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Cost-effectiveness of losartan versus atenolol in treating hypertension: an analysis of the LIFE study from a Swiss perspective |
Szucs T D, Burnier M, Erne P |
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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 The study compared the use of an angiotensin II receptor blocker (losartan) with the use of a beta-blocker (atenolol) in patients with essential hypertension.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a hypothetical cohort of 1,000 60-year-old patients with essential hypertension.
Setting The study setting was secondary care. The economic study was undertaken in Switzerland.
Dates to which data relate The effectiveness data were derived from a study published in 2002. The price year was 2003.
Source of effectiveness data The effectiveness data were derived from a single study, the Losartan Intervention For Endpoint Reduction (LIFE; Dahlof et al. 2002, see 'Other Publications of Related Interest' below for bibliographic details).
Link between effectiveness and cost data The costing study was undertaken retrospectively on the same patient population as that used in the effectiveness study.
Study sample The authors only provided a brief summary of the LIFE study used to determine the effectiveness of atenolol and losartan. A total of 9,138 patients were included in the LIFE study, of which 59% were male. The average age of patients in both the losartan and atenolol groups was 66.9 years. Further details on the study sample were given in the parent study (Dahlof et al. 2002).
Study design The LIFE study was a double-blind, randomised, parallel-group trial undertaken in six European countries and the USA. The mean follow-up in the LIFE study was 4.8 years. The authors reported that the overall drop-out rates were 2.2% for losartan-treated patients and 2.0% for atenolol-treated patients. Adverse events causing drop-out from the study were more common in the atenolol group (18%) than in the losartan group (12%). Further details on the study design were given in the parent study (Dahlof et al. 2002).
Analysis of effectiveness The primary objective of the LIFE study was to determine whether there was a difference in primary cardiovascular events between losartan and atenolol. The primary health outcomes were cardiovascular mortality, stroke and myocardial infarction. Also assessed in the trial was new onset diabetes mellitus. Further details on the analysis of effectiveness undertaken in the LIFE study were given in the parent study (Dahlof et al. 2002).
Effectiveness results The results of the LIFE study showed the following.
The event-free survival rate was 85.5% (35.6 per 1,000 patient-years) in the losartan group and 83.6% (31.4 per 1,000 patient-years) in the atenolol group, (p=0.04).
The rate of cardiovascular mortality was 9.2 per 1,000 patient-years in the losartan group and 10.6 per 1,000 patient-years in the atenolol group (adjusted hazard ratio 0.89, 95% confidence interval, CI: 0.73 - 1.07).
The rate of stroke was 10.8 per 1,000 patient-years in the losartan group and 14.5 per 1,000 patient-years in the atenolol group (adjusted hazard ratio 0.75, 95% CI: 0.63 - 0.89).
The rate of myocardial infarction was 9.2 per 1,000 patient-years in the losartan group and 8.7 per 1,000 patient-years in the atenolol group (adjusted hazard ratio 1.07, 95% CI: 0.88 - 1.31).
The rate of new onset diabetes mellitus was 13.0 per 1,000 patient-years in the losartan group and 17.4 per 1,000 patient-years in the atenolol group (adjusted hazard ratio 0.75, 95% CI: 0.63 - 0.88).
Clinical conclusions The results of the LIFE study showed losartan to be significantly more effective than atenolol in terms of the event-free (i.e. stroke and myocardial infarction) survival rate.
Modelling The trial data were extrapolated using the declining exponential approximation to the life expectancy model (DEALE).
Measure of benefits used in the economic analysis The measure of benefits used was the life-years gained (LYG). The authors estimated the average life expectancy of hypertensive patients by the DEALE method, using the all-cause mortality of the Swiss population analogous to the LIFE study population in terms of age and gender distribution. The excess mortality due to hypertension was then derived from the LIFE study.
Direct costs The direct costs included in the analysis were those to the social health insurance provider. Three cost categories were included in the analysis. First, the medication costs for losartan and atenolol. Second, the acute and 2-year follow-up costs of a myocardial infarction. Third, the acute and 2-year follow-up costs of a stroke. The costs of treatment were based on pharmacy prices in Switzerland, with a patient co-payment of 10% being deducted from the pharmacy price. The costs of myocardial infarction and stroke included medication costs, interventions, hospitalisation, outpatient treatment and rehabilitation. These costs were derived from Levy et al. (2003, see 'Other Publications of Related Interest' below for bibliographic details) and were evaluated using a decision analysis model, supplemented by information from Delphi panels. Since the costs were incurred over a 4.8-year period, the future costs were appropriately discounted at an annual rate of 5%. The study reported the total costs. All of the costs were adjusted to 2003 values.
Statistical analysis of costs The study reported the total costs per 1,000 patients. Differences in the total costs were reported alongside their 95% CIs.
Indirect Costs Inline with the perspective adopted by the authors, the indirect costs were not included.
Sensitivity analysis Sensitivity analyses were performed to test the accuracy and sensitivity of the results. Only certain parameters were varied. Such parameters included the medication costs for losartan, the treatment costs for the events observed and the approximated life expectancy. They were varied by +/- 20%. The authors judged these to be the most important, costly parameters. In addition, the authors also varied the discount rate between 3 and 7%.
Estimated benefits used in the economic analysis The incremental life expectancy of losartan treatment in comparison with atenolol was 0.0495 years per patient.
Cost results The undiscounted total costs of treating 1,000 patients with losartan for 4.8 years were Sfr9,922,691, compared with Sfr9,953,311 for treating 1,000 patients with atenolol. This translated into total savings when using losartan of Sfr30,620 (95% CI: cost-savings Sfr1,188,505 - additional costs Sfr1,447,896).
When the costs were discounted at 5%, losartan was found to generate cost-savings of Sfr24,227 per 1,000 patients in comparison with atenolol (95% CI: cost-savings Sfr940,356 - additional costs Sfr1,145,589).
Synthesis of costs and benefits The costs and benefits were combined using an incremental cost-effectiveness ratio (i.e. the additional cost per LYG when using losartan as opposed to atenolol). In the base-case, the authors found that losartan was dominant over atenolol (i.e. it was both more effective and less costly).
The results of the sensitivity analysis showed that when using a worse-case scenario, the incremental cost-effectiveness ratio of using losartan over atenolol was Sfr25,336. According to the authors, this would still be considered a worthwhile health care investment.
Authors' conclusions The use of a losartan-based regimen in hypertensive patients in Switzerland was net cost-saving when compared with an atenolol-based regimen.
CRD COMMENTARY - Selection of comparators Although no explicit justification was given for using atenolol as the comparator, it would appear to represent current practice in the authors' setting. You should decide if this treatment represents current practice in your own setting.
Validity of estimate of measure of effectiveness The analysis was based on a large double-blind randomised controlled trial (RCT). This would appear to be appropriate for the study question, as well-conducted RCTs are considered to be the 'gold' standard study design when comparing health interventions. The authors provided a brief summary of the LIFE study (i.e. the study they used to derive the measures of effectiveness). The study appears to have been a well-conducted study based on a large patient sample (>9,000 patients) and, therefore, to be internally valid. More details on the LIFE study were given in the parent publication (Dahlof et al. 2002).
Validity of estimate of measure of benefit The estimation of benefits was modelled. The authors did not discount the measures of benefits, although this was relevant as the benefits were accrued during a 4.8 year period. Since the costs were discounted, for consistency and in line with recent health economics guidelines, the benefits should have been discounted at the same rate as the costs.
Validity of estimate of costs All the categories of cost relevant to the perspective adopted appear to have been included in the analysis. The authors reported that their results were conservative as the potential savings in the avoidance of intensive care, loss of working time or rehabilitation measures were not evaluated. The costs and the quantities were not reported separately, which will limit the generalisability of the authors' results. The costs were derived from published sources, with a sensitivity analysis of the costs being undertaken. Since the costs were incurred during a 4.8-year period, discounting was relevant and was appropriately performed. The price year was reported, which will aid any potential inflation exercises.
Other issues The authors did not compare their findings with those from other studies. The issue of generalisability to other settings was partly addressed in 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 reported a number of further limitations to their study. First, the results of the LIFE study were transferred to the situation in Switzerland, and the estimated life expectancy of Swiss patients with coronary heart disease was used to calculate the cost-effectiveness. Second, the results were conservative as the potential savings in the avoidance of intensive care, loss of working time or rehabilitation measures were not evaluated. Third, the authors did not value the benefits of losartan in reducing new onset of diabetes. Fourth, the costs were limited to the duration of the LIFE trial, and any costs or savings accrued later than the 4.8-year follow-up period were not included. Finally, the authors assumed 100% compliance with drug treatment and omitted the costs of hydrochlorothiazide.
Implications of the study The authors would appear to recommend the use of a losartan-based treatment regimen for patients with hypertension in Switzerland.
Source of funding Partially supported by an unrestricted educational grant from Merck Sharp & Dohme Chibret AG, Glattbrugg, Switzerland.
Bibliographic details Szucs T D, Burnier M, Erne P. Cost-effectiveness of losartan versus atenolol in treating hypertension: an analysis of the LIFE study from a Swiss perspective. Cardiovascular Drugs and Therapy 2004; 18(5): 391-397 Other publications of related interest Dahlof G, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;23:995-1003.
Levy E, Gabriel S, Dinet J. The comparative medical costs of atherothrombotic disease in European countries. Pharmacoeconomics 2003;21:651-9.
Goldmann L, Sia ST, Cook EF, et al. Costs and effectiveness of routine therapy with long-term beta-adreneric antagonists after acute myocardial infarction. N Engl J Med 1988;319:152-7.
Cathomas G, Erne P, Schewnkglenks M, et al. The economic efficiency of amlodipine on the treatment of coronary artherosclerosis - an analysis based on the PREVENT study. Cardiovasc Drugs Ther 2002;16:61-6.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Antihypertensive Agents /economics /therapeutic use; Atenolol /economics /therapeutic use; Cost-Benefit Analysis; Economics, Pharmaceutical; Female; Humans; Hypertension /drug therapy /economics; Life Expectancy; Losartan /economics /therapeutic use; Male; Pharmacoepidemiology; Retrospective Studies; Switzerland AccessionNumber 22005000817 Date bibliographic record published 30/04/2006 Date abstract record published 30/04/2006 |
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