Study population The study population comprised patients receiving ibutilide for acute chemical conversion of AF or flutter.

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1 Cost effectiveness of ibutilide with prophylactic magnesium in the treatment of atrial fibrillation Coleman C I, Kalus J S, White C M, Spencer A P, Tsikouris J P, Chung J O, Kenyon K W, Ziska M, Kluger J, Reddy P 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 ibutilide in the presence and absence of magnesium prophylaxis for the conversion of atrial fibrillation (AF). The mean dose of ibutilide was 2.2 (+/- 1) g. Type of intervention Treatment. Economic study type Cost-effectiveness analysis. Study population The study population comprised patients receiving ibutilide for acute chemical conversion of AF or flutter. Setting The setting was secondary care in one hospital and two medical centres. The economic study was conducted in the USA. Dates to which data relate The effectiveness data and resource use data were gathered between August 1996 and December The costs were adjusted to 2002 US dollars. Source of effectiveness data The evidence for the final outcomes was derived from a single study. Link between effectiveness and cost data The costs from one of the participating institutions were used, but it was unclear whether the costs related to the sample of patients coming from that institution. The costing was conducted retrospectively. Study sample The sample size was calculated in the planning phase of the study so as to assure a power of 80%. The result was that 112 patients would be necessary to detect significant differences between the groups. However, it was decided, a priori, to include all eligible patients at three participating institutions. Patients receiving magnesium within 2 hours of ibutilide administration, not intended for the treatment of Torsade de Pointes, served as the active group. Patients who did not receive magnesium, either before or during ibutilide therapy, served as the control patients. A total of 321 patients were identified, 107 in the active group and 214 in the control group. Page: 1 / 5

2 Study design The economic evaluation was based on a parent clinical study, the Treatment with Ibutilide and Magnesium Evaluation (TIME) study, (see 'Other Publications of Related Interest' below for bibliographic details). The TIME study was a multi-centre, retrospective cohort study that was conducted at Hartford Hospital, Medical University of South Carolina Medical Centre and Texas Tech University Medical Centre. The reader is referred the parent study for further details of the study design. Analysis of effectiveness The method of analysis of effectiveness (intention to treat or treatment completers) was not stated, but the study design suggests that it was likely to have been treatment completers only. The primary health outcome was the conversion of AF. The groups were found to be comparable in terms of age, gender, weight, type of atrial arrhythmia and ibutilide dose. The active group had a lower baseline plasma magnesium level than the control group. No adjustment for this difference was made in the analysis. Effectiveness results The proportion of patients achieving successful chemical conversion from AF was 72% (95% confidence interval, CI: 62-79; p=0.040) in the active group and 60.3% (95% CI: 53-67; p=0.04) in the control group. The improvement in conversion rate was statistically (odds ratio 1.69, 95% CI: ; p=0.04)) and clinically significant. Clinical conclusions The relative increase in the rate of successful chemical conversion in patients receiving magnesium, compared with those not receiving magnesium, was both clinically and statistically significant. Measure of benefits used in the economic analysis The primary health outcome, chemical conversion of AF or flutter, was also used as the measure of benefit. Direct costs The costs were not discounted given that only initial treatment costs were included over a short period (less than 1 year). The unit costs and the resource quantities were not reported separately. The resource use data were gathered between 1996 and Standardised costs from a single institution were used. These were obtained directly from the provider and were adjusted to 2002 US dollars. The costs included in the analysis were for ibutilide, magnesium, intravenous administration (including nursing time) and admixture, physician fees, electrocardiography and adverse events. The costs of adverse events were calculated. These covered drug therapy (e.g. magnesium, phenytoin, lidocaine and isoprenaline), conversion, pacing, and physician fess for conversion and the treatment of adverse events. Statistical analysis of costs The cost data were presented as means +/- standard deviations. The authors reported that categorical variables were compared using a chi-squared analysis of Fischer's test, while continuous data were compared using an unpaired t-test. It is assumed that the costs were treated as a continuous variable. A p-value of less than 0.05 was considered statistically significant. Indirect Costs The indirect costs were not included. Page: 2 / 5

3 Currency US dollars ($). Sensitivity analysis A one-way sensitivity analysis was carried out. Efficacy (percentage of patients who underwent successful chemical conversion) was varied by the 95% CI, while the costs of ibutilide, magnesium, intravenous administration and admixture, direct current cardioversion, physician fees, electrocardiographs and adverse events were varied by +/- 50%. Estimated benefits used in the economic analysis Since the effectiveness measure was used as the measure of benefit, the reader is referred to the 'Effectiveness Results' section. Cost results The total costs per patient were $1, 075 for the active group and $1,201 for the control group. The difference was not statistically significant, (p=0.116). The costs associated with the treatment of adverse events were minimal and were similar for both groups. Synthesis of costs and benefits An incremental cost-effectiveness ratio (ICER) for treatment with ibutilide plus magnesium versus ibutilide alone was calculated. To determine an estimate of the uncertainty of the ICER, the non-parametric bootstrap method was used. Actual patient level data for both costs and effects were treated as an empirical probability distribution that is repeated with random components many times. The data were re-sampled 25,000 times in such a manner that all cost-effect pairings were equally likely to be selected. The resultant incremental cost-effectiveness estimates were then plotted upon the cost-effectiveness plane and used to estimate confidence intervals. Of the 25,000 total re-samplings, 4.5% would be more effective and more costly, 0.5% would be less effective and more costly, 1.6% would be less effective and less costly, and 93.4% would be more effective and less costly. When the efficacy of ibutilide plus magnesium and ibutilide alone was increased or lowered by the 95% CIs, ibutilide plus magnesium remained cost-effective compared with ibutilide alone. The findings were robust when the costs of ibutilide, magnesium, intravenous administration and admixture, direct current conversion, physician fees, electrocardiography and adverse events were varied by +/- 50%. Authors' conclusions From the perspective of a US hospital payer, the addition of prophylactic magnesium to ibutilide may be cost-effective for the acute conversion of patients in atrial fibrillation (AF), or flutter, compared with ibutilide alone. CRD COMMENTARY - Selection of comparators The reason for the choice of the comparator was clear. The comparator was chosen because it reflected standard practice for the treatment of AF in the authors' setting. You should decide if this is a widely used health technology in your own setting. Validity of estimate of measure of effectiveness The analysis was based on a retrospective cohort study, which was adequate for the study question although susceptible to bias. The authors acknowledged that a prospective randomised trial would be the ideal. It was not clear from this paper whether the study sample was representative of the study population; the reader is referred to the parent study for Page: 3 / 5

4 further information (see 'Other Publications of Related Interest' below for bibliographic details). With the exception of plasma magnesium level, which was higher in the active group, the patient groups were shown to be comparable at analysis. The analysis of effectiveness was handled credibly, with appropriate statistical analyses being undertaken and reported. Validity of estimate of measure of benefit The estimation of benefits was obtained directly from the estimate of effectiveness and, as such, is a condition-specific outcome. The use of quality-adjusted life-years, if feasible, would have facilitated comparisons with other health care programmes. Validity of estimate of costs All the categories of cost relevant to the perspective adopted were included in the analysis and the price year was given. However, the unit costs and the resource quantities were not reported separately. This limits the generalisability of the cost results, although the sensitivity analysis of the costs helps in this matter. Since all the costs were related to the initial treatment, discounting was unnecessary. Other issues The authors made appropriate comparisons of their findings with those from other studies. In addition, the issue of generalisability to other settings was addressed. The authors did not present their results selectively. The authors acknowledged a number of further limitations to their study. First, the study was a piggyback cost-effectiveness analysis of a retrospective cohort study and it was not powered to detect significant differences in the total costs between the groups. There was a lack of quality of life data and no multivariate sensitivity analysis. Finally, all the costs used in the investigation were standardised costs from one hospital. Implications of the study The authors proposed a prospective evaluation of magnesium to provide more firm evidence of its efficacy and costeffectiveness when utilised as a strategy for conversion of AF. However, they acknowledged that, given the generic availability of intravenous magnesium and the extensive study population that would be required, it is unlikely that such a trial would ever be conducted. In this situation they noted that modelling studies may be a reasonable alternative. Source of funding Funded by an American College of Clinical Pharmacy/Merck Cardiovascular Fellowship award. Bibliographic details Coleman C I, Kalus J S, White C M, Spencer A P, Tsikouris J P, Chung J O, Kenyon K W, Ziska M, Kluger J, Reddy P. Cost effectiveness of ibutilide with prophylactic magnesium in the treatment of atrial fibrillation. PharmacoEconomics 2004; 22(13): PubMedID Indexing Status Subject indexing assigned by NLM MeSH Aged; Anti-Arrhythmia Agents /economics /therapeutic use; Atrial Fibrillation /economics /prevention & control /therapy; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Hospitalization /economics; Humans; Magnesium /economics /therapeutic use; Male; Middle Aged; Retrospective Studies; Sulfonamides /economics /therapeutic use; United States Page: 4 / 5

5 Powered by TCPDF ( AccessionNumber Date bibliographic record published 31/10/2005 Date abstract record published 31/10/2005 Page: 5 / 5