Setting The setting was primary care. The economic study was carried out in the UK and the USA.

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1 Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study McInnes G, Burke T A, Carides G 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 authors studied losartan (50 mg) and compared it with atenolol (50 mg) in patients with hypertension and left ventricular hypertrophy. Type of intervention Secondary prevention Economic study type Cost-effectiveness analysis. Study population The study population comprised patients with essential hypertension (sitting blood pressure / mmhg) and electrocardiogram evidence of left ventricle hypertrophy (LVH). Patients were excluded for various reasons. For example, secondary hypertension, myocardial infarction or stroke in the last 6 months, and angina pectoris requiring treatment with a beta-blocker or calcium antagonist. Setting The setting was primary care. The economic study was carried out in the UK and the USA. Dates to which data relate The effectiveness and resource use data referred to patients enrolled between June 1995 and May The prices related to Source of effectiveness data The effectiveness data were derived from a single study. Link between effectiveness and cost data The costing was carried out prospectively on the same sample of patients as that used in the effectiveness analysis. Study sample The authors reported that a parent study was used for the effectiveness data (Dahlof et al. 2002, see 'Other Publications of Related Interest' below for bibliographic details). A total of 9,193 patients (age range: 55 to 80 years; 54% female) were enrolled into the study. There were no details in the current report of power calculations, the method of sample selection, or the comparability of patients between the two patient groups. Page: 1 / 5

2 Study design The source of the effectiveness data was a double-blind, randomised, parallel-group study based at centres in the Nordic countries, the UK and the USA. The patients were followed for 5.5 years. Details of losses to follow-up, the method of blinding and the specifics of randomisation were not given in the current report. Analysis of effectiveness It was unclear whether the analysis was conducted on an intention to treat basis, although this might have been stated in the parent study. The primary health outcome was the incidence of a composite end point (cardiovascular death, myocardial infarction or stoke). The comparability of the groups at baseline was not reported. Effectiveness results There was a 13% reduction in the incidence of the composite end point. The authors reported that this was due primarily to a significant reduction in the incidence of fatal and nonfatal stroke (25%). In addition, there was a lower incidence of discontinuation due to adverse events in the losartan-based therapy group. Clinical conclusions The authors concluded that the 25% reduction in stroke incidence compared with atenolol-based treatment "clearly demonstrated the clinical benefit of losartan-based therapy in hypertensive patients with LVH". Modelling A model was used to extrapolate the incidence of stoke beyond the length of the initial trial and to combine clinical and cost outcomes. Methods used to derive estimates of effectiveness Assumptions were made to assist in the extrapolation of clinical data over a longer time horizon. Estimates of effectiveness and key assumptions The authors assumed "there was no additional stroke risk reduction with losartan-based therapy beyond the trial period and that patients stopped study treatment after 5.5 years or at the time of stroke, whichever occurred first". Measure of benefits used in the economic analysis The summary measures of health benefit were the cumulative incidence of stoke, and the life-years and qualityadjusted life-years (QALYs) saved. The cumulative incidence of stoke was estimated directly from the clinical trial. The life-years saved were estimated by multiplying the absolute risk reduction in stroke by the difference in life expectancy for patients with and without a stroke. The QALYs were estimated by weighting the life-years gained by health-related quality of life, as measured in the parent study (Dahlof et al. 2002). Within the parent study, a visual analogue scale was used at the randomisation visit and every 6 months thereafter. The benefits were discounted at a rate of 3.5%. Direct costs The costing analysis was carried out from the perspective of the UK NHS. It focused on study medication costs and stroke-related costs. For study medication costs, resource use was derived from the parent clinical study while the unit costs were based on current prices within the UK. The authors reported that only the costs of intervention drugs were included, as the use of other drugs was comparable between the patient groups. The authors estimated base-case strokerelated costs from a published study (Caro et al. 1999, see 'Other Publications of Related Interest' below for bibliographic details), and then projected them over the lifetime of the patient. The costs were analysed using 2003 Page: 2 / 5

3 prices and reflated using the Consumer Price Index for health. The costs were discounted at a rate of 6%. Statistical analysis of costs Bootstrap analyses were used to estimate the probability of reaching different thresholds for cost-effectiveness and to generate cost-effectiveness acceptability curves. Indirect Costs The indirect costs were not estimated and were not relevant to the perspective of the study. Currency UK pounds sterling (). Sensitivity analysis Sensitivity analyses were conducted around different cost estimates, which were taken from alternative published studies that included and excluded the cost of informal care. Further analyses explored the impact of patients continuing to take losartan for their lifetime. Estimated benefits used in the economic analysis The cumulative incidence of stroke over 5.5 years was for losartan and for atenolol. The difference was (95% confidence interval, CI: to 0.026). Life expectancy was 12.8 years without stoke and 8.4 years with stroke. Thus, the life-years saved by preventing stroke were 4.4 (95% CI: 3.0 to 5.8). The life-years saved by losartan through stoke reduction were (95% CI: to 0115). On the visual analogue scale, the mean quality of life was 71.4 for stroke-free patients and 63.8 for patients with a stroke. First stroke was therefore associated with a quality of life decline of 7.6 (95% CI: 6.6 to 8.7; p<0.0001). The QALYs saved by losartan through stroke reduction were (95% CI: to 0.088). Cost results The cost of study medication was 1,128 for losartan and 44 for atenolol. The difference was 1,084 (95% CI: 1,054 to 1,114). The stroke costs were 2,984 for losartan and 3,953 for atenolol. The difference was -968 (95% CI: -1,931 to -5). The total costs were 4,112 for losartan and 3,997 for atenolol. The difference was 115 (95 CI: -846 to 1,076). Synthesis of costs and benefits The incremental cost per life-year saved was 1,643 (95% CI: -10,104 to 27,181). The incremental cost per QALY saved was 1,643 (95% CI: -12,549 to 34,875). The authors reported that the base-case cost-effectiveness ratios were robust to changes in the cost of stoke. The probability of achieving a particular cost-effectiveness threshold was reduced most markedly when the most conservative estimate of stoke was incorporated. Page: 3 / 5

4 Authors' conclusions The clinical benefit of losartan was achieved at a cost well within the range considered cost-effective in other studies. CRD COMMENTARY - Selection of comparators Losartan was identified as the technology of interest. Atenolol was identified as the comparator because it represented the most commonly prescribed antihypertensive therapy. This choice of comparator helps make this study applicable and useful to a broad range of readers. Validity of estimate of measure of effectiveness A parent study was identified that provided the effectiveness estimates for the current cost-effectiveness analysis. The authors used a double-blind, randomised, parallel-group study to inform their clinical estimates. The nature of this design reduced the possibility of systematic differences between patients in the study groups, thus improving the internal validity of the results presented. It was not clear from the current report how well the study sample represented the study population, and whether the patient groups were comparable at analysis. Whilst many details of the clinical study were provided, further details can be obtained from the parent study (Dahlof et al. 2002). Validity of estimate of measure of benefit Several summary measures of health benefit were used. These ranged from clinical benefit obtained directly from the effectiveness analysis, to QALYs that were modelled using quality of life data from the effectiveness analysis. These measures enable readers to really understand the results presented and make comparisons across a range of alternative health care technologies. Validity of estimate of costs The costs were estimated from the perspective of the UK NHS. The costs relevant to this perspective (i.e. study medication and stroke-related costs) were included. However, it was unclear from the report exactly what aspects of treatment were included in the estimate of stroke cost, for instance whether medical personnel time and overhead costs were included in the analysis. The authors provided a reference to the source of stroke costs, so that readers can obtain more information. Although the authors broke down the total cost estimate into study medication and stroke sub-costs, a more thorough breakdown of stroke costs might have enabled the reader to better understand the key components. Other issues The authors were able to compare their results with other studies of cost-effectiveness, and reported that the clinical benefit of losartan was achieved at a cost within a range considered cost-effective. The issue of generalising the results was considered, with the authors warning against generalising the data to other drugs within the same class. Generalisation beyond the current sample is not recommended without first examining the parent study and obtaining further detail of the study sample. The authors do not appear to have presented the results selectively, and their conclusions were an accurate reflection of their results and related well to the scope of the study. Several limitations of the study were presented. First, the lack of survival data relating directly to the study cohort. Second, the clinical data were derived from a study that was based on non-specialist stroke units that may not be representative of current clinical practice. Finally, the fact that informal care costs were not incorporated in the costing analysis. Implications of the study The authors suggested that "the widespread adoption of losartan for routine use in patients with hypertension and LVH would potentially have a major impact on public health in the UK". In addition, losartan-based therapy should be chosen in preference to atenolol-based therapy for routine use. Page: 4 / 5

5 Powered by TCPDF ( Source of funding None stated. Bibliographic details McInnes G, Burke T A, Carides G. Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. Journal of Human Hypertension 2006; 20(1): PubMedID DOI /sj.jhh Other publications of related interest Dahlof B, 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;359: Caro JJ, Huybrechts KF. Stroke treatment economic model (STEM): predicting long-term costs from functional status. Stroke 1999;30: Indexing Status Subject indexing assigned by NLM MeSH Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers /economics /therapeutic use; Cost-Benefit Analysis; Female; Follow-Up Studies; Humans; Hypertension /complications /drug therapy /economics; Hypertrophy, Left Ventricular /complications /drug therapy /economics; Losartan /economics /therapeutic use; Male; Middle Aged; Retrospective Studies; Stroke /economics /etiology /prevention & control; Treatment Outcome AccessionNumber Date bibliographic record published 30/11/2006 Date abstract record published 30/11/2006 Page: 5 / 5