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The economic efficiency of amlodipine in the treatment of coronary atherosclerosis: an analysis based on the PREVENT study |
Cathomas G, Erne P, Schwenkglenks M, Szucs T D |
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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 The use of the calcium antagonist amlodipine (initially 5 mg/day, then 10 mg/day) in patients with coronary atherosclerosis.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients with CHD. The inclusion criteria specified a total cholesterol level of less than 325 mg/dL, a fasting glucose level of less than 200 mg/dL, diastolic blood pressure of less than 95 mmHg, one focal coronary stenosis (at least 30%) not situated in a vessel with a stenosis of greater than or equal to 60%, and lesions demonstrated by coronary angiography. These detailed inclusion criteria were derived from the PREVENT study, which was the main source of the effectiveness evidence (see Other Publications of Related Interest). The mean age of the patients in the trial was 56.9 years.
Setting The setting was not stated clearly. The economic study was carried out in Switzerland.
Dates to which data relate The effectiveness and resource use data were derived from studies published in 1997 and 2000. The price year was not reported.
Source of effectiveness data The effectiveness evidence came from two published studies.
Link between effectiveness and cost data The cost data were derived separately from the effectiveness data.
Study sample The study sample included 825 patients with a mean age of 56.9 years, of whom 19.9% were women. The amlodipine group contained 417 patients and the placebo group 408. The mean age in the amlodipine group was 56.9 years and 19.6% were women. The mean age in the placebo group was 56.8 years and 20.1% were women. The study sample was not compared to the study population.
Study design The paper only briefly referred to the clinical study (see Other Publications of Related Interest). The PREVENT study was a multi-centre, double-blind, randomised placebo-controlled trial. The observation period was 3 years.
Analysis of effectiveness The method of analysis (intention to treat or per protocol) was not mentioned. The major outcome used in this economic evaluation was the CAD-related fatal events (fatal myocardial infarction, stroke, other vascular deaths and lethal bleedings) per 1,000 patients in each treatment group over a 3-year period. The age and gender were comparable in the treatment groups.
Effectiveness results There were 14.39 fatal events per 1,000 patients in the amlodipine group and 19.61 per 1,000 in the placebo group. Thus, 5.22 events per 1,000 patients were prevented.
The annual mortality rates were 4.5% in the amlodipine group and 6.2% in the placebo group, but this difference was not statistically significant, (p=0.57).
Clinical conclusions Amlodipine had no demonstrable effect on angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events.
Modelling The average life expectancy for Swiss CHD patients was calculated using the DEALE method, where the Swiss all-cause mortality rate was adjusted for the CAD-related mortality rate of the placebo group in the observational study, in order to calculate the years of life saved from avoiding fatal events through the use of amlodipine instead of placebo during the 3 years of observation (see 'Estimates of Effectiveness and Key Assumptions' section). In the paper, "CAD" appears to stand for clinically-defined angiography disease.
Methods used to derive estimates of effectiveness The life expectancy and years of life saved were derived using the DEALE method (see 'Modelling' section).
Estimates of effectiveness and key assumptions The average life expectancy for a 60-year old individual in Switzerland was 16.2 years for men and 22.3 years for women. This is possibly different from the 56.9 years included in the trial, because the life expectancy would be multiplied by the number of people who did not die during the 3 years of the trial due to the intervention.
Measure of benefits used in the economic analysis The summary benefit measure used in the economic analysis was the life-years gained. The adjusted life expectancy, which was required to evaluate the life-years gained, was calculated using the DEALE method (see 'Modelling' section). Future benefits were discounted using a 5% rate.
Direct costs A 5% discount rate was applied as the costs were incurred over 3 years. The unit costs were reported separately for most categories of costs. The health services included in the economic evaluation were grouped into five categories, namely, medication, myocardial infarction, stroke, bypass operation and coronary interventions. Coronary interventions included percutaneous transluminal coronary angioplasty, coronary stent and arthrectomy). The cost/resource boundary adopted in the study was that of the health insurance companies. Resource consumption was estimated using data collected alongside the clinical trial. The authors also made some assumptions on patient compliance. The unit costs of the drugs were obtained from public acquisition prices for drugs, whereas the unit costs for the remaining items were taken from another study by the authors of the present study. No price year was reported.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs The indirect costs were not included.
Sensitivity analysis One-way sensitivity analyses were conducted to test the robustness of the estimated cost-effectiveness results. The life expectancy and costs of both medication and treatment for the observed events were varied in the analysis.
Estimated benefits used in the economic analysis The adjusted life expectancy calculated using the DEALE approach was 18.43 years. Thus, the discounted life-years gained due to amlodipine therapy over placebo was 0.083 years per patient.
Cost results The total costs per 100 patients were Sfr 639,323 for amlodipine and Sfr 505,672 for placebo.
The additional costs (Sfr 133,651) observed in the amlodipine group mainly arose from the high initial drug costs.
Synthesis of costs and benefits An incremental cost-effectiveness ratio was calculated to combine the costs and benefits of amlodipine and placebo therapies. The extra cost per life-year gained was Sfr 14,650. This figure did not change greatly in the sensitivity analyses.
Authors' conclusions Compared with placebo, the use of amlodipine in patients with coronary heart disease (CHD) was a cost-effective option in Switzerland. The cost per life-year gained compared favourably with that of other interventions funded in the Swiss health care system.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparator was clear. Placebo was selected since the aim of the study was to evaluate the active value of amlodipine. It may or may not represent the best alternative treatment. You should decide whether it represents a valid comparator in your own setting.
Validity of estimate of measure of effectiveness The analysis of the effectiveness mainly used the results of a published study, which were then combined with Switzerland-specific data on expected survival. Since few details of the earlier study were reported, it was hard to assess its quality. The authors admitted that the main limitation of the analysis was that data collected in the USA were then transferred to Switzerland, without accounting for differences in the population characteristics and risk factors. The authors performed a sensitivity analysis where survival was varied over a reasonable range of values. However, a critical point of the analysis was that the PREVENT study showed that there was no statistically significant difference in terms of survival between the amlodipine and placebo groups, but the authors stated that their analysis was based on the assumption that future studies would confirm a significant difference. A sensitivity analysis to investigate the effects of varying the difference in fatal events between the treatment groups would have been useful. It is also uncertain whether the better survival rate will persist over the 3-year study period.
Validity of estimate of measure of benefit The benefit measure in the economic analysis was the gain in survival with amlodipine. This appears to have been appropriate, as it allowed comparisons to be made with the benefits of other interventions. Survival was calculated using the DEALE method and discounting was appropriately conducted. Quality of life issues were not discussed.
Validity of estimate of costs The perspective adopted in the study was clearly reported. It appears that all the relevant categories of cost have been included in the analysis. The unit costs and the quantities of resources used were sometimes reported separately. The sources of the data for both costs and resource consumption were reported. The costs were treated deterministically, although sensitivity analyses were conducted on those categories of costs that appeared to be more subject to uncertainty. Appropriate discounting was performed. The price year was not mentioned, thus making reflation exercises in other settings difficult. The cost estimates were specific to the study setting. The authors noted that the economic analysis was conservative, as potential cost-savings due to lower hospitalisation episodes and fewer rehabilitation measures were not accounted for in the analysis.
Other issues The authors compared their findings with those from other studies and other interventions implemented in the health system. However, the issue of the generalisability of the study results to other settings was not addressed. The external validity of the analysis was low, as few sensitivity analyses were performed and the cost estimates appeared specific to the study setting. The authors reported some limitations of their analysis, which have been highlighted already.
Implications of the study The study shows that amlodipine is a cost-effective treatment for patients with CHD. However, this conclusion should be interpreted with caution due to the limitations of the study. The authors stress the importance of risk stratification for the optimal allocation of resources in the secondary prevention of coronary events in patients with CHD.
Bibliographic details Cathomas G, Erne P, Schwenkglenks M, Szucs T D. The economic efficiency of amlodipine in the treatment of coronary atherosclerosis: an analysis based on the PREVENT study. Cardiovascular Drugs and Therapy 2002; 16(1): 61-66 Other publications of related interest Byington RP, Miller ME, Herrington D, et al for the PREVENT investigators. Rationale, design and baseline characteristics of the prospective Randomised Evaluation of the Vascular Effects of Norvase Trial (PREVENT). American Journal of Cardiology 1997;80:1087-90.
Indexing Status Subject indexing assigned by NLM MeSH Amlodipine /economics /therapeutic use; Calcium Channel Blockers /economics /therapeutic use; Coronary Artery Disease /drug therapy /economics; Cost-Benefit Analysis; Economics, Pharmaceutical; Female; Humans; Life Expectancy; Male; Middle Aged AccessionNumber 22002000918 Date bibliographic record published 30/11/2003 Date abstract record published 30/11/2003 |
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