Cost-effectiveness of percutaneous coronary intervention with cobalt-chromium everolimus eluting stents versus bare metal stents: Results from a patient level meta-analysis of randomized trials.

BACKGROUND: Second-generation drug eluting stents (DES) may reduce costs and improve clinical outcomes compared to first-generation DES with improved cost-effectiveness when compared to bare metal stents (BMS). We aimed to conduct an economic evaluation of a cobalt-chromium everolimus eluting stent (Co-Cr EES) compared with BMS in percutaneous coronary intervention (PCI). OBJECTIVE: To conduct a cost-effectiveness analysis (CEA) of a cobalt-chromium everolimus eluting stent (Co-Cr EES) versus BMS in PCI. METHODS: A Markov state transition model with a 2-year time horizon was applied from a US Medicare setting with patients undergoing PCI with Co-Cr EES or BMS. Baseline characteristics, treatment effects, and safety measures were taken from a patient level meta-analysis of 5 RCTs (n = 4,896). The base-case analysis evaluated stent-related outcomes; a secondary analysis considered the broader set of outcomes reported in the meta-analysis. RESULTS: The base-case and secondary analyses reported an additional 0.018 and 0.013 quality-adjusted life years (QALYs) and cost savings of $236 and $288, respectively with Co-Cr EES versus BMS. Results were robust to sensitivity analyses and were most sensitive to the price of clopidogrel. In the probabilistic sensitivity analysis, Co-Cr EES was associated with a greater than 99% chance of being cost saving or cost effective (at a cost per QALY threshold of $50,000) versus BMS. CONCLUSIONS: Using data from a recent patient level meta-analysis and contemporary cost data, this analysis found that PCI with Co-Cr EES is more effective and less costly than PCI with BMS. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.

Human recombinant activated protein C-coated stent for the prevention of restenosis in porcine coronary arteries.

Activated protein C (APC), an endogenous protein, inhibits inflammation and thrombosis and interrupts the coagulation cascade. Here, we investigated the effect of human recombinant APC on the development of neointimal hyperplasia in porcine coronary arteries. Yukon Choice bare metal stents were coated with 2.6 µg APC/mm(2). Under general anesthesia, APC-coated and bare stents were implanted in the left anterior descending and circumflex coronary arteries of 10 domestic pigs. During the 4-week follow-up, animals were treated with dual antiplatelet therapy and neointimal hyperplasia was evaluated via histology. Scanning electron microscopy indicated successful but unequal coating of stents with APC; nearly complete drug release occurred within 4 h. Enzyme-linked immunosorbent assay revealed that intracoronary stent implantation rapidly increased the levels of monocyte chemoattractant protein-1, an effect that was inhibited by APC release from the coated stent. Fibrin deposition and adventitial inflammation were significantly decreased 1 month after implanting APC-coated stents versus bare stents, paralleled by significantly smaller neointimal area (0.98 ± 0.92 vs. 1.44 ± 0.91 mm(2), P = 0.028), higher lumen area (3.47 ± 0.94 vs. 3.06 ± 0.91 mm(2), P = 0.046), and lower stenosis area (22.2 ± 21.2% vs. 32.1 ± 20.1%, P = 0.034). Endothelialization was complete with APC-coated but not bare (90%) stents. P-selectin immunostaining revealed significantly fewer activated endothelial cells in the neointima in the APC group (4.6 ± 1.9 vs. 11.6 ± 4.1%, P < 0.001). Thus, short exposure of coronary arteries to APC reduced inflammatory responses, neointimal proliferation, and in-stent restenosis, offering a promising therapy to improve clinical outcomes of coronary stenting. However, coating stents with APC for prolonged, controlled drug release remains technically challenging.

Economic analysis of endovascular interventions for femoropopliteal arterial disease: a systematic review and budget impact model for the United States and Germany.

OBJECTIVES: To study the economic impact on payers and providers of the four main endovascular strategies for the treatment of infrainguinal peripheral artery disease. BACKGROUND: Bare metal stents (BMS), drug-eluting stents (DES), and drug-coated balloons (DCB) are associated with lower target lesion revascularization (TLR) probabilities than percutaneous transluminal angioplasty (PTA), but the economic impact is unknown. METHODS: In December 2012, PubMed and Embase were systematically searched for studies with TLR as an endpoint. The 24-month probability of TLR for each treatment was weighted by sample size. A decision-analytic Markov model was used to assess the budget impact from payers' and facility-providers' perspectives of the four index procedure strategies (BMS, DES, DCB, and PTA). Base cases were developed for U.S. Medicare and the German statutory sickness fund perspectives using current 2013 reimbursement rates. RESULTS: Thirteen studies with 2,406 subjects were included. The reported probability of TLR in the identified studies varied widely, particularly following treatment with PTA or BMS. The pooled 24-month probabilities were 14.3%, 19.3%, 28.1%, and 40.3% for DCB, DES, BMS, and PTA, respectively. The drug-eluting strategies had a lower projected budget impact over 24 months compared to BMS and PTA in both the U.S. Medicare (DCB: $10,214; DES: $12,904; uncoated balloons $13,114; BMS $13,802) and German public health care systems (DCB €3,619; DES €3,632; BMS €4,026; PTA €4,290). CONCLUSIONS: DCB and DES, compared to BMS and PTA, are associated with lower probabilities of target lesion revascularization and cost savings for U.S. and German payers.

Polymer-based drug-eluting stent treatment extends the time to reintervention for patients with symptomatic femoropopliteal artery disease: clinical evidence and potential economic value.

Aim: Use long-term follow-up data from the IMPERIAL study to determine whether drug-eluting polymer-based nitinol stent treatment can delay the time to repeat intervention for femoropopliteal artery disease and how such a delay may result in cost savings in a value-based episode of care. Patients & methods: The IMPERIAL randomized controlled trial was an international study of a paclitaxel-eluting polymer-coated stent (Eluvia, Boston Scientific, MA, USA) versus a polymer-free paclitaxel-coated stent (Zilver PTX, Cook Corporation, IN, USA) for treating lesions of the femoropopliteal arterial segment. Study patients (n = 465) had symptomatic lower limb ischemia. Safety and efficacy assessments were performed through 5 years. Mean time to first reintervention was calculated in post-hoc analysis for patients who underwent a clinically driven target lesion revascularization (CD-TLR) through 3 or 5 years following the index procedure. To simulate potential cost savings associated with differential CD-TLR burden over time, a cost-avoidance analysis using input parameters from IMPERIAL and US 100% Medicare standard analytical files was developed. Results: Among patients with a first CD-TLR through 3 years of follow-up, mean time to reintervention was 5.5 months longer (difference 166 days, 95% CI: 51, 282 days; p = 0.0058) for patients treated with Eluvia (n = 56) than for those treated with Zilver PTX (n = 30). Through the 5-year study follow-up period, CD-TLR rates were 29.3% (68/232) for Eluvia and 34.2% (39/114) for Zilver PTX (p = 0.3540) and mean time to first reintervention exceeded 2 years for patients treated with Eluvia at 737 days versus 645 days for the Zilver PTX group (difference 92 days, 95% CI: -85, 269 days; p = 0.3099). Simulated savings considering reinterventions occurring over 1 and 5 years following initial use of Eluvia over Zilver PTX were US $1,395,635 and US $1,531,795, respectively, when IMPERIAL CD-TLR rates were extrapolated to 1000 patients. Conclusion: IMPERIAL data suggest initial treatment with Eluvia extends the time patients spend without undergoing reintervention. This extension may be associated with cost savings in relevant time frames.

The Market Reacts Quickly: Changes in Paclitaxel Vascular Device Purchasing Within the Ascension Healthcare System.

BACKGROUND: A meta-analysis of trials in endovascular therapy suggested an increased mortality associated with treatment exposure to paclitaxel. Multiple publications and corrections of prior data were performed, and the United States Food and Drug Administration has issued multiple advisories regarding paclitaxel use. We analyzed how this controversy impacted device purchasing and related utilization patterns in the period immediately following publication of the meta-analysis. METHODS AND RESULTS: Ascension Healthcare System purchase data over a 14-month period were synthesized across centers for both paclitaxel and non-paclitaxel devices. A fixed-effects regression model and a binary regression model with facility-level controls were used to compare purchasing patterns before and after the meta-analysis. Purchase volumes of each paclitaxel device fell. Pooled purchase volumes of all paclitaxel devices decreased from a 14-month peak of 631 devices in October 2018 to a 14-month nadir of 359 devices in February 2019. An F-test comparing the pooled-month specific fixed effects for the months before vs after the publication of the meta-analysis has an F-statistic of 11.64, suggesting that average purchasing levels in the two periods are statistically different (P<.001). Utilization of non-paclitaxel devices did not decline. CONCLUSIONS: Purchase volumes of paclitaxel devices decreased immediately during the months following publication of the related meta-analysis. Total Ascension-wide paclitaxel device purchase volume in February 2019 demonstrated a 43.1% reduction from peak monthly purchase volume during the assessed period and a 32.5% reduction compared with November 2019, the last month preceding publication of the meta-analysis.

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.

Polymer-Free Drug-Coated Coronary Stents Are Cost-Effective in Patients at High Bleeding Risk: Economic Evaluation of the LEADERS FREE Trial.

AIMS: In patients at high risk of bleeding who undergo PCI the biolimus A9 polymer-free drug coated stent (DCS) has superior efficacy and safety compared to a bare metal stent (BMS). We estimated the cost effectiveness of DCS vs. BMS. METHODS AND RESULTS: The Leaders FREE-based economic evaluation estimated service use and quality of life data collected prospectively. The entire trial population was analysed using cost-weights from England, France, Germany, Italy, Scotland and Spain. Country-specific QALYs were derived from EQ-5D scores. We estimated cost per event averted and per QALY gained. DCS use resulted in -0.095 cardiac deaths, target vessel MI, stent thrombosis and revascularization per patient (0.152 vs. 0.237;p<0.001). One-year QALYs were non-significantly higher in the DCS group. Total costs for the index admission were similar between groups. One-year costs using cost-weights from each of the 6 countries, including the additional €300 per DCS stent, ranged from €4,664-8,593 for DCS and €4,845-9,742 for BMS and were lower in the DCS group (England:€-428, France:€-137, Germany:€-33, Italy:€-522, Scotland:€-298, Spain:€-854). CONCLUSIONS: The probability that DCS dominated BMS was >50% in all countries. At a threshold of €10,000 per event averted DCS had a 98% probability of being cost-effective in all 6 countries.

Cost-effectiveness analysis of biodegradable polymer versus durable polymer drug-eluting stents incorporating real-world evidence.

AIM: Compared with second-generation durable polymer drug-eluting stents (DP-DES), the cost-effectiveness of biodegradable polymer drug-eluting stents (BP-DES) remains unclear in the real-world setting. We assessed the cost-effectiveness of BP-DES in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). METHODS: We developed a decision-analytic model to compare the cost-effectiveness of BP-DES to DP-DES over 1 year and 5 years from healthcare payer perspective. Relative treatment effects during the first year post-PCI were obtained from a real-world population analysis while clinical event risks in the subsequent 4 years were derived from a meta-analysis of published studies. RESULTS: At 1 year, based on the clinical data analysis of 497 propensity-score matched pairs of patients, BP-DES were associated with an incremental cost-effectiveness ratio (ICER) of USD20 503 per quality-adjusted life-year (QALY) gained. At 5 years, BP-DES yielded an ICER of USD4062 per QALY gained. At the willingness-to-pay threshold of USD50 400 (one gross domestic product per capita in Singapore in 2015), BP-DES were cost-effective. Sensitivity analysis showed that the cost of stents had a significant impact on the cost-effectiveness of BP-DES. Threshold analysis demonstrated that if the cost difference between BP-DES and DP-DES exceeded USD493, BP-DES would not be cost-effective in patients with 1 year of follow-up. CONCLUSIONS: Biodegradable polymer drug-eluting stents were cost-effective compared with DP-DES in patients with coronary artery disease at 1 year and 5 years after PCI. It is worth noting that the cost of stents had a significant impact on the findings.

BAlloon versus Stenting in severe Ischaemia of the Leg-3 (BASIL-3): study protocol for a randomised controlled trial.

BACKGROUND: Severe limb ischaemia (SLI) is defined as the presence of rest pain and/or tissue loss secondary to lower extremity atherosclerotic peripheral arterial disease. The superficial femoral and popliteal arteries are the most commonly diseased vessels in such patients and are being increasingly treated using endovascular revascularisation techniques. However, it is currently unknown whether drug-eluting stents and drug-coated balloons confer additional clinical benefits over more established techniques using plain balloons and bare metal stents, or whether they represent a cost-effective use of NHS resources. METHODS: The BASIL-3 trial is a UK National Institute for Health Research, Health Technology Assessment Programme-funded, multicentre, randomised controlled trial (RCT) comparing the clinical and cost-effectiveness of plain balloon angioplasty with or without bail-out bare metal stenting, drug-coated balloon angioplasty with or without bail-out bare metal stenting, and primary stenting with drug-eluting stents for SLI secondary to femoro-popliteal disease. Patients with 'multilevel' disease may receive aorto-iliac and/or infrapopliteal treatments concurrently with their randomised femoro-popliteal intervention. The primary clinical outcome is amputation-free survival defined as the time to major (above the ankle) amputation of the index limb or death from any cause. The primary outcome for the economic analysis is cost per quality-adjusted life year. Secondary outcome measures include overall survival, major adverse limb events, major adverse cardiac events, relief of ischaemic pain, healing of tissue loss, and quality of life. The required sample size has been calculated at 861 participants (287 on each arm). These patients will be recruited over 3 years and followed-up for between 2 and 5 years. DISCUSSION: BASIL-3 is a pragmatic RCT designed to reflect current UK clinical practice. The results will inform decision-making regarding the appropriateness of funding the use of drug-coated balloons and drug-eluting stents, by the NHS, for the management of SLI due to femoro-popliteal disease. TRIAL REGISTRATION: ISRCTN Registry, identifier: ISRCTN14469736 . Registered on 22 October 2015.

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.

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).

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.