Cohen, David Jonathan

Background: The CREST trial demonstrated that for patients at standard risk of surgical complications, there was no significant difference in the primary composite outcome of periprocedural death, MI, or stroke, or late ipsilateral stroke between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although CAS had a higher rate of stroke, and CEA had a higher rate of MI. The economic implications of these two strategies are unknown. Methods: We performed a prospective health economic study alongside the CREST trial. Costs were assessed from the perspective of the US health care system in 2008 dollars using a combination of resource-based and event-based methods. Costs for carotid revascularization procedures were based on measured resource use and unit costs derived from a sample of study hospitals. Non-procedural costs for these hospitalizations were estimated using hospital billing data (charges) and cost-center-specific cost-to-charge-ratios. Costs for follow-up events were estimated using national average DRG reimbursements. The primary analysis was based on a modified intention-to-treat population for which the assigned procedure was attempted (n=1212 CAS; 1193 CEA). Results: CAS was associated with higher total procedural costs (Δ=$675, see Table), driven mainly by higher costs for disposable supplies. Length of stay was shorter for CAS, with associated reductions in non-procedural hospital costs (Δ = -$436). Total cost for the index hospitalization remained slightly higher for CAS (Δ=$239) with similar differences at 1 year. Conclusions: For patients at standard risk of surgical complications, total 1-year costs are slightly higher for CAS vs. CEA, driven largely by higher initial procedural costs. Cost-utility analysis will be performed to determine whether differences in quality of life observed in CREST render CAS an economically attractive strategy. CAS (n= 1212) CEA (n=1193) Δ CAS - CEA (95% CI via bootstrap) Index Procedure Costs, $ Excluding MD Fees 6782 ± 1412 5743 ± 1370 1039 (926, 1148) MD Fees 1114 ± 240 1478 ± 108 -364 (-379, -349) Total 7896 ± 1551 7221 ± 1450 675 (555, 800) Index Hospital Stay 7159 ± 5108 7595 ± 7482 -436 (-951, -59) TOTAL Index Hosp Costs 15055 ± 5539 14816 ± 7709 239 (-302, 778) Index Hosp LOS (days) ICU LOS 0.7 ± 1.1 0.8 ± 1.4 -0.1 (-0.24, -0.04) Non-ICU LOS 1.9 ± 3.2 2.2 ± 4.1 -0.2 (-0.55, 0.06) TOTAL LOS 2.6 ± 3.3 3.0 ± 4.5 -0.4 (-0.7, -0.06) 1-year Rehosp Costs: Repeat Revasc - CAS 295 ± 2097 273 ± 2126 -21 (-142, 201) Repeat Revasc - CEA 287 ± 2088 477 ± 2510 -190 (-371, -11) Ipsilateral Stroke 556 ± 3273 384 ± 2580 172 (-75, 402) TIA 48 ± 520 33 ± 487 16 (-25, 56) Death 63 ± 846 45 ± 779 18 (-49, 85) TOTAL Rehosp costs 1321 ± 4827 1293± 4502 28 (-334, 396) TOTAL 1-year costs 16375 ± 7730 16108 ± 9030 267 (-366, 961)

Background: In the ACUITY Trial, patients (pts) with chronic renal insufficiency (CRI) had significantly higher rates of ischemic events and major bleeding compared to pts without CRI at 30 days. Bivalirudin (Biv) monotherapy provided similar protection from ischemic events but with significantly less bleeding compared to heparin + a GPIIb/IIIa inhibitor (Hep+GPI). The impact of a Biv alone strategy on one year mortality is unknown. Methods: Pts with moderate and high risk acute coronary syndromes (ACS) were randomized to Hep + GPI, Biv + GPI, or Biv monotherapy. CRI was defined as baseline creatinine clearance (CrCl) <60 mL/min. We evaluated the impact of CRI and antithrombotic strategy on composite ischemia (death, MI, or revascularization) and mortality at one year. Results: Of the pts enrolled, 12,933 had baseline CrCl data: 2468 (19.1%) pts had CrCl ≥60 mL/min and 10,465 (80.9%) pts had CrCl <60 mL/min. Rates of major bleeding at 30 days in pts with CRI were significantly lower with Biv alone vs Hep+GPI (6.2% vs 9.8%, p<0.01). Pts with CRI had higher mortality at one year compared to those without CRI (8.7% vs 3.0%, p<0.001). There was no difference in composite ischemia for pts who received Biv monotherapy vs Hep + GPI (23.0% vs 21.4%, p=0.10). One year mortality by antithrombin strategy is shown in the Figure . Conclusions: CRI in pts with ACS is associated with higher rates of one year mortality. In these high risk pts, Biv monotherapy improved early clinical outcomes compared to Hep + GPI by reducing major bleeding, and resulted in similar rates of one year mortality. Cumulative Mortality at One Year, Patients with CRI

Introduction: Occurrence of stroke and myocardial infarction (MI) after carotid endarterectomy or stenting have each been associated with increased later mortality. Methods: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) 69 strokes, 37 protocol MIs, and 19 biomarker + only events occurred within 30 days among 2272 patients followed up to 10 years. Mortality was determined and compared for patients with stroke, MI, or biomarker + only to those without. Cox proportional hazard models adjusting for age, sex, symptomatic status and treatment were calculated to assess the relationship between mortality and stroke and mortality and MI status. Kaplan-Meier survival curves were plotted. Results: Patients with peri-procedural stroke had a 67% greater likelihood of long-term mortality compared to those without stroke (HR=1.67, 95% CI 1.15,2.43; p<0.007)(Figure A). Patients with a protocol MI had a 249% greater likelihood of mortality, and biomarker+ only patients had a 104% greater likelihood of mortality, compared to those without MI (HR=3.49; 95%CI 2.20,5.53, p<0.0001; and HR=2.04; 95% CI 1.09,3.83, p=0.03)(Figure B). Discussion: Stroke, MI, and biomarker + only events following CEA or CAS are associated with increased long-term mortality. The higher risk for MI may be a marker for patients with serious underlying heart disease, rather than causal, providing an opportunity to decrease long-term mortality through aggressive diagnostic evaluation and preventive treatment.

Background: Open surgical closure and small-bore suture-based preclosure devices have limitations when used for transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or percutaneous thoracic endovascular aortic aneurysm repair. The MANTA vascular closure device is a novel collagen-based technology designed to close large bore arteriotomies created by devices with an outer diameter ranging from 12F to 25F. In this study, we determined the safety and effectiveness of the MANTA vascular closure device. Methods and Results: A prospective, single arm, multicenter investigation in patients undergoing transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or thoracic endovascular aortic aneurysm repair at 20 sites in North America. The primary outcome was time to hemostasis. The primary safety outcomes were accessed site-related vascular injury or bleeding complications. A total of 341 patients, 78 roll-in, and 263 in the primary analysis cohort, were entered in the study between November 2016 and September 2017. For the primary analysis cohort, transcatheter aortic valve replacement was performed in 210 (79.8%), and percutaneous endovascular abdominal aortic aneurysm repair or thoracic endovascular aortic aneurysm repair was performed in 53 (20.2%). The 14F MANTA was used in 42 cases (16%), and the 18F was used in 221 cases(84%). The mean effective sheath outer diameter was 22F (7.3 mm). The mean time to hemostasis was 65±157 seconds with a median time to hemostasis of 24 seconds. Technical success was achieved in 257 (97.7%) patients, and a single device was deployed in 262 (99.6%) of cases. Valve Academic Research Consortium-2 major vascular complications occurred in 11 (4.2%) cases: 4 received a covered stent (1.5%), 3 had access site bleeding (1.1%), 2 underwent surgical repair (0.8%), and 2 underwent balloon inflation (0.8%). Conclusions: In a selected population, this study demonstrated that the MANTA percutaneous vascular closure device can safely and effectively close large bore arteriotomies created by current generation transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, and thoracic endovascular aortic aneurysm repair devices. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02908880.

Background: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) previously reported increased mortality in patients who sustained a periprocedural stroke or cardiac event (myocardial infarction [MI] or biomarker only) in follow-up to 4 years. We now extend these observations to 10 years. Methods and Results: CREST is a randomized controlled trial designed to compare the outcomes of carotid stenting versus carotid endarterectomy. Proportional hazards models were used to assess the association between mortality and periprocedural stroke, MI, or biomarker-only events. For 10-year follow-up, patients with periprocedural stroke were at 1.74× the risk of death compared with those without stroke (adjusted hazard ratio [HR]=1.74; 95% CI, 1.21–2.50; P <0.003). This increased risk was driven by increased early (between 0 and 90 days) mortality (adjusted HR=14.41; 95% CI, 5.33–38.94; P <0.0001), with no significant increase in late (between 91 days and 10 years) mortality (adjusted HR=1.40; 95% CI, 0.93–2.10; P =0.11). Patients with a protocol MI were at 3.61× increased risk of death compared with those without MI (adjusted HR=3.61; 95% CI, 2.28–5.73; P <0.0001), with an increased hazard both early (adjusted HR=8.20; 95% CI, 1.86–36.2; P =0.006) and late (adjusted HR=3.40; 95% CI, 2.09–5.53; P <0.0001). Patients with a biomarker-only event were at 2.04× increased risk overall (adjusted HR=2.04; 95% CI, 1.09–3.84; P =0.03) than those without MI, with an increased early hazard (adjusted HR=8.44; 95% CI, 1.09–65.5; P =0.04) and a suggestive but nonsignificant association toward higher 91-day to 10-year risk (1.88; 95% CI, 0.97–3.64; P =0.062) contributing to the increased risk. Conclusions: In the CREST trial, patients with periprocedural events demonstrate a substantial increase in future mortality to 10 years. For stroke, this risk is largely confined to an early time frame while periprocedural MI or biomarker-only events confer a continuous increased mortality for 10 years. Strategies to reduce periprocedural events and to optimize the evaluation and management of patients with cardiac events should be considered in efforts to reduce not only early but also long-term mortality. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00004732.

Background— Peripheral artery disease (PAD) is associated with increased cardiovascular mortality, and PAD risk factors overlap with those for aortic stenosis. The prevalence and outcomes associated with PAD in a population undergoing transcatheter aortic valve replacement (TAVR) are unknown. Methods and Results— Using the Society of Thoracic Surgeons/Transcatheter Valve Therapy Registry linked to Medicare claims data, we identified patients ≥65 years old undergoing TAVR from 2011 to 2015. We calculated hazard ratios for 1-year adverse outcomes, including mortality, readmission, and bleeding, for patients with PAD compared with those without, adjusting for baseline characteristics and postprocedure medications. Analyses were performed separately by access site (transfemoral and nontransfemoral). Of 19 660 patients undergoing transfemoral TAVR, 4810 (24.5%) had PAD; 3730 (47.9%) of 7780 patients undergoing nontransfemoral TAVR had PAD. In both groups, patients with PAD were significantly more likely to have coronary and carotid artery diseases. At 1-year follow-up, patients with PAD undergoing TAVR via transfemoral access had a higher incidence of death (16.8% versus 14.4%; adjusted hazard ratio, 1.14; P =0.01), readmission (45.5% versus 42.1%; hazard ratio, 1.11; P <0.001), and bleeding (23.1% versus 19.7%; hazard ratio, 1.18; P <0.001) compared with patients without PAD. Patients with PAD undergoing TAVR via nontransfemoral access did not have significantly higher rates of 1-year mortality or readmission compared with patients without PAD. Conclusions— PAD is common among patients undergoing commercial TAVR via transfemoral and nontransfemoral access. Among patients undergoing transfemoral TAVR, PAD is associated with a higher incidence of 1-year adverse outcomes compared with absence of PAD. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01737528.

Background— The use of transcatheter aortic valve replacement (TAVR) to treat aortic stenosis in the United States is growing, yet little is known about the variation in procedural outcomes in community practice. We developed a TAVR in-hospital mortality risk model and used it to quantify variation in mortality rates across United States (US) TAVR centers. Methods and Results— We analyzed data from 22 248 TAVR procedures performed at 318 sites participating in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry (November 2011 to October 2014). A Bayesian hierarchical model was developed to estimate hospital-specific risk-adjusted mortality rates adjusting for 40 patient baseline factors. A total of 1130 in-hospital deaths (5.1%) were observed. Reliability-adjusted risk-adjusted mortality rate estimates ranged from 3.4% to 7.7% with an interquartile range of 4.8% to 5.4%. A patient’s predicted odds of dying was 80% higher if treated by a hospital 1 standard deviation above the mean compared with a hospital 1 standard deviation below the mean (odds ratio =1.8; 95% credible interval, 1.4%–2.2%). Conclusions— Risk modeling of TAVR in-hospital mortality revealed variation in risk-adjusted mortality rates during the US early commercial experience. Transcatheter Valve Therapy Registry analyses using this model will support research, feedback reporting, and the identification of factors associated with quality.

Background Despite guideline recommendations, a significant number of patients with non– ST elevation myocardial infarction ( NSTEMI ) do not receive dual antiplatelet therapy ( DAPT ) before angiography “pretreatment.” While there may be valid clinical reasons to not pretreat, such as concern for bleeding or multivessel disease warranting coronary artery bypass graft surgery, the degree of variability and factors associated with DAPT pretreatment are unknown. Methods and Results From the multicenter TRIUMPH registry, 1632 NSTEMI patients were not taking DAPT on admission and were included in the study cohort. Among the study patients, only 22% patients received DAPT pretreatment. A multivariable logistic regression model showed that race other than white or black (odds ratio [ OR] 0.41, 95% CI 0.21–0.83), hemoglobin level ( OR 1.18, 95% CI 1.08–1.29), patients’ bleeding risk (assessed with NCDR Cath PCI Bleeding Risk Score) ( OR 0.85, 95% CI 0.74–0.99), and severe left ventricular dysfunction ( OR 0.3, 95% CI 0.13–0.65) were the main predictors of pretreatment with DAPT , whereas likelihood of needing coronary artery bypass graft surgery ( GRACE prediction model) was not ( OR 1.09, 95% CI 0.88–1.35). Median ORs were calculated to assess variability of receiving DAPT pretreatment across sites after adjustment for patient characteristics. Receiving DAPT pretreatment varied substantially across sites (range 0–100%, mean OR 3.94, P <0.0001). Conclusions While deviating from guideline‐recommended DAPT pretreatment in patients with NSTEMI was associated with patient factors (eg, bleeding risk), marked variation was present across sites after accounting for patient‐level characteristics. This suggests that site‐level interventions are needed to improve concordance with current guidelines.