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Cost-effectiveness of HMG coenzyme reductase inhibitors: whom to treat? |
van Hout B A, Simoons M L |
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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 Lipid lowering drugs, namely the use of HMG coenzyme reductase inhibitors (statins) in primary and secondary prevention of coronary heart disease as compared to placebo.
Type of intervention Primary and secondary prevention.
Economic study type Cost-effectiveness analysis.
Study population The population studied comprised patients in the Netherlands with elevated risk of coronary heart disease (CHD). The populations studied in the source studies had varying inclusion/exclusion criteria (reported below in "investigation of differences between primary studies").
Setting This study was aimed at treatment in primary care. The study was conducted in the Netherlands.
Dates to which data relate Effectiveness and resource use evidence was based on five studies published between 1994 and 1998. Unit prices appear to have been from 1999.
Source of effectiveness data Effectiveness estimates were based on a review of the literature.
Modelling Models were used to extrapolate survival data, to synthesise costs and effectiveness, and to identify sensitive parameters in the cost-effectiveness estimate.
Outcomes assessed in the review The probabilities of several clinical outcomes were identified through a literature review. These were: stroke (fatal and non-fatal); myocardial infarction (definite, probable, non-fatal and fatal); coronary bypass surgery; percutaneous transluminal coronary angioplasty; and all deaths and CHD deaths.
Study designs and other criteria for inclusion in the review All five trials that formed the basis for the evaluation were randomised-controlled trials. Further trial inclusion criteria were not specified.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Five primary studies were included in the review. These were the 4S study, the CARE study, the WOSCOPS study, the LIPID study and the AFCAPS/TexCAPS study.
Methods of combining primary studies Two analyses were conducted. The first re-evaluated the data from published studies and presented the results from each in a disaggregated fashion. The first analysis calculated cost per life-year saved per study. The second analysis pooled data from all five trials to arrive at estimates of occurrence of CHD death, myocardial infarction (MI) and stroke. The results from the second analysis were presented in cost-effectiveness profiles according to age, gender and individuals' risk profile.
Investigation of differences between primary studies The patient inclusion criteria differed between the five studies. For example, the 4S study included Scandinavian women and men aged between 35 and 70 with CHD and relatively high cholesterol levels, whereas the CARE study included patients with average cholesterol levels after a MI. In contrast, WOSCOPS included patients without a known history of heart disease but with otherwise high risk of developing CHD. These differences in patient populations enabled the authors of this paper to present cost-effectiveness as a function of risk of cardiovascular event, age and gender.
Results of the review The studies showed similarities in risk reduction estimates. After a period of no clinical effects on initiating treatment with statins, there was significant reduction of about 35% in the incidence of cardiovascular deaths, MI's, strokes and revascularisations.
Methods used to derive estimates of effectiveness Authors estimates about effectiveness were also used.
Estimates of effectiveness and key assumptions The trials that formed the basis for the effectiveness estimates had average follow-up time of less than five years. In the base-case analysis the authors assumed that risk reduction would persist after a treatment period of 25 years.
Measure of benefits used in the economic analysis The authors used an estimate of cost per life year gained in the economic analysis.
Direct costs Costs included in the model were direct medical costs associated with the observed events reported earlier (e.g. stroke, MI, etc.). Costs also included treatment with statins. Estimates of resource quantities were taken from the trials. Two quantity/cost boundaries were adopted for the analysis of cost per life year saved: 13,500 Euros and 18,000 Euros. The authors identified patients who were cost-effective to treat under these boundaries. Unit costs appear to have been from 1999. Costs were discounted at 5%.
Statistical analysis of costs The authors did not specify statistical tests for the analysis of the costs.
Indirect Costs Indirect costs were not included in the study.
Currency The results were expressed in Dutch guilders (Dfl) and Euros.
Sensitivity analysis Cost and effectiveness estimates were varied by 25% each way in a univariate sensitivity analysis. Furthermore, a sensitivity analysis of duration of therapy was conducted. Treatment for 5 and 10 years, respectively, was compared to the baseline assumption of therapy duration of 25 years.
Estimated benefits used in the economic analysis The survival benefits from statins ranged from zero (AFCAPS) to 0.01 years (CARE) to 0.05 years (4S) at 5-year study follow-up as compared to placebo. Survival at 25 years was not expressed explicitly.
Cost results The average cost of medication was about 550 Euros per year. Total incremental costs for the treatment strategies of statin versus placebo were not reported in the paper.
Synthesis of costs and benefits The first analysis estimated cost-effectiveness based on the five studies included in the review. For each study, an incremental cost-effectiveness ratio was presented for statin versus placebo.
The following estimates were presented for the cost per life year gained: 4S 6,695 Euros; CARE 9,970 Euros; WOSCOPS 26,013 Euros; LIPID 8,028 Euros; and for AFCAPS/TexCAPS cost per life year saved was 51,400 Euros.
The authors comment that the variation in cost-effectiveness ratios reflects patient demographics and the cardiovascular risk profile of the patients included in the studies.
The second analysis was a threshold analysis identifying patients for whom the expected cost per life year saved was less than 18,000 Euros (40,000 Dfl). This threshold would be achieved for individuals with a 10-year risk of developing cardiovascular disease of more than 25.2%. This cut-off point of cost-effectiveness increased with age, reflecting shorter life expectancy for patients in higher age groups.
The authors stated that the sensitivity analysis revealed that the results were mainly driven by the cost of medication and the assumption about drug effectiveness, and were not sensitive to the costs per event.
Authors' conclusions The authors concluded that statins are less cost-effective in elderly patients and patients with a 10-year risk of cardiovascular disease of less than 25%. In terms of decision-makers' thresholds, when cost-effectiveness ratios up to 18,000 Euros per life year gained are deemed acceptable, statin treatment should be considered in most patients with known cardiovascular disease (secondary prevention), and in a limited group of subjects who are at high risk of developing coronary heart disease (primary prevention).
CRD COMMENTARY - Selection of comparators The authors included studies evaluating simvastatin (4S), pravastatin (CARE, WOSCOPS and LIPID) and lovastatin (AFCAPS/TexCAPS). These are the most commonly prescribed statins and are relevant for a study such as this.
Validity of estimate of measure of effectiveness The measures of effectiveness were based on large-scale multi-centre prospective randomised studies, a study design that should maximise the validity of the results. However, the search strategy was not specified and other relevant studies may have been missed in the literature. Additionally, there was a good deal of heterogeneity in the populations studied in the source trials, although the model allowed for sensitivity analyses to assess the impact on the results of variability in the models' parameters. The authors assigned differences in study results to the baseline risk of the populations included in each study rather than to the potential differing pharmacological effects of each statin. It may have been useful to see head to head comparisons of the statins rather than the assumed therapeutic equivalence of the treatments.
Validity of estimate of measure of benefit The benefits were appropriately modelled based on the primary data derived from the trials. The source trials also demonstrated additional benefits to life years gained, such as avoided myocardial infarction and stroke due to statin therapy.
Validity of estimate of costs The authors included only direct treatment costs and cost of avoided coronary heart events. The perspective was that of the health service, however other relevant costs incurred by the patient or social services might not have been discussed in this paper. Resource use estimates were taken from prospective randomised controlled trials and can therefore be considered reliable and valid.
Other issues The authors appropriately discussed other studies in relation to their findings and the differing decision-making perspectives that are relevant in considering such programmes (including total budgetary impacts in The Netherlands). The authors also argued that other health promotion initiatives (such as quitting smoking) might reduce the risks of coronary heart disease and should be considered when allocating resources. The issue of generalisability was not specifically addressed, although the sensitivity analyses did address this issue to some degree. The model was based on some assumptions, which may limit the strength of the findings.
Implications of the study The authors' comment that cost-effectiveness was sensitive to treatment costs and that treatment with statins would be cost-effective for all patients included in the trials reviewed in this study if the annual cost of treatment was reduced to 100 Euros. The implications for decision-makers are reported in the authors' conclusions. The model developed in this study is suitable for testing under varying decision-making criteria and perspectives.
Bibliographic details van Hout B A, Simoons M L. Cost-effectiveness of HMG coenzyme reductase inhibitors: whom to treat? European Heart Journal 2001; 22(9): 751-761 Other publications of related interest Comment In: European Heart Journal. 2001 May;22(9):720-721.
Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9.
Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. New England Journal of Medicine 1996;335:1001-9.
Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. New England Journal of Medicine 1995;333:1301-7.
Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998;279:1615-22.
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. New England Journal of Medicine 1998;339:1349-57.
Indexing Status Subject indexing assigned by NLM MeSH Analysis of Variance; Coronary Disease /economics /prevention & Cost-Benefit Analysis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /economics /therapeutic use; Practice Guidelines as Topic; control AccessionNumber 22001001157 Date bibliographic record published 30/06/2002 Date abstract record published 30/06/2002 |
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