Sirolimus Versus Tacrolimus as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

Sirolimus and tacrolimus are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of sirolimus and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane controlled trials register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection (AR), and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and QALYs gained and incremental cost-effectiveness. Altogether, 1189 patients from 8 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of AR and patient withdrawn. Nevertheless, tacrolimus increased the risk of infection. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events after renal transplant. Tacrolimus is an effective and safe immunosuppressive agent, and it may be more cost-effective than cyclosporine for the primary prevention of AR in renal transplant recipients. However, it should be noted that such superiority was reversal when the cost of sirolimus and tacrolimus changed.

Cost-effectiveness analysis of everolimus plus exemestane versus exemestane alone for treatment of hormone receptor positive metastatic breast cancer.

Everolimus in combination with exemestane significantly improved progression-free survival compared to exemestane alone in patients previously treated with non-steroidal aromatase inhibitors in the BOLERO-2 trial. As a result, this combination has been approved by the food and drug administration to treat postmenopausal women with hormone receptor positive and HER2 negative metastatic breast cancer. A cost-effectiveness analysis was conducted to determine whether everolimus represents good value for money, utilizing data from BOLERO-2. A decision-analytic model was used to estimate the incremental cost-effectiveness ratio between treatment arms of the BOLERO-2 trial. Costs were obtained from the Center for Medicare Services drug payment table and physician fee schedule. Benefits were expressed as quality-adjusted progression-free survival weeks (QAPFW) and quality-adjusted progression-free years (QAPFY), with utilities/disutilities derived from the literature. Deterministic and probabilistic sensitivity analyses were performed. A willingness to pay threshold of 1-3 times the per capita gross domestic product was adopted, as per the definition of the World Health Organization. The U.S. per capita gross domestic product in 2013 was $49,965; thus, a threshold varying between $49,965 and $149,895 was considered. Everolimus/exemestane had an incremental benefit of 11.88 QAPFW (0.22 QAPFY) compared to exemestane and an incremental cost of $60,574. This translated into an ICER of $265,498.5/QAPFY. Univariate sensitivity analyses showed important variations of the ICER, ranging between $189,836.4 and $530,947/QAPFY. A tornado analysis suggested that the key drivers of our model, by order of importance, included health utility value for stable disease, everolimus acquisition costs, and transition probabilities from the stable to the progression states. The Monte-Carlo simulation showed results that were similar to the base-case analysis. This cost-effectiveness analysis showed that everolimus plus exemestane is not cost-effective compared to exemestane alone. Further research is needed to investigate the cost-effectiveness of the drug combination within sub-groups of the population studied in BOLERO-2.

Cost-Effectiveness Analysis of Pharmacological Treatment for Adult Kidney Transplant Recipients in Colombia.

OBJECTIVES: To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system. METHODS: A decision tree model for the induction phase and a Markov model for the maintenance phase were built. A review of the clinical literature was conducted to extract probabilities, and the life-years were used as the outcome. Costs were calculated using the administrative databases. The evaluating treatment schemes are organized by groups of evidence with direct comparisons. RESULTS: In the induction phase, anti-thymocyte immunoglobulin+ methylprednisolone is dominant, more effective, and less expensive, compared with basiliximab+methylprednisolone. In the maintenance phase, azathioprine (AZA) is dominant in contrast to mycophenolate mofetil (MFM) both with cyclosporine (CIC)+ corticosteroids (CE); CIC is dominant relative to sirolimus (SIR) and tacrolimus (TAC) (both with MFM+CE or AZA+CE), and TAC is dominant compared with SIR (in addition with MFM+CE or mycophenolate sodium [MFS]+CE); MFM is dominant in relation to MFS and everolimus, and SIR is more effective MFM but it does not exceed the threshold (in sum with TAC+CE); MFS and MFM are dominant relative to everolimus, and SIR is more effective than MFM, but it does not exceed the threshold (in addiction with CIC+CE); MFM is dominant in relation to TAC (in sum with SIR+CE), and CIC+AZA+CE is dominant in relation to TAC+MFM+CE. CONCLUSIONS: The base-case results for all evidence groups are consistent with the different sensitivity analyses.

Randomized comparison of cost-saving and effectiveness of oral rapamycin plus bare-metal stents with drug-eluting stents: three-year outcome from the randomized oral rapamycin in Argentina (ORAR) III trial.

OBJECTIVES: The Oral Rapamycin in ARgentina (ORAR) III trial is a randomized study comparing a strategy of oral rapamycin (OR) plus bare-metal stent (BMS) versus a strategy of drug-eluting stents (DES) in patients with de novo coronary lesions. The purpose of this study was to assess the 3 years cost-effectiveness outcome of each strategy. BACKGROUND: OR after BMS has been associated with reduction of target vessel revascularization (TVR) although its value in long-term efficacy in comparison with DES is unknown. METHODS: In three hospitals in Buenos Aires, Argentina, 200 patients were randomized to OR plus BMS (n = 100) or DES (n = 100). Primary objectives were costs and effectiveness. Cost analysis included in-hospital and follow-up costs. Safety was defined as the composite of death, myocardial infarction (MI), and stroke. Efficacy was defined as TVR. RESULTS: Baseline characteristics between groups were similar. The 3-year follow-up rate was 99%. Cardiac mortality was 2% and 5% in OR group and DES group, respectively (P = 0.44). The composite of death, MI and stroke rate was 11% in OR group and 20% in DES group (P = 0.078). TVR rate was 14.5% in OR group and 17.6% in DES group (P = 0.50), respectively. Three year cumulative costs were significantly lower in the OR arm as compared to the DES arm (P = 0.0001) and DES strategy did not result cost-effective according to the non-inferiority test. CONCLUSIONS: At 3 years follow-up, there were no differences in effectiveness between the two strategies, and DES strategy was not more cost-effective as compared to OR plus BMS.

Economic evaluation of everolimus versus sorafenib for the treatment of metastatic renal cell carcinoma after failure of first-line sunitinib.

BACKGROUND: A recent indirect comparison study showed that sunitinib-refractory metastatic renal cell carcinoma (mRCC) patients treated with everolimus are expected to have improved overall survival outcomes compared to patients treated with sorafenib. This analysis examines the likely cost-effectiveness of everolimus versus sorafenib in this setting from a US payer perspective. METHODS: A Markov model was developed to simulate a cohort of sunitinib-refractory mRCC patients and to estimate the cost per incremental life-years gained (LYG) and quality-adjusted life-years (QALYs) gained. Markov states included are stable disease without adverse events, stable disease with adverse events, disease progression, and death. Transition probabilities were estimated using a subset of the RECORD-1 patient population receiving everolimus after sunitinib, and a comparable population receiving sorafenib in a single-arm phase II study. Costs of antitumor therapies were based on wholesale acquisition cost. Health state costs accounted for physician visits, tests, adverse events, postprogression therapy, and end-of-life care. The model extrapolated beyond the trial time horizon for up to 6 years based on published trial data. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The estimated gain over sorafenib treatment was 1.273 LYs (0.916 QALYs) at an incremental cost of $81,643. The deterministic analysis resulted in an incremental cost-effectiveness ratio (ICER) of $64,155/LYG ($89,160/QALY). The probabilistic sensitivity analysis demonstrated that results were highly consistent across simulations. CONCLUSIONS: As the ICER fell within the cost per QALY range for many other widely used oncology medicines, everolimus is projected to be a cost-effective treatment relative to sorafenib for sunitinib-refractory mRCC.

Everolimus: a new mammalian target of rapamycin inhibitor for the treatment of advanced renal cell carcinoma.

OBJECTIVE: To review clinical trials and main characteristics of everolimus, with focus on treatment of advanced renal cell carcinoma. DATA SOURCES: Pertinent data were identified primarily through a search of MEDLINE and PubMed (1966-November 2010) using the primary search terms everolimus, RAD001, renal cell carcinoma, and mTOR inhibitors. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the safety and efficacy of everolimus in patients with cancer were evaluated, including Phase 1, 2, and 3 trials. Preference was given to Phase 2 and 3 studies evaluating use of everolimus in patients with renal cell carcinoma. DATA SYNTHESIS: Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor approved for the management of patients with advanced renal cell carcinoma who progressed on tyrosine kinase inhibitor therapy. Actions of everolimus within the mTOR pathway result in decreased protein synthesis and cell cycle arrest, as well as decreased angiogenesis. A usual starting dose for patients with renal cell carcinoma is 10 mg daily. Everolimus undergoes extensive hepatic metabolism, primarily through the CYP3A4 isoenzyme, which predisposes it to drug interactions with inducers and inhibitors of this enzyme. Most commonly reported adverse events associated with everolimus include anemia, hyperglycemia, hypercholesterolemia, mucositis, fatigue, and rash. Approval of everolimus was based on the results of a Phase 3 trial that demonstrated an increase in median progression-free survival by 2.1 months in patients receiving everolimus therapy as compared to placebo. The drug was recently added to the National Comprehensive Cancer Network guidelines as a treatment option for patients with advanced renal cell carcinoma who have progressed on tyrosine kinase therapy. CONCLUSIONS: Based on a review of the currently available literature, everolimus provides a safe and efficacious treatment option for patients with renal cell carcinoma who have progressed on treatment with sunitinib and/or sorafenib.

[Level of evidence for therapeutic drug monitoring of everolimus]. / Évaluation du niveau de preuve du suivi thérapeutique pharmacologique de l'évérolimus.

Everolimus has proven efficacy for prevention of rejection in adult de novo renal and cardiac transplant recipient in combination with ciclosporine and corticosteroids. Therapeutic drug monitoring (TDM) with target trough concentration (C0) value from 3 to 8 µg/L has been proposed. Through a systematic review of the literature, this work explored a level of recommendation for this TDM. Everolimus exhibits both wide interindividual pharmacokinetic variability and poor relationship between dose and exposure. A good relationship has been reported between C0 values and global exposure to the drug (i.e. AUC). Although C0 > 3 µg/L has been associated with a decreased incidence of rejection, the upper limit of 8 µg/L has never been formally validated. No clinical trial testing other exposure indices or comparing efficacy and/or toxicity of everolimus therapy with and without TDM has been published so far. Consequently the level of recommendation for everolimus monitoring is "recommended".

Cost-effectiveness of temsirolimus for first line treatment of advanced renal cell carcinoma.

OBJECTIVES: To estimate the cost-effectiveness of temsirolimus compared to interferon-alpha for first line treatment of patients with advanced, poor prognosis renal cell carcinoma, from the perspective of the UK National Health Service. METHODS: A decision-analytic model was developed to estimate the cost-effectiveness of temsirolimus. The clinical effectiveness of temsirolimus compared with interferon-alpha and the utility values (using EQ-5D tariffs) were taken from a recent phase III randomized clinical trial. Cost data were obtained from published literature and based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses. RESULTS: Compared to interferon-alpha, temsirolimus treatment resulted in an incremental cost per QALY gained of pound94,632; based on an estimated mean gain of 0.24 quality-adjusted life years (QALYs) per patient, at a mean additional cost of pound22,331 (inflated to 2007/8). The cost per QALY for patient subgroups ranged from pound74,369 to pound154,752. The probability that temsirolimus is cost-effective compared to interferon-alpha at a willingness to pay threshold of pound30,000 per QALY for all patient groups is expected to be close to zero. The cost per QALY was sensitive to the clinical effectiveness parameters, health state utilities, drug costs and the cost of administration of temsirolimus. CONCLUSIONS: Temsirolimus has been shown to be clinically effective compared to interferon-alpha offering additional health benefits, however, with a cost per QALY in excess of pound90,000, it may not be regarded as a cost-effective use of resources in some health care settings.

Cost effectiveness of sirolimus-eluting stents compared with bare metal stents in acute myocardial infarction: insights from the TYPHOON trial.

BACKGROUND: Drug-eluting stents have been shown to reduce the rate of repeat revascularization after percutaneous coronary intervention for acute myocardial infarction (AMI) as compared with bare metal stents (BMS). A few studies have reported the cost effectiveness of sirolimus-eluting stents (SES) in several countries, but none in the particular setting of AMI in France. OBJECTIVES: To assess the cost effectiveness of SES compared with BMS in a pre-specified subgroup of French patients with AMI in the randomized, multicentre TYPHOON trial. METHODS: A prospective economic evaluation was conducted for the 337 patients in the TYPHOON trial who were enrolled in the French centres. In the TYPHOON trial, patients with AMI with ST-segment elevation less than 12 hours after the onset of chest pain were randomized to undergo percutaneous coronary intervention with either SES or BMS. Data on clinical outcomes and resource use were collected prospectively over a 1-year follow-up period (from October 2003 to October 2005). Unit costs were applied to the resource utilization data. The main outcome measure was the incremental cost-effectiveness ratio (ICER) for additional cost per target-vessel revascularization (TVR) avoided. The perspective of the study was the French healthcare system and costs were expressed in 2007 values. RESULTS: SES significantly reduced the rate of TVR (6.6% vs 22.2% with BMS, p < 0.0001). There was no difference in the rate of death, recurrent myocardial infarction or stent thrombosis after 1 year of follow-up between the SES and BMS groups. Mean index admission costs, including the angioplasty procedure, were increased by 282 Euro per patient in the SES group, mostly driven by the price of the SES. Mean follow-up costs were 140 Euro per patient lower in the SES group. Mean aggregate 1-year costs showed a euro 1142 per-patient increase in the SES group compared with the BMS group. The ICER was 7321 Euro per TVR avoided. CONCLUSIONS: In this pre-specified subgroup analysis of the TYPHOON trial, the use of SES in patients with AMI with ST-segment elevation less than 12 hours after the onset of chest pain reduced the rate of TVR compared with BMS. However, SES had a debatable ICER for the payer if it was based only on the specific benefit of TVR avoided.

Health Economic Evaluation of an Ultrathin, Bioresorbable-Polymer Sirolimus-Eluting Coronary Stent Compared to a Thin, Durable-Polymer Everolimus-Eluting Stent.

OBJECTIVES: The study estimated the health economic impact of a latest generation coronary stent with ultrathin struts and bioresorbable polymer coating. BACKGROUND: The recent BIOFLOW V trial, an international FDA approval trial (ClinicalTrials.gov: NCT02389946), has shown that an ultrathin, bioresorbable polymer sirolimus-eluting stent had a significantly lower rate of target lesion failure and target vessel-related myocardial infarction than a thin, durable polymer everolimus-eluting stent at 12 months, driven by a lower rate of peri-procedural myocardial infarction (ppMI). METHODS: We used a Markov model to project mortality and cost outcomes of that lower ppMI rate from a U.S. health system perspective over a 12-month horizon. Model parameters were derived from BIOFLOW V trial data, a systematic literature review and expert interviews. RESULTS: Use of the bioresorbable polymer sirolimus-eluting stent compared to durable polymer everolimus-eluting stent is associated with net reductions in medical cost of $124 (Interquartile Range (IQR) $97-154) per patient in 2018 US$, of which $115 (IQR $76-124) accrues to the initial admission and $10 (IQR $7-72) to cost of follow-up. The lower rate of ppMI translates into a gain of 0.000017 (IQR 0.000011-0.000022) quality-adjusted life-years (QALY) per patient. CONCLUSIONS: Lower ppMI rates of bioresorbable polymer sirolimus-eluting stent translate into reductions in direct medical cost, while improving patient outcomes. Most of the cost reduction is attributed to the initial admission with moderate savings up to 12 months post-discharge.

Cost-effectiveness of drug-eluting stents in patients at high or low risk of major cardiac events in the Basel Stent KostenEffektivitäts Trial (BASKET): an 18-month analysis.

BACKGROUND: Our aim was to determine whether drug-eluting stents are good value for money in long-term, everyday practice. METHODS: We did an 18-month cost-effectiveness analysis of the Basel Stent KostenEffektivitäts Trial (BASKET), which randomised 826 patients 2:1 to drug-eluting stents (n=545) or to bare-metal stents (281). We used non-parametric bootstrap techniques to determine incremental cost-effectiveness ratios (ICERs) of drug-eluting versus bare-metal stents, to compare low-risk (> or =3.0 mm stents in native vessels; n=558, 68%) and high-risk patients (<3.0 mm stents/bypass graft stenting; n=268, 32%), and to do sensitivity analyses by altering costs and event rates in the whole study sample and in predefined subgroups. Quality-adjusted life-years (QALYs) were assessed by EQ-5D questionnaire (available in 703/826 patients). FINDINGS: Overall costs were higher for patients with drug-eluting stents than in those with bare-metal stents (11,808 euros [SD 400] per patient with drug-eluting stents and 10,450 euros [592] per patient with bare-metal stents, mean difference 1358 euros [717], p<0.0001), due to higher stent costs. We calculated an ICER of 64,732 euros to prevent one major adverse cardiac event, and of 40,467 euros per QALY gained. Stent costs, number of events, and QALYs affected ICERs most, but unrealistic alterations would have been required to achieve acceptable cost-effectiveness. In low-risk patients, the probability of drug-eluting stents achieving an arbitrary ICER of 10,000 euros or less to prevent one major adverse cardiac event was 0.016; by contrast, it was 0.874 in high-risk patients. INTERPRETATION: If used in all patients, drug-eluting stents are not good value for money, even if prices were substantially reduced. Drug-eluting stents are cost effective in patients needing small vessel or bypass graft stenting, but not in those who require large native vessel stenting.

Cost-effectiveness of sirolimus-eluting stents compared with vascular brachytherapy for the treatment of in-stent restenosis.

BACKGROUND: Sirolimus-eluting stents (SESs) were recently shown to be superior to vascular brachytherapy for the treatment of restenosis within a bare metal stent. No economic comparison of these alternative strategies has yet been reported. METHODS: We conducted a prospective health economic study involving all patients randomized to SES (n = 259) or brachytherapy (n = 125) in the SISR trial. Procedural, hospital, and outpatient costs, as well as physician fees, were estimated through 12 months based on measured resource use and itemized hospital bills. Cost-effectiveness was assessed in terms of the cost per repeat revascularization avoided, cost per major adverse cardiac event avoided, and cost per event-free patient. RESULTS: Although initial device costs were approximately $1100/patient higher in the SES group, this was offset by higher physician fees associated with brachytherapy, such that initial hospitalization costs were similar for the 2 groups. Because SES significantly reduced repeat revascularization procedures and major adverse cardiac event compared with brachytherapy during follow-up, cumulative 12-month costs were significantly lower in the SES group ($16,482 vs $19,435, mean difference -$2953, 95% CI -$5470 to -$792). Sirolimus-eluting stenting was thus both more effective and less expensive than brachytherapy, as confirmed in >98% of bootstrap replications for each of the cost-effectiveness outcomes. CONCLUSIONS: Compared with vascular brachytherapy, SES is an economically dominant strategy for the treatment of in-stent restenosis.

Economic evaluation of everolimus and mycophenolate mofetil versus azathioprine in de novo heart transplantation.

UNLABELLED: Both the proliferation signal inhibitor everolimus (1.5 mg/day) and mycophenolate mofetil (MMF) (3 g/day) have shown superior efficacy versus azathioprine in de novo heart transplantation. The cost-effectiveness of everolimus and MMF versus azathioprine was assessed to 6 months posttransplantation. METHODS: The evaluation was performed from the German health insurance payer perspective. The composite efficacy endpoint in the everolimus trial was death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR) grade>or=3A, rejection with hemodynamic compromise, and loss to follow-up. The composite endpoint in the MMF trial included only death, retransplantation, and BPAR with hemodynamic compromise. To mimic the everolimus endpoint, an estimated number of patients with BPAR>or=3A was added to the MMF trial results, using two mapping scenarios. RESULTS: The incremental 6-month cost versus azathioprine was euro2535 for everolimus and euro3007 for MMF. The absolute reduction in efficacy failure versus azathioprine was 10.4% for everolimus and 9.8% and 10.1% for MMF, respectively, using scenarios 1 and 2. The incremental cost per efficacy failure avoided (ie, the incremental cost versus azathioprine divided by the reduction in efficacy failure) was euro24,457 for everolimus, and euro30,628 and euro29,912 for MMF in scenarios 1 and 2. CONCLUSION: This analysis, based on findings from two clinical trials, suggested that everolimus was more cost-effective than MMF versus azathioprine in the first 6 months after heart transplantation. Data from a head-to-head trial are required to confirm these results.

Economic analysis of the use of drug-eluting stents from the perspective of Belgian health care.

OBJECTIVE: Recent evidence shows that drug-eluting stent devices (DES) substantially reduce the risk of in-stent restenosis compared with classic bare metal stent devices (BMS). In Belgium, however, the use of BMS is still standard procedure due to the higher prices of the newer DES. Although the use of DES is more expensive in the short term it might be beneficial in the long term due to the avoidance of revascularization costs. The primary objective of this study is to compare the net cost of DES and BMS from the perspective of Belgian health care. METHODS AND RESULTS: Cost differences between DES and BMS are determined by the difference in stent price and the difference in the rate of re-intervention. The cost of revascularization of patients with in-stent restenosis was estimated based on data gathered at the Antwerp University hospital (UZA). Data on effectiveness were obtained from a literature meta-analysis. Because of some important study limitations, a sensitivity analysis was included in this study. In general, the use of DES was cost saving as compared with BMS, with savings amounting to E 165 for Cypher stent devices and Euro 128 for Taxus stent devices in the base case scenario. For patients with a high risk of restenosis net savings persist in almost all sensitivity analyses. CONCLUSION: The use of DES in patients with a high in-stent restenosis risk is cost saving. Price evolutions in the stent device market predict that the use of DES, if not yet cost saving, will become cost saving in the near future for all types of patients. Recent evidence, however, casts some doubt on the long-term effectiveness of DES.

Everolimus: a review of its use in renal and cardiac transplantation.

Everolimus (Certican) is an orally administered mammalian target of rapamycin inhibitor (proliferation signal inhibitor) derived from sirolimus (rapamycin), which is used as part of immunosuppressant therapy in kidney and heart transplantation. When evaluated as part of triple therapy with ciclosporin and corticosteroids, everolimus showed equivalent efficacy to mycophenolate mofetil after renal transplantation, and superiority to azathioprine in cardiac transplant recipients, in terms of reducing efficacy failure after transplantation. Everolimus potentiates ciclosporin-associated nephrotoxicity, and it is recommended that concentration-controlled everolimus is used with reduced-dosage ciclosporin in order to limit renal toxicity while retaining immunosuppressive efficacy. Ongoing trials with everolimus, such as the evaluation of ciclosporin-withdrawal strategies, should help clarify its optimal usage. The use of everolimus may be associated with reduced rates of cytomegalovirus (CMV) infection and of cardiac allograft vasculopathy. Available data suggest that everolimus may be cost-neutral for healthcare providers.

Cost effectiveness of the sirolimus-eluting stent in high-risk patients in Canada: an analysis from the C-SIRIUS trial.

BACKGROUND: The cost effectiveness of drug-eluting stents in Canada is debated and deserves further evaluation in high-risk patients. METHODS: We performed an economic analysis from the third-party payer perspective based on the clinical results and resource-utilization data of the C-SIRIUS (The Canadian Study of the Sirolimus-Eluting Stent in the Treatment of Patients with Long De Novo Lesions in Small Native Coronary Arteries) trial, which examined the safety and efficacy of sirolimus-eluting stents (SES) versus bare metal stents (BMS) in high-risk patients with single long de novo lesions in small coronary arteries. Only inpatient costs were considered, including physician fees. We postulated that the incremental cost required to avoid a repeat revascularization (RR) procedure with BMS versus simple balloon angioplasty (BA) could be considered the willingness to pay (WTP) to avoid restenosis in Canada. We assessed the incremental cost-effectiveness ratio (ICER) of SES compared with BMS in these high-risk patients compared with WTP. Results are expressed in 2003 Canadian dollars. RESULTS: With a 7% absolute reduction in the need for RR compared with BA, BMS are associated on average with an ICER of US dollars 12,551/RR avoided (RRA) in Canada. In C-SIRIUS, SES further reduced the need for RR at 1 year from 22% to 4% (p = 0.015) compared with BMS. With a 1.5 stent-to-lesion (STL) ratio and an SES retail price of US dollars 2,700 compared with US dollars 700 for BMS, the ICER of SES versus BMS was US dollars 11,275/RRA -- borderline cost effective compared with the implicit WTP of US dollars 12,551 for such health benefit in Canada. Using a lower STL ratio (1.2) would improve the ICER to US dollars 7941/RRA. CONCLUSIONS: Treatment of long lesions in small vessels with SES increases net healthcare costs. However, the ICER for SES compares favorably with the currently accepted comparator, i.e. BMS, to reduce coronary restenosis -- at least for higher risk patients undergoing single-vessel revascularization.