|
Amiodarone versus implantable defibrillator (AMIOVIRT): background, rationale, design, methods, results and implications |
Wijetunga M, Strickberger S A |
|
|
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 study compared the use of amiodarone versus implantable defibrillator (ICD) therapy in patients with non-ischaemic dilated cardiomyopathy (NIDCM) and asymptomatic non-sustained ventricular tachycardia (NSVT). Amiodarone was initiated at a dose of 800 mg/day for the first week, followed by 400 mg/day for one year, and then 300 mg/day.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients with NIDCM, with a left ventricular ejection fraction of less than or equal to 0.35, documented asymptomatic NSVT, and New York Heart Association functional Class I to III. Patients with syncope, pregnancy, or an NIDCM diagnosed within 6 months were excluded from the study. Also excluded were patients with a contraindication to amiodarone or ICD treatment, and those having ongoing therapy with a Class I anti-arrhythmic drug.
Setting The study setting was secondary care. The economic study was carried out at the Washington Hospital Centre, USA.
Dates to which data relate The effectiveness data were collated between August 1996 and June 2001.
Source of effectiveness data The effectiveness and resource use data were derived from a single study, the Amiodarone versus Implantable Defibrillator Randomised Trial (AMORVIRT). The price year was not reported.
Link between effectiveness and cost data The costing was undertaken prospectively on a sample of 24 patients, all of whom were treated at one centre.
Study sample A sample of 219 patients in each group was calculated when using a power of 80% to observe a reduction in mortality from 20% to 10%, (p<0.05, two-sided t-test). However, at the first scheduled interim analysis of the first deaths, the previously determined stopping rule for futility (mortality difference at a significance level of < 0.025 or > 0.025, 90% power, assuming enrolment of 600 patients) was reached and the study was stopped. Therefore, only 103 patients were randomised into the study. Of these, 51 were randomised to treatment with amiodarone and the remaining 52 were randomised to ICD therapy. The mean age (all patients) was 59 (+/- 11) years and 30% of the patients were females. The authors did not report the proportion of females or age for each group of patients.
Study design The AMIOVIRT was an unblinded, randomised trial that was conducted at 10 medical centres in the USA. The mean follow-up was 2.0 (+/- 1.3) years (range: 0.1 - 4.8). The authors did not report the loss to follow-up. Although the study was unblinded, the authors reported that the events committee, which evaluated and determined the cause of each death, was blinded to patient randomisation.
Analysis of effectiveness The analysis of the clinical study was conducted on an intention to treat basis (i.e. the analysis was based on the initially assigned treatment for each patient). The outcome measures included death, cause of death, arrhythmia-free survival and quality of life. Arrhythmia-free survival was determined by the absence of death, syncope, life-threatening ventricular arrhythmias, or appropriate ICD therapies. Quality of life was measured using the Quality of Well Being Schedule and the State Trait Anxiety Inventory. The authors reported that the patients' baseline characteristics did not differ between the two treatment groups.
Effectiveness results There were no statistically significant differences in the 1- and 3-year survival rates in patients who received amiodarone and those who received an ICD (90% and 87% for amiodarone versus 96% and 88% for ICD; p=0.8).
The authors found a trend towards improved arrhythmia-free survival rates in patients treated with amiodarone, (p=0.1).
The quality of life measures were not significantly different between the treatment groups.
Clinical conclusions The major clinical finding of the AMIOVIRT was that 1- and 3-year mortality rates were not different in patients with NIDCM and asymptomatic NSVT who were treated with amiodarone as compared with an ICD.
Measure of benefits used in the economic analysis The authors did not derive a measure of health benefits. The analysis was therefore categorised as a cost-consequences analysis.
Direct costs It was unclear whose direct costs were included in the analysis, although they would appear to have been those of the hospital. The authors did not clearly report the costs included in the analysis, stating only that the costs of both in- and outpatient treatment were included. Discounting was relevant, as the costs could have been incurred over 4 years (i.e. maximum follow-up), but was not performed. The study reported the mean costs. The price year was not reported.
Statistical analysis of costs The costs were treated stochastically. Statistically significant differences were determined using a two-sided t-test, with the level of significance being set at 5%.
Indirect Costs The indirect costs were not included.
Sensitivity analysis Sensitivity analyses were not performed.
Estimated benefits used in the economic analysis See 'Effectiveness Results' section.
Cost results The cost of medical care was $8,879 for patients treated with amiodarone and $22,039 for those treated with an ICD, (p=0.1).
Synthesis of costs and benefits The costs and benefits were not combined.
Authors' conclusions The major findings of the Amiodarone versus Implantable Defibrillator Randomised Trial (AMORVIRT) were that 1- and 3-year mortality rates were not different in patients with non-ischaemic dilated cardiomyopathy (NIDCM), a left ventricular ejection fraction of less than or equal to 0.35, and asymptomatic non-sustained ventricular tachycardia (NSVT) who were treated with amiodarone as compared with an ICD. The authors also concluded that there were trends towards improved arrhythmia-free survival and lower costs of medical care in patients treated with amiodarone, although the quality of life measurements were similar for both patient groups.
CRD COMMENTARY - Selection of comparators Although the authors did not explicitly report why ICDs were used as the comparator, they would appear to represent current practice in the authors' setting. The authors did report, however, that they did not include a standard medical treatment group in addition to the amiodarone and ICD group. According to the authors, without a control group, the present study could not exclude the possibility that neither amiodarone nor an ICD affected mortality or improved clinical outcomes.
Validity of estimate of measure of effectiveness The analysis was based on a randomised controlled trial (RCT). This was appropriate for the study question as well-conducted RCTs are considered the 'gold' standard when comparing health interventions. The study sample appears to have been representative of the study group. However, the study sample was much lower than that required to detect any statistically significant results, as determined by the a priori power calculations. The reason for this was that the study had to be stopped because of the prospective rule used to identify inability to differentiate between ICD and amiodarone therapy. The authors also reported that, based on their results, approximately 12,000 randomised patients would be required to achieve a statistical power of 80% if the study were to be continued.
Although the authors reported that the patient groups were shown to be comparable at analysis, they did not provide the actual baseline characteristics for each of the two groups. Instead, they only reported characteristics for all patients. The clinical study was conducted on an intention to treat, and all differences were tested for statistical significance using appropriate statistical techniques.
Validity of estimate of measure of benefit The authors did not derive a measure of health benefits. The analysis was therefore categorised as a cost-consequences analysis.
Validity of estimate of costs As the authors did not report the perspective adopted in the economic analysis, it was unclear if all the relevant categories of cost were included in the analysis. Further, the authors also failed to report the costs included in the analysis, mentioning only that in- and outpatient treatment costs were included. It was therefore unclear if any major costs were omitted from the analysis. The costs and the quantities were not reported separately, which will limit the generalisability of the authors' results. Resource use was determined for 24 patients in the trial, all of whom were treated at one centre. It would appear, although the authors did not report it, that the unit costs were derived from that hospital centre.
Appropriate statistical techniques were used to detect statistically significant cost-differences between the two groups. However, as the sample was so small, even though the difference in costs was large, the study did not find any statistically significant results. Discounting was not performed, even though the costs could have been incurred over a 4-year period. The price year was not reported, which will hamper any future inflation exercises.
Other issues The authors reported that their results were comparable with those of the Cardiomyopathy Trial (CAT), which found no difference in survival between the ICD group and the medical therapy group. However, the authors acknowledged that this trial was also based on a small patient sample (n=104). The authors also reported that their results were higher than the 1-year survival rate among patients treated with amiodarone, as reported in other trials. The issue of generalisability to other settings was not addressed. The authors do not appear to have reported their results selectively and their conclusions reflected the scope of the analysis. No further limitations to the study were reported.
Implications of the study The authors reported that the implication of the AMIOVIRT was that treatment with amiodarone could be reasonable as an initial approach to improve survival in patients with NIDCM and NSVT.
Bibliographic details Wijetunga M, Strickberger S A. Amiodarone versus implantable defibrillator (AMIOVIRT): background, rationale, design, methods, results and implications. Cardiac Electrophysiology Review 2003; 7(4): 452-456 Other publications of related interest Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable defibrillator study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000;101:1297-302.
Kuck KH, Cappato R, Siebels J, et al. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation 2000;102:748-54.
Bansch D, Antz M, Boczor S, et al. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation 2002;105:1453-8.
Indexing Status Subject indexing assigned by NLM MeSH Amiodarone /therapeutic use; Anti-Arrhythmia Agents /therapeutic use; Arrhythmias, Cardiac /mortality; Cardiomyopathy, Dilated /drug therapy /mortality /therapy; Defibrillators, Implantable; Disease-Free Survival; Female; Humans; Male; Middle Aged; Quality of Life; Stroke Volume AccessionNumber 22004006444 Date bibliographic record published 30/11/2005 Date abstract record published 30/11/2005 |
|
|
|