Long-term Cost-effectiveness of Insulin Degludec Versus Insulin Glargine U100 in the UK: Evidence from the Basal-bolus Subgroup of the DEVOTE Trial (DEVOTE 16).

OBJECTIVES: To evaluate the cost-effectiveness of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in basal-bolus regimens for patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk based on the DEVOTE CV outcomes trial. METHODS: A microsimulation model, informed by clinical outcomes from the subgroup of patients using basal-bolus insulin therapy in DEVOTE (NCT01959529) and by the UKPDS Outcomes Model 2 risk equations, was used to model direct costs (2018 GBP) and effectiveness outcomes [quality-adjusted life years (QALYs)] with degludec versus glargine U100 over a 40-year time horizon. The model captured the development of eight diabetes-related complications, death, severe hypoglycemia and insulin dosing. This analysis was conducted from the perspective of National Health Service (NHS) England. RESULTS: Treatment with degludec versus glargine U100 in basal-bolus regimens was associated with improved clinical outcomes at a higher cost per patient [incremental cost effectiveness ratio (ICER): £14,956 GBP/QALY]. Degludec remained cost effective versus glargine U100 in all exploratory sensitivity analyses, with ICERs below the widely accepted willingness-to-pay threshold, although the result was most sensitive to assumptions regarding the persistence of treatment effects. CONCLUSIONS: Our long-term modeling analysis suggested that degludec was cost effective (from the perspective of NHS England) versus glargine U100 in basal-bolus regimens for patients with T2D at high CV risk. Our findings raise important questions regarding how to model the health economics of diabetes therapies.

DEVOTE 5: Evaluating the Short-Term Cost-Utility of Insulin Degludec Versus Insulin Glargine U100 in Basal-Bolus Regimens for Type 2 Diabetes in the UK.

INTRODUCTION: The aim of this study was to evaluate the short-term cost-utility of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) for the treatment of type 2 diabetes in the basal-bolus subgroup of the head-to-head cardiovascular (CV) outcome trial, DEVOTE. METHODS: A cost-utility analysis was conducted over a 2-year time horizon using a decision analytic model to compare costs in patients receiving once daily degludec or glargine U100, both as part of a basal-bolus regimen, in addition to standard care. Clinical outcomes and patient characteristics were taken exclusively from DEVOTE, whilst health-related quality of life utilities and UK-specific costs (expressed in 2016 GBP) were obtained from the literature. The analysis was conducted from the perspective of the National Health Service. RESULTS: Degludec was associated with mean cost savings of GBP 28.78 per patient relative to glargine U100 in patients with type 2 diabetes at high CV risk. Cost savings were driven by the reduction in risk of diabetes-related complications with degludec, which offset the higher treatment costs relative to glargine U100. Degludec was associated with a mean improvement of 0.0064 quality-adjusted life-years (QALYs) compared with glargine U100, with improvements driven predominantly by lower rates of severe hypoglycemia with degludec versus glargine U100. Improvements in quality-adjusted life expectancy combined with cost neutrality resulted in degludec being dominant over glargine U100. Sensitivity analyses demonstrated that the incremental cost-utility ratio was stable to variations in the majority of model inputs. CONCLUSION: The present short-term modeling analysis found that for the basal-bolus subgroup of patients in DEVOTE, with a high risk of CV events, degludec was cost neutral (no additional costs) compared with glargine U100 over a 2-year time horizon in the UK setting. Furthermore, there were QALY gains with degludec, particularly due to the reduction in the risk of severe hypoglycemia. FUNDING: Novo Nordisk A/S. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01959529.

Costs Associated With Access Site and Same-Day Discharge Among Medicare Beneficiaries Undergoing Percutaneous Coronary Intervention: An Evaluation of the Current Percutaneous Coronary Intervention Care Pathways in the United States.

OBJECTIVES: The aim of this study was to examine the independent impact of various care pathways, including those involving transradial intervention (TRI) and same-day discharge (SDD) after elective percutaneous coronary intervention (PCI), on hospital costs. BACKGROUND: PCI is associated with costs of $10 billion annually. Alternative payment models for PCI are being implemented, but few data exist on strategies to reduce costs. Various PCI care pathways, including TRI and SDD, exist, but their association with costs and outcomes is unknown. METHODS: In total, 279,987 PCI patients eligible for SDD in the National Cardiovascular Data Registry CathPCI Registry linked to Medicare claims files were analyzed. Hospital costs in 2014 U.S. dollars were estimated using cost-to-charge ratios. Propensity scores for TRI and SDD, with propensity adjustment via inverse probability weighting, was performed. RESULTS: Of the 279,987 PCI procedures, TRI was used in 9.0% (13.5% of which were SDD), and SDD was used in 5.3% of cases (23.1% of which were TRI). TRI (vs. transfemoral intervention) was associated with lower adjusted costs of $916 (95% confidence interval [CI]: $778 to $1,035), as was SDD ($3,502; 95% CI: $3,486 to $3,902). The adjusted cost associated with TRI and SDD was $13,389 (95% CI: $13,161 to $13,607), while the cost associated with transfemoral intervention and non-same-day discharge was $17,076 (95% CI: $16,999 to $17,147), a difference of $3,689 (95% CI: $3,486 to $3,902; p < 0.0001). Shifting current practice from transfemoral intervention non-same-day discharge to TRI SDD by 30% could potentially save a hospital performing 1,000 PCIs each year $1 million and the country $300 million annually. CONCLUSIONS: Among Medicare beneficiaries, TRI with SDD was independently associated with fewer complications and lower in-hospital costs. These findings have important implications for changing the current PCI care pathways to improve outcomes and reduce costs.

The Outcomes, Patient Health Status, and Efficiency IN Chronic Total Occlusion Hybrid Procedures registry: rationale and design.

BACKGROUND: Patients with chronic total occlusions of a coronary artery represent a complex, yet common, clinical conundrum among patients with ischemic heart disease. Chronic total occlusion angioplasty is increasingly being used as a treatment for these complex lesions. There is a compelling need to better quantify the safety, efficacy, benefits, and costs of the procedure. METHODS: To address these gaps in knowledge, we designed the Outcomes, Patient Health Status, and Efficiency IN Chronic Total Occlusion Hybrid Procedures (OPEN CTO) study, an investigator-initiated multicenter, single-arm registry including 12 centers with a planned enrollment of 1000 patients. To ensure the accuracy of our observations, we used a unique auditing process through the National Cardiovascular Disease Registries' Cath/PCI Registry, angiographic core lab analysis, clinical events adjudication, and a systematic collection of patient-reported outcomes and costs. RESULTS: Between 21 January 2014 and 22 July 2015, 1000 patients were enrolled in OPEN CTO. A total of 28 patients either refused (N=26) or were missed by the screening process (N=2). In the National Cardiovascular Disease Registry Cath/PCI registry audit, there were 1096 chronic total occlusion-percutaneous coronary intervention procedures that were performed by participating operators during the time they enrolled in OPEN CTO. Overall, 987 of those patients could be definitively matched to an OPEN CTO enrolled patient (enrolled group). The remaining 109 were considered to be not enrolled in OPEN CTO (not enrolled group). Compared with the enrolled group, the patients in the nonenrolled group were less frequently of White race and more frequently of Hispanic origin. Procedural outcomes including National Cardiovascular Disease Registry-defined technical success, procedural success, and major adverse coronary events rates were similar. CONCLUSION: OPEN CTO is the most comprehensive and rigorously collected dataset to date that will provide unique insights into the success, safety, benefits, and the costs of chronic total occlusion-percutaneous coronary intervention using a reproducible technical approach to patients with these complex lesions.

Costs of transradial percutaneous coronary intervention.

OBJECTIVES: This study sought to evaluate the costs of transradial percutaneous coronary intervention (TRI) and transfemoral percutaneous coronary intervention (TFI) from a contemporary hospital perspective. BACKGROUND: Whereas the TRI approach to percutaneous coronary intervention (PCI) has been shown to reduce access-site complications compared with TFI, whether it is associated with lower costs is unknown. METHODS: TRI and TFI patients were identified at 5 U.S. centers. The primary outcome was the cost of percutaneous coronary intervention (PCI) hospitalization, defined as cost on the day of PCI through hospital discharge. Cost was obtained from each hospital's cost accounting system. Independent costs of TRI were identified using propensity-scoring methods with inverse probability weighting. Secondary outcomes of interest were bleeding, in-hospital mortality, and length of stay, which were stratified by pre-procedural risk and PCI indication. RESULTS: In 7,121 PCI procedures performed from January 1, 2010, to March 31, 2011, TRI was performed in 1,219 (17%) patients and was associated with shorter lengths of stay (2.5 vs. 3.0 days; p < 0.001) and lower bleeding events (1.1% vs. 2.4%, adjusted odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.34 to 0.79; p = 0.002). TRI was associated with a total cost savings of $830 (95% CI: $296 to $1,364; p < 0.001), of which $130 (95% CI: -$99 to $361; p = 0.112) were procedural savings and $705 (95% CI: $212 to $1,238; p < 0.001) were post-procedural savings. There was an associated graded increase in savings among patients at higher predicted risk of bleeding: low risk: $642 (95% CI: $43 to $1,236; p = 0.035); moderate risk: $706 (95% CI: $104 to $1,308; p = 0.029); and high risk: $1,621 (95% CI: $271 to $2,971, p = 0.039). CONCLUSIONS: TRI was associated with a cost savings exceeding $800 per patient relative to TFI. Increased adoption of TRI may result in cost savings at hospitals.

Comparison of costs between transradial and transfemoral percutaneous coronary intervention: a cohort analysis from the Premier research database.

BACKGROUND: Transradial intervention (TRI) for percutaneous coronary intervention (PCI) is associated with shorter length of stay, fewer bleeding complications, and higher patient satisfaction. Less is known about the economic implications of TRI in contemporary practice. METHODS: This is a retrospective inpatient cohort analysis using medical data from the Premier research database (Premier Inc, Charlotte, NC), which contains approximately one-fifth of all acute care hospitalizations in the US annually. The database was queried to identify patients undergoing PCI from 2004 to 2009. Patients with TRI were identified by center-level charge codes for radial-specific devices and matched one-to-many with patients undergoing transfemoral intervention (TFI). Adjusted total hospitalization costs were compared between patients undergoing TRI and TFI. Patients were additionally classified by periprocedural risk of bleeding as low (<1%), moderate (1%-3%), and high (>3%). RESULTS: There were 609 TRI cases matched with 60,900 TFI cases. Total adjusted costs for TRI were $11,736 ± $6,748 vs $12,288 ± $23,418 for TFI, a difference of $553 favoring TRI (95% CI $45-$1,060, P = .033). Day-of-procedure costs were similar, at $17 higher for TRI compared with TFI (95% CI -$318 to $353, P = .37); however, costs from the following day until discharge were significantly lower for TRI (-$571, 95 % CI -$912 to $229, P = .001). Postprocedure costs were lower for patients with TRI vs patients with TFI at moderate (-$478, 95% CI -$887 to $69, P = .022) and high (-$917, 95% CI -$1,814 to $19, P = .045) risk of bleeding. CONCLUSIONS: In a nationwide administrative hospital database, transradial compared with transfemoral PCI access was associated with lower average direct hospital costs and shorter length of hospital stay. Postprocedure costs associated with TRI were also lower in patients at greater bleeding risk.

The impact of bivalirudin on percutaneous coronary intervention-related bleeding.

AIMS: We studied the clinical and economic impact of bivalirudin in clinical practice. METHODS AND RESULTS: Consecutive patients undergoing PCI via the common femoral artery for stable, unstable, or atypical angina, silent ischaemia, or non-ST-elevation myocardial infarction indications during 2007-2008 were prospectively studied. In-hospital bleeding events were systematically assessed and classified as either major or minor. Use of bivalirudin, vascular closure devices, heparin and/or glycoprotein (GP) IIb/IIIa inhibitor was at the operator's discretion. Among 1,364 patients, 503 received bivalirudin and 861 received usual care consisting of either heparin monotherapy (n=687) or heparin+GP IIb/IIIa (n=174). Any post-PCI bleeding occurred in 356 (26.1%) patients, including 32 (2.3%) major and 324 (23.8%) minor events. Compared with usual care, bivalirudin was associated with reduced bleeding before adjustment (any: 17.3% vs. 31.2%, P<0.001; major: 1.2% vs. 3.0%, P=0.03; minor: 16.1% vs. 28.2%, P<0.01) and after propensity-matching (OR 0.46, 95% CI 0.34-0.63, P<0.001). Use of vascular closure devices was associated with an increase in any bleeding (32.2% vs. 17.7%, P<0.001), primarily due to an increase in minor bleeding (30.8% vs. 14.1%, P<0.001) while there was a significant decrease in major bleeding (1.4% vs. 3.7%, P=0.007). Bivalirudin was associated with total hospitalisation costs that were lower than usual care (mean cost savings, $463/patient; 95% CI 1,594 less to 621 more). CONCLUSIONS: In this prospective PCI cohort, bivalirudin was associated with reduced major and minor bleeding without a significant increase in hospital costs compared with other anticoagulation regimens. Closure device use was associated with decreased major but increased minor bleeding.

Cost-effectiveness of targeting patients undergoing percutaneous coronary intervention for therapy with bivalirudin versus heparin monotherapy according to predicted risk of bleeding.

BACKGROUND: Although bivalirudin compared with unfractionated heparin with glycoprotein IIb/IIIa inhibitors reduces bleeding and hospitalization costs in patients undergoing percutaneous coronary intervention (PCI), little is known about the economic impact of bivalirudin versus heparin alone and at what threshold of procedural bleeding risk bivalirudin would be considered cost-effective. METHODS AND RESULTS: A validated model was used to predict risk of major bleeding for 81,628 National Cardiovascular Data Registry (NCDR) CathPCI Registry patients from 2004 to 2006 who received unfractionated heparin only. Costs were derived from multiple sources including wholesale acquisition costs (for drugs) and single-center data (for PCI-related complications). Based on ISAR-REACT 3, we assumed that bivalirudin would reduce the risk of major bleeding by 33% compared with unfractionated heparin alone. A Markov model was used to estimate lost life expectancy associated with a major bleed. Major bleeding was predicted to occur in 2.2% of patients. Bivalirudin for all patients was estimated to increase costs by $571 per patient, yielding cost-effectiveness ratios of $287,473 per bleeding event averted and $1,173,360 per quality-adjusted life-year gained. Bivalirudin was cost saving for patients with a predicted bleeding risk >20% (0.16% of CathPCI population). At willingness-to-pay thresholds of $50K and $100K per quality-adjusted life-year gained, bivalirudin was cost-effective for patients with a bleeding risk > or = 8% (2.5% patients) and > or = 5% (7.9% patients), respectively. CONCLUSIONS: This decision-analytic modeling study demonstrates that for patients undergoing PCI, substitution of bivalirudin for unfractionated heparin monotherapy is projected to increase costs for virtually all patients and would be considered cost-effective for only a minority of patients with a high bleeding risk. From a policy standpoint, studies such as this, aimed at identifying the appropriate risk threshold for initiating treatment, may help in the development of informed guidelines for the use of expensive therapies.

Chronic total occlusion angioplasty in the United States.

Coronary chronic total occlusions (CTOs) are commonly encountered complex lesions identified in 15% of all patients referred for coronary angiography. Chronic total occlusion remains the most powerful predictor of referral for coronary bypass surgery. The benefits of CTO percutaneous coronary intervention (PCI) include symptom relief, improved left ventricular function, and potentially a survival advantage associated with success when compared with failed CTO-PCI. Data from the NCDR (National Cardiovascular Data Registry) suggest that CTO-PCI attempt rates in the U.S. have not changed over the past 5 years despite significant advances in techniques and technology, some of which we review here. Additionally, these data highlight a major disparity in attempt rates based on operator PCI volume. Remaining barriers to attempting CTO-PCI in the U.S. include operator inexperience, the perception of increased risk of CTO-PCI, and financial disincentives to operators and hospitals. To overcome operator inexperience, participation in CTO clubs, the invitation of guest operators, and a dedicated CTO day can be implemented at institutions committed to learning advanced CTO-PCI techniques so that operators can overcome the barriers and offer patients access to percutaneous therapy when it is clinically indicated.

Intravascular ultrasound measures of coronary atherosclerosis are associated with the Framingham risk score: an analysis from a global IVUS registry.

AIMS: In addition to an adjunctive imaging platform during coronary angiography, intravascular ultrasound (IVUS) with Virtual Histology (VH) is increasingly being used to quantify coronary atherosclerosis. The relationship between VH-IVUS measures of coronary atherosclerosis and traditional cardiovascular risk factors has not been completely described. The objective of this study was to determine if an association exists between VH-IVUS measures of coronary atherosclerosis and the Framingham risk score in a prospective, multinational registry. METHODS AND RESULTS: Patients enrolled from 2004-2006 at 37 multinational centres in the prospective VHIVUS Global Registry were analysed. All subjects underwent diagnostic coronary angiography followed by IVUS. A Framingham risk score (FRS) was calculated for each subject, then stratified into three exclusive estimates (<10%, 10-19%, or >or= 20%) for future coronary heart disease (CHD) event risk over 10 years. Among 531 patients, plaque volume of the most diseased 10 mm segment increased with increasing FRS (P=0.006, adjusted for multiple comparisons). Patients with higher FRS estimates of CHD risk had a higher proportion of plaque classified as thin cap fibroatheroma compared with patients in the middle and lower risk score categories (21.4% vs 15.2% and 11.3%, respectively, P=0.008, adjusted for multiple comparisons). CONCLUSIONS: Using data from a large, multinational VH-IVUS registry we describe an association between the Framingham risk score and VH-IVUS measures of atherosclerosis within the most diseased 10 mm segment, namely plaque volume and the proportion of thin cap fibroatheroma.

Intravascular ultrasound radiofrequency analysis of coronary atherosclerosis: an emerging technology for the assessment of vulnerable plaque.

Evaluation of atherosclerotic plaque composition and morphometry may yield insight into plaque biology and the mechanisms of plaque-associated thrombosis. Analysis of intravascular ultrasound radiofrequency (IVUS-RF) backscatter signal is one technology that provides in vivo assessment of both atherosclerotic plaque composition and morphometry. We summarize three different approaches to IVUS-RF and critique the studies using this technology. In addition, we address the potential application of IVUS-RF to assess vulnerable plaque.