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Cost-effectiveness of simvastatin in the secondary prevention of coronary artery disease in Canada |
Riviere M, Wang S, Leclerc C, Fitzsimon C, Tretiak R |
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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 Simvastatin, a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor, for reducing serum cholesterol concentrations.
Economic study type Cost-effectiveness analysis.
Study population 4,444 patients, mean age of 59.4 years (at the beginning of the study) with angina pectoris or previous myocardial infarction (MI) and a serum cholestrol level of 5.5 - 8.0mmol
Setting Secondary care sector. The data on effectiveness were taken from the Scandinavian Simvastatin Survival Study (4S study) and cost and resource use was taken from Canadian sources. The economic study was undertaken in Montreal, Canada.
Dates to which data relate The effectiveness data were mainly taken from the 4S study published in 1994. Resource use data and the price date related to 1995-1996.
Source of effectiveness data Evidence for final outcomes was primarily derived from a single study (4S). Information on resource use was opinion-based.
Link between effectiveness and cost data Costing was obtained retrospectively (Canadian model) and not from the same patient sample as that used in the 4S effectiveness study.
Study sample The study sample was randomly assigned to either simvastatin treatment (2,221 individuals, 82% men) or usual treatment (2,223 individuals, 81% men).
Study design The study was a double-blind, randomised trial. The median length of follow up was 5.4 years. There were 231 and 288 dropouts in the simvastatin and usual care groups respectively, due to patient refusal to continue the study or because of adverse events. The authors assumed equal numbers of dropouts in the 20-mg and 40-mg simvastatin groups.
Analysis of effectiveness It is not clear whether the analysis of the clinical study was based on intention to treat or treatment completers only. The primary outcomes used in the analysis were the overall death rate, as well as the incidence of 5 major nonfatal events associated with CAD: myocardial infarction (MI), coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), stroke or transient ischaemic attack. The study did not report whether the 4S study analysed the comparability of the groups.
Effectiveness results In the simvastatin group there was a 35% reduction in LDL (risk factor) levels and an 8% increase in HDL (protective factor). The cholestrol level of the control group was not reported. There was a 42% lower death rate from CAD and 37% lower non-fatal MI rate in the treatment arm compared to the control group. There was a 30% lower mortality rate in the treatment arm together with some evidence of a decrease in the incidence of fatal and non-fatal cerebrovascular events in the simvastatin group.
Clinical conclusions Long-term use of simvastatin appears to have positive effects on the prevalence of risk factors in an at-risk population as well as its consequent impact on mortality and morbidity.
Modelling A model was used to estimate the costs and effects of using simvastatin on a Canadian population by extrapolating the results of the 4S study over a 15 year period.
Methods used to derive estimates of effectiveness The estimates of effectiveness were based on the results of the 4S study and the authors designed a model to establish the survival function of the treatment and control groups over a 15 year period.
Estimates of effectiveness and key assumptions Three different scenarios were evaluated based on the life-table method. The Gompertz-Makeham distribution provided the best fit for the period 3.0-5.4 years in the 4S trial and was therefore used to extend the survival curve to 15 years. The simvastatin group survival curve was carried out in the following 3 ways:
Premise A: effects of simvastatin as estimated at 5.4 years (duration of the 4S study) extended to 15 years and the control care group continued in parallel;
Premise B: based on cumulative effects of 15 years of treatment with simvastatin diluted by other-cause morbidity and mortality;
Premise C: based on cumulative effects of 15 years of treatment with simvastatin.
Measure of benefits used in the economic analysis An estimate of Years of Life Gained (YLG) was obtained by applying the effectiveness results of the 4S study to the appropriate life tables, on the basis of the three premises detailed above.
Direct costs Costs were discounted at 5% per year. Quantities were reported separately from costs. Costs were calculated for CAD-related events (MI, CBAG, PTCA, stroke and transient ischaemic attack). Resource utilisation data were obtained for five Canadian provinces (New Brunswick, Alberta, British Columbia, Ontario and Quebec) from a panel of 19 experts. Data were obtained for number of ambulance trips, length of stay in hospital, inpatient and outpatient physician consultations, inpatient and outpatient laboratory and diagnostic tests, inpatient and outpatient procedures (e.g. CAT scans), outpatient rehabilitation and outpatient prescriptions. Unit costs, calculated from the perspective of the provinicial ministries of health were obtained from a variety of sources (e.g. physician fees were calculated from provincial ministries schedules), and those for hospitals were calculated as a national average for 1995-96. Costs were presented as a weighted average for the 5 provinces. The treatment costs for CAD in Canada were calculated by multiplying the event costs in both simvastatin and usual care groups by the number of expected events. Then the differences in the costs for the two groups was expressed as a ratio per YLG. Length of hospital stay was the biggest cost item.
Statistical analysis of costs Indirect Costs Not relevant given the study perspective.
Currency Canadian dollars (Can$) (1995-1996).
Sensitivity analysis A one-way simple sensitivity analysis was undertaken and costs were varied by 20% to test for robustness of the results. The use of three different premises relating to the different estimated clinical advantages of simvastatin provide further sensitivity analysis.
Estimated benefits used in the economic analysis The probability of survival was 26.6% at 15 years in the usual care group and in the Simvastatin group was 29.7% (Premise A), 38.7% (Premise B) and 54.4% (Premise C).
Cost results Costs per YLG were Can$29,888 (premise A), Can$9,867 (premise B)and Can$6,108 (premises C).
Synthesis of costs and benefits The most favourable premise is C in which the cost per YLG is Can$6,108. This differential appears robust to costs assumptions. Following sensitivity analysis, the resulting variations in the cost-effectiveness ratios were 24%, 29% and 34% from premises A, B and C respectively.
Authors' conclusions Simvastatin appears to provide a cost-effective approach to secondary prevention of CAD in Canada. This is likely to be underestimated because of the non-inclusion of indirect costs in the analysis.
CRD COMMENTARY - Selection of comparators The choice of comparator is clear, although, when cost-effectiveness ratios were determined, the cost-effectiveness of usual care was not provided. Validity of estimate of measure of benefit The estimate of measure of benefit appears to be internally valid. However, there was no report of any potential adverse effects of simvastatin. Validity of estimate of costs Prices and resource quantities were reported separately and adequate details of quantity/cost estimation were reported. Other issues Appropriate comparisons were made with other studies. Source of funding Funded by a grant from Merck Frosst Canada Inc.
Bibliographic details Riviere M, Wang S, Leclerc C, Fitzsimon C, Tretiak R. Cost-effectiveness of simvastatin in the secondary prevention of coronary artery disease in Canada. CMAJ: Canadian Medical Association Journal 1997; 156(7): 991-997 Other publications of related interest Comment in: CMAJ 1997;156(7):1005-7.
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;344:1382-1289.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Canada /epidemiology; Coronary Disease /drug therapy /economics /mortality; Cost-Benefit Analysis; Enzyme Inhibitors /administration & Health Resources /economics /statistics & Health Services Research; Humans; Hypolipidemic Agents /administration & Lovastatin /administration & Middle Aged; Models, Economic; Prognosis; Simvastatin; Survival Analysis; Time Factors; derivatives /economics; dosage /analogs & dosage /economics; dosage /economics; numerical data /utilization AccessionNumber 21997008098 Date bibliographic record published 31/10/1999 Date abstract record published 31/10/1999 |
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