Abstract
Summary
Synopsis
The Scandinavian Simvastatin Survival Study (4S) has confirmed the link between the cholesterol-reducing effects of simvastatin and improved survival in patients with hypercholesterolaemia and pre-existing coronary heart disease (CHD). Pharmacoeconomic analyses of the 4S trial. using prospectively col/ected data for cost-generating events. demonstrate that the cost per year of life saved for simvastatin in such patients falls within the range considered cost effective. Reductions in resource utilisation costs (numbers ofhospitalisations and revascularisation procedures) largely offset the acquisition cost of long term simvastatin treatment in the US.
Models of primary prevention incorporating epidemiological data to predict CHD events generally suffer from deficiencies in the methods and assumptions used. and no firm conclusions can be made at present regarding relative cost effectiveness of the drugs studied. including simvastatin. It is generally agreed that cost effectiveness will improve in patients with higher absolute risk of CHD.
In summary. simvastatin has been shown in a major clinical trial and its companion economic analyses to reduce mortality and to be cost effective in patients with hypercholesterolaemia and existing CHD. As is the case for others of its class. its cost-effectiveness ratio in primary prevention remains to be ascertained. This issue aside. simvastatin is a rational choice of cholesterol-lowering agent in secondary prevention whose use can be justified on an economic basis.
Economic Implications of Dysllpldaemla and Coronary Heart Disease
Coronary heart disease (CHD) is the major cause of death in industrialised nations. Treatment of cardiovascular diseases consumes about 10 to 15% of total healthcare budgets in OECD countries. Annual costs in the US alone approach $US 100 bilIion for treatment and lost wages. Dyslipidaemia is one of several established risk factors for CHD: a 10% reduction in serum cholesterol levels is linked to a decrease of 15 to 20% in the 2-year incidence of CHD. Furthermore, the Scandinavian Simvastatin Survival Study (4S) using simvastatin as secondary prevention has established that reducing cholesterol levels improves survival.
Costs of treating dyslipidaemia include those related to initial screening, which vary considerably depending on whether programmes are comprehensive or selective, and ensuing treatment (dietary consultations, physician visits, nursing time, laboratory tests and drug acquisition). For an intervention programme in the UK, it was calculated that lipid-measuring accounted for 7%, dietary counselIing 3% and drug therapy 89% of total costs. As a rule, the cost effectiveness of intervention increases with increasing risk. The incremental cost effectiveness of various interventions has not been measured extensively. In the UK, the incremental cost-effectiveness ratio for therapy with HMG-CoA reductase inhibitors versus diet was estimated to be £ 13 500/quality-adjusted life-year (QALY).
Factors Influencing Phamacoeconomic Analyses of Slmvastatin
In the 4S trial, simvastatin therapy decreased total mortality by 30% and coronary mortality by 42%, and reduced the incidence of cost-generating CHD event~ over a 5.4-year period (see Pharmacoeconomic Assessments summary). Clinical benefit was greatest in men aged <60 years, but gains were also obtained in women and the elderly.
Serum cholesterol reduction is a surrogate end-point which nonetheless has been extensively incorporated into economic analyses. The effects of simvastatin on lipids and lipoproteins are well established. Serum levels of total cholesterol are reduced by about 20 to 40%, low density lipoprotein (LDL) cholesterol by 35 to 45% and triglycerides by 10 to 20%; high density lipoprotein (HDL) cholesterollevels rise by 5 to 15%. Simvastatin is effective in patients with dyslipidaemia and non-insulin-dependent diabetes mellitus and does not worsen glucose control or renal function.
Simvastatin reduces total and LDL cholesterol levels to a greater extent than bile acid sequestrants or fibrates. whereas fibrates more effectively increase HDL cholesterol and lower triglyceride levels. Compared with other HMG-CoA reductase inhibitors. simvastatin 10 mg/day is therapeutically equivalent to lovastatin 20 mg/day. pravastatin 20 mg/day and tluvastatin 40 or 80 mg/day. Like other HMG-CoA reductase inhibitors. simvastatin is well tolerated and is rarely associated with serious adverse events. The cost of adverse events is unlikely to be significant but has been incorporated into some economic analyses of simvastatin.
Pharmacoeconomic Assessments
Simvastatin provides clinical benefits and is cost effective in secondary prevention. as evidenced by findings of the 4S trial. A cost analysis of the 4S trial used prospectively collected data on cost-generating events to demonstrate that. compared with placebo. simvastatin produces significant reductions in the number of hospitalisations for acute cardiovascular disease (by 26%), CHD events (32%), revascularisation procedures (32%) and days spent in hospital for these events (34%). Applying diagnosis-related group (DRG) costs in the US yielded a 31 % saving in the cost of these events over 5.4 years, reducing the discounted acquisition costs of simvastatin treatment by 88%.
Using Swedish cost data and the 4S trial results, a subsequent costeffectiveness analysis estimated a 32% saving in total cost of hospitalisations which translated into an incremental cost per year of life saved (YLS) of SEK56 400 (= £ 5502) for simvastatin. assuming a discounted gain of 0.24 lifeyears. This figure is well below the cut-off point for interventions deemed cost effective in Sweden (SEKIOO 0(0) and was robust to varying assumptions regarding life expectancy. costs of treatment and discount rates for costs and benefits. The cost-effectiveness ratio ranged from £ 4137 to £ 8824/YLS after conversion of these data to pounds sterling using DRG weights for costs in 10 other countries. These cost-effectiveness data are. however, valid only if extrapolated to countries with healthcare systems comparable to those in the Scandinavian countries studied. and in patients similar to those in the 4S trial.
Investigators of simvastatin economics in the setting of primary prevention have attempted to compensate for a lack of clinical trial data regarding CHD events by extrapolating epidemiological and observational study results. Simvastatin consistently proved more cost effective than cholestyramine in these models of primary prevention. Present data. however. do not permit firm conclusions regarding relative cost effectiveness among HMG-CoA reductase inhibitors. particularly as acquisition costs will vary across markets. The same cautionary note applies to results of simple cost-effectiveness analyses using cholesterol reduction as a surrogate clinical end-point and drug acquisition costs in various countries to determine relative cost effectiveness among HMG-CoA reductase inhibitors, particularly as acquisition costs will vary across markets.
The same cautionary note applies to results of simple cost-effectiveness analyses using cholesterol reduction as a surrogate clinical end-point and drug acquisition costs in various countries to determine relative cost effectiveness among HMG-CoA reductase inhibitors.
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Various sections of the manuscript reviewed by: I. Aursnes, Department of Phannacotherapeutics, University of Oslo, Oslo, Norway; G. Davey Smith, Department of Social Medicine, University of Bristol, Bristol, England; R. Guibert, Department of Family Medicine, McGill University, Montreal, Quebec, Canada; B. Jönsson, Stockholm School of Economics, Centre for Health Economics, Stockholm, Sweden; S. Kinlay, Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA; M. Nakamura, Department of Epidemiology and Mass Examination for Cardiovascular Disease, The Center for Adult Diseases, Osaka, Japan; A. Okayama, Department of Health Science, Shiga University of Medical Science, Ohtsu, Japan; M.F. Oliver, Imperial College of Science, Technology and Medicine at the National Heart & Lung Institute, London, England; J.P.D. Reckless, Royal United Hospital, Bath, England.
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Goa, K.L., Barradell, L.B. & McTavish, D. Simvastatin. Pharmacoeconomics 11, 89–110 (1997). https://doi.org/10.2165/00019053-199711010-00010
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DOI: https://doi.org/10.2165/00019053-199711010-00010