No 1102
Study Quality:1+Using clopidogrel in non-ST-segment elevation acute coronary syndrome patients: A cost-utility analysis in Spain
Author:Latour-Perez J; Navarro-Ruiz A; Ridao-Lopez M; Cervera-Montes M; 2004
Intervention:Clopidogrel + aspirin
Comparison:Aspirin alone
Population:Patients with non-ST-segment elevation acute coronary syndrome
Perspective:SOCIETAL
Study type:CUA, stroke, reinfaction, death, refractory ischemia, bleeding, ICERs.
Methods:RCT, CURE study, the Framingham study, and the Spanish age-sex-specific mortality rates
Health valuations:NOT STATED, values derived from literature
Cost components:direct medical cost, treatment and cost of procedures derived from DRGs and Spanish Ministry of Health
Currency:EURO
Cost year:1999
Time horizon:lifetime
Discount rate:3%
Results-cost:Clopidogrel + ASA: euro 24806
Aspirin: euro 23962
Results-effectiveness:Clopidogrel + ASA: 8.77 QALYs
ASA: 8.70 QALYs
Results-ICER:Euro 12221 95%CI (8392-28041) for men
Euro 10299 for women
Results were presented according to age and base baseline risk of events. The base case results shown above were of a 64 year old medium risk case.
For 40 year old
Low risk: 10846 euros/QALY
Medium risk 7778 euros /QALY
High risk 5272 euros/QALY
80 year old
Low risk: 37726 euros/QALY
Medium risk 23803 euros /QALY
High risk 9831 euros/QALY
Results-Uncertainty:a one way, two way and probabilistic sensitivity analysis was done. Main attention was given to the effect of age, sex and baseline risk. Results were sensitive to age of the patient, the base risk of cardiovascular events, and the precision of the estimated effectiveness of clopidogrel.
Source of Funding:not stated
Comments:The study was well reported used standard acceptable methodology. They did an elaborate sensitivity analysis and sub-group analysis which were helpful. The authors concluded that clopidogrel is cost effective in non-ST-segment elevation, however in the results section authors reported results stratified by men and women in the base case, but it’s not clear in the paper which figures or results applied to men.
No 1103
Study Quality:1+The long-term cost-effectiveness of clopidogrel plus aspirin in patients undergoing percutaneous coronary intervention in Sweden
Author:Lindgren P, Stenestrand U; Malmberg K; Jonsson B; 2005
Intervention:Clopidogrel + Aspirin
Comparison:Aspirin
Population:Patients with unstable coronary artery disease (CAD) undergoing PCI in Sweden
Perspective:SOCIETAL
Study type:CEA, reinfaction, cardiovascular and other death
Methods:RCT, PCI-CURE study, Swedish Register of Heart and Intensive care Admissions (RIKS-HIA)
Health valuations:NOT APPLICABLE
Cost components:direct medical costs and indirect costs, Costs were derived from DRGs and literature
Currency:EURO
Cost year:2004. Converted using PCI
Time horizon:lifetime
Discount rate:3%
Results-cost:Aspirin + Clopidogrel:
Direct costs=2726 euros
Indirect =282 euros
Total=3132 euros
Patients with Diabetes
50 year olds-16 euros

60 year olds-72 euros
80 year olds-374 euros
Patients without Diabetes
50 year olds -211 euros
60 year olds-261 euros
80 year olds-430 euros
Aspirin
Direct costs=2277 euros
Indirect =523 euros
Total=2799 euros
Results-effectiveness:Aspirin + Clopidogrel: 14.16 years
Aspirin alone: 14.12 years
Difference 0.04 years
Patients with Diabetes
50 year olds -0.03
60 year olds-0.04
80 year olds-0.09
Patients without Diabetes
50 year olds -0.03
60 year olds-0.05
80 year olds-0.09
Results-ICER:Direct medical costs: 10993 euros/LYG

Total costs: 8127 euros/LYG

Cost utility was done in sensitivity analysis. 6506 euros/QALY

Patients with Diabetes
50 year olds -dominance
60 year olds-1969 euros/LYG
80 year olds-3961 euros/LYG
Patients without Diabetes
50 year olds -7243 euros/LYG
60 year olds-6929 euros/LYG
80 year olds-4609 euros/LYG

In sensitivity analysis they considered post MI patients that occurred 7 days after admission and combination therapy dominated aspirin alone.
Results-Uncertainty:the model was robust to changes in variables such as costs and discounting.
Source of Funding:Private
Comments:Methodologically the paper was well reported. Sources of effectiveness and cost data were clearly reported and both deterministic and probabilistic sensitivity analysis was done. They also did a sub-group analysis in which the conclusions remained the same with either age or diabetes mellitus. ICERs were more favorable for the younger patients aged 50 years with diabetes mellitus and less favorable for the 70 year olds with or without diabetes. Their model predicted fewer/less events than the CURE study did making their estimates more conservative. Their results can not be generalized to the post MI population
No 1111
Study Quality:1+Long-term cost-effectiveness of clopidogrel given for up to one year in patients with acute coronary syndromes without ST-segment elevation
Author:Weintraub WS; Mahoney EM; Lamy A; Culler S; Yuan Y; Caro J; Gabriel S; Yusuf S; CURE S; 2005
Intervention:Clopidogrel + ASA
Comparison:ASA/placebo
Population:Patients who had experienced an acute coronary syndrome (ACS) without ST-segment elevation
Perspective:NHS
Study type:CEA, outcomes were death, stroke, and myocardial infarction, ICERs
Methods:RCT CURE study, observational data from the Saskatchewan and Framingham Heart study
Health valuations:NOT APPLICABLE
Cost components:direct medical costs 9hospitalisations) and medication costs. These costs were derived from DRGs, Medicare and MEDSTAT data base.
Currency:US$
Cost year:2001
Time horizon:12 months
Discount rate:3%
Results-cost:Using Medicare DRG costs
Clopidogrel: $13019
Placebo: $12578

Using MEDSTAT (private reimbursement) costs
Clopidogrel: $17924
Placebo: $17586
Results-effectiveness:Total number of events using Framingham data
Clopidogrel: 0.5327
Placebo: 0.6026
LYG with clopidogrel: 0.0699
Total number of events using Saskatchewan data
Clopidogrel: 0.3910
Placebo: 0.4592
LYG with clopidogrel: 0.0682
Results-ICER:Using Framingham data
Medicare costs: $9144/LYG and 92.8% probability of being cost effective at $50000/LYG

Using MEDISTAT costs: $ 7654/LYG and 93.4% probability of being cost effective at $50000/LYG

Using Saskatchewan data
Medicare costs: $9343/LYG and 97% probability of being cost effective at $50000/LYG

Using MEDISTAT costs: $ 7833/LYG and 97.6% probability of being cost effective at $50000/LYG

Sub-groups

Using Framingham database
<65 years $5022/LYG
>65years $7569/LYG
Male $2362/LYG
Female $70396/LYG
Diabetes $9857/LYG
No diabetes $5583/LYG
Prior MI $1404/LYG
No prior MI $14171/LYG
Results-Uncertainty:results remained robust in sensitivity analysis even when baseline data from the Saskatchewan database was used.
Source of Funding:not stated
Comments:The authors were very detailed in their reporting of the methods they used. For costing they used three different credible methods and for effectiveness data they used the CURE trial and two observational databases the Framingham and Saskatchewan to estimate life expectancy, which yielded comparable results.
No 1109
Study Quality:1+A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone.
Author:Schleinitz MD, Heidenreich PA; 2005
Intervention:Clopidogrel, 75 mg/d, plus Aspirin, 325 mg/d, for 1 year,
Comparison:Aspirin alone
Population:Patients with unstable angina and electrocardiographic changes or non-Q-wave myocardial infarction over a lifetime
Perspective:SOCIETAL
Study type:CUA, reinfaction, stroke, mortality, quality-adjusted life-years (QALYs), hemorrhagic events & ICERs
Methods:RCT, CURE study
Health valuations:derived the values from the literature
Cost components:direct medical costs incurred during hospitalisation incusing nursing care and procedures, wholesale price for medications. Used a GDP deflator to update costs to 2002.
Currency:US$
Cost year:2002
Time horizon:lifetime
Discount rate:3%
Results-cost:Patients treated with aspirin alone costs $127700
Addition of clopidogrel costs $129300
Results-effectiveness:Patients treated with aspirin alone lived 9.51 QALYs
Addition of clopidogrel increased life expectancy to 9.61 QALYs
Results-ICER:The incremental cost-effectiveness ratio for clopidogrel plus aspirin compared with aspirin alone was 15,400 dollars per QALY.

Duration of therapy
The marginal costs of the second year of therapy was $31600/QALY,
Third year $61300/QALY
Fourth year $136500/QALY
Fifth year $730000/QALY
Before the end of the third year the efficacy of clopidogrel was reduced by about 25% in the model.
Results-Uncertainty:results were not sensitive to changes in risk reduction and costs of clopidogrel in both deterministic and one way sensitivity analysis.
Source of Funding:Public
Comments:This analysis may not apply to patients with severe heart failure, those undergoing long-term anticoagulant therapy or those recently managed with revascularization. The study did not focus on a particular ACS which might limit its applicability to the Post MI population. Otherwise the study was well reported, proving details of sources of data, how the data was incorporated as well as a clear model structure.
No 1099
Study Quality:1+Cost effectiveness of aspirin, clopidogrel, or both for secondary prevention of coronary heart disease
Author:Gaspoz J; Coxson PG; Goldman PA; Williams LW; Kuntz KM; Hunnink M; Goldman L; 2002
Intervention:Aspirin, clopidogrel,
Comparison:Aspirin or aspirin + clopidogrel
Population:Patients aged 35 to 84 years in which CHD developed and evaluated over a 25 year period.
Perspective:THIRD PAYER
Study type:Deterministic decision analysis, CUA. The outcomes were deaths from coronary/non coronary, MIs
Methods:Framingham heart study, Scandinavian Simvastatin Survey, CURE study, CAPRIE and Antiplatelets T Collaborators
Health valuations:Literature
Cost components:direct medical costs including drug costs and costs of side effects like gastrointestinal. Costs were derived from literature (refs given) and National medical expenditure survey.
Currency:US$
Cost year:2000
Time horizon:25 years
Discount rate:3%
Results-cost:Incremental costs are estimated over the 30 year period in millions.
Aspirin (ASA) for all eligible patients: $8000 000
Addition of Clopidogrel for those that are not eligible for ASA: $14 000 000
Clopidogrel alone for all patients: $156 000 000
Clopidogrel for all + Aspirin for all eligible: $182000 000
Results-effectiveness:Incremental QALYs
Aspirin (ASA) for all eligible patients: 682000 QALYs
Addition of Clopidogrel for those that are not eligible for ASA: 456000 QALYs
Clopidogrel alone for all patients: 632 000 QALYs
Clopidogrel for all + Aspirin for all eligible: 1437 000 QALYs
Results-ICER:Aspirin (ASA) for all eligible patients: $1100/QALY
Addition of Clopidogrel for those that are not eligible for ASA: $31000/QALY
Clopidogrel alone for all patients: $250000/QALY
Clopidogrel for all + Aspirin for all eligible: $130000/QALY
Results-Uncertainty:results were sensitive to the effect of the intervention on revascularisation. Aspirin and clopidogrel will save money if they reduced the rate of revascularisation as much as they did on MI. The cost of clopidogrel was also assessed but the results were not reported as they did not change the conclusions.
Source of Funding:Charitable
Comments:This is a detailed study but does not focus on a particular disease area of CHD, limiting its relevance to post MI patients. Baseline event rates and costs differ for subtypes of CHD which might alter cost effectiveness conclusions. Thus the generalisability of these results to the post MI patients is not clear.
No 1104
Study Quality:++Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment-elevation acute coronary syndromes: a systematic review and economic evaluation
Author:Main C; Palmer S; Griffin S; Jones L; Orton V; Sculpher M; 2004
Intervention:Clopidogrel + ASA
Comparison:ASA
Population:patients with non-ST-elevation ACS
Perspective:NHS
Study type:CUA, death from cardiovascular causes, non-fatal myocardial infarction or stroke
Methods:CURE study, PRAIS-UK and NHAR
Health valuations:Quality of life weights were derived from the literature
Cost components:Direct medical costs of treatment, procedures and side effects. Costs data was derived from the literature, BNF and NHS reference costs
Currency:£
Cost year:2002
Time horizon:lifetime
Discount rate:6% for costs and 1.5% for benefits
Results-cost:Clopidogrel + ASA: £12695
ASA:£12225
Results-effectiveness:Clopidogrel + ASA: 8.2795 QALYS
ASA:8.2022 QALYS
Results-ICER:£6078/QALY
Probability of being cost effective at £10000 and £30000 WTP is 32% and 21% respectively.
Sub-groups
For high risk group there was a reduction in the ICER to about £4939/QALY and low risk the ICER increased to £8734/QALY.
The Assessment Group explored the cost effectiveness of using clopidogrel for periods shorter than 1 year. The ICER for 1 month of treatment with clopidogrel compared with standard care alone was calculated to be £824 per QALY with a 6% probability that clopidogrel is cost effective at £30000/QALY. The strategies of using clopidogrel for 3 or 6 months were ruled out by extended dominance, and the ICER for 12 months of treatment with clopidogrel compared with 1 month was £5159 per QALY, with a 83% probability that clopidogrel is cost effective at £30000/QALY.
Results-Uncertainty:The results were most sensitive to the inclusion of additional strategies which assessed alternative treatment durations with clopidogrel for example reducing the treatment duration to 5 years more than doubled the ICERs to about £15000/QALY. Although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. Discount rate and impact of the cost of stroke did not affect the baseline ICER.
Source of Funding:Public
Comments:One paper and a company submission met the inclusion criteria for this HTA. The results are in agreement and indicate that there is a benefit in the short term and the ICERs are favorable, the ICERs becomes less favorable in the long-term but remain within acceptable range of cost effectiveness. Authors did a sub-group analysis stratifying results according to low or high risk defined as patients with at least one of the following over 70years, those with an ST-depression on an ECG and diabetes.

From: Appendix D, Health Economic Extractions

Cover of Post Myocardial Infarction
Post Myocardial Infarction: Secondary Prevention in Primary and Secondary Care for Patients Following a Myocardial Infarction [Internet].
NICE Clinical Guidelines, No. 48.
National Collaborating Centre for Primary Care (UK).
Copyright © 2007, National Collaborating Centre for Primary Care.

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