Setting Community. The economic study was carried out in Cambridge, United Kingdom.

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1 Cost effectiveness of lowering cholesterol concentration with statins in patients with and without pre-existing coronary heart disease: life table method applied to health authority population Pharoah P D, Hollingworth W 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 use of statins to lower cholesterol concentration in patients with and without pre-existing coronary heart disease (CHD). Type of intervention Primary prevention and secondary prevention. Economic study type Cost-effectiveness analysis. Study population A hypothetical cohort of men and women aged 45 to 64. Setting Community. The economic study was carried out in Cambridge, United Kingdom. Dates to which data relate Effectiveness data were derived from the studies published in 1994 and Resource use and cost data were derived from reports and studies published during the period from 1988 to The price year was not clearly stated. Source of effectiveness data Single study and opinion. Study sample Men and women with and without pre-existing coronary heart disease (angina pectoris or previous myocardial infarction) and serum cholesterol mmol/l on a lipid-lowering diet were included in the study. From a total of 7,027 patients recruited for the diet period, 4,444 patients were allocated to one of two groups: treatment with simvastatin 20 mg (n = 2,221) and placebo (n = 2,223). Of those excluded from the study due to failure to meet the entry criteria, 396 patients were unwilling to participate. Power calculations were reported. Study design The study was a randomised controlled trial conducted in 94 centres in Scandinavia (five countries: Denmark, Finland, Iceland, Norway, and Sweden). The allocation was performed using stratification by clinical site and previous myocardial infarction (MI). The duration of follow-up was 5.4 years (median). Page: 1 / 5

2 Analysis of effectiveness The analysis was based on the intention to treat principle. The primary end point of the analysis was total mortality. The groups were shown to be comparable at baseline in terms of age, gender, diagnosis, time since first diagnosis of angina or infarction, secondary diagnosis, body mass index, heart rate, blood pressure, and cholesterol levels. Effectiveness results There were 111 and 189 coronary deaths in the simvastatin and placebo groups, respectively (relative risk 0.58, 95% CI: ). Thus, a reduction in cardiovascular mortality of 42% was observed with statins. Clinical conclusions Lowering cholesterol levels is safe and effective for patients with or without pre-existing CHD. Modelling A probabilistic model using a life table was used to calculate total costs and benefits for different risk groups and to estimate treatment effects for a 10-year period. Hypothetical cohorts of 1,000 individuals (split into two age bands 45 to 54 and 55 to 64) were selected for the following groups: with/without previous CHD, with angina and with previous myocardial infarction. Each group was then sub divided into five different cholesterol level groupings. The hypothetical cohorts were taken from the Cambridge and Huntingdon Health Commission population of 95,800 adults between the ages of 45 and 64. Methods used to derive estimates of effectiveness The prevalence rates of angina, previous myocardial infarction, proportion of myocardial infarctions prevented to life years saved, proportion of coronary angiographies prevented to life years saved and theproportion of revascularisation procedures prevented to life years saved, and the relative risk of fatal CHD were assumed to be within certain ranges according to the available evidence in the literature. Estimates of effectiveness and key assumptions In the four groups women and men aged and the midpoints for angina prevalence were found to be 0.02, 0.02, 0.05 and 0.05 respectively. Similarly for prevalence of previous myocardial infarctions the estimates were , , 0.02 and 0.05 respectively. The proportion of non-fatal myocardial infarctions prevented to life years saved was The proportion of coronary angiographies prevented to life years saved was 0.4. The proportion of revascularisation procedures prevented to life years saved was The mean relative risk of fatal CHD was found to be as follows (Standard deviation in parentheses): For patient with angina 2.4 (0.4), patient with previous myocardial infarction 6.0 (0.8), patient in cholesterol Group One 1.0 (0.0), patient in cholesterol Group Two 1.5 (0.15), patient in cholesterol Group Three 1.8 (0.2), patient in cholesterol Group Four 2.4 (0.2), patient in cholesterol Group Five 3.8 (0.3), patients with pre-existing disease treated with statins 0.58 (0.06), Page: 2 / 5

3 patients without pre-existing disease treated with statins 0.67 (0.08). Measure of benefits used in the economic analysis The benefit measure was life years saved. Direct costs The estimates of costs have been limited to those of drugs, non-fatal myocardial infarction treatment and those of revascularisation procedures, all of which were derived from the literature, namely, the Scandinavian Simvastatin Study group 1994, and studies from 1988 and 1992 respectively. Price years are not stated although prices were stated to be 'current'. The costs were discounted and total estimates were derived using a model. Statistical analysis of costs The Latin hypercube sampling technique was used to recalculate the model 1,000 times so that parameters were sampled across their putative distributions. Currency UK pounds sterling (). Sensitivity analysis A sensitivity analysis (presumably multi-way) was performed over each parameter using 1,000 replications (simulations), with parameters drawn from their own pre-specified sample distributions. The discount rate (costs) was varied between a range of 0 and 10%. Estimated benefits used in the economic analysis For those with pre-existing CHD, 442 life years would be saved and 137 deaths, 128 non-fatal myocardial infarctions, 164 revascularisation procedures and 177 coronary angiographies would be prevented. For men without CHD, 512 life years would be saved and 90 deaths prevented. The duration of benefits was 10 years. Side effects of the treatment were not considered in the economic analysis. Cost results In the group with pre-existing CHD, 35,619 treatment years were needed at a cost of 540 each (per annum). The net cost of treatment amounted to some 14.1 million for the entire cohort. For the cohort of men without CHD, treatment costs were 74.6 million over the period, with 174,364 treatment years being used. In all the above calculations, the discount rate was set at 5%. Synthesis of costs and benefits For the group with pre-existing CHD the average cost per life saved was 103,000 and 32,000 per life year saved. Average costs in the male group without pre-existing CHD were 800,000 per life saved and 147,000 per life year saved. An analysis of supplying treatment based on risk category was performed. The marginal cost-effectiveness per life year saved extending the treatment to lesser risk groups is as follows: Group 1: men aged and women aged with previous myocardial infarction and a cholesterol concentration >5.4 mmol/l, 16,000; Group 2: men aged and women aged with angina and a cholesterol concentration >5.4 mmol/l, 47,000; Page: 3 / 5

4 Group 3: men aged with no history of CHD and cholesterol > 6.5 mmol/l, 81,000; Group 4: women aged with angina or previous myocardial infarction and a cholesterol concentration >5.4 mmol/l, 143,000; Group 5: men aged with no history of CHD and a cholesterol concentration >6.5 mmol/l, 230,000. In all the above cases the comparator was that of 'no-treatment'. Authors' conclusions The authors concluded that the cost effectiveness of statin treatment differs greatly between different risk groups. Statin treatment should only be used where it is most cost-effective given that there are other interventions such as antiplatelet treatment and dietary education that are cheaper and equally effective, especially given the restrictions on spending within the UK National Health Service. CRD Commentary Validity of estimate of measure of benefit:the main effectiveness data were derived from a well-known, well-designed study (Scandinavian simvastatin survival study) which is likely to produce valid estimates of effectiveness for the respective population. Validity of estimate of costs:price years were not clearly stated by the authors although they are said to be current. Other issues:side effects of the treatment were not mentioned although other studies have suggested that there may be some increase in mortality from lowering serum cholesterol levels. As the authors themselves noted, the socio-economic status of the Huntingdon/Cambridge area is above that of the average in the UK, and it may therefore be inappropriate to generalise these results to other areas. The authors also note that they have assumed that the benefits of treatment begin immediately when in fact this is not often the case. Source of funding None stated. Bibliographic details Pharoah P D, Hollingworth W. Cost effectiveness of lowering cholesterol concentration with statins in patients with and without pre-existing coronary heart disease: life table method applied to health authority population. BMJ 1996; 312: PubMedID Original Paper URL Other publications of related interest Comment in: ACP Journal Club 1996;125(3):81. Comments in: BMJ 1996;313(7065):1142-4, discussion :1144. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study. Lancet 1994;344: Indexing Status Page: 4 / 5

5 Powered by TCPDF ( Subject indexing assigned by NLM MeSH Age Distribution; Aged; Anticholesteremic Agents /economics /therapeutic use; Cholesterol /blood; Coronary Disease /economics /prevention & control; Cost of Illness; Cost-Benefit Analysis; Female; Great Britain /epidemiology; Humans; Hypercholesterolemia /economics /prevention & control; Life Tables; Male; Middle Aged; Models, Economic; Sensitivity and Specificity; Sex Distribution; Survival Analysis; Survival Rate; Treatment Outcome; Value of Life AccessionNumber Date bibliographic record published 31/08/1999 Date abstract record published 31/08/1999 Page: 5 / 5