|
Cost-effectiveness analysis of invasive and noninvasive tests in high risk patients treated with amiodarone after acute myocardial infarction |
Pedretti R F, Migliori G B, Mapelli V, Daniele G, Podrid P J, Tramarin R |
|
|
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 Invasive and non-invasive diagnostic tests and amiodarone treatment after acute myocardial infarction.
Study population The study population were hypothetical high-risk survivors of a recent acute myocardial infarction (men in 79% of cases, mean age of 57 years), free from contra-indications to amiodarone. 54% were treated with thrombolysis and 40% with beta-blockers.
Setting Hospital. The study was carried out in Tradate and Milan, Italy and Boston, Massachusetts, USA.
Dates to which data relate The effectiveness data were collected from studies published in the period 1989-1997. Data on resources used were collected in 1994. The price year was 1994.
Source of effectiveness data Effectiveness data were derived from a synthesis of previously completed studies.
Modelling A Markov simulation model was constructed to simulate the prognosis of each cohort and monitor their progress at 1-year intervals for a 20-year period tracking relevant events, total survival time and costs.
Outcomes assessed in the review The review assessed outcomes such as arrhythmic cardiac mortality rates, non-arrhythmic cardiac mortality rates, non-cardiac mortality rates, and all-cause mortality rates for each year up to 20 years. Probabilities of heart rate variability, left ventricular ejection fraction, premature ventricular complexes, ventricular tachycardia, signal-averaged electrocardiogram, and ventricular tachycardia at electrophysiologic study were also included in the review. Finally, the impact of amiodarone on arrhythmic death rates, non-arrhythmic death rates, and non-cardiac death rates, on the probability of withdrawal and the probability of severe adverse reactions was assessed.
Study designs and other criteria for inclusion in the review Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Approximately 17 studies have been included in the review.
Methods of combining primary studies Investigation of differences between primary studies Results of the review Patients at very high risk who showed a first-year cardiac mortality rate >0.11 were assumed to have a 0.075 annual cardiac mortality rate for years 2 to 10. Patients with a first-year cardiac mortality rate of 0.10 to 0.11 were defined as being at high risk and were assumed to have a 0.065 subsequent annual cardiac mortality rate. Patients with a first-year cardiac mortality rate of 0.07 to 0.08 were defined as being at intermediate risk and were assumed to have a 0.05 annual cardiac mortality rate in the following years. Patients with negative results on non-invasive testing were defined as being at low risk, with an annual cardiac mortality rate of 0.015 for years 1 to 10. First-year cardiac mortality rates in the low-risk group ranged from 0.016 to 0.032. The annual cardiac mortality rates for subsequent years ranged from 0.016 to 0.024. The 1 to 10-year non-cardiac death rate was assumed to be 0.012. Ten years after myocardial infarction, the annual all-cause mortality rate of the survivors was assumed to be 0.037.
Probability estimates were as follows:
heart rate variability (HRV) <20 U, 0.25;
left ventricular ejection fraction (LVEF) <40%, 0.31;
premature ventricular complexes/h (PVC) >10, 0.17;
unsustained ventricular tachycardia (VT) positives, 0.13;
signal-averaged electrocardiogram (SAECG) positives, 0.23;
LVEF and HRV, 0.13;
LVEF and PVCs, 0.10;
LVEF and unsustained VT, 0.06;
LVEF and SAECG, 0.08;
inducible sustained ventricular tachycardia at electrophysiologic study, 0.24.
It was assumed that amiodarone reduced arrhythmic cardiac mortality by 39%, and increased non-arrhythmic cardiac and non-cardiac mortality by 3% and 18%, respectively, in the first two years after myocardial infarction. The probability of withdrawal and of severe adverse reactions were assumed to be 0.034 and 0.023, respectively. These data were the principal input variables for the Markov model.
Measure of benefits used in the economic analysis The main measure of benefit was quality-adjusted life years (QALYs) and life expectancy. The best and worst quality of life values were assigned to the "well" and "dead" states, respectively. Patients remaining in the well state for 1 year were credited with 1 QALY. On the basis of previously published estimates, 2 and 3 weeks were deducted for execution of electrophysiologic testing and drug side effects, respectively.
Direct costs The direct costs measure included the costs of diagnostic tests (such as costs of staff time, supplies, equipment, and overhead), treatment costs (such as costs of therapy, drugs and testing during follow-up or monitoring and surveillance of patients and costs of treating side effects related to long-term amiodarone toxicity). Costs were discounted at 0%, 3%, and 5%. Quantities and costs were not reported separately. The quantity/cost boundary adopted was that of the hospital. The estimation of quantities and costs was based on actual data. Cost figures used in the model were derived from costs calculated at the Tradate Rehabilitation Institute (Italy) and from actual charges at Boston University Medical Center Hospital (Massachusetts, USA). The Italian centre is a small hospital, whereas the American center is a high-cost, teaching hospital. The price year was 1994.
Statistical analysis of costs No statistical analysis was used to examine cost differences.
Indirect Costs No indirect costs, such as patient time or production losses, were included.
Currency US dollars ($), with 1 US dollar = 1,586 Italian lire.
Sensitivity analysis An extensive sensitivity analysis was performed to assess whether variations in the estimates or assumptions significantly altered the results. The results of the model were tested for different combinations of non-invasive testing, for variations in diagnostic accuracy of electrophysiologic testing, for changes in amiodarone effectiveness and follow-up design.
Estimated benefits used in the economic analysis The number of QALYs gained by each of the three therapeutic strategies was:
13.95, 14.05, and 13.98 using a 0% discount rate;
10.65, 10.74, and 10.68 using a 3% discount rate;
9.08, 9.15, 9.10 using a 5% discount rate.
Extra life years gained for each of the three therapeutic strategies were 10.65, 10.74, and 10.68 years, respectively.
Cost results Direct costs associated with amiodarone treatment after the use of non-invasive testing combined with electrophysiologic study and with amiodarone treatment after the use of non-invasive testing were $402 and $970 under a 0% discount rate; $399 and $957 under a 3% discount rate; $397 and $948 under a 5% discount rate when costs collected at the Tradate Rehabilitation Institute are used. Using costs collected at the Boston University Medical Center Hospital, direct costs associated with amiodarone treatment after the use of non-invasive testing combined with electrophysiologic study and with amiodarone treatment after the use of non-invasive testing were $1,728 and $3,591 under a 0% discount rate; $1,717 and $3,548 under a 3% discount rate; $1,711 and $3,520 under a 5% discount rate.
Synthesis of costs and benefits When cost-effectiveness ratios were calculated, the strategy of amiodarone treatment after the use of non-invasive testing combined with electrophysiologic study was eliminated by extended dominance, irrespective of the discount rate. Compared with the no-treatment strategy, the incremental cost-effectiveness ratio of amiodarone treatment after the use of non-invasive testing was $10,633/QALY and $39,422/QALY gained (3% discount rate); $13,543/QALY and $50,286/QALY (5% discount rate); and $9,700/QALY and $35,910/QALY (0% discount rate) using Italian costs and American charges, respectively. Compared with the no-treatment strategy, costs per extra life year were $10,633/QALY and $39,422/QALY using Italian costs and American charges, respectively (costs were discounted at a 3% rate).
The strategy based on amiodarone treatment after the use of non-invasive testing combined with electrophysiologic study was dominated by a blend of the two alternatives in five of the eight analysed scenarios for both Italian costs and American charges. Compared with the no-treatment strategy, the incremental cost-effectiveness ratios ranged from $16,275 to $10,167 and from $60,350/QALYto $37,767/QALY gained for Italian costs and American charges. Compared with the no-treatment strategy, the strategy based on amiodarone given to patients with abnormalities on both non-invasive testing and electrophysiologic study had an incremental cost-effectiveness ratio that ranged from $12,500 to $6,967 and from $53,650 to $29,900/QALY gained for Italian costs and American charges, respectively.
The strategy based on amiodarone in all patients with positive results on non-invasive testing further increased quality-adjusted life expectancy, with an incremental cost-effectiveness ratio that ranged from $35,050 to $17,400 and from $115,000 to $57,133 for Italian costs and American charges. The authors also examined how changes in the sensitivity of programmedstimulation for cardiac arrhythmic (from 40% to 78%) and non-arrhythmic deaths (from 14% to 20%) and specificity (from 77% to 80%) affected cost-effectiveness ratios.
Compared with the no-treatment option, amiodarone after electrophysiologic study increased quality-adjusted life expectancy, with an incremental cost-effectiveness ratio of $4,900 (Italian) and $21,150/QALY gained (American). Amiodarone, when given to all patients with depressed heart rate variability, further increased quality-adjusted life expectancy, with an incremental cost-effectiveness ratio of $56,500 (Italian) and $185,600/QALY (American). When amiodarone effectiveness and follow-up design were changed, the results of the baseline analysis were confirmed in 3 of the 4 tested alternative scenarios for both Italian costs and American charges. The incremental cost-effectiveness ratio of electrophysiologic study-guided therapy was $19,950 (Italian) and $85,800/QALY gained (American). Amiodarone, if given after heart rate variability assessment only, further increased quality-adjusted life expectancy, with an incremental cost-effectiveness ratio of $27,600 (Italian) and $90,600/QALY gained (American).
Authors' conclusions The combined use of electrophysiologic study and heart rate variability assessment may significantly reduce the total costs of therapy, but the gain in quality-adjusted life expectancy due to amiodarone is small. Therefore, compared with the no-treatment strategy, amiodarone in patients at risk after heart rate variability analysis seems to be a more cost-effective approach. Moreover, the cost-effectiveness ratio of amiodarone therapy in post-infarction patients with depressed heart rate variability seems to be consistent with that of most currently accepted programmes.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparator is clear.
Validity of estimate of measure of benefit Three main measures of benefit were used in the study: mortality rates, life expectancy, and QALYs. More detail could have been provided on the methods of quality of life adjustments and whose values were elicited. The fact that the number of QALYs discounted at 3% exactly equalled the number of life years for each therapeutic strategy seems to be a surprising coincidence. No explanation of this phenomenon was provided by the authors.
Validity of estimate of costs Only direct costs were included in the study. The authors should be applauded for using both Italian costs and American charges as this increases the generalisability of the study. However, it is widely acknowledged that charges do not represent true opportunity costs. No sensitivity analysis on costs was performed.
Other issues More details about the methodology used in the literature review could have been provided. A statistical analysis of cost differences was not included. The authors assumed that routine use of amiodarone for all post-infarction patients would not be realistic due to the risk of sudden death. It would have nevertheless been helpful to have included both the "treat all patients" and the "treat no one" strategies in any cost-effectiveness analysis of the use of diagnostic testing to select patients for treatment. It is only by comparing these two alternatives against the effect of testing followed by selective treatment that the effect of diagnostic testing can be identified separately from the overall effect of treatment in unselected patients.
Implications of the study Because of the uncertainty surrounding certain parameters and the sensitivity of the results to other parameters, the findings require validating against the results of large, randomised controlled trials as these become available.
Source of funding Supported in part by funds for 1995 current research from the Italian Ministry of Health, Rome, Italy.
Bibliographic details Pedretti R F, Migliori G B, Mapelli V, Daniele G, Podrid P J, Tramarin R. Cost-effectiveness analysis of invasive and noninvasive tests in high risk patients treated with amiodarone after acute myocardial infarction. Journal of the American College of Cardiology 1998; 31(7): 1481-1489 Other publications of related interest 1.Comment in: Journal of the American College of Cardiology 1998;31(7):1490-2.
2. Di Salvo T G, Paul S D, Lloyd-Jones D, Smith A J C, Villarreal-Levy G, Bamezai V, Hussain S I, Eagle K A, Ogara P T. Care of acute myocardial infarction by noninvasive and invasive cardiologists: procedure use, cost and outcome. Journal of the American College of Cardiology 1996;27(2):262-269.
3. Owens D K, Sanders G D, Harris R A, McDonald K M, Heidenreich P A, Dembitzer A D, Hlatky M A. Cost-effectiveness of implantable cardioverter defibrillators relative to amiodarone for prevention of sudden cardiac death. Annals of Internal Medicine 1997;126(1):1-12.
4. Larsen G G, Manolis A S, Sonnenberg F A, Beshansky J R, Estes N A M, Pauker S G. Cost-effectiveness of the implantable cardioverter-defibrillator: effect of improved battery life and comparison with amiodarone therapy. Journal of the American College of Cardiology 1992;19:1323-34.
Indexing Status Subject indexing assigned by NLM MeSH Amiodarone /economics /therapeutic use; Anti-Arrhythmia Agents /economics /therapeutic use; Arrhythmias, Cardiac /etiology /prevention & Cost-Benefit Analysis; Decision Support Techniques; Electrocardiography, Ambulatory; Heart Function Tests /economics; Humans; Italy; Markov Chains; Models, Statistical; Myocardial Infarction /complications /drug therapy /economics /mortality; Quality-Adjusted Life Years; Risk Assessment; Survival Analysis; United States; control AccessionNumber 21998000898 Date bibliographic record published 30/04/1999 Date abstract record published 30/04/1999 |
|
|
|