Cost effectiveness of drug eluting coronary artery stenting in a UK setting: cost-utility study Bagust A, Grayson A D, Palmer N D, Perry R A, Walley T

Transcription

1 Cost effectiveness of drug eluting coronary artery stenting in a UK setting: cost-utility study Bagust A, Grayson A D, Palmer N D, Perry R A, Walley T 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 examined the use of drug-eluting stents (DES) after percutaneous transluminal coronary angioplasty (PTCA) for the treatment of symptomatic coronary artery disease (CAD). Two types of DES were considered, one coated with sirolimus and one with paclitaxel. Type of intervention Treatment. Economic study type Cost-utility analysis. Study population The study population comprised a hypothetical cohort of patients with symptomatic CAD. Setting The setting was tertiary care. The economic study was carried out in the UK. Dates to which data relate The effectiveness data were obtained from studies published between 2001 and 2004, as well from a database of patients covering the period between January 2000 and December The resource use data were derived from the database of patients (January December 2002). The price year was Source of effectiveness data The effectiveness evidence was derived from published studies, a series of patient records, and authors' opinions. Outcomes assessed in the review The outcomes estimated from the literature were: the rates of TVR at 12-month follow-up for the two types of DES and for BMS; clinical or angiographic risk factors predisposing patients to subsequent revascularisation; and several utility values. Study designs and other criteria for inclusion in the review To ensure consistency with the time point employed in teh cost-effectiveness analysis, only trials reporting at least 12 months follow-up were used. Page: 1 / 7

2 Treatment effectiveness (rate of TVR) was obtained from clinical trials: the RAVEL (randomised study with the sirolimus-eluting Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) trial, the SIRIUS (sirolimus-eluting balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) trial, the TAXUS (treatment of de novo coronary disease using a single paclitaxel-eluting stent) I trial, the TAXUS II (slow-release cohort) trial, and the TAXUS IV trial. Risk factors were estimated using statistical tests for a consecutive series of 2,884 patients (1,951 elective surgery and 933 non-elective) undergoing stent placement at the Cardiothoracic Centre in Liverpool between January 2000 and December The utility values were estimated from EQ-5D results reported for the Arterial Revascularisation Therapies study and SoS (stent or surgery) clinical trials. Sources searched to identify primary studies Not reported. Criteria used to ensure the validity of primary studies The use of clinical trials and a large series of patients to derive clinical data was appropriate. Methods used to judge relevance and validity, and for extracting data Not reported. Number of primary studies included Nine primary studies provided the clinical data. Methods of combining primary studies A meta-analysis was used to combine some estimates. For other data, a narrative approach appears to have been used. Investigation of differences between primary studies Not reported. Results of the review For sirolimus-based DES, the TVR was 7.5% with DES and 24.9% with BMS. The relative risk reduction was 69.8% (95% confidence interval, CI: 59.3 to 77.7; p<0.001). For paclitaxel-based DES, the TVR was 7.3% with DES and 16.3% with BMS. The relative risk reduction was 55.3% (95% CI: 40.3 to 66.5; p<0.001). The analysis of the patient series revealed that four clinical variables were found to be significant independent predictors of repeat revascularisation after elective surgery within 12 months (calcification, angulation >45 degrees, restenotic lesion and triple-vessel disease), while there were only two for non-elective surgery (vessel diameter <2 mm, prior coronary artery bypass graft). Page: 2 / 7

3 The hazard ratios for risk of repeat revascularisation (with respect to patient without any risk factor) after elective surgery were as follows: for calcification, 1.89, (p=0.002); for angulation >45 degrees, 1.51, (p=0.019); for restenotic lesion, 2.19, (p=0.032); for triple-vessel disease, 1.56, (p=0.042). The hazard ratios for risk of repeat revascularisation (with respect to patient without any risk factor) after non-elective surgery were as follows: for vessel diameter <2 mm, 2.90, (p=0.004); for prior coronary artery bypass graft (CABG), 2.27, (p=0.015). The absolute risk of repeat revascularisation in the 12-month follow-up was estimated for patients undergoing elective or non-elective surgery according to the number of risk factors (from none to 4 for elective surgery and from none to 2 for non-elective surgery). For example, the absolute risk of repeat revascularisation in a patients undergoing elective surgery with only one risk factor such as triple-vessel disease was 7.7% (95% CI: 4.9 to 10.7). Most patients fell within the sub-group with lowest risk (57% of the elective surgery group with 5.6% risk, and 91% of the non-elective surgery group with 9.9% risk). The annual quality-adjusted life-years (QALYs) lost to angina were (95% CI: to 0.148). The QALYs lost per PTCA were (95% CI: to ). The QALYs lost per CABG were (95% CI: to 0.035). Methods used to derive estimates of effectiveness The authors made some assumptions that were used in the analysis. Estimates of effectiveness and key assumptions It was assumed that cardiologists do not mix stent types when treating a patient so as not to compromise the effectiveness of the most efficacious device. It was also assumed that a patient undergoing a repeat intervention received the same stent as in the index procedure. Based on the results of the systematic review, it was assumed that no gain could be attributed to DES in relation to mortality, stroke and myocardial infarction. Measure of benefits used in the economic analysis The summary benefit measure used was the expected QALYs associated with DES or BMS in a hypothetical cohort of patients with symptomatic CAD. The QALYs were calculated using utility weights derived from the literature over a 12-month time horizon. The difference in utility scores before and after treatment was combined with the duration of the disutility due to the intervention (1 month for PTCA procedures but up to 6 months for CABG). Discounting was not applied because of the short time horizon of the analysis. Direct costs Page: 3 / 7

4 The analysis of the costs was carried out from the perspective of the NHS. It included the costs of specialist consultations for patients with recurrent symptoms, hospital investigations (e.g. angiogram), repeat interventions undertaken (PTCA, stented percutaneous coronary intervention or CABG), and specialist follow-up. The unit costs were presented separately from quantities of resources used. The costs were estimated on the basis of NHS tariff costs, NHS reference costs and market averages. The price of a DES was taken from official UK list prices and was set at 500 higher than a BMS. Resource consumption was derived from the Cardiothoracic Centre audit (January December 2002). Discounting was not relevant as the costs were incurred over a 12-month time horizon. The costs were expressed using 2003 values. Statistical analysis of costs The costs were treated deterministically in the base-case. Indirect Costs The indirect costs were not considered. Currency UK pounds sterling (). Sensitivity analysis Sensitivity analyses were carried out to address the issue of uncertainty around some clinical and economic data using 95% CIs. An analysis of extremes was also performed. Alternative assumptions made by the authors were tested in the sensitivity analysis and were described in detail in an appendix to the original paper. Estimated benefits used in the economic analysis The expected QALYs were not reported. Cost results The estimated costs were not reported. Synthesis of costs and benefits Incremental cost-utility ratios were calculated to combine the costs and benefits of the alternative strategies in all possible sub-groups of patients defined according to both the number of risk factors (from none to 4 for elective surgery and from none to 2 for non-elective surgery) and the number of stents placed (from 1 to 3). A threshold of 30,000 per QALY defined an intervention as cost-effective. In synthesis, in the case of elective treatment, DES were cost-effective from the perspective of the NHS only when a single DES (sirolimus- or paclitaxel-based) was implanted in patients with at least two risk factors present. In the case of non-elective treatment, DES were cost-effective only in patients with two risk factors. The use of a single DES was always cost-effective if at least one risk factor was present, and up to two (paclitaxel) or three (sirolimus) DES could be justified if both risk factors applied. For a hospital able to negotiate discounts, the additional price per stent that could be justified in order to achieve an incremental cost per QALY gained of 30,000 or less or for cost-neutrality after 12 months of follow-up was estimated: for more than 50% usage of sirolimus-based DES, the price premium should be less than 221 (cost-effectiveness) or 146 (cost-neutrality); and Page: 4 / 7

5 for 90% usage, the price premium should be no more than 112 and 80, respectively. The price thresholds for paclitaxel DES were slightly lower. The sensitivity analysis showed that, although the cost-effectiveness results were borderline in some risk groups, in general, the conclusions of the base-case analysis were robust. The authors discussed the main assumptions (and their sources) and the potential impact on the cost-effectiveness results. Authors' conclusions At current unit pricing of drug-eluting stents (DES) in the UK (500 higher than for bare metal stents, BMS), the use of DES can be considered cost-effective only for any patient with a 12-month risk of requiring a second intervention that is greater than 12% (sirolimus) or 15% (paclitaxel), and only (for elective surgery) for a patient who can be treated with a single DES. Consequently, the use of DES in the UK would be justifiable on efficiency grounds for only about 4% of patients. CRD COMMENTARY - Selection of comparators The selection of BMS as the basic comparator was appropriate since they represent a widely used approach for the treatment of patients with symptomatic CAD. The two types of DES were appropriately chosen. The number of DES needed was varied between one and three to represent different clinical situations. You should decide whether they are valid comparators in your own setting. Validity of estimate of measure of effectiveness The effectiveness data were obtained from the literature and from some authors' opinions. The primary studies used to provide the clinical evidence might have been identified selectively since the methods and conduct of a review of the literature were not reported. Most of the evidence came from clinical trials, which ensures a high internal validity. Estimates of treatment effectiveness were derived from more than one study and were combined using a meta-analysis. Other estimates were combined using a narrative approach or were derived from a single source. The issue of heterogeneity among the primary studies was not addressed. The authors stated that, at the time of their study, there had been no direct comparative clinical trial between sirolimus- and paclitaxel-based DES. Thus, the analysis combined data from clinical trials with patient samples that were not directly comparable. The use of some assumptions was tested in the sensitivity analysis, as the authors acknowledged that this could represent a source of uncertainty. Validity of estimate of measure of benefit QALYs were an appropriate benefit measure because they capture the impact of the intervention on quality of care and survival, which are the most relevant dimensions of health. The utility was derived from the literature (clinical trials) and the instrument used to assess utility weights was reported. The use of QALYs permits comparisons with the benefits of other health care interventions. Validity of estimate of costs The analysis of the costs was consistent with the perspective adopted in the study. A detailed breakdown of the costs was given and, in general, comprehensive information on unit costs, quantities of resources, used, price year and the source of the data was provided. These enhance the possibility of replicating the results of the analysis in other settings and facilitate reflation exercises in other time periods. Resource consumption reflected actual treatment patterns in England. The costs reflected national tariffs, which represent typical NHS costs. The uncertainty surrounding some cost estimates was addressed in the sensitivity analysis, where alternative scenarios for resource use and costs were taken into account. However, the costs were treated deterministically. Discounting was not relevant and was not applied. Other issues The authors reported the results from two other economic evaluations of DES versus BMS, but their findings could not Page: 5 / 7

6 be directly compared because of differences in the settings of the studies (one was carried out in Spain and the other in the USA). The authors did not explicitly address the issue of generalisability of the study results to other settings, but stated that their analysis was UK specific. Caution will therefore be required when extrapolating the results of the analysis to other settings. However, the sensitivity analyses identified key areas of uncertainty. The authors noted some limitations of their analysis. Such limitations were mainly related to the use of data from small and unblinded clinical trials. A further drawback of the analysis was the short time horizon, although the authors justified their decision to restrict the analysis to a 1-year period. In particular, the study was based on a key assumption that DES does not provide any benefit in survival with respect to BMS, and this had a strong impact on the costeffectiveness results. The study referred to patients with symptomatic CAD and this was reflected in the authors' conclusions. The authors reported cost-utility ratios for each risk sub-group, and this represents a strong feature of the analysis. The results of the base-case were extensively reported unlike the results of the sensitivity analysis. Implications of the study The study results suggested that the use of DES should be restricted to high-risk patients with symptomatic CAD. However, any advantage in survival for DES with respect to BMS would change the results of this study and invalidate the model. Source of funding Supported by the National Institute for Clinical Excellence and the NHS Health Technology Assessment Programme. Bibliographic details Bagust A, Grayson A D, Palmer N D, Perry R A, Walley T. Cost effectiveness of drug eluting coronary artery stenting in a UK setting: cost-utility study. Heart 2006; 92(1): PubMedID DOI /hrt Other publications of related interest Cohen DJ, Bakhai A, Shi C, et al. Cost-effectiveness of sirolimus-eluting stents for treatment of complex coronary stenoses: results from the sirolimus-eluting balloon expandable stent in the treatment of patients with de novo native coronary artery lesions (SIRIUS) trial. Circulation 2004;110: Hill R, Bagust A, Bakhai A, et al. Coronary artery stents: a rapid systematic review and economic evaluation. Health Technol Assess 2004;8: Oliva G, Espallargues M, Pons J. Antiproliferative drug-eluting stents: systematic review of the benefits and estimate of economic impact. Rev Esp Cardiol 2004;57: Indexing Status Subject indexing assigned by NLM MeSH Aged; Coronary Restenosis /economics /prevention & control; Cost-Benefit Analysis; Drug Implants /economics; Female; Humans; Male; Middle Aged; Myocardial Revascularization /economics; Paclitaxel /administration & dosage; Retreatment; Sirolimus /administration & dosage; Stents /economics AccessionNumber Page: 6 / 7

7 Powered by TCPDF ( Date bibliographic record published 31/10/2006 Date abstract record published 31/10/2006 Page: 7 / 7