NEVBD Pesticide Resistance Monitoring Network: Establishing a Centralized Network to Increase Regional Capacity for Pesticide Resistance Detection and Monitoring.

Pesticide resistance in arthropod vectors of disease agents is a growing issue globally. Despite the importance of resistance monitoring to inform mosquito control programs, no regional monitoring programs exist in the United States. The Northeastern Regional Center for Excellence in Vector-Borne Diseases (NEVBD) is a consortium of researchers and public health practitioners with a primary goal of supporting regional vector control activities. NEVBD initiated a pesticide resistance monitoring program to detect resistant mosquito populations throughout the northeastern United States. A regionwide survey was distributed to vector control agencies to determine needs and refine program development and in response, a specimen submission system was established, allowing agencies to submit Culex pipiens (L.) (Diptera:Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) for pesticide resistance testing. NEVBD also established larvicide resistance diagnostics for Bacillus thuringiensis israelensis (Bti) and methoprene. Additional diagnostics were developed for Cx. pipiens resistance to Lysinibacillus sphaericus. We received 58 survey responses, representing at least one agency from each of the 13 northeastern U.S. states. Results indicated that larvicides were deployed more frequently than adulticides, but rarely paired with resistance monitoring. Over 18,000 mosquitoes were tested from six states. Widespread low-level (1 × LC-99) methoprene resistance was detected in Cx. pipiens, but not in Ae. albopictus. No resistance to Bti or L. sphaericus was detected. Resistance to pyrethroids was detected in many locations for both species. Our results highlight the need for increased pesticide resistance testing in the United States and we provide guidance for building a centralized pesticide resistance testing program.

Differential Use and Impact of Bleeding Avoidance Strategies on Percutaneous Coronary Intervention-Related Bleeding Stratified by Predicted Risk.

BACKGROUND: Procedural anticoagulation with bivalirudin (BIV), trans-radial intervention (TRI), and use of a vascular closure device (VCD) are thought to mitigate percutaneous coronary intervention (PCI)-related bleeding. We compared the impact of these bleeding avoidance strategies (BAS) for PCIs stratified by bleeding risk. METHODS: We performed a retrospective cohort analysis of PCIs from 18 facilities within one health care system from 2009Q3 to 2017Q4. Bleeding risk was assessed per the National Cardiovascular Data Registry CathPCI bleeding model, with procedures stratified into 6 categories (first, second, third quartiles, 75th-90th, 90th-97.5th, and top 2.5th percentiles). Regression models were used to assess the impact of BAS on bleeding outcome. RESULTS: Of 74 953 PCIs, 9.4% used no BAS, 12.0% used BIV alone, 20.8% used TRI alone, 26.8% used VCD alone, 5.4% used TRI+BIV, and 25.6% used VCD+BIV. The crude bleeding rate was 4.4% overall. Only 2 comparisons showed significant trends across all risk strata: VCD+BIV versus no BAS, odds ratio (95% CI) range: first quartile, 0.36 (0.18-0.72) to top 2.5th percentile, 0.50 (0.32-0.78); TRI versus no BAS, odds ratio (95% CI) range: first quartile, 0.15 (0.06-0.38) to top 2.5th percentile, 0.49 (0.28-0.86). TRI had lower odds of bleeding compared with BIV for all risk strata except the top 2.5th percentile. Addition of BIV to TRI did not change the odds of bleeding for any risk strata. Factors potentially limiting use of TRI (renal failure, shock, cardiac arrest, and mechanical circulatory support) were present in ≤10% of procedures below the 90th percentile. CONCLUSIONS: Among individual BAS, only TRI had consistently lower odds of bleeding across all risk strata. Factors potentially limiting TRI were found infrequently in procedures below the 90th percentile of bleeding risk. For transfemoral PCI, VCD+BIV had lower odds of bleeding compared with no BAS across all risk strata.

2-Year Outcomes After Stenting of Lipid-Rich and Nonrich Coronary Plaques.

BACKGROUND: Autopsy studies suggest that implanting stents in lipid-rich plaque (LRP) may be associated with adverse outcomes. OBJECTIVES: The purpose of this study was to evaluate the association between LRP detected by near-infrared spectroscopy (NIRS) and clinical outcomes in patients with coronary artery disease treated with contemporary drug-eluting stents. METHODS: In this prospective, multicenter registry, NIRS was performed in patients undergoing coronary angiography and possible percutaneous coronary intervention (PCI). Lipid core burden index (LCBI) was calculated as the fraction of pixels with the probability of LRP >0.6 within a region of interest. MaxLCBI4mm was defined as the maximum LCBI within any 4-mm-long segment. Major adverse cardiac events (MACE) included cardiac death, myocardial infarction, definite or probable stent thrombosis, or unplanned revascularization or rehospitalization for progressive angina or unstable angina. Events were subcategorized as culprit (treated) lesion-related, nonculprit (untreated) lesion-related, or indeterminate. RESULTS: Among 1,999 patients who were enrolled in the COLOR (Chemometric Observations of Lipid Core Plaques of Interest in Native Coronary Arteries Registry), PCI was performed in 1,621 patients and MACE occurred in 18.0% of patients, of which 8.3% were culprit lesion-related, 10.7% were nonculprit lesion-related, and 3.1% were indeterminate during 2-year follow-up. Complications from NIRS imaging occurred in 9 patients (0.45%), which resulted in 1 peri-procedural myocardial infarction and 1 emergent coronary bypass. Pre-PCI NIRS imaging was obtained in 1,189 patients, and the 2-year rate of culprit lesion-related MACE was not significantly associated with maxLCBI4mm (hazard ratio of maxLCBI4mm per 100: 1.06; 95% confidence interval: 0.96 to 1.17; p = 0.28) after adjusting clinical and procedural factors. CONCLUSIONS: Following PCI with contemporary drug-eluting stents, stent implantation in NIRS-defined LRPs was not associated with increased periprocedural or late adverse outcomes compared with those without significant lipid.

Intact and Isolated Human Cadaveric Coronary Artery Perfusion Models to Facilitate Research and Education Regarding Coronary Anatomy and Pathology.

Cadaveric tissue-perfusion models are well established in the fields of structural heart and peripheral vascular disease; however, less consideration has been given toward coronary artery disease despite comparable prevalence and morbidity. Two tissue-perfusion models were developed to address this need. The first, an intact heart model, allows simulation of percutaneous coronary interventional procedures. The second focuses upon isolated arteries, allowing quantification of simulated procedures. Both models were applied for clinical training and for investigations into medical device behavior. The manner of preparation facilitates access to clinically relevant disease, thus providing a platform to further research on coronary artery disease.

Percutaneous Tricuspid Valve Regurgitation Repair With the MitraClip Device Using an Edge-to-Edge Bicuspidization Technique.

Patients who present with both severe mitral and tricuspid regurgitation who are symptomatic despite optimal medical therapy and at prohibitive risk for surgery pose a significant therapeutic challenge. The MitraClip device (Abbott Vascular) is approved for percutaneous mitral valve repair in high-risk and non-operative patients, and has also been used for tricuspid valve repair. Imaging support for percutaneous edge-to-edge tricuspid valve repair has not been reported and is a vital part of the procedure. Here, we present a periprocedural imaging strategy for percutaneous tricuspid valve repair with the MitraClip device using a bicuspidization technique.

Costs of periprocedural complications in patients treated with transcatheter aortic valve replacement: results from the Placement of Aortic Transcatheter Valve trial.

BACKGROUND: In patients with severe aortic stenosis, transcatheter aortic valve replacement (TAVR) improves survival when compared with nonsurgical therapy but with higher in-hospital and lifetime costs. Complications associated with TAVR may decrease with greater experience and improved devices, thereby reducing the overall cost of the procedure. Therefore, we sought to estimate the effect of periprocedural complications on in-hospital costs and length of stay of TAVR. METHODS AND RESULTS: Using detailed cost data from 406 TAVR patients enrolled in the Placement of Aortic Transcatheter Valve (PARTNER) I trial, we developed multivariable models to estimate the incremental cost and length of stay associated with specific periprocedural complications. Attributable costs and length of stay for each complication were calculated by multiplying the independent cost of each event by its frequency in the treatment group. Mean cost for the initial hospitalization was $79 619±40 570 ($50 891 excluding the valve); 49% of patients had ≥1 complication. Seven complications were independently associated with increased hospital costs, with major bleeding, arrhythmia, and death accounting for the largest attributable cost per patient. Renal failure and the need for repeat TAVR, although less frequent, were also associated with substantial incremental and attributable costs. Overall, complications accounted for $12 475 per patient in initial hospital costs and 2.4 days of hospitalization. CONCLUSIONS: In the PARTNER trial, periprocedural complications were frequent, costly, and accounted for ≈25% of non-implant-related hospital costs. Avoidance of complications should improve the cost-effectiveness of TAVR for inoperable and high-risk patients, but reductions in the cost of uncomplicated TAVR will also be necessary for optimal efficiency. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Prognostic significance of bleeding location and severity among patients with acute coronary syndromes.

OBJECTIVES: This study sought to determine if there is an association between bleed location and clinical outcomes in acute coronary syndromes (ACS) patients. BACKGROUND: The prognostic significance of bleeding location among ACS patients undergoing cardiac catheterization is not well known. METHODS: We analyzed in-hospital bleeding events among 9,978 patients randomized in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) study. Bleeding events were categorized by location as access site, systemic, surgical, or superficial, and severity was graded using the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definition. We assessed the association of each bleeding location and severity with 6-month risk of death or myocardial infarction using a multicovariate-adjusted Cox proportional hazard model. RESULTS: A total of 4,900 bleeding events were identified among 3,694 ACS patients with in-hospital bleeding. Among 4,679 GUSTO mild/moderate bleeding events, only surgical and systemic bleeds were associated with an increased risk of 6-month death or myocardial infarction (adjusted hazard ratio [HR]: 2.52 [95% confidence interval (CI): 2.16 to 2.94, and 1.40 [95% CI: 1.16 to 1.69], respectively). Mild/moderate superficial and access-site bleeds were not associated with downstream risk (adjusted HR: 1.17 [95% CI: 0.97 to 1.40], and 0.96 [95% CI: 0.82 to 1.12], respectively). Among 221 GUSTO severe bleeds, surgical bleeds were associated with the highest risk (HR: 5.27 [95% CI: 3.80 to 7.29]), followed by systemic (HR: 4.48 [95% CI: 2.98 to 6.72]), and finally access-site bleeds (HR: 3.57 [95% CI: 2.35 to 5.40]). CONCLUSIONS: Among ACS patients who develop in-hospital bleeding, systemic and surgical bleeding are associated with the highest risks of adverse outcomes regardless of bleeding severity. Although the most frequent among bleeds, GUSTO mild/moderate access-site bleeding is not associated with increased risk. These data underscore the importance of strategies to minimize overall bleeding risk beyond vascular access site management.

Autopsy validation study of the academic research consortium stent thrombosis definition.

OBJECTIVES: This study sought to validate the sensitivity and specificity of the Academic Research Consortium's (ARC) classification of stent thrombosis. BACKGROUND: Classification of stent thrombosis according to ARC criteria has become widely accepted. The criteria have not been validated against an autopsy standard. METHODS: An autopsy registry of 139 subjects with prior coronary stenting underwent detailed histopathological analysis to assess for stent thrombosis. Based on clinical data only, cases were adjudicated according to ARC stent thrombosis criteria, including a proposed modification of the possible classification to include death beyond 30 days due only to sudden death or acute ischemia. RESULTS: Autopsy results confirmed 51 cases as positive and 88 as negative for stent thrombosis. Clinical adjudication classified 105 cases as definite (10), probable (31), or possible (64) ARC stent thrombosis. Specificity was high for definite (99%) and definite plus probable (83%) criteria, but sensitivity was poor at 18% and 51%, respectively. Including the possible cases improved sensitivity to 92% but reduced specificity to 34% (58 false positives). The modified possible criteria eliminated 13 false positive cases (specificity = 49%) and was the best approximation of a hypothetical gold standard in a sensitivity analysis if late death represented at least 20% of all stent thrombosis cases. CONCLUSIONS: In a selected autopsy sample, restricting ARC stent thrombosis to definite or definite plus probable criteria results in substantial under-reporting of confirmed cases. Inclusion of a modified possible classification may provide the best estimate of late and very late stent thrombosis rates.

Heparin-associated anti-Xa activity and platelet-derived prothrombotic and proinflammatory biomarkers in moderate to high-risk patients with acute coronary syndrome.

Heparin compounds, to include fractionated and unfractionated preparations, exert both antithrombotic and antiinflammatory effects through combined inhibition of factor Xa and thrombin. The contribution of modulated platelet activity in vivo is less clearly defined. The SYNERGY library was a prospectively designed repository for candidate clinical, hemostatic, platelet, and molecular biomarkers from patients participating in SYNERGY--a large-scale, randomized clinical trial evaluating the comparative benefits of unfractionated heparin (UFH) and enoxaparin in high-risk patients with acute coronary syndrome (ACS). Samples were collected from 201 patients enrolled at 26 experienced, participating sites and shipped to established core laboratories for analysis of platelet, endothelium-derived, inflammatory and coagulation activity biomarkers. Tissue factor pathway inhibitor (TFPI)--a vascular endothelial cell-derived factor Xa regulatory protein-correlated directly with plasma anti-Xa activity (unadjusted: r = 0.23, P < 0.0001; adjusted: ß = 0.10; P = 0.001), as did TFPI-fXa complexes (unadjusted: r = 0.34, P < 0.0001; adjusted: ß = 0.38; P = < 0.0001). In contrast, there was a direct and inverse relationship between anti-Xa activity and two platelet-derived biomarkers-plasminogen activator inhibitor-1 (unadjusted: r = -0.18, P = 0.0012; adjusted: ß = -0.10; P = 0.021) and soluble CD40 ligand (unadjusted: r = -0.11, P = 0.05; adjusted: ß = -0.13; P = 0.049). All measured analyte relationships persisted after adjustment for age, creatinine clearance, weight, sex, and duration of treatment. Differences in biomarkers between patients receiving UFH and those randomized to enoxaparin were not observed. The ability of heparin compounds to affect the prothrombotic and proinflammatory states which characterize ACS may involve factor Xa-related modulation of platelet activation and expression. Whether this potentially beneficial effect is direct or indirect and achieved, at least in part, through the release of endothelial cell-derived coagulation regulatory proteins will require further investigation.

Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.

BACKGROUND: Many patients with severe aortic stenosis and coexisting conditions are not candidates for surgical replacement of the aortic valve. Recently, transcatheter aortic-valve implantation (TAVI) has been suggested as a less invasive treatment for high-risk patients with aortic stenosis. METHODS: We randomly assigned patients with severe aortic stenosis, whom surgeons considered not to be suitable candidates for surgery, to standard therapy (including balloon aortic valvuloplasty) or transfemoral transcatheter implantation of a balloon-expandable bovine pericardial valve. The primary end point was the rate of death from any cause. RESULTS: A total of 358 patients with aortic stenosis who were not considered to be suitable candidates for surgery underwent randomization at 21 centers (17 in the United States). At 1 year, the rate of death from any cause (Kaplan­Meier analysis) was 30.7% with TAVI, as compared with 50.7% with standard therapy (hazard ratio with TAVI, 0.55; 95% confidence interval [CI], 0.40 to 0.74; P<0.001). The rate of the composite end point of death from any cause or repeat hospitalization was 42.5% with TAVI as compared with 71.6% with standard therapy (hazard ratio, 0.46; 95% CI, 0.35 to 0.59; P<0.001). Among survivors at 1 year, the rate of cardiac symptoms (New York Heart Association class III or IV) was lower among patients who had undergone TAVI than among those who had received standard therapy (25.2% vs. 58.0%, P<0.001). At 30 days, TAVI, as compared with standard therapy, was associated with a higher incidence of major strokes (5.0% vs. 1.1%, P=0.06) and major vascular complications (16.2% vs. 1.1%, P<0.001). In the year after TAVI, there was no deterioration in the functioning of the bioprosthetic valve, as assessed by evidence of stenosis or regurgitation on an echocardiogram. CONCLUSIONS: In patients with severe aortic stenosis who were not suitable candidates for surgery, TAVI, as compared with standard therapy, significantly reduced the rates of death from any cause, the composite end point of death from any cause or repeat hospitalization, and cardiac symptoms, despite the higher incidence of major strokes and major vascular events. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

Clopidogrel use and clinical events after drug-eluting stent implantation: findings from the HealthCore Integrated Research Database.

BACKGROUND: Relationships between long-term use and level of dual antiplatelet therapy and outcomes after drug-eluting stent implantation are not well established. METHODS: This is a retrospective cohort study of 9,256 patients receiving drug-eluting stents between January 2003 and August 2006. We classified patients according to tertiles of clopidogrel use during the 12 months after stent implantation. We used inverse probability weighting to account for differential selection into levels of clopidogrel use and logistic regression to estimate propensity scores for levels of clopidogrel use. We used Cox proportional hazards models to estimate effects of level of clopidogrel use on risk of bleeding events, death, and death or nonfatal myocardial infarction. RESULTS: There were 3,102 patients in the high-use group, 3,069 in the medium-use group, and 3,085 in the low-use group. Compared with the high-use group, risk of death or nonfatal myocardial infarction was greater in the medium-use group (hazard ratio [HR] 1.46, 95% CI 1.09-1.99, P = .01) and the low-use group (HR 1.59, 95% CI 1.18-2.14, P = .002). The risk of bleeding events was lower in the medium-use group (HR 0.84, 95% CI 0.71-0.98, P = .03) and the low-use group (HR 0.77, 95% CI 0.65-0.90, P = .002). CONCLUSIONS: Higher clopidogrel use 12 months after drug-eluting stent implantation was associated with a greater risk of subsequent bleeding events. Lower use was associated with a greater risk of death or nonfatal myocardial infarction.

Metabolic syndrome is not associated with increased mortality or cardiovascular risk in nondiabetic patients with a new diagnosis of coronary artery disease.

BACKGROUND: Metabolic syndrome (MetSyn) is associated with increased cardiovascular risk in the general population. Its prognostic implications are less well defined in patients with coronary artery disease. METHODS AND RESULTS: We analyzed patients in the Duke Database for Cardiovascular Disease with a diagnosis of incident obstructive coronary artery disease. Diabetes mellitus (DM) was classified as a clinical history of DM, use of hypoglycemic drugs, or fasting glucose of >or=126 mg/dL. MetSyn was defined as having 3 of 5 characteristics: fasting glucose >or=100 and <126 mg/dL, low high-density lipoprotein cholesterol (men, <40 mg/dL; women, <50 mg/dL), triglycerides >150 mg/dL, blood pressure >or=130/85 mm Hg, or use of antihypertensive therapy, or body mass index >or=27. Death, myocardial infarction, or stroke was assessed at 6 months, 1 year, then annually. Cox proportional hazards models were generated to compare mortality and cardiovascular events between groups. The primary cohort consisted of 5744 patients; 1831 (31.9%) had DM, 2491 (43.4%) had MetSyn, and 1422 (24.7%) had no DM/MetSyn. Median follow-up was 5 years. Compared with no DM/MetSyn patients, DM patients had a higher adjusted risk for mortality (hazard ratio, 1.47; 95% CI, 1.28 to 1.69) but MetSyn patients did not (hazard ratio, 0.94; 95% CI, 0.81 to 1.08). Similar results were found for the combined end points of death or myocardial infarction, and death, myocardial infarction, or stroke. CONCLUSIONS: In a population of consecutive patients with a new diagnosis of coronary artery disease by angiography, MetSyn without DM was not an independent predictor of mortality or cardiovascular events.

Standardized reporting of bleeding complications for clinical investigations in acute coronary syndromes: a proposal from the academic bleeding consensus (ABC) multidisciplinary working group.

BACKGROUND: Clinical trials of antithrombotic agents for the treatment of ACS routinely assess bleeding as a safety endpoint, but variation in bleeding definitions makes comparison of the relative safety of these agents difficult. METHODS: The ABC Multidisciplinary Working Group, an informal working group comprising clinical researchers and representatives from the US Food and Drug Administration, the National Institutes of Health, and the pharmaceutical industry, sought to develop a consensus approach to measuring the incidence and severity of bleeding complications during clinical trials of acute coronary syndromes (ACS). A meeting of the ABC was convened in April 2008 in Washington, DC, with the goal of developing a consensus approach to measuring the incidence and severity of hemorrhagic complications during clinical trials of ACS. Relevant literature on bleeding was reviewed through a series of short lectures and intensive group discussion. RESULTS: Using existing evidence on bleeding and outcomes as well as clinical judgment, criteria for the assessment of bleeding were developed through expert consensus. This consensus statement divides bleeding-related data elements into three categories: essential, recommended, and optional. CONCLUSIONS: The ABC Group recommendations for collection and reporting of bleeding complications provide a framework for consistency in the collection of information on hemorrhagic complications in trials of ACS. Widespread adoption of the statement recommendations will facilitate understanding of the mechanisms of adverse outcomes after bleeding and comparisons of the relative safety of antithrombotic agents, as well as the interpretation of safety results from future studies.

Vascular disease burden and in-hospital outcomes among patients undergoing percutaneous coronary intervention in New York State.

BACKGROUND: The presence of atherosclerosis in extracardiac vascular beds is associated with an increased risk of adverse cardiovascular outcomes among stable patients with coronary artery disease (CAD). However, there is little data regarding the impact of the presence and extent of vascular disease on outcomes in patients with CAD undergoing percutaneous coronary intervention. METHODS AND RESULTS: We analyzed 69,045 consecutive patients from the New York State Coronary Angioplasty Reporting System database who underwent percutaneous coronary intervention between 1998 and 1999. Vascular disease burden was assessed by history of aortoiliac, femoral-popliteal, and carotid disease. Patients were stratified into 3 groups: CAD alone, CAD and 1 additional site, and CAD and 2 or 3 additional sites. A logistic regression model was constructed to determine the relation between vascular disease burden and in-hospital mortality. Any history of vascular disease was present in 5915 (8.6%) of the population, of whom 4840 (82%) had CAD and 1 other disease location and 1075 (18%) had CAD and 2 or 3 other disease locations. There was a significant relationship between the number of disease locations and hospital mortality, ranging from 0.7% in patients with CAD alone to 2.0% and 2.6% for patients with 1 or >or =2 disease locations, respectively (P<0.001). In unadjusted analysis, in-hospital mortality was approximately 3-fold higher (odds ratio, 2.89; 95% CI, 2.31 to 3.60; P<0.001) and 4-fold higher (odds ratio, 3.78; 95% CI, 2.57 to 5.56; P<0.001) for inpatients with CAD and additional vascular disease at 1 site and > or =2 sites, respectively. After multivariable adjustment, each additional vascular bed affected was associated with a 50% increase in in-hospital mortality (odds ratio, 1.50; 95% CI, 1.27 to 1.78; P<0.001). CONCLUSIONS: Among patients with CAD undergoing percutaneous coronary intervention, vascular disease burden is associated with higher rates of adverse events and is an independent predictor of in-hospital mortality.

In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques: initial results of the SPECTACL study.

OBJECTIVES: To determine whether catheter-based near-infrared spectroscopy (NIRS) signals obtained with a novel catheter-based system from coronaries of patients are similar to those from autopsy specimens and to assess initial safety of NIRS device. BACKGROUND: An intravascular NIRS system for detection of lipid core-containing plaques (LCP) has been validated in human coronary autopsy specimens. The SPECTACL (SPECTroscopic Assessment of Coronary Lipid) trial was a parallel first-in-human multicenter study designed to demonstrate the applicability of the LCP detection algorithm in living patients. METHODS: Intracoronary NIRS was performed in patients undergoing percutaneous coronary intervention. Acquired spectra were blindly compared with autopsy NIRS signals with multivariate statistics. To meet the end point of spectral similarity, at least two-thirds of the scans were required to have >80% of spectra similar to the autopsy spectra. RESULTS: A total of 106 patients were enrolled; there were no serious adverse events attributed to NIRS. Spectroscopic data could not be obtained in 17 (16%) patients due to technical limitations, leaving 89 patients for analysis. Spectra from 30 patients were unblinded to test the calibration of the LCP detection algorithm. Of the remaining 59 blinded cases, after excluding 11 due to inadequate data, spectral similarity was demonstrated in 40 of 48 spectrally adequate scans (83% success rate, 95% confidence interval: 70% to 93%, median spectral similarity/pullback: 96%, interquartile range 10%). The LCP was detected in 58% of 60 spectrally similar scans from both cohorts. CONCLUSIONS: This intravascular NIRS system safely obtained spectral data in patients that were similar to those from autopsy specimens. These results demonstrate the feasibility of invasive detection of coronary LCP with this novel system. (SPECTACL: SPECTroscopic Assessment of Coronary Lipid; NCT00330928).

Randomized comparison of everolimus-eluting and paclitaxel-eluting stents: two-year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial.

BACKGROUND: In the prospective randomized Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial, an everolimus-eluting stent (EES) compared with a widely used paclitaxel-eluting stent (PES) resulted in a statistically significant reduction in angiographic in-segment late loss at 8 months and noninferior rates of target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 1 year. The safety and efficacy of EES after 1 year have not been reported. METHODS AND RESULTS: A total of 1002 patients with up to 2 de novo native coronary artery lesions (reference vessel diameter, 2.5 to 3.75 mm; lesion length < or =28 mm) were randomized 2:1 to EES versus PES. Antiplatelet therapy consisted of aspirin indefinitely and a thienopyridine for > or =6 months. Between 1 and 2 years, patients treated with EES compared with PES tended to have fewer episodes of protocol-defined stent thrombosis (0.2% versus 1.0%; P=0.10) and myocardial infarctions (0.5% versus 1.7%; P=0.12), with similar rates of cardiac death (0.3% versus 0.3%; P=1.0) and target vessel revascularization (2.9% versus 3.0%; P=1.0). As a result, at the completion of the 2-year follow-up, treatment with EES compared with PES resulted in a significant 32% reduction in target vessel failure (10.7% versus 15.4%; hazard ratio, 0.68; 95% confidence interval, 0.48 to 0.98; P=0.04) and a 45% reduction in major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization; 7.3% versus 12.8%; hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.83; P=0.004). Among the 360 patients who discontinued clopidogrel or ticlopidine after 6 months, stent thrombosis subsequently developed in 0.4% of EES patients versus 2.6% of PES patients (P=0.10). CONCLUSIONS: Patients treated with EES rather than PES experienced significantly improved event-free survival at a 2-year follow-up in the SPIRIT III trial, with continued divergence of the hazard curves for target vessel failure and major adverse cardiac events between 1 and 2 years evident. The encouraging trends toward fewer stent thrombosis episodes after 6 months in EES-treated patients who discontinued a thienopyridine and after 1 year in all patients treated with EES rather than PES deserve further study.

Early intervention: which patients and how early?

Despite advances in preventive therapy, acute coronary syndromes (ACS) remain a significant cause of morbidity and mortality. Patient risk varies widely along a spectrum from unstable angina to ST-segment elevation myocardial infarctions (STEMIs) and can be estimated using risk prediction algorithms. Estimated risk is useful to select therapeutic options ranging from aggressive medical therapy for patients at low risk to revascularization for high-risk patients in whom bypass or percutaneous coronary intervention (PCI) is feasible. Appropriate timing of an invasive strategy is crucial, with early intervention maximally benefiting the highest-risk patients. Facilitated PCI's role in patients who present with STEMI and the most appropriate timing of interventional therapy in patients at moderate risk after a non-ST-elevation ACS remain the subject of ongoing debate.

Clinical and angiographic outcomes in diabetic patients following single or multivessel stenting in the COSTAR II randomized trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is associated with increased clinical and angiographic restenosis in diabetic patients. Stent-based elution of paclitaxel from a biostable polymer reduces restenosis and major adverse cardiovascular events (MACE) when compared with bare-metal stent deployment. The safety and efficacy of paclitaxel elution from a bioresorbable polymer has not been studied in diabetic patients. METHODS: Patients (n = 1700) with single- or multivessel coronary disease were randomized (3:2) to receive the CoStar or Taxus stent. All patients had glycolated hemoglobin (HbA1c) obtained at enrollment. RESULTS: Medically-treated diabetes was present in 469 patients (117 insulin-treated) and 77 patients had elevated HbA1c > 6.5% in the absence of previously diagnosed diabetes. MACE were increased in diabetics and were greatest in those requiring insulin. Elevated HbA1c, in the absence of diagnosed diabetes, was not associated with adverse outcomes. MACE (8 months) in the diabetic cohort trended lower with Taxus versus CoStar (10.9 vs. 14.4%, respectively; p = 0.271) due to a reduction in target vessel revascularization. Late lumen loss in-segment (9 months) was reduced by Taxus compared to CoStar (0.20 vs. 0.52 mm, respectively; p < 0.05). CONCLUSION: Diabetes is associated with adverse outcomes following stent deployment. Taxus stents improved angiographic outcomes with a trend toward improved clinical outcomes when compared with CoStar stents following PCI in diabetic patients. As a measure of preprocedural glycemic control, the HbA1c level was weakly correlated with outcomes.

A novel bioresorbable polymer paclitaxel-eluting stent for the treatment of single and multivessel coronary disease: primary results of the COSTAR (Cobalt Chromium Stent With Antiproliferative for Restenosis) II study.

OBJECTIVES: The aim was to compare safety and effectiveness of the CoStar drug-eluting stent (DES) (Conor MedSystems, Menlo Park, California) with those of the Taxus DES (Boston Scientific, Maple Grove, Minnesota) in de novo single- and multivessel percutaneous coronary intervention (PCI). BACKGROUND: Paclitaxel elution from a stent coated with biostable polymer (Taxus) reduces restenosis after PCI. The CoStar DES is a novel stent with laser-cut reservoirs containing bioresorbable polymer loaded to elute 10 microg paclitaxel/30 days. METHODS: Patients undergoing PCI for a single target lesion per vessel in up to 3 native epicardial vessels were randomly assigned 3:2 to CoStar or Taxus. Primary end point was 8-month major adverse cardiac events (MACE), defined as adjudicated death, myocardial infarction (MI), or clinically driven target vessel revascularization (TVR). Protocol-specified 9-month angiographic follow-up included 457 vessels in 286 patients. RESULTS: Of the 1,700 patients enrolled, 1,675 (98.5%) were evaluable (CoStar = 989; Taxus = 686), including 1,330 (79%) single-vessel and 345 (21%) multivessel PCI. The MACE rate at 8 months was 11.0% for CoStar versus 6.9% for Taxus (p < 0.005), including adjudicated death (0.5% vs. 0.7%, respectively), MI (3.4% vs. 2.4%, respectively), and TVR (8.1% vs. 4.3%, respectively). Per-vessel 9-month in-segment late loss was 0.49 mm with CoStar and 0.18 mm with Taxus (p < 0.0001). Findings were consistent across pre-specified subgroups. CONCLUSIONS: The CoStar DES is not noninferior to the Taxus DES based on per-patient clinical and per-vessel angiographic analyses. The relative benefit of Taxus is primarily attributable to reduction in TVR. Follow-up to 9 months showed no apparent difference in death, MI, or stent thrombosis rates.