should decide if atorvastatin at these dosages is available and relevant in their own setting, and whether there are other relevant interventions that may compete in value for money.
Effectiveness/benefits:The effectiveness data were derived from the TNT trial (a multinational randomised controlled trial) and are likely to provide internally valid evidence for this study. Full details of the TNT trial design were not reported, but the statistical approaches for treatment effects in the TNT trial were described. As details of the other literature relied on for model parameters were only referenced, users should refer to those papers for an assessment on the validity of the clinical endpoints. Utility values derived from a US population may not have been ideal for a European population, however, the source was from a national survey where the methods would be consistent across health conditions. The instruments or methods used for deriving the utility scores were not identified.
Costs:Direct medical costs were included in the analysis and appeared appropriate for the perspective taken. It was unclear whether costs for any adverse side-effects of intensive atorvastatin therapy were included. The sources of resource use, event and unit costs were clearly presented. Data on event costs were based on point estimates and their distributions were assigned and varied by using the standard deviation around the cost estimate.
Analysis and results:Incremental cost-effectiveness ratios were calculated and all results were fully reported and illustrated. Patient-level analyses for hazard ratios and probability estimates were thorough and transparent. Comparisons with other atorvastatin trial findings were discussed and the authors emphasised the unique nature of their study, which compared moderate and intensive therapy rather than a placebo comparator. Limitations of the study were acknowledged, including the sensitivity of the results to drug costs and treatment differences in mortality, use of US-based utility weights and assumptions used for long-term cardiovascular events for which there was no evidence.
Concluding remarks:The analytical approach and methods of the study were comprehensive and transparent. The conclusions reached by the authors reflected the scope of the analysis undertaken. Bibliographic details Taylor DC, Pandya A, Thompson D, Chu P, Graff J, Shepherd J, Wenger N, Greten H, Carmena R, Drummond M, Weinstein MC. Cost-effectiveness of intensive atorvastatin therapy in secondary cardiovascular prevention in the United Kingdom, Spain, and Germany, based on the Treating to New Targets study. European Journal of Health Economics 2009; 10(3): 255-265 Other publications of related interest LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. New England Journal of Medicine 2005; 352: 1425-1435.
Waters DD, Guyton JR, Herrington DM, McGowan MP, Wenger N, Shear C. TNT steering committee and investigators: treating to new targets (TNT) study: does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit? American Journal of Cardiology 2004; 93: 154-158.
Sullivan PW, Lawrence WF, Ghushchyan V. A national catalog of preference-based scores for chronic conditions in the United States. Medical Care. 2005; 43: 736-749. Indexing Status Subject indexing assigned by NLM MeSH Anticholesteremic Agents /administration & Atorvastatin Calcium; Cardiovascular Diseases /drug therapy /prevention & Cost-Benefit Analysis; Dose-Response Relationship, Drug; Europe; Heptanoic Acids /administration & Humans; Markov Chains; Pyrroles /administration & Quality-Adjusted Life Years; control; dosage /economics /therapeutic use; dosage /economics /therapeutic use; dosage /economics /therapeutic use AccessionNumber 22009102381 Date bibliographic record published 30/09/2009 Date abstract record published 11/11/2009 |
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