Economic Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis and Low Surgical Risk: Results from the PARTNER 3 Trial.

BACKGROUND: In patients with severe symptomatic aortic stenosis at low surgical risk, transfemoral transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve has been shown to reduce the composite of death, stroke, or rehospitalization at 2-year follow-up compared with surgical aortic valve replacement (SAVR). Whether TAVR is cost-effective compared with SAVR for low-risk patients remains uncertain. METHODS: Between 2016 and 2017, 1000 low-risk patients with aortic stenosis were randomly assigned to TAVR with the SAPIEN 3 valve or SAVR in the PARTNER 3 trial (Placement of Aortic Transcatheter Valves). Of these patients, 929 underwent valve replacement, were enrolled in the United States, and were included in the economic substudy. Procedural costs were estimated using measured resource use. Other costs were determined by linkage with Medicare claims or by regression models when linkage was not feasible. Health utilities were estimated using the EuroQOL 5-item questionnaire. With the use of a Markov model informed by in-trial data, lifetime cost-effectiveness from the perspective of the US health care system was estimated in terms of cost per quality-adjusted life-year gained. RESULTS: Although procedural costs were nearly $19 000 higher with TAVR, total index hospitalization costs were only $591 more with TAVR compared with SAVR. Follow-up costs were lower with TAVR such that TAVR led to 2-year cost savings of $2030/patient compared with SAVR (95% CI, -$6222 to $1816) and a gain of 0.05 quality-adjusted life-years (95% CI, -0.003 to 0.102). In our base-case analysis, TAVR was projected to be an economically dominant strategy with a 95% probability that the incremental cost-effectiveness ratio for TAVR would be <$50 000/quality-adjusted life-year gained (consistent with high economic value from a US health care perspective). These findings were sensitive to differences in long-term survival, however, such that a modest long-term survival advantage with SAVR would render SAVR cost-effective (although not cost saving) compared with TAVR. CONCLUSIONS: For patients with severe aortic stenosis and low surgical risk similar to those enrolled in the PARTNER 3 trial, transfemoral TAVR with the SAPIEN 3 valve is cost saving compared with SAVR at 2 years and is projected to be economically attractive in the long run as long as there are no substantial differences in late death between the 2 strategies. Long-term follow-up will be critical to ultimately determine the preferred treatment strategy for low-risk patients from both a clinical and economic perspective.

Economics of Minimalist Transcatheter Aortic Valve Replacement: Results From the 3M-TAVR Economic Study.

BACKGROUND: The 3M-TAVR trial (3M-Transcatheter Aortic Valve Replacement) demonstrated the feasibility and safety of next-day hospital discharge after transfemoral TAVR with implementation of a minimalist pathway. However, the economic impact of this approach is unknown. Therefore, we evaluated costs for patients undergoing minimalist TAVR compared with conventional TAVR. METHODS: We used propensity matching to compare resource utilization and costs (from a US health care system perspective) for patients in the 3M-TAVR trial with those for transfemoral TAVR patients enrolled in the contemporaneous S3i trial (PARTNER SAPIEN-3 Intermediate Risk). Procedural costs were estimated using measured resource utilization for both groups. For the S3i group, all other costs through 30-day follow-up were assessed by linkage with Medicare claims; for 3M, these costs were assessed using regression models derived from S3i cost and resource utilization data. RESULTS: After 1:1 propensity matching, 351 pairs were included in our study (mean age 82, mean Society of Thoracic Surgery risk score 5.3%). There were no differences in death, stroke, or rehospitalization between the 3M-TAVR and S3i groups through 30-day follow-up. Index hospitalization costs were $10 843/patient lower in the 3M-TAVR cohort, driven by reductions in procedure duration, anesthesia costs, and length of stay. Between discharge and 30 days, costs were similar for the 2 groups such that cumulative 30-day costs were $11 305/patient lower in the 3M-TAVR cohort compared with the S3i cohort ($49 425 versus $60 729, 95% CI for difference $9378 to $13 138; P<0.001). CONCLUSIONS: Compared with conventional transfemoral TAVR, use of a minimalist pathway in intermediate-risk patients was associated with similar clinical outcomes and substantial in-hospital cost savings, which were sustained through 30 days. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02287662.

Cost-Effectiveness of Percutaneous Coronary Intervention Versus Bypass Surgery for Patients With Left Main Disease: Results From the EXCEL Trial.

BACKGROUND: The EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) demonstrated in patients with left main coronary artery disease, no significant difference between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) with everolimus-eluting stents for the composite end point of death, stroke, or myocardial infarction at 5 years. However, all-cause mortality at 5 years was higher with PCI. Long-term cost-effectiveness of these 2 strategies has heretofore not been evaluated. METHODS: From 2010 to 2014, 1905 patients with left main coronary artery disease were randomized to CABG (n=957) or PCI (n=948). Costs ($2019) were assessed over 5 years using resource-based costing and Medicare reimbursement rates. Health utilities were assessed using the EuroQOL 5-dimension questionnaire. Five-year EXCEL data in combination with US lifetables were used to develop a Markov model to evaluate lifetime cost-effectiveness. An incremental cost-effectiveness ratio <$50 000 per quality-adjusted life year (QALY) gained was considered highly cost-effective. RESULTS: Index revascularization procedure costs were $4,850/patient higher with CABG, and total costs for the index hospitalization were $17 610/patient higher with CABG ($32 297 versus $19 687, P<0.001). Cumulative 5-year costs were $20 449/patient higher with CABG. CABG was projected to increase lifetime costs by $21 551 while increasing quality-adjusted life expectancy by 0.49 QALYs, yielding an incremental cost-effectiveness ratio of $44 235/QALY. In a post hoc sensitivity analysis using mortality hazard ratios from a meta-analysis of all randomized CABG versus PCI in left main disease trials, the gain associated with CABG was 0.08 to 0.14 QALYs, resulting in an incremental cost-effectiveness ratio of $139 775 to $232 710/QALY gained. CONCLUSIONS: Based on data from the EXCEL trial, CABG is an economically attractive revascularization strategy compared with PCI over a lifetime horizon for patients with significant left main coronary artery disease. However, this conclusion is sensitive to the long-term mortality rates with the 2 strategies, and CABG is no longer highly cost-effective when substituting the pooled treatment effect from the 4 major PCI versus CABG trials for left main disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01205776.

Cost-effectiveness of transcatheter edge-to-edge repair in secondary mitral regurgitation.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair (TMVr) improves symptoms and survival for patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and severe secondary mitral regurgitation despite guideline-recommended medical therapy (GRMT). Whether TMVr is cost-effective from a UK National Health Service (NHS) perspective is unknown. METHODS: We used patient-level data from the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial to perform a cost-effectiveness analysis of TMVr +GRMT versus GRMT alone from an NHS perspective. Costs for the TMVr procedure were based on standard English tariffs and device costs. Subsequent costs were estimated based on data acquired during the trial. Health utilities were estimated using the Short-Form 6-Dimension Health Survey. RESULTS: Costs for the index procedural hospitalisation were £18 781, of which £16 218 were for the TMVr device. Over 2-year follow-up, TMVr reduced subsequent costs compared with GRMT (£10 944 vs £14 932, p=0.006), driven mainly by reductions in heart failure hospitalisations; nonetheless, total 2-year costs remained higher with TMVr (£29 165 vs £14 932, p<0.001). When survival, health utilities and costs were projected over a lifetime, TMVr was projected to increase life expectancy by 1.57 years and quality-adjusted life expectancy by 1.12 quality-adjusted life-years (QALYs) at an incremental cost of £21 980, resulting in an incremental cost-effectiveness ratio (ICER) of £23 270 per QALY gained (after discounting). If the benefits of TMVr observed in the first 2 years were maintained without attenuation, the ICER improved to £12 494 per QALY. CONCLUSIONS: For patients with HFrEF and severe secondary mitral regurgitation similar to those enrolled in COAPT, TMVr increases life expectancy and quality-adjusted life expectancy compared with GRMT at an ICER that represents good value from an NHS perspective.

Catheter-directed thrombolysis for deep vein thrombosis: 2021 update.

Catheter-directed thrombolysis (CDT) has been utilized as an adjunct to anticoagulant therapy in selected patients with deep vein thrombosis (DVT) for approximately 30 years. CDT used to be limited to patients with DVT causing acute limb threat and those exhibiting failure of initial anticoagulation, but has expanded over time. Randomized trials evaluating the first-line use of CDT for proximal DVT have demonstrated that CDT does not produce a major reduction in the occurrence of post-thrombotic syndrome (PTS) and that it is poorly suited for elderly patients and those with limited thrombus extent or major risk factors for bleeding. However, CDT does offer selected patients with acute iliofemoral DVT improvement in reducing early DVT symptoms, in achieving reduction in PTS severity, and in producing an improvement in health-related quality of life (QOL). Clinical practice guidelines from medical and surgical societies are now largely aligned with the randomized trial results. This review offers the reader an update on the results of recently completed clinical trials, and additional guidance on appropriate selection of patients with DVT for catheter-directed thrombolytic therapy.

Two-year PAD-related health care costs in patients undergoing lower extremity endovascular revascularization: results from the LIBERTY 360° trial.

BACKGROUND: Multiple studies have demonstrated the high economic burden related to the management of lower extremity peripheral artery disease (PAD). This is the first study to examine long-term PAD-related costs among unselected patients undergoing endovascular intervention, and to investigate how clinical and anatomic factors impact cost outcomes over time. METHODS AND RESULTS: We performed a prospective health economic study alongside the LIBERTY 360° trial (ClinicalTrials.gov; identifier NCT01855412) - a prospective, multi-center study evaluating the long-term outcomes of endovascular revascularization to treat claudication or critical limb ischemia. Costs (2018) were calculated using a combination of standard "bottom-up" cost accounting methods (for index procedures), itemized hospital charges and department level cost-to-charge ratios (for non-procedural hospital resources), national Medicare Severity-Diagnosis Related Group-specific average reimbursements (for follow-up hospitalizations) and Medicare payments (for outpatient/chronic care). Methods for the analysis of censored cost data were used to adjust cost estimates for patients with incomplete follow-up. Independent predictors of cumulative 2-year costs were explored using generalized linear models. A total of 1,189 patients were included (500 Rutherford 2-3, 589 Rutherford 4-5, 100 Rutherford 6). Mean total costs associated with the index procedure hospitalization increased with Rutherford classification ($10,304, $11,418, and $19,403 for Rutherford 2-3, 4-5, and 6, respectively; p < 0.01 in all pairwise comparisons). Mean total 2-year follow-up costs were $11,416, $24,846, and $25,720 for Rutherford 2-3, 4-5, and 6, respectively (p < 0.001 comparing Rutherford 2-3 to the other 2 groups; p = 0.09 comparing Rutherford 4-5 and Rutherford 6). Key predictors of higher cumulative 2-year costs included female sex, pedal lesion location, severe lesion calcification, the presence of one or more chronic total occlusions, the number of wounds present on the target limb at baseline, and Rutherford classification. CONCLUSIONS: Among patients with symptomatic lower extremity PAD undergoing endovascular revascularization, initial treatment costs and total 2-year costs vary significantly according to clinical and lesion-level characteristics, as well as symptom burden.

Predicting the EQ-5D utilities from the Kansas City Cardiomyopathy Questionnaire in patients with heart failure.

INTRODUCTION: Evaluation of health status benefits, cost-effectiveness, and value of new heart failure therapies is critical for supporting their use. The Kansas City Cardiomyopathy Questionnaire (KCCQ) measures patients' heart failure-specific health status but does not provide utilities needed for cost-effectiveness analyses. We mapped the KCCQ scores to EQ-5D scores so that estimates of societal-based utilities can be generated to support economic analyses. METHODS: Using data from two US cohort studies, we developed models for predicting EQ-5D utilities (3L and 5L versions) from the KCCQ (23- and 12-item versions). In addition to predicting scores directly, we considered predicting the five EQ-5D health state items and deriving utilities from the predicted responses, allowing different countries' health state valuations to be used. Model validation was performed internally via bootstrap and externally using data from two clinical trials. Model performance was assessed using R2, mean prediction error, mean absolute prediction error, and calibration of observed vs. predicted values. RESULTS: The EQ-5D-3L models were developed from 1000 health status assessments in 547 patients with heart failure and reduced ejection fraction (HFrEF), while the EQ-5D-5L model was developed from 3925 patients with HFrEF. For both versions, models predicting individual EQ-5D items performed as well as those predicting utilities directly. The selected models for the 3L had internally validated R2 of 48.4-50.5% and 33.7-45.6% on external validation. The 5L version had validated R2 of 57.7%. CONCLUSION: Mappings from the KCCQ to the EQ-5D can yield the estimates of societal-based utilities to support cost-effectiveness analyses when EQ-5D data are not available.

Five-Year Health Status After Self-expanding Transcatheter or Surgical Aortic Valve Replacement in High-risk Patients With Severe Aortic Stenosis.

Importance: In the CoreValve High-Risk Trial, patients with severe symptomatic aortic stenosis had similar clinical outcomes with transcatheter aortic valve replacement (TAVR) vs surgical aortic valve replacement (SAVR) over 5 years of follow-up, with mortality rates of more than 50% in both groups. Objective: To describe the long-term health status of surviving patients randomized to self-expanding TAVR vs SAVR. Design, Setting, and Participants: This randomized clinical trial included patients at high surgical risk with severe aortic stenosis who completed a baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) and were randomized to either self-expanding TAVR or SAVR from 45 US clinical sites. Patients were enrolled from February 2011 to September 2012. Analysis began May 2018 and ended June 2020. Main Outcomes and Measures: Change in KCCQ and the 12-Item Short-Form Health Survey over 5 years, as assessed by repeated-measures analysis of covariance. Because there were significant interactions between access site and treatment for 1-month health status outcomes, all analyses were stratified by access site (iliofemoral or noniliofemoral). Results: Of 713 patients, 377 (53%) were men, and the mean (SD) age was 83 (7) years. Prior to treatment, the mean (SD) KCCQ overall summary score (range, 0-100; higher score indicated better health status) was 47 (23), indicating substantial health status impairment. Among surviving patients, the KCCQ overall summary score increased significantly in both groups with greater early benefit with iliofemoral TAVR than SAVR (1-month difference, 16.8 points; 95% CI, 12.4-21.2). However, this early treatment difference between TAVR and SAVR was no longer apparent by 6 months, and there was no significant difference in health status between groups thereafter. At 5 years, 44% (134 of 305) of patients who underwent iliofemoral TAVR and 39% (105 of 266) who underwent SAVR were alive in this high-risk elderly cohort. Among surviving patients for whom health status data were available, 61% (48 of 79) in the TAVR group and 65% (46 of 71) in the SAVR group had KCCQ overall summary score more than 60 (P = .61). In the noniliofemoral cohort, there were no significant health status differences at any time between TAVR and SAVR. Results were similar for individual KCCQ domains and the Short-Form Health Survey. Conclusions and Relevance: In high-risk patients with severe symptomatic aortic stenosis, there was an early health status benefit with self-expanding iliofemoral TAVR vs SAVR but no difference between groups in long-term health status. Although mortality at 5 years was high in this population, the majority of surviving patients continued to report reasonable health status. Trial Registration: ClinicalTrials.gov Identifier: NCT01240902.

Cardiovascular- and Bleeding-Related Hospitalization Rates With Edoxaban Versus Warfarin in Patients With Atrial Fibrillation Based on Results of the ENGAGE AF-TIMI 48 Trial.

Background The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) demonstrated noninferiority of once-daily 60 mg (30 mg dose-reduced) edoxaban compared with warfarin for prevention of stroke/systemic embolism in patients with atrial fibrillation. No previous analysis has explored the impact of treatment with edoxaban versus warfarin on rates of hospitalizations. Methods Detailed healthcare resource utilization data from ENGAGE AF-TIMI 48 for the 14 024 randomized patients who received at least one dose of study drug were used to compare the rates of bleeding- and cardiovascular-related hospitalizations for edoxaban versus warfarin. Hospitalization rates were calculated for each treatment group, and relative rates were estimated using Poisson regression. The influence of patient characteristics on the impact of edoxaban versus warfarin was evaluated through the inclusion of interaction terms. Results The overall rate of cardiovascular- or bleeding-related hospitalization was significantly lower for edoxaban than warfarin (relative rate [RR], 0.91 [95% CI, 0.85-0.97], P=0.003). Rates of hospitalizations for cardiovascular reasons (RR, 0.91 [95% CI, 0.85-0.97], P=0.004), stroke (RR, 0.80 [95% CI, 0.72-0.88], P<0.0001), and for each stroke subtype (ischemic: RR, 0.89 [95% CI, 0.81-0.99], P=0.03; hemorrhagic: RR, 0.60 [95% CI, 0.54-0.68], P<0.0001) were also lower for edoxaban. Notably, significantly greater reductions with edoxaban versus warfarin were seen for ischemic stroke-related hospitalizations in vitamin K antagonist naive patients and patients with CHADS2 scores 4 to 6, previous stroke or transient ischemic attack, age ≥75, and no previous coronary artery disease. For nonstroke bleeding-related hospitalizations, greater reductions with edoxaban were seen in vitamin K antagonist naive patients, patients with CHADS2 scores 4 to 6, and patients with moderate renal dysfunction. Conclusions Edoxaban 60 mg (30 mg dose-reduced) was associated with a significantly lower overall rate of cardiovascular- or bleeding-related hospitalization and significant reductions in the subcategories of cardiovascular-related, stroke-related, bleed-related, and nonstroke cardiovascular-related hospitalizations, when compared with warfarin. These results suggest the potential for cost offsets with edoxaban, with even greater reductions in higher-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00781391.

Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep venous thrombosis.

BACKGROUND: After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT. METHODS: The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups. RESULTS: Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P < .0001) and 6 months (8.8; P < .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups. CONCLUSIONS: Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.

Cost-Effectiveness of Pharmacomechanical Catheter-Directed Thrombolysis Versus Standard Anticoagulation in Patients With Proximal Deep Vein Thrombosis: Results From the ATTRACT Trial.

BACKGROUND: In patients with acute deep vein thrombosis (DVT), pharmacomechanical catheter-directed thrombolysis (PCDT) in conjunction with anticoagulation therapy is increasingly used with the goal of preventing postthrombotic syndrome. Long-term costs and cost-effectiveness of these 2 treatment strategies from the perspective of the US healthcare system have not been compared. METHODS AND RESULTS: Between 2009 and 2014, the ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) randomized 692 patients with acute proximal DVT to PCDT plus anticoagulation (n=337) or standard treatment with anticoagulation alone (n=355). Costs (2017 US dollars) were assessed over a 24-month follow-up period using a combination of resource-based costing, hospital bills, Medicare reimbursement rates, and the Drug Topics Red Book. Health state utilities were obtained from the Short Form-36. In-trial results and US life tables were used to develop a Markov cohort model to evaluate lifetime cost-effectiveness. For the PCDT group, mean costs of the initial procedure were $13 600; per-patient costs associated with the index hospitalization were $21 509 for PCDT and $3877 for standard care (difference=$17 632; 95% CI, $16 117-$19 243). The 24-month difference in costs was $20 045 (95% CI, $16 093-$24 120). Utility scores increased significantly between baseline and 6 months for both groups, with no significant differences between groups at any follow-up time point. Projected differences in lifetime costs of $16 740 and quality-adjusted life years (QALYs) of 0.08, yield an incremental cost-effectiveness ratio for PCDT of $222 041/QALY gained. In probabilistic sensitivity analysis, the probability that PCDT would achieve a lifetime incremental cost-effectiveness ratio <$50 000/QALY or <$150 000/QALY was 1% and 25%, respectively. For iliofemoral DVT, QALY gains with PCDT were greater, yielding an incremental cost-effectiveness ratio of $137 526/QALY; for femoral-popliteal DVT, standard therapy was an economically dominant strategy. CONCLUSIONS: With an incremental cost-effectiveness ratio >$200 000/QALY gained, PCDT is not an economically attractive treatment for proximal DVT. PCDT may be of intermediate value in patients with iliofemoral DVT. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00790335.

Health Status After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis.

BACKGROUND: In patients with severe aortic stenosis (AS) at low surgical risk, treatment with transcatheter aortic valve replacement (TAVR) results in lower rates of death, stroke, and rehospitalization at 1 year compared with surgical aortic valve replacement; however, the effect of treatment strategy on health status is unknown. OBJECTIVES: This study sought to compare health status outcomes of TAVR versus surgery in low-risk patients with severe AS. METHODS: Between March 2016 and October 2017, 1,000 low-risk patients with AS were randomized to transfemoral TAVR using a balloon-expandable valve or surgery in the PARTNER 3 (Placement of Aortic Transcatheter Valves) trial. Health status was assessed at baseline and 1, 6, and 12 months using the KCCQ (Kansas City Cardiomyopathy Questionnaire), SF-36 (Short Form-36 Health Survey), and EQ-5D (EuroQoL). The primary endpoint was change in KCCQ-OS (KCCQ Overall Summary) score over time. Longitudinal growth curve modeling was used to compare changes in health status between treatment groups over time. RESULTS: At 1 month, TAVR was associated with better health status than surgery (mean difference in KCCQ-OS 16.0 points; p < 0.001). At 6 and 12 months, health status remained better with TAVR, although the effect was reduced (mean difference in KCCQ-OS 2.6 and 1.8 points respectively; p < 0.04 for both). The proportion of patients with an excellent outcome (alive with KCCQ-OS ≥75 and no significant decline from baseline) was greater with TAVR than surgery at 6 months (90.3% vs. 85.3%; p = 0.03) and 12 months (87.3% vs. 82.8%; p = 0.07). CONCLUSIONS: Among low-risk patients with severe AS, TAVR was associated with meaningful early and late health status benefits compared with surgery.

Cost-Effectiveness of Transcatheter Mitral Valve Repair Versus Medical Therapy in Patients With Heart Failure and Secondary Mitral Regurgitation: Results From the COAPT Trial.

BACKGROUND: The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) demonstrated that edge-to-edge transcatheter mitral valve repair (TMVr) with the MitraClip resulted in reduced mortality and heart failure hospitalizations and improved quality of life compared with maximally tolerated guideline-directed medical therapy (GDMT) in patients with heart failure and 3 to 4+ secondary mitral regurgitation. Whether TMVr is cost-effective compared with GDMT in this population is unknown. METHODS: We used data from the COAPT trial to perform a formal patient-level economic analysis of TMVr+GDMT versus GDMT alone for patients with heart failure and 3 to 4+ secondary mitral regurgitation from the perspective of the US healthcare system. Costs for the index TMVr hospitalization were assessed using a combination of resource-based accounting and hospital billing data (when available). Follow-up medical care costs were estimated on the basis of medical resource use collected during the COAPT trial. Health utilities were estimated for all patients at baseline and 1, 6, 12, and 24 months with the Short Form Six-Dimension Health Survey. RESULTS: Initial costs for the TMVr procedure and index hospitalization were $35 755 and $48 198, respectively. Although follow-up costs were significantly lower with TMVr compared with GDMT ($26 654 versus $38 345; P=0.018), cumulative 2-year costs remained higher with TMVr because of the upfront cost of the index procedure ($73 416 versus $38 345; P<0.001). When in-trial survival, health utilities, and costs were modeled over a lifetime horizon, TMVr was projected to increase life expectancy by 1.13 years and quality-adjusted life-years by 0.82 years at a cost of $45 648, yielding a lifetime incremental cost-effectiveness ratio of $40 361 per life-year gained and $55 600 per quality-adjusted life-year gained. CONCLUSIONS: For symptomatic patients with heart failure and 3 to 4+ secondary mitral regurgitation, TMVr increases life expectancy and quality-adjusted life expectancy compared with GDMT at an incremental cost per quality-adjusted life-year gained that represents acceptable economic value according to current US thresholds. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01626079.

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.

Health Status After Transcatheter Mitral-Valve Repair in Heart Failure and Secondary Mitral Regurgitation: COAPT Trial.

BACKGROUND: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) led to reduced heart failure (HF) hospitalizations and improved survival in patients with symptomatic HF and 3+ to 4+ secondary mitral regurgitation (MR) on maximally-tolerated medical therapy. Given the advanced age and comorbidities of these patients, improvement in health status is also an important treatment goal. OBJECTIVES: The purpose of this study was to understand the health status outcomes of patients with HF and 3+ to 4+ secondary MR treated with TMVr versus standard care. METHODS: The COAPT trial randomized patients with HF and 3+ to 4+ secondary MR to TMVr (n = 302) or standard care (n = 312). Health status was assessed at baseline and at 1, 6, 12, and 24 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the SF-36 health status survey. The primary health status endpoint was the KCCQ overall summary score (KCCQ-OS; range 0 to 100; higher = better; minimum clinically important difference = 5 points). RESULTS: At baseline, patients had substantially impaired health status (mean KCCQ-OS 52.4 ± 23.0). While health status was unchanged over time in the standard care arm, patients randomized to TMVr demonstrated substantial improvement in the KCCQ-OS at 1 month (mean between-group difference 15.9 points; 95% confidence interval [CI]: 12.3 to 19.5 points), with only slight attenuation of this benefit through 24 months (mean between-group difference 12.8 points; 95% CI: 7.5 to 18.2 points). At 24 months, 36.4% of TMVr patients were alive with a moderately large (≥10-point) improvement versus 16.6% of standard care patients (p < 0.001), for a number needed to treat of 5.1 patients (95% CI: 3.6 to 8.7 patients). TMVr patients also reported better generic health status at each timepoint (24-month mean difference in SF-36 summary scores: physical 3.6 points; 95% CI: 1.4 to 5.8 points; mental 3.6 points; 95% CI: 0.8 to 6.4 points). CONCLUSIONS: Among patients with symptomatic HF and 3+ to 4+ secondary MR receiving maximally-tolerated medical therapy, edge-to-edge TMVr resulted in substantial early and sustained health status improvement compared with medical therapy alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).

In-Hospital Costs and Costs of Complications of Chronic Total Occlusion Angioplasty: Insights From the OPEN-CTO Registry.

OBJECTIVES: The aim of this study was to describe the costs of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and the association of complications during CTO PCI with costs and length of stay (LOS). BACKGROUND: CTO PCI generally requires more procedural resources and carries higher risk for complications than PCI of non-CTO vessels. The costs of CTO PCI using the hybrid approach have not been described, and no studies have examined the impact of complications on in-hospital costs and LOS in this population. METHODS: Costs were calculated for 964 patients in the 12-center OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry using prospectively collected resource utilization and billing data. Multivariate models were developed to estimate the incremental costs and LOS associated with complications. Attributable costs and LOS were calculated by multiplying the independent cost of each event by its frequency in the population. RESULTS: Mean costs for the index hospitalization were $17,048 ± 9,904; 14.5% of patients experienced at least 1 complication. Patients with complications had higher mean hospital costs (by $8,603) and LOS (by 1.5 days) than patients without complications. Seven complications were independently associated with increased costs and 6 with LOS; clinically significant perforation and myocardial infarction had the greatest attributable cost per patient. Overall, complications accounted for $911 per patient in hospital costs (5.3% of the total costs) and 0.2 days of additional LOS. CONCLUSIONS: Complications have a significant impact on both LOS and in-hospital costs for patients undergoing CTO PCI. Methods to identify high-risk patients and develop strategies to prevent complications may reduce CTO PCI costs.