Exploring the potential cost-effectiveness of a novel platelet assay for guiding dual antiplatelet therapy duration in acute coronary syndrome patients following percutaneous coronary intervention.

OBJECTIVE: Duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) influences ischemic and bleeding events. Platelet expression of constant fragment of immunoglobulin, low affinity IIa, receptor (FcγRIIa) independently predicts risk of ischemic complications and is proposed as a tool to guide individualized care. METHODS: We used a Markov model to predict lifetime ischemic and bleeding events and healthcare costs in acute myocardial infarction (MI) patients treated with PCI and DAPT and to project cost-effectiveness of platelet FcγRIIa-assay-guided care (30:3 months DAPT for patients at high: low ischemic risk) versus current standard care (12 months DAPT) from the perspective of the US healthcare system. Model inputs included assay sensitivity and specificity, ischemic and bleeding event rates, and impacts on quality of life, mortality, and costs. Assay cost was $90. Sensitivity analyses were conducted over a range of plausible clinical and cost assumptions. RESULTS: Under base case assumptions, platelet FcγRIIa-assay-guided DAPT duration was projected to increase lifetime costs by $19 versus standard care, with an associated incremental cost-effectiveness ratio (ICER) of $436 per quality-adjusted life-year (QALY) gained. Assay-guided DAPT duration was consistent with high-value care (ICER < $50 000/QALY gained) over a broad range of alternative assumptions. CONCLUSION: Based on a decision-analytic model, for patients with MI treated with PCI, the additional costs of the platelet FcγRIIa assay for guiding DAPT duration would be largely offset by reductions in downstream event-related costs, and assay-guided care would be highly cost-effective by current standards. These findings require confirmation in prospective studies and in a randomized clinical trial of assay-guided versus nonassay-guided DAPT duration.

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.

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.

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.

Weighing the potential late benefits versus early hazard associated with bioresorbable vascular scaffolds in percutaneous coronary interventions: a Markov decision analytic model.

OBJECTIVE: Use of poly-L-lactic acid-based bioresorbable scaffolds (BRS) has been associated with increased risk of device thrombosis during the first 3 years after implantation as compared to metallic everolimus-eluting stents (EES). The long-term performance of BRS relative to EES remains unknown. METHODS: We used a Markov decision analysis model to evaluate the effectiveness of BRS vs. EES over a lifetime horizon. In addition to one-way sensitivity analyses of key variables, we evaluated the impact of optimal implantation technique and limiting procedures to larger vessels (>2.6 mm in diameter) on model results. RESULTS: Assuming no risk of target lesion revascularization for BRS after 3 years, we found a small increment in quality-adjusted life expectancy (QALE) of 0.02 with the use of BRS relative to EES, with benefit being observed after 21.8 years. Optimal implantation technique and limiting to larger vessels resulted in larger gains in QALE (0.08 and 0.06, respectively) with BRS and shorter times to equipoise (6.7 and 8.3 years, respectively). Model results were highly sensitive to variations in the relative risk of stent thrombosis (BRS vs. EES). CONCLUSIONS: Based on currently available data, it would take approximately 21.8 years for the presumed late benefits of current BRS relative to EES to overcome the early hazard associated with their use under favorable assumptions. Optimal implantation technique and limiting procedures to larger vessels improved BRS performance and reduced time to equipoise. Eliminating the higher BRS thrombosis risk is necessary in developing future generations of BRS as an acceptable alternative to EES.

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.

Cost-Effectiveness of Long-Term Ticagrelor in Patients With Prior Myocardial Infarction: Results From the PEGASUS-TIMI 54 Trial.

BACKGROUND: In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding. OBJECTIVES: The authors evaluated cost-effectiveness of ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years. METHODS: The authors performed a prospective economic substudy alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162 patients to ASA alone, ticagrelor 60 mg twice daily + low-dose ASA, or ticagrelor 90 mg twice daily + low-dose ASA. Medical resource use data were collected over a median 33-month follow-up. Costs were assessed from the U.S. health care system perspective. In-trial data relating to survival, utility, and costs were combined with lifetime projections to evaluate lifetime cost-effectiveness of the Food and Drug Administration-approved lower-dose ticagrelor regimen (60 mg twice daily). RESULTS: Hospitalization costs were similar for ticagrelor 60 mg and placebo ($2,262 vs. $2,333; 95% confidence interval for difference -$303 to $163; p = 0.54); after inclusion of a daily ticagrelor 60 mg cost of $10.52, total costs were higher for ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p < 0.001). In-trial quality-adjusted life-years (QALYs) were similar (2.28 vs. 2.27; p = 0.34). Over a lifetime horizon, ticagrelor was associated with QALY gains of 0.078 and incremental costs of $7,435, yielding an incremental cost-effectiveness ratio (ICER) of $94,917/QALY gained. Several high-risk groups had more favorable ICERs, including patients with >1 prior MI, multivessel disease, diabetes, renal dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age <75 years (ICER = $44,779/QALY gained), and patients with peripheral artery disease (ICER = $13,427/QALY gained). CONCLUSIONS: For patients with a history of MI >1 year previously, long-term treatment with ticagrelor 60 mg + low-dose ASA yields a cost-effectiveness ratio suggesting intermediate value based on current guidelines. Ticagrelor appears to provide higher value for patients in several recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

Cost-Effectiveness of Edoxaban vs. Warfarin in Patients with Atrial Fibrillation Based on Results of the ENGAGE AF - TIMI 48 Trial: Taiwanese Perspective.

BACKGROUND: Novel anticoagulants, such as factor Xa inhibitors, have entered clinical practice as alternatives to warfarin for the prevention of stroke and systemic embolic event (SEE) in patients with atrial fibrillation (AF). It is not known whether edoxaban, the fourth-to-market factor Xa inhibitor approved for this indication, will be cost-effective in Taiwan, where the cost of warfarin monitoring is prohibitive. METHODS: A Markov model projecting lifetime results of edoxaban 60 mg/30 mg dose-reduced versus warfarin in patients with nonvalvular AF, based on the ENGAGE AF - TIMI 48 trial, found edoxaban to be of high value relative to warfarin, from the perspective of the US health care system. We applied Taiwan-specific cost inputs to this model structure to assess the relative cost-effectiveness of edoxaban versus warfarin from the perspective of the Taiwanese health care system. Event rates and hazard ratios from the ENGAGE AF - TIMI 48 East Asian subpopulation were explored in sensitivity analyses. RESULTS: Edoxaban was found to be highly cost-effective compared with warfarin, based on guidelines proposed by the World Health Organization (WHO), with a base case incremental cost-effectiveness ratio of $12,902 per quality-adjusted life year gained. These results were robust to variation of key model parameters, including assumptions regarding the cost and quality-of-life impact of stroke and bleeding events, and assuming East Asian-specific (as opposed to full-trial-population) rates for combinations of ischemic stroke, SEE, and major bleeding. CONCLUSIONS: Despite its higher acquisition cost, edoxaban is an economically attractive alternative to warfarin for the prevention of stroke and SEE in patients with AF in Taiwan.

Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and Associated Costs Among Patients With a Recent Acute Coronary Syndrome: Results From the IMPROVE-IT Trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

BACKGROUND: Ezetimibe, when added to simvastatin therapy, reduces cardiovascular events after recent acute coronary syndrome. However, the impact of ezetimibe on cardiovascular-related hospitalizations and associated costs is unknown. METHODS AND RESULTS: We used patient-level data from the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) to examine the impact of simvastatin-ezetimibe versus simvastatin-placebo on cardiovascular-related hospitalizations and related costs (excluding drug costs) over 7 years follow-up. Medicare Severity-Diagnosis Related Groups were assigned to all cardiovascular hospitalizations. Hospital costs were estimated using Medicare reimbursement rates for 2013. Associated physician costs were estimated as a percentage of hospital costs. The impact of treatment assignment on hospitalization rates and costs was estimated using Poisson and linear regression, respectively. There was a significantly lower cardiovascular hospitalization rate with ezetimibe compared with placebo (risk ratio, 0.95; 95% confidence interval, 0.90-0.99; P=0.031), mainly attributable to fewer hospitalizations for percutaneous coronary intervention, angina, and stroke. Consequently, cardiovascular-related hospitalization costs over 7 years were $453 per patient lower with ezetimibe (95% confidence interval, -$38 to -$869; P=0.030). Although all prespecified subgroups had lower cost with ezetimibe therapy, patients with diabetes mellitus, patients aged ≥75 years, and patients at higher predicted risk for recurrent ischemic events had even greater cost offsets. CONCLUSIONS: Addition of ezetimibe to statin therapy in patients with a recent acute coronary syndrome leads to reductions in cardiovascular-related hospitalizations and associated costs, with the greatest cost offsets in high-risk patients. These cost reductions may completely offset the cost of the drug once ezetimibe becomes generic, and may lead to cost savings from the perspective of the healthcare system, if treatment with ezetimibe is targeted to high-risk patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00202878.

Economic Outcomes of Bioresorbable Vascular Scaffolds Versus Everolimus-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention: 1-Year Results From the ABSORB III Trial.

OBJECTIVES: The purpose of this study was to evaluate the economic impact of the Absorb bioresorbable vascular scaffold compared with the Xience everolimus-eluting stent in patients undergoing percutaneous coronary intervention. BACKGROUND: The ABSORB III trial (Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease) demonstrated that the Absorb scaffold was noninferior to the Xience stent with respect to target lesion failure at 1 year. Whether health care costs differ between the Absorb scaffold and the Xience stent is unknown. METHODS: We performed a prospective health economic study alongside the ABSORB III trial, in which patients undergoing percutaneous coronary intervention for stable or unstable angina were randomized to receive the Absorb scaffold (n = 1,322) or Xience stent (n = 686). Resource use data were collected through 1 year of follow-up. Costs were assessed using resource-based accounting (for procedures), MedPAR data (for other index hospitalization costs), and Medicare reimbursements (for follow-up costs and physician fees). RESULTS: Initial procedural costs were higher with the Absorb scaffold than the Xience stent ($6,316 ± 1,892 vs. $6,103 ± 1,895; p = 0.02), driven mainly by greater balloon catheter use and the higher cost of the scaffold in the Absorb group. Nonetheless, index hospitalization costs ($15,035 ± 2,992 for Absorb vs. $14,903 ± 3,449 for Xience; p = 0.37) and total 1-year costs ($17,848 ± 6,110 for Absorb vs. $17,498 ± 7,411 for Xience; p = 0.29) were similar between the 2 groups. CONCLUSIONS: Although initial procedural costs were higher with the Absorb scaffold, there were no differences in total 1-year health care costs between the 2 cohorts. Longer term follow-up is needed to determine whether meaningful cost savings emerge after scaffold resorption. (A Clinical Evaluation of Absorb™ BVS, the Everolimus-Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT01751906).

Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke: Results From the SWIFT-PRIME Trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

BACKGROUND AND PURPOSE: Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions. METHODS: In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors. RESULTS: Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates. CONCLUSIONS: Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

Cost-Effectiveness of Endovascular Femoropopliteal Intervention Using Drug-Coated Balloons Versus Standard Percutaneous Transluminal Angioplasty: Results From the IN.PACT SFA II Trial.

OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of drug-coated balloon (DCB) angioplasty versus standard percutaneous transluminal angioplasty (PTA). BACKGROUND: Recent trials have reported lower rates of target lesion revascularization with DCB angioplasty versus standard PTA. However, the cost-effectiveness of DCB angioplasty is unknown. METHODS: A prospective economic study was performed alongside the IN.PACT SFA II (IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA]) trial, which randomized 181 patients with femoropopliteal disease to the IN.PACT DCB versus standard PTA. Resource use data were collected over 2-year follow-up, and costs were assigned using resource-based accounting and billing data. Health utilities were assessed using the EuroQol 5-dimensions questionnaire. Cost-effectiveness was assessed as cost per quality-adjusted life-year (QALY) gained using a decision-analytic model on the basis of empirical data from the trial assuming identical long-term mortality. RESULTS: Initial costs were $1,129 per patient higher with DCB angioplasty than standard PTA, driven by higher costs for the DCB itself. Between discharge and 24 months, target limb-related costs were $1,212 per patient lower with DCB angioplasty such that discounted 2-year costs were similar for the 2 groups ($11,277 vs. $11,359, p = 0.97), whereas QALYs tended to be greater among patients treated with DCBs (1.53 ± 0.44 vs. 1.47 ± 0.42, p = 0.40). The probability that DCB angioplasty is cost-effective compared with standard PTA was 70% using a threshold of $50,000 per QALY gained and 79% at a threshold of $150,000 per QALY gained. CONCLUSIONS: For patients with femoropopliteal disease, DCB angioplasty is associated with better 2-year outcomes and similar target limb-related costs compared with standard PTA. Formal cost-effectiveness analysis on the basis of these results suggests that use of the DCB angioplasty is likely to be economically attractive.

Cost-Effectiveness of Transcatheter Aortic Valve Replacement With a Self-Expanding Prosthesis Versus Surgical Aortic Valve Replacement.

BACKGROUND: Previous studies of the cost-effectiveness of transcatheter aortic valve replacement (TAVR) have been based primarily on a single balloon-expandable system. OBJECTIVES: The goal of this study was to evaluate the cost-effectiveness of TAVR with a self-expanding prosthesis compared with surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis and high surgical risk. METHODS: We performed a formal economic analysis on the basis of individual, patient-level data from the CoreValve U.S. High Risk Pivotal Trial. Empirical data regarding survival and quality of life over 2 years, and medical resource use and hospital costs through 12 months were used to project life expectancy, quality-adjusted life expectancy, and lifetime medical costs in order to estimate the incremental cost-effectiveness of TAVR versus SAVR from a U.S. RESULTS: Relative to SAVR, TAVR reduced initial length of stay an average of 4.4 days, decreased the need for rehabilitation services at discharge, and resulted in superior 1-month quality of life. Index admission and projected lifetime costs were higher with TAVR than with SAVR (differences $11,260 and $17,849 per patient, respectively), whereas TAVR was projected to provide a lifetime gain of 0.32 quality-adjusted life-years ([QALY]; 0.41 LY) with 3% discounting. Lifetime incremental cost-effectiveness ratios were $55,090 per QALY gained and $43,114 per LY gained. Sensitivity analyses indicated that a reduction in the initial cost of TAVR by ∼$1,650 would lead to an incremental cost-effectiveness ratio <$50,000/QALY gained. CONCLUSIONS: In a high-risk clinical trial population, TAVR with a self-expanding prosthesis provided meaningful clinical benefits compared with SAVR, with incremental costs considered acceptable by current U.S. STANDARDS: With expected modest reductions in the cost of index TAVR admissions, the value of TAVR compared with SAVR in this patient population would become high. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement [Medtronic CoreValve U.S. Pivotal Trial]; NCT01240902).

Cost-effectiveness of edoxaban vs warfarin in patients with atrial fibrillation based on results of the ENGAGE AF-TIMI 48 trial.

BACKGROUND: In 21,105 patients with atrial fibrillation (AF), the ENGAGE AF-TIMI 48 trial demonstrated that both higher dose (60mg/30mg dose reduced) and lower dose (30mg/15mg dose reduced) once-daily regimens of edoxaban were non-inferior to warfarin for the prevention of stroke or systemic embolism (SE), with significantly lower rates of bleeding and cardiovascular death. Higher dose edoxaban was associated with a greater reduction in the risk of ischemic stroke than lower dose edoxaban, and the FDA approved higher dose edoxaban in patients with creatinine clearance ≤95mL/min. This study evaluated the economic value of higher dose edoxaban vs warfarin based on data from patients in ENGAGE within the FDA-approved population. METHODS: We assessed the cost-effectiveness of edoxaban vs warfarin over a lifetime horizon from the US healthcare system perspective using a Markov model based on a combination of ENGAGE AF-TIMI 48 trial data, US life tables, and published literature on the costs and long-term outcomes of non-fatal cardiovascular and bleeding events. Data from the ENGAGE AF-TIMI 48 trial were used to calculate age-adjusted event rates for warfarin and hazard ratios (HRs) for the relative impact of edoxaban on embolic and bleeding complications. Based on the wholesale acquisition price, edoxaban and warfarin were assumed to cost $9.24 and $0.36/day, respectively. RESULTS: For edoxaban vs warfarin, lifetime incremental costs and QALYs were $16,384 and 0.444, respectively, yielding an incremental cost-effectiveness ratio (ICER) of $36,862/QALY gained, using data from patients with creatinine clearance ≤95mL/min in ENGAGE AF-TIMI 48. ICERs were more favorable for patients without compared to those with prior warfarin use; ICERs differed minimally by CHADS2 score. CONCLUSIONS: Despite its higher acquisition cost, edoxaban is an economically attractive alternative to warfarin for the prevention of stroke and SE in patients with atrial fibrillation and creatinine clearance ≤95mL/min. These results were robust to variation of key model parameters, including assumptions regarding the cost and quality-of-life impact of stroke and bleeding events, and were favorable across both CHADS2 score stroke-risk categories.

Cost-effectiveness of percutaneous coronary intervention versus bypass surgery from a Dutch perspective.

AIMS: Recent cost-effectiveness analyses of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) have been limited by a short time horizon or were restricted to the US healthcare perspective. We, therefore, used individual patient-level data from the SYNTAX trial to evaluate the cost-effectiveness of PCI versus CABG from a European (Dutch) perspective. METHODS AND RESULTS: Between 2005 and 2007, 1800 patients with three-vessel or left main coronary artery disease were randomised to either CABG (n=897) or PCI with drug-eluting stents (DES; n=903). Costs were estimated for all patients based on observed healthcare resource usage over 5 years of follow-up. Health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on Dutch life-tables was used to extrapolate the 5-year in-trial data to a lifetime horizon. Although initial procedural costs were lower for CABG, total initial hospitalisation costs per patient were higher (€17 506 vs €14 037, p<0.001). PCI was more costly during the next 5 years of follow-up, due to more frequent hospitalisations, repeat revascularisation procedures and higher medication costs. Nevertheless, total 5-year costs remained €2465/patient higher with CABG. When the in-trial results were extrapolated to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with gains in both life expectancy and quality-adjusted life expectancy. The incremental cost-effectiveness ratio (ICER) (€5390/quality-adjusted life year (QALY) gained) was favourable and remained <€80 000/QALY in >90% of the bootstrap replicates. Outcomes were similar when incorporating the prognostic impact of non-fatal myocardial infarction and stroke, as well as across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs. However, DES-PCI was economically dominant compared with CABG in patients with a SYNTAX Score ≤22 or in those with left main disease. In patients for whom the SYNTAX Score II favoured PCI based on lower predicted 4-year mortality, PCI was also economically dominant, whereas in those patients for whom the SYNTAX Score II favoured surgery, CABG was highly economically attractive (ICER range, €2967 to €3737/QALY gained). CONCLUSIONS: For the broad population with three-vessel or left main disease who are candidates for either CABG or PCI, we found that CABG is a clinically and economically attractive revascularisation strategy compared with DES-PCI from a Dutch healthcare perspective. The cost-effectiveness of CABG versus PCI differed according to several anatomic factors, however. The newly developed SYNTAX Score II provides enhanced prognostic discrimination in this population, and may be a useful tool to guide resource allocation as well. TRIAL REGISTRATION NUMBER: Clinical trial unique identifier: NCT00114972 (http://www.clinical-trials.gov).

Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with 3-vessel or left main coronary artery disease: final results from the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial.

BACKGROUND: The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial demonstrated that in patients with 3-vessel or left main coronary artery disease, coronary artery bypass graft surgery (CABG) was associated with a lower rate of cardiovascular death, myocardial infarction, stroke, or repeat revascularization compared with percutaneous coronary revascularization with drug-eluting stents (DES-PCI)). The long-term cost-effectiveness of these strategies is unknown. METHODS AND RESULTS: Between 2005 and 2007, 1800 patients with left main or 3-vessel coronary artery disease were randomized to CABG (n=897) or DES-PCI (n=903). Costs were assessed from a US perspective, and health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on the 5-year in-trial data was used to extrapolate costs, life expectancy, and quality-adjusted life expectancy over a lifetime horizon. Although initial procedural costs were $3415 per patient lower with CABG, total hospitalization costs were $10 036 per patient higher. Over the next 5 years, follow-up costs were higher with DES-PCI as a result of more frequent hospitalizations, revascularization procedures, and higher medication costs. Over a lifetime horizon, CABG remained more costly than DES-PCI, but the incremental cost-effectiveness ratio was favorable ($16 537 per quality-adjusted life-year gained) and remained <$20 000 per quality-adjusted life-year in most bootstrap replicates. Results were consistent across a wide range of assumptions about the long-term effect of CABG versus DES-PCI on events and costs. In patients with left main disease or a SYNTAX score ≤22, however, DES-PCI was economically dominant compared with CABG, although these findings were less certain. CONCLUSIONS: For most patients with 3-vessel or left main coronary artery disease, CABG is a clinically and economically attractive revascularization strategy compared with DES-PCI. However, among patients with less complex disease, DES-PCI may be preferred on both clinical and economic grounds. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique identifier: NCT00114972.

Cost-effectiveness of percutaneous coronary intervention with drug eluting stents versus bypass surgery for patients with diabetes mellitus and multivessel coronary artery disease: results from the FREEDOM trial.

BACKGROUND: Studies from the balloon angioplasty and bare metal stent eras have demonstrated that coronary artery bypass grafting (CABG) is cost-effective compared with percutaneous coronary intervention (PCI) for patients undergoing multivessel coronary revascularization-particularly among patients with complex coronary artery disease or diabetes mellitus. Whether these results apply in the drug-eluting stent (DES) era is unknown. METHODS AND RESULTS: Between 2005 and 2010, 1900 patients with diabetes mellitus and multivessel coronary artery disease were randomized to PCI with DES (DES-PCI; n=953) or CABG (n=947). Costs were assessed from the perspective of the U.S. health care system. Health state utilities were assessed using the EuroQOL 5 dimension 3 level questionnaire. A patient-level microsimulation model based on U.S. life-tables and in-trial results was used to estimate lifetime cost-effectiveness. Although initial procedural costs were lower for CABG, total costs for the index hospitalization were $8622 higher per patient. Over the next 5 years, follow-up costs were higher with PCI, owing to more frequent repeat revascularization and higher outpatient medication costs. Nonetheless, cumulative 5-year costs remained $3641 higher per patient with CABG. Although there were only modest gains in survival with CABG during the trial period, when the in-trial results were extended to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with substantial gains in both life expectancy and quality-adjusted life expectancy and incremental cost-effectiveness ratios <$10 000 per life-year or quality-adjusted life-year gained across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs. CONCLUSIONS: Despite higher initial costs, CABG is a highly cost-effective revascularization strategy compared with DES-PCI for patients with diabetes mellitus and multivessel coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinical-trials.gov. Unique identifier: NCT00086450.

Cost-effectiveness of transcatheter aortic valve replacement compared with surgical aortic valve replacement in high-risk patients with severe aortic stenosis: results of the PARTNER (Placement of Aortic Transcatheter Valves) trial (Cohort A).

OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (AVR) for patients with severe aortic stenosis and high surgical risk. BACKGROUND: TAVR is an alternative to AVR for patients with severe aortic stenosis and high surgical risk. METHODS: We performed a formal economic analysis based on cost, quality of life, and survival data collected in the PARTNER A (Placement of Aortic Transcatheter Valves) trial in which patients with severe aortic stenosis and high surgical risk were randomized to TAVR or AVR. Cumulative 12-month costs (assessed from a U.S. societal perspective) and quality-adjusted life-years (QALYs) were compared separately for the transfemoral (TF) and transapical (TA) cohorts. RESULTS: Although 12-month costs and QALYs were similar for TAVR and AVR in the overall population, there were important differences when results were stratified by access site. In the TF cohort, total 12-month costs were slightly lower with TAVR and QALYs were slightly higher such that TF-TAVR was economically dominant compared with AVR in the base case and economically attractive (incremental cost-effectiveness ratio <$50,000/QALY) in 70.9% of bootstrap replicates. In the TA cohort, 12-month costs remained substantially higher with TAVR, whereas QALYs tended to be lower such that TA-TAVR was economically dominated by AVR in the base case and economically attractive in only 7.1% of replicates. CONCLUSIONS: In the PARTNER trial, TAVR was an economically attractive strategy compared with AVR for patients suitable for TF access. Future studies are necessary to determine whether improved experience and outcomes with TA-TAVR can improve its cost-effectiveness relative to AVR.

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

BACKGROUND AND PURPOSE: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. METHODS: We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. RESULTS: Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, -$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. CONCLUSIONS: Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00004732.

Use of drug-eluting stents as a function of predicted benefit: clinical and economic implications of current practice.

BACKGROUND: Benefits of drug-eluting stents (DES) in percutaneous coronary intervention (PCI) are greatest in those at the highest risk of target-vessel revascularization (TVR). Drug-eluting stents cost more than bare-metal stents (BMS) and necessitate prolonged dual antiplatelet therapy (DAPT), which increases costs, bleeding risk, and risk of complications if DAPT is prematurely discontinued. Our objective was to assess whether DES are preferentially used in patients with higher predicted TVR risk and to estimate if lower use of DES in low-TVR-risk patients would be more cost-effective than the existing DES use pattern. METHODS: We analyzed more than 1.5 million PCI procedures in the National Cardiovascular Data Registry (NCDR) CathPCI registry from 2004 through 2010 and estimated 1-year TVR risk with BMS using a validated model. We examined the association between TVR risk and DES use and the cost-effectiveness of lower DES use in low-TVR-risk patients (50% less DES use among patients with <10% TVR risk) compared with existing DES use. RESULTS: There was marked variation in physicians' use of DES (range 2%-100%). Use of DES was high across all predicted TVR risk categories (73.9% in TVR risk <10%; 78.0% in TVR risk 10%-20%; and 83.2% in TVR risk >20%), with a modest relationship between TVR risk and DES use (relative risk, 1.005 per 1% increase in TVR risk [95% CI, 1.005-1.006]). Reducing DES use by 50% in low-TVR-risk patients was projected to lower US health care costs by $205 million per year while increasing the overall TVR event rate by 0.5% (95% CI, 0.49%-0.51%) in absolute terms. CONCLUSIONS: Use of DES in the United States varies widely among physicians, with only a modest correlation to patients' risk of restenosis. Less DES use among patients with low risk of restenosis has the potential for significant cost savings for the US health care system while minimally increasing restenosis events.