Impact of stent diameter and length on in-stent restenosis after DES vs BMS implantation in patients needing large coronary stents-A clinical and health-economic evaluation.

AIMS: The British National Institute of Clinical Excellence (NICE) guidelines recommend to use drug-eluting stents (DES) instead of bare-metal stents (BMS) only in lesions >15 mm in length or in vessels <3 mm in diameter. We analyzed the impact of stent length and stent diameter on in-stent restenosis (ISR) in the BASKET-PROVE study population and evaluated the cost-effectiveness of DES compared to BMS. METHODS/RESULTS: The BASKET-PROVE trial compared DES vs BMS in large coronary arteries (≥3 mm). We calculated incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves with regard to quality-adjusted life years (QALYs) gained and target lesion revascularizations (TLRs) avoided. A total of 2278 patients were included in the analysis. A total of 74 ISR in 63 patients were observed. In-stent restenosis was significantly more frequent in segments treated with a BMS compared to segments treated with a DES (5.4% vs 0.76%; P<.001). The benefit of a DES compared to a BMS regarding ISR was consistent among the subgroups of stent length >15 mm and ≤15 mm, respectively. With the use of DES in short lesions, there was only a minimal gain of 0.005 in QALYs. At a threshold of 10 000 CHF per TLR avoided, DES had a high probability of being cost-effective. CONCLUSION: In the BASKET-PROVE study population, the strongest predictor of ISR is the use of a BMS, even in patients in need of stents ≥3.0 mm and ≤15 mm lesion length and DES were cost-effective. This should prompt the NICE to reevaluate its recommendation to use DES instead of BMS only in vessels <3.0 mm and lesions >15 mm length.

The NICE recommendation for drug-coated balloons and its global impact.

OBJECTIVES: The clinical efficacy and safety of drug-coated balloon (DCB) angioplasty in patients with coronary in-stent restenosis (ISR) has been demonstrated. The objective of this article is to provide comparative cost efficacy data for DCB angioplasty in various countries based on the original methodology of the Medical Technologies Evaluation Programme (MTEP) at the National Institute for Health and Clinical Excellence (NICE) in 2010. STUDY DESIGN: Published and unpublished Health Technology Assessment (HTA) reports were evaluated for comparison in selected countries. Furthermore, a systematic review of economic evaluations of DCB angioplasty versus standard treatments (uncoated balloon angioplasty or drug-eluting stent implantations) was conducted. METHODS: National cost efficacy data were evaluated using Markov state transition models which were adapted to fit each country's device and procedure related costs. The clinical input for adverse events was defined with two relevant trials for in-stent restenosis of bare metal stents (BMS-ISR) and of drug-eluting stents (DES-ISR). RESULTS: In the UK, Germany, Switzerland, South Africa, Japan and Brazil, DCB angioplasty is cost-effective when compared with drug-eluting stents to treat either BMS-ISR or DES-ISR. CONCLUSIONS: DCB angioplasty ought to be the preferred treatment option for patients with BMS-ISR and DES-ISR from the payers' point of view.

Cost-effectiveness of paclitaxel-coated balloon angioplasty in patients with drug-eluting stent restenosis.

BACKGROUND: The economic impact of drug-eluting stent (DES) in-stent restenosis (ISR) is substantial, highlighting the need for cost-effective treatment strategies. HYPOTHESIS: Compared to plain old balloon angioplasty (POBA) or repeat DES implantation, drug-coated balloon (DCB) angioplasty is a cost-effective therapy for DES-ISR. METHODS: A Markov state-transition model was used to compare DCB angioplasty with POBA and repeat DES implantation. Model input parameters were obtained from the literature, and the cost analysis was conducted from a German healthcare payer's perspective. Extensive sensitivity analyses were performed. RESULTS: Initial procedure costs amounted to €3488 for DCB angioplasty and to €2782 for POBA. Over a 6-month time horizon, the DCB strategy was less costly (€4028 vs €4169) and more effective in terms of life-years (LYs) gained (0.497 versus 0.489) than POBA. The DES strategy incurred initial costs of €3167 and resulted in 0.494 LYs gained, at total costs of €4101 after a 6-month follow-up. Thus, DCB angioplasty was the least costly and most effective strategy. Base-case results were influenced mostly by initial procedure costs, target lesion revascularization rates, and the costs of dual antiplatelet therapy. CONCLUSIONS: DCB angioplasty is a cost-effective treatment option for coronary DES-ISR. The higher initial costs of the DCB strategy compared to POBA or repeat DES implantation are offset by later cost savings.

Stent choice and the hidden consequences of cost savings.

Amin and colleagues have attempted to estimate the cost savings to the US health-care system if drug-eluting coronary stents were more selectively used in patients at low risk of restenosis. Their results and conclusions raise statistical, societal, and ethical issues that need to be considered before this approach should be widely embraced.

Cost-effectiveness of paclitaxel-coated balloon angioplasty and paclitaxel-eluting stent implantation for treatment of coronary in-stent restenosis in patients with stable coronary artery disease.

BACKGROUND: Recent studies have demonstrated the safety and efficacy of drug-coated balloon (DCB) angioplasty for the treatment of coronary in-stent restenosis (ISR). The cost-effectiveness of this practice is unknown. METHODS: A Markov state-transition decision analytic model accounting for varying procedural efficacy rates, complication rates, and cost estimates was developed to compare DCB angioplasty with drug-eluting stent (DES) placement in patients with bare-metal stent (BMS)-ISR. Data on procedural outcomes associated with both treatment strategies were derived from the literature, and the cost analysis was conducted from a health care payer perspective. Effectiveness was expressed as life-years gained. RESULTS: In the base-case analysis, initial procedure costs amounted to €3,604.14 for DCB angioplasty and to €3,309.66 for DES implantation. Over a 12-month time horizon, the DCB strategy was found to be less costly (€4,130.38 vs. €5,305.30) and slightly more effective in terms of life expectancy (0.983 vs. 0.976 years) than the DES strategy. Extensive sensitivity analyses indicated that, in comparison with DES implantation, the cost advantage of the DCB strategy was robust to clinically plausible variations in the values of key model input parameters. The variables with the greatest impact on base-case results were the duration of dual antiplatelet therapy with acetylsalicylic acid and clopidogrel after DCB angioplasty, the use of generic clopidogrel, and variations in the costs associated with the DCB device. CONCLUSION: DCB angioplasty is a cost-effective treatment option for coronary BMS-ISR. The higher initial costs of DCB are more than offset by later cost-savings, predominantly as a result of reduced medication costs.

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.

Drug-eluting versus bare-metal coronary stents: where are we now?

Drug-eluting stents have dramatically reduced the risk of restenosis, but concerns of an increased risk of stent thrombosis have provided uncertainty about their use. Recent studies have continued to show improved procedural and clinical outcomes with drug-eluting stents both in the setting of acute coronary syndromes and stable coronary artery disease. Newer generation drug-eluting stents (especially everolimus-eluting stents) have been shown to be not only efficacious but also safe with reduced risk of stent thrombosis when compared with bare-metal stents, potentially changing the benchmark for stent safety from bare-metal stents to everolimus-eluting stents. While much progress is being made in the development of bioabsorbable polymer stents, nonpolymer stents and bioabsorbable stent technology, it remains to be seen whether these stents will have superior safety and efficacy outcomes compared with the already much improved rates of revascularization and stent thrombosis seen with newer generation stents (everolimus-eluting stents and resolute zotarolimus-eluting stents).

Predicting the restenosis benefit of drug-eluting versus bare metal stents in percutaneous coronary intervention.

BACKGROUND: Drug-eluting stents (DES) for percutaneous coronary intervention decrease the risk of restenosis compared with bare metal stents. However, they are costlier, require prolonged dual antiplatelet therapy, and provide the most benefit in patients at highest risk for restenosis. To assist physicians in targeting DES use in patients at the highest risk for target vessel revascularization (TVR), we developed and validated a model to predict TVR. METHODS AND RESULTS: Preprocedural clinical and angiographic data from 27 107 percutaneous coronary intervention hospitalizations between October 1, 2004, and September 30, 2007, in Massachusetts were used to develop prediction models for TVR at 1 year. Models were developed from a two-thirds random sample and validated in the remaining third. The overall rate of TVR was 7.6% (6.7% with DES, 11% with bare metal stents). Significant predictors of TVR included prior percutaneous coronary intervention, emergency or salvage percutaneous coronary intervention, prior coronary bypass surgery, peripheral vascular disease, diabetes mellitus, and angiographic characteristics. The model was superior to a 3-variable model of diabetes mellitus, stent diameter, and stent length (c statistic, 0.66 versus 0.60; P<0.001) and was well calibrated. The predicted number needed to treat with DES to prevent 1 TVR compared with bare metal stents ranged from 6 (95% confidence interval, 5.4-7.6) to 80 (95% confidence interval, 62.7-116.3), depending on patients' clinical and angiographic factors. CONCLUSIONS: A predictive model using commonly collected variables can identify patients who may derive the greatest benefit in TVR reduction from DES. Whether use of the model improves the safety and cost-effectiveness of DES use should be tested prospectively.

Clinical and economic outcomes of liberal versus selective drug-eluting stent use: insights from temporal analysis of the multicenter Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry.

BACKGROUND: Although the benefits of drug-eluting stents (DES) for reducing restenosis after percutaneous coronary intervention are well established, the impact of alternative rates of DES use on population-level outcomes is unknown. METHODS AND RESULTS: We used data from the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry to examine the clinical impact and cost-effectiveness of varying DES use rates in routine care. Between 2004 and 2007, 10,144 patients undergoing percutaneous coronary intervention were enrolled in the EVENT registry at 55 US centers. Clinical outcomes and cardiovascular-specific costs were assessed prospectively over 1 year of follow-up. Use of DES decreased from 92 in 2004 to 2006 (liberal use era; n=7587) to 68 in 2007 (selective use era; n=2557; P<0.001). One-year rates of death or myocardial infarction were similar in both eras. Over this time period, the incidence of target lesion revascularization increased from 4.1 to 5.1, an absolute increase of 1.0 (95 confidence interval, 0.1 to 1.9; P=0.03), whereas total cardiovascular costs per patient decreased by $401 (95 confidence interval, 131 to 671; P=0.004). The risk-adjusted incremental cost-effectiveness ratio for the liberal versus selective DES era was $16,000 per target lesion revascularization event avoided, $27,000 per repeat revascularization avoided, and $433 000 per quality-adjusted life-year gained. CONCLUSIONS: In this prospective registry, a temporal reduction in DES use was associated with a small increase in target lesion revascularization and a modest reduction in total cardiovascular costs. These findings suggest that although clinical outcomes are marginally better with unrestricted DES use, this approach represents a relatively inefficient use of healthcare resources relative to several common benchmarks for cost-effective care.

[Economic evaluation and budget impact analysis of the Endeavor drug-eluting stent in Spain]. / Evaluación económica e impacto presupuestario del stent recubierto Endeavor en España.

OBJECTIVES: Endeavor is a drug-eluting stent (DES) with superior results to the bare metal stent (BMS) and similar efficacy to other DES in terms of revascularization. The aim of this study was to assess the costs and benefits of Endeavor, other DES, BMS and coronary artery bypass grafts (CABG) in Spain. METHODS: A Markov model with a 5-year time was used to reflect the management of patients with de novo coronary artery lesions in Spain. Model probabilities were derived from systematic reviews and randomized controlled trials of Endeavor. Health resources and costs were obtained from local data and were validated by experts. Effectiveness was measured as the number of revascularizations avoided, the major adverse coronary events (MACE) avoided and the quality adjusted life-years (QALYs) gained. RESULTS: Endeavor had higher total costs than the BMS. The cost per revascularization avoided with Endeavor was 6,851 euro (at 1 year) and 10,831 euro (at 5 years). In terms of cost per MACE avoided with Endeavor, the results were 7,003 euro and 11,322 euro, respectively, and in terms of costs of QALY gained were 132,877 euro, 34,229 euro and 10,505 euro at 1, 2, and 5 years, respectively. The budget impact of the progressive introduction of Endeavor would be practically null, representing 0.4% of the total cost of percutaneous coronary interventions at 5 years. CONCLUSIONS: The use of the Endeavor stent compared with BMS and CABG represents efficient resource use in patients with coronary artery disease, with cost-effectiveness results below the threshold of efficiency defined in Spain.

Cost-effectiveness of the real-world use of drug-eluting stents at 9-month follow-up: results from the Sicilian DES Registry.

BACKGROUND: With the aim of reducing restenosis after percutaneous coronary intervention with bare-metal stents (BMSs) for the treatment of ischemic heart disease, drug-eluting stents (DESs) were introduced in the field of percutaneous coronary intervention in 2002. However, the higher cost of DES in comparison with BMS made it necessary to determine whether their use brings a real economic advantage. METHODS: In order to verify the clinical and economic benefit of DES in comparison with BMS and surgical treatment with coronary artery bypass graft (CABG), the Sicily Regional Government arranged for the creation of a directory where patients receiving at least one DES (with sirolimus or with paclitaxel) were enrolled from June 2004 to February 2005. The cost-effectiveness analysis for DES was carried out by means of two decisional models: one referring to patients treated with DES who, without such a device, would have undergone CABG, and the second one referring to patients treated with DES who, without such device, would have received BMS. Cost analysis was carried out from the point of view of the SSR (Servizio Sanitario Regionale, Regional Health Service). RESULTS: The use of DES on patients destined to CABG generated average unitary differential savings of euro9003, after 9 months of follow-up, and average total differential savings of euro4 438 479. The use of DES on patients destined to BMS gave average unitary differential savings of euro1075, after 9 months of follow-up, and average total differential savings of euro1 052 425. The use of DES instead of BMS and CABG allowed SSR to make average differential savings of euro3760 per successful case. The refund threshold value of DES, setting to zero the SSR average differential savings for patients treated with DES who would otherwise have been treated with BMS, was euro2489. CONCLUSION: The medium-term results of the proposed models, tested with sensitivity analysis, demonstrate the use of DES to be justified; moreover, these results could positively influence the attitude of the SSR toward these new therapeutic strategies, which are an improvement on standard therapies, both from a clinical and a financial standpoint.

A multicenter, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: cortisone plus BMS or DES versus BMS alone to eliminate restenosis (CEREA-DES) - study design and rationale.

BACKGROUND: Several randomized trials and registries have shown a reduction of restenosis after coronary angioplasty with drug-eluting stents (DESs) compared with bare metal stents (BMSs). However, cost-efficacy analysis and long-term outcome of DESs compared to BMSs deserve further assessment. Moreover, concern has been raised regarding adverse clinical events occurring late after DES implantation, in particular, late stent thrombosis related to the suspension of dual antiplatelet therapy. The use of a short-cycle oral treatment with prednisone at immunosuppressive dose after BMS implantation has shown remarkable efficacy in reducing restenosis in nondiabetic patients, with very low additional cost and without the need for long-term dual antiplatelet therapy. Such results are however limited by small sample size. STUDY DESIGN: Cortisone plus BMS or DES versus BMS alone to Eliminate Restenosis is an independent, prospective, multicenter, randomized study. It will randomize 375 nondiabetic patients with coronary artery disease in three different arms to BMS (control group), DES (DES group) or BMS followed by a 40-day prednisone treatment (prednisone group). The DES and the prednisone groups will be compared to the control group to investigate the expected clinical advantage. The primary endpoint of the study is the event-free survival of cardiovascular death, myocardial infarction and recurrence of ischemia-needing repeated target vessel revascularization at 1 year. Secondary endpoints are the event-free survival analysis at 2 and 3 years, the restenosis rate at 9 months, and cost-effectiveness at 1, 2 and 3 years. SAMPLE SIZE: The expected primary endpoint rates are 90% for DESs and for prednisone-treated patients and 77% for BMSs. The study was designed as a superiority trial, to compare DES, and BMS and prednisone, with BMS alone. A sample size of 118 patients per group provides an 80% power, assuming a complete 12-month follow-up information available for each patient. To obviate for cases of drop out, the sample size was increased to 375 patients to be enrolled in five Italian hospitals. CONCLUSION: This study will provide a magnitude of the net clinical and economic benefits of DES and of the safety and efficacy of BMS and cortisone compared to the standard use of BMS alone in nondiabetic patients with coronary artery disease.

Percutaneous coronary intervention with oral sirolimus and bare metal stents has comparable safety and efficacy to treatment with drug eluting stents, but with significant cost saving: long-term follow-up results from the randomised, controlled ORAR III (Oral Rapamycin in ARgentina) study.

AIMS: Previous randomised studies have shown a significant reduction in restenosis when oral rapamycin (OR) is administered to patients undergoing bare metal stent (BMS) implantation. How this regimen compares to drug eluting stents (DES) is unknown. METHODS AND RESULTS: Two-hundred patients with de novo coronary lesions were randomised to treatment with OR plus BMS (100 pts) or with DES (100 pts). OR was given as a bolus of 10 mg per day before PCI followed by daily doses of 3 mg during following 13 days. Primary endpoints were to compare hospital, follow-up and overall cost at one, two, three and five years of follow-up. The secondary endpoints included death, myocardial infarction (MI) and stroke and were analysed as major adverse cardiovascular events (MACCE). Target vessel (TVR) and target lesion revascularisation (TLR) were independently analysed. Costs included procedural resources, hospitalisation, medications, repeat revascularisation procedures and professional fees. Baseline demographic, clinical and angiographic characteristics were similar. At 18.3 +/- 7 months of follow-up, the initial strategy of OR plus BMS resulted in significant cost saving when compared to DES (p=0.0001). TLR rate was 8.2% with DES and 7.0% with OR plus BMS (p=0.84), similarly no differences in TVR rate in both groups was seen (10.6% and 10.5% in OR and DES group respectively, p=0.86). Non-inferiority testing, determined that DES therapy failed to be cost saving compared to OR in all possible cost scenarios. CONCLUSIONS: A strategy of OR plus BMS is cost saving compared to DES in patients undergoing PCI for de novo coronary lesions.

Comparison of multiple drug-eluting stent percutaneous coronary intervention and surgical revascularization in patients with multivessel coronary artery disease: one-year clinical results and total treatment costs.

PURPOSE: Consecutive patients with multivessel coronary artery disease treated with multiple drug-eluting-stent (DES) percutaneous coronary intervention (PCI) (111 patients) or coronary artery bypass graft (CABG) (95 patients) on the basis of clinico-anatomical judgment were examined to investigate mediumterm clinical results and initial and total costs. METHODS: Clinical and procedural characteristics, duration of hospital stay, initial and total costs and 12-month follow-up events were considered in both groups. RESULTS: Previous revascularization procedures and acute coronary syndromes were more frequent in the PCI group, while triple-vessel and left main disease occurred more often in the CABG group. The mean number of treated vessels in multiple DES PCI was 2.7/patient, with 2.8 DES/patient. Complete revascularization was achieved in 70% of cases. Inhospital events were postprocedural non-Q-wave acute myocardial infarction in 5.4%, and 2 retroperitoneal hemorrhages. CABG was performed with a mean of 3.9 grafts/patient; 16 patients (17%) had early complications; mean hospital stay was significantly longer than for the PCI patients (23.5 +/- 10 vs. 5.3 +/- 3 days; p < 0.001). Twelve-month total mortality and acute myocardial infarction incidents were similar, while target vessel revascularization was significantly more frequent in the PCI group (12.6% PCI vs. 2.1% CABG; p < 0.001); cumulative major adverse cardiac events were not significantly different (15.3% PCI vs. 9.5% CABG; p = 0.271). Initial and final costs were lower for multivessel PCI with DES (20,050 +/- 2,702 for CABG vs. 10,214 +/- 4,184 for PCI; p < 0.001), but not completely covered by current DRG reimbursement. CONCLUSIONS: Multiple DES PCI showed good earlyand medium-term results with substantially lower costs than CABG.