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| An economic evaluation of atorvastatin for primary prevention of cardiovascular events in type 2 diabetes |
| Ramsey S D, Clarke L D, Roberts C S, Sullivan S D, Johnson S J, Liu L Z |
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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 determined the cost-effectiveness of atorvastatin, compared with no statin therapy, for the primary prevention of cardiovascular (CV) events in patients with Type 2 diabetes, normal low-density lipoprotein cholesterol, no history of CV disease, but one additional risk factor for CV disease. The authors concluded that atorvastatin was a cost-effective strategy from the perspective of the US payer, especially over time, with cost-savings after approximately 10 years. The quality of the study methodology was good, with appropriate sources and clear presentation of the results. Type of economic evaluation Study objective The objective of the study was to determine the cost-effectiveness of atorvastatin in comparison with no statin therapy for the primary prevention of cardiovascular (CV) events in patients with Type 2 diabetes, normal low-density lipoprotein cholesterol, no history of CV disease, but one additional risk factor for CV disease (retinopathy, albuminuria, current smoking or hypertension). Interventions The study compared atorvastatin (10 mg/day) with no lipid-lowering therapy for the primary prevention of CV events in patients with Type 2 diabetes. Location/setting USA. Primary/community care. Methods Analytical approach:A Markov model was developed in order to determine the costs and benefits of the alternative treatments under examination. Three different time horizons were considered in the analysis: 5, 10 and 25 years. The authors stated that the perspective of the health care payer was adopted.
Effectiveness data:The clinical estimates used in the decision model were based on a selection of known relevant studies. Data on treatment effect (presented as hazard ratios) were derived from the Collaborative Atorvastatin Diabetes Study (CARDS), a prospective, double-blind, multi-centre randomised controlled trial (RCT) with a median follow-up of 3.9 years. Transition probabilities among health states were calculated from a risk equation reported in the UK Prospective Diabetes Study, recalibrated to reflect the probability of events in the CARDS trial. Patient characteristics were obtained from the US National Health and Nutrition Survey, a nationally representative survey using health interview and physical examination data. These key sources were supplemented with data from other studies, details of which were not fully reported.
Monetary benefit and utility valuations:The health state utilities used in the model were based on a published study that used the time trade-off method in a sample of 519 patients with diabetes and no complications. The values associated with complications were obtained from a cross-sectional survey of 6,361 Type 2 diabetes patients (self-reported values).
Measure of benefit:Several benefit measures were estimated using the decision model, then combined with the costs. Specifically, these were CV events avoided, disease-free life-years (DFLYs), life-years (LYs) and quality-adjusted life-years (QALYs). An annual rate of 3% was applied.
Cost data:The economic analysis included the costs of atorvastatin and all health care costs associated with CV events (angina, myocardial infarction and stroke). Adverse events associated with atorvastatin were not included as they were negligible in the CARDS trial. The cost of atorvastatin was based on the wholesale acquisition cost, but it was assumed that the generic price (simvastatin) would be applied since generic versions would become available within 6 months of losing patent protection in early 2010. The health care costs of CV events were based on an incidence-based, multistate insurance claims analysis of patient charts. The long-term costs were discounted at an annual rate of 3%. The price year was 2005 and the costs were in US dollars ($).
Analysis of uncertainty:The issue of uncertainty was addressed by carrying out a one-way sensitivity analysis of all model inputs. The ranges of values used were based on confidence intervals and standard errors derived from published sources. A probabilistic sensitivity analysis was also undertaken in order to generate cost-effectiveness acceptability curves; stochastic distributions were given to all model parameters. Results The additional cost per person with atorvastatin over no statin was $1,730 after 5 years and $187 after 10 years, while atorvastatin was cost-saving (-$4,936) after 25 years.
Atorvastatin reduced the number of events per person and improved the number of DFLYs per person, regardless of the time horizon.
The additional LYs gained with atorvastatin were 0.01 after 5 years, 0.05 after 10 years and 0.30 after 25 years.
The additional QALYs gained with atorvastatin were 0.01 after 5 years, 0.05 after 10 years and 0.28 after 25 years.
The incremental cost per LY gained with atorvastatin was $135,901 after 5 years and $3,573 after 10 years.
The incremental cost per QALY gained with atorvastatin was $137,276 after 5 years and $3,640 after 10 years.
After 25 years, atorvastatin was dominant (both more effective and less expensive) in comparison with no statin therapy. Dominance started at approximately 11 years.
The sensitivity analysis identified the most influential model inputs, such as hazards ratios for CV events, adherence rate and drug costs (in the pre-generic era). The probabilistic sensitivity analysis suggested that, at a payer's willingness-to-pay of $4,566 per QALY gained, there was a 50% probability that atorvastatin would be cost-effective over 10 years. Authors' conclusions The authors concluded that the use of atorvastatin for the primary prevention of CV events in patients with Type 2 diabetes and no history of CV disease was a cost-effective strategy from the perspective of the US payer. The cost-effectiveness of atorvastatin improved over time and, after 25 years from commencement of treatment, atorvastatin was more effective and less expensive than no prevention strategy. However, atorvastatin was not cost-effective in the short term from the perspective of the health care payer. CRD commentary Interventions:The selection of the comparator (i.e. no statin) appears to have been appropriate as it represented the current pattern of care for patients with no CV history. The study results may not be applicable to other statins because of the existence of a class effect and differences in acquisition costs.
Effectiveness/benefits:The clinical data were obtained from a selection of known sources. Most of the evidence came from a large RCT, the design of which should ensure the robustness of the clinical estimates. Strengths of this study were the randomised process of patient allocation to treatment groups, the double-blind design, the appropriate length of follow-up and the large sample size. These estimates were augmented with other published sources such as national databases, which make the study population representative of the wider patient population under examination. Nevertheless, the authors pointed out the uncertainty surrounding some estimates. The multiple benefit measures are appropriate, not only because they are validated measures such as QALYs, but also because they can be compared with the benefits of other health care interventions.
Costs:The analysis of the costs was consistent with the authors' stated perspective, in terms of both the types of costs included and the sources used. The authors justified their exclusion of costs associated with adverse events. The costs were presented as macro-categories and a breakdown of detailed cost items was not given. This may limit the external validity of the analysis. However, the costs of CV complications are often presented as macro-categories in other economic evaluations. The price year was reported, which will help if replicating the analysis in other time periods.
Analysis and results:The synthesis of the costs and benefits was appropriate and the results of both the base-case and sensitivity analyses were presented clearly. The issue of uncertainty was satisfactorily addressed using both deterministic and probabilistic sensitivity analyses. Details of the decision model were presented clearly in terms of its structure, health states and main patterns of care. The generalisability of the study results to other settings was not explicitly discussed, although extensive sensitivity analyses were also conducted on economic items.
Concluding remarks:The quality of the study methodology was good, with satisfactory reporting of the methods and results. Clear information on the sources used and the approaches used to derive the costs and benefits of the interventions was provided. The authors' conclusions appear valid. Funding Funding received from Pfizer Inc. Bibliographic details Ramsey S D, Clarke L D, Roberts C S, Sullivan S D, Johnson S J, Liu L Z. An economic evaluation of atorvastatin for primary prevention of cardiovascular events in type 2 diabetes. PharmacoEconomics 2008; 26(4): 329-339 Other publications of related interest Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): a multicentre randomised placebo-controlled trial. Lancet 2004;364:685-96.
Raikou M, McGuire A, Colhoun HM, et al. Cost-effectiveness of primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes: results from the Collaborative Atorvastatin Diabetes Study (CARDS). Diabetologia 2007;50:733-40.
Stevens RJ, Kothari V, Adler AI, et al. The UKPDS risk engine: a model for the risk of coronary heart disease in type II diabetes (UKPDS 56). Clin Sci 2001;101:671-9. Indexing Status Subject indexing assigned by NLM MeSH Cardiovascular Diseases /economics /epidemiology /prevention & Cost-Benefit Analysis; Diabetes Mellitus, Type 2 /complications; Female; Heptanoic Acids /economics /therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /economics /therapeutic use; Male; Middle Aged; Models, Economic; Pyrroles /economics /therapeutic use; Quality-Adjusted Life Years; control AccessionNumber 22008100408 Date bibliographic record published 09/08/2008 Date abstract record published 30/09/2008 |
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