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Background: Glycoprotein (GP) IIb/IIIa inhibitors can improve outcomes in patients with non-ST-segment elevation acute coronary syndromes but raise the risk of bleeding, particularly if dosed in excess. The impact of GP IIb/IIIa dosing feedback on safety and major bleeding is unknown.Methods: Glycoprotein IIb/IIIa dosing feedback was added to the CRUSADE quarterly site reports in the first quarter of 2006. We describe GP IIb/IIIa use and dosing among 25,641 patients with non-ST-segment elevation acute coronary syndromes from the fourth quarter of 2005 to the fourth quarter of 2006.Results: Eleven thousand eight hundred forty-six patients received GP IIb/IIIa inhibitors, including 4,031 women and 2,609 elderly patients (age, ≥75 years). Among GP IIb/IIIa-treated patients, unadjusted rates of excess GP IIb/IIIa dosing declined overall (26.4%-22.4%, Ptrend=.01) and among the elderly (65.6%-52.1%, Ptrend<.001). After adjustment, declines in excess dosing remained significant only for the elderly, although more than half of GP IIb/IIIa-treated elderly patients continued to receive excess dosing at the end of the study period (64.1%-51.3%, Ptrend<.001). There were concurrent declines in unadjusted major bleeding rates overall (9.6%-8.0%, Ptrend=.02), but declines among women (14.4%-11.5%, Ptrend=.08) and the elderly (17.1%-11.0%, Ptrend=.05) did not reach statistical significance. After adjustment for baseline characteristics and excess dosing, declines in major bleeding rates were no longer significant overall or for any subgroup.Conclusion: Within 9 months of initiating a safety feedback program, we observed early decreases in excess GP IIb/IIIa dosing among the elderly but minimal changes in excess dosing overall. Further work is needed to promote safe and effective medication use in vulnerable patients who are most at risk of harm. [ABSTRACT FROM AUTHOR]

Background: Because acute occlusion of coronary arteries supplying the inferolateral myocardium frequently eludes standard 12-lead electrocardiogram (ECG) diagnosis, these patients may present as non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Methods: We examined culprit artery occlusion among 1,957 NSTE-ACS patients in the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network trial who underwent diagnostic coronary angiography. We compared baseline characteristics, electrocardiographic findings, in-hospital treatment, and long-term outcomes between patients with and without occluded culprit arteries. Results: The culprit artery was occluded in 528 (27%) patients. Culprit lesions were more frequently identified in the inferolateral territory among patients with an occluded culprit artery (63%) compared with those with a nonoccluded artery (45%, P < .0001). Patients with an occluded culprit artery were younger, more often male, and more likely to have had a prior myocardial infarction. Despite similar in-hospital treatment, patients with an occluded culprit artery had larger infarcts (median peak creatine kinase-MB 4.3 vs 2.1 x upper limit of normal, P < .0001) and higher risk-adjusted 6-month mortality (hazard ratio 1.72, 95% CI 1.07-2.79). Conclusions: More than 25% of NSTE-ACS patients had an occluded culprit artery on angiography. These patients may represent ST-segment elevation myocardial infarction equivalents; thus, improved early risk stratification techniques would help more rapidly triage these high-risk patients to an early invasive management strategy. [ABSTRACT FROM AUTHOR]

Introduction: Despite the growing use of temporary mechanical circulatory support (tMCS), little data exists to inform management and weaning of these devices., Methods: We performed an online survey among cardiac intensive care unit directors in North America to examine current practices in the management of patients treated with intraaortic balloon pump and Impella., Results: We received responses from 84% of surveyed centers (n=37). Our survey focused on three key aspects of daily management: 1. Hemodynamic monitoring; 2. Hemocompatibility; and 3. Weaning and removal. We found substantial variability surrounding all three areas of care., Conclusion: Our findings highlight the need for consensus around practices associated with improved outcomes in patients treated with tMCS., Competing Interests: Declaration of Competing Interest Christopher Barnett receives research funding from Merck and is a consultant for Abiomed, Zoll, and Abbott. Michael Kontos is a consultant for Beckman Coulter. Barbara Pisani has self-funded personal investments in Abbott, Amgen, GlaxoSmithKline, Bristol Myers Squibb. Andrea Thompson is supported by NIH-NHLBI [K08HL163328]. The remaining authors have no conflicts of interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The infection caused by severe acute respiratory syndrome coronavirus-2, or COVID-19, can result in myocardial injury, heart failure, and arrhythmias. In addition to the viral infection itself, investigational therapies for the infection can interact with the cardiovascular system. As cardiologists and cardiovascular service lines will be heavily involved in the care of patients with COVID-19, our division organized an approach to manage these complications, attempting to balance resource utilization and risk to personnel with optimal cardiovascular care. The model presented can provide a framework for other institutions to organize their own approaches and can be adapted to local constraints, resource availability, and emerging knowledge., Competing Interests: Disclosures Dr Loungani and Dr Rehorn receive research support from Pfizer and Boston Scientific. Dr Katz receives research support from Abbott Corporation. Dr Klem receives research support from Medtronic and serves as a speaker and consultant to Bayer. Dr Mentz receives research support from the National Institutes of Health (U01HL125511-01A1 and R01AG045551-01A1), Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Gilead, InnoLife, Luitpold/American Regent, Medtronic, Merck, Novartis and Sanofi and honoraria from Abbott, Amgen, AstraZeneca, Bayer, Boston Scientific, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, Roche, Sanofi, and Vifor and has served on an advisory board for Amgen, AstraZeneca, Luitpold, Merck, Novartis, and Boehringer Ingelheim. Dr Vemulapalli receives support from Abbott Vascular, Boston Scientific, National Institutes of Health, Patient Centered Outcomes Research Institute, FDA (Nest), American College of Cardiology, and Society of Thoracic Surgeons and serves on advisory boards for Janssen, Boston Scientific, and HeartFlow. Dr Patel receives research support from NHLBI, Janssen, Bayer, Phillips, and Heartflow and serves on Advisory Boards for Janssen, Bayer, and Medscape. All other authors report no relevant disclosures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Medicare insurance claims may provide an efficient means to ascertain follow-up of older participants in clinical research. We sought to determine the accuracy and completeness of claims- versus site-based follow-up with clinical event committee (+CEC) adjudication of cardiovascular outcomes., Methods: We performed a retrospective study using linked Medicare and Duke Database of Clinical Trials data. Medicare claims were linked to clinical data from 7 randomized cardiovascular clinical trials. Of 52,476 trial participants, linking resulted in 5,839 (of 10,497 linkage-eligible) Medicare-linked trial participants with fee-for-service A and B coverage. Death, myocardial infarction (MI), stroke, and revascularization incidences were compared using Medicare inpatient claims only, site-reported events (+CEC) only, or a combination of the 2. Randomized treatment effects were compared as a function of whether claims-based, site-based (+CEC), or a combined system was used for event detection., Results: Among the 5,839 study participants, the annual event rates were similar between claims- and site-based (+CEC) follow-up: death (overall rate 5.2% vs 5.2%; adjusted κ 0.99), MI (2.2% vs 2.3%; adjusted κ 0.96), stroke (0.7% vs 0.7%; adjusted κ 0.99), and any revascularization (7.4% vs 7.9%; adjusted κ 0.95). Of events detected by claims yet not reported by CEC, a minority were reported by sites but negatively adjudicated by CEC (39% of MIs and 18% of strokes). Differences in individual case concordance led to higher event rates when claims- and site-based (+CEC) systems were combined. Randomized treatment effects were similar among the 3 approaches for each outcome of interest., Conclusions: Claims- versus site-based (+CEC) follow-up identified similar overall cardiovascular event rates despite meaningful differences in the events detected. Randomized treatment effects were similar using the 2 methods, suggesting claims data could be used to support clinical research leveraging routinely collected data. This approach may lead to more effective evidence generation, synthesis, and appraisal of medical products and inform the strategic approaches toward the National Evaluation System for Health Technology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Peripheral blood metabolite profiles have yielded mechanistic insights into various cardiovascular disease states. We hypothesized that peripheral blood metabolite profiles would be associated with new onset atrial fibrillation (AF)., Methods and Results: The study population comprised 1892 patients without AF at baseline, who, as part the MURDOCK Cardiovascular Disease Study molecular profiling cohort (n = 2023), had previously had determination of levels of 69 metabolites from frozen, fasting plasma specimens obtained during coronary angiography. We used Cox proportional hazards models to examine the association of 13 uncorrelated metabolite factors created from these data using principal components analysis (PCA) with new occurrences of AF during a median follow up of 2.8 (0.1-4.9) years. A total of 233 patients developed new AF (12.3%) during follow up. Patients with new onset AF were older (median 67 vs. 60 years); more often white (82 vs. 71%) and male (68 vs. 60%), and had more comorbidities than those who did not develop AF. After adjustment, PCA factor 1 (medium chain acylcarnitines; hazard ratio [HR]: 1.11 [1.01-1.22]), factor 2 (short chain dicarboxylacylcarnitines; HR: 1.21 [1.09-1.34]) and factor 5 (long chain acylcarnitines; HR: 1.19 [1.06-1.34]) were associated with new onset AF., Conclusion: Metabolite profiles were associated with new onset AF among patients referred for coronary angiography. Validation of these observations in broader patient populations may provide better mechanistic insight into the development of AF, and may provide new opportunities for prevention and treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: There is substantial variability among hospitals in critical care unit (CCU) utilization for patients admitted with non-ST-Segment Elevation Acute Coronary Syndromes (NSTE ACS). We estimated the potential cost saving if all hospitals adopted low CCU utilization practices for patients with NSTE ACS., Methods: National hospital claims data were used to identify all patients with a primary diagnosis of NSTE ACS initially admitted to an acute care hospital between 2007 and 2013. Hospital CCU utilization was classified as low (<30%), medium (30-70%), or high (>70%)., Results: Among the 270,564 NSTE ACS hospitalizations (71.6% non-ST-segment elevation myocardial infarction; 28.4% unstable angina) admitted to 261 hospitals, 41.9% (inter-hospital range 0.3%-95.1%) were admitted to a CCU. The proportion of patients admitted to a CCU in low, medium and high utilization hospitals was 16.3%, 49.5%, and high 81.1%, respectively. No differences in adjusted inpatient mortality were observed by hospital CCU utilization. The overall inpatient costs of caring for NSTE ACS were $1.1 billion. CCU care accounted for 45.2% of all hospitalization costs including 22.6%, 49.9%, and 69.0% (P < .001) of costs in low, medium and high utilization centers. The national potential direct cost savings of medium and high CCU utilization centers adopting low NSTE ACS CCU utilization practices was $113.4 million over the study period., Conclusions: In a population-based contemporary cohort, CCU utilization for patients with NSTE ACS varied widely and in-hospital mortality was similar between low, medium and high utilization centers. CCU care accounted for 45% of hospitalization costs; thus, implementing policies and admission practices to align hospital resources with patient care needs have the potential to reduce overall health care costs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Length of stay after non-ST-segment elevation myocardial infarction (NSTEMI) continues to decrease, but information to guide duration of hospitalization is limited., Methods: We used landmark analyses, in which the landmark defined potential days of discharge, to estimate complication rates on the first day the patient would have been out of the hospital, and estimated associations between timing of discharge and 30-day and 1-year event-free survival after discharge among NSTEMI patients., Results: Among 20,410 NSTEMI patients, median length of stay was 7 (4, 12) days; 3,209 (15.7%) experienced a cardiac complication on days 0 to 2 and 1,322 (6.5%) were discharged without complications during hospital days 0 to 2. At the start of day 3, 15,879 patients (77.8%) were still hospitalized without complications. Of these, 1,689 (10.6%) were discharged event-free on day 3. Adjusted event-free survival rates of death or myocardial infarction from day 4 to 30 days after among the 1,689 patients was 99.1% compared with 93.1% for the 14,190 who remained hospitalized at the end of day 3. For 1-year mortality, these rates were 98.1% and 96.4%, respectively. Among 13,334 patients hospitalized without complications at the start of day 4, 1,706 were discharged event-free that day. Adjusted survival rates among these patients, compared with those still hospitalized at the end of day 4, were 98.0% versus 93.7% for 30-day death or myocardial infarction and 97.8% versus 96.1% for 1-year mortality., Conclusions: Patients with NSTEMI who had no serious complications during the first 2 hospital days were at low risk of subsequent short- and intermediate-term death or ischemic events., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: Perioperative myocardial infarction (MI) after coronary artery bypass graft surgery (CABG) has been associated with adverse outcome. Whether perioperative MI should be treated with dual antiplatelet therapy (DAPT) is unknown. We compared the effect of DAPT versus aspirin alone on short-term outcomes among patients with perioperative MI following CABG., Methods: We used data from 3 clinical trials that enrolled patients undergoing isolated CABG: PREVENT IV (2002-2003), MEND-CABG II (2004-2005), and RED-CABG (2009-2010) (n = 9117). Perioperative MI was defined as CK-MB >5 times the upper limit of normal within 24 h of surgery (n = 2052). DAPT was defined as DAPT given after surgery and prior to discharge. A Cox regression model was used to assess the association between DAPT and 30-day nonfatal MI, stroke, or mortality after adjustment for baseline covariates., Results: DAPT (n = 527) and aspirin alone (n = 1525) cohorts were similar in baseline comorbidities. Off pump bypass was used in 5.2% (n = 106) of patients. There was no difference in the 30-day composite of death, MI or stroke between patients receiving DAPT versus aspirin alone, nor in any of the individual components. There were fewer all-cause re-hospitalizations at 30 days following surgery among patients in the DAPT group (adjusted HR 0.71, CI 0.52-0.97, P = .033)., Conclusion: One-quarter of CABG patients who had perioperative MI were treated with DAPT. DAPT was not associated with a difference in MI, stroke, or mortality at 30 days, but was associated with fewer re-hospitalizations. Further studies are needed to determine the optimal antiplatelet regimen following perioperative MI. What is already known about this subject? Perioperative myocardial infarction portends poor outcome but optimal management is currently unclear. While dual antiplatelet therapy is standard of care for acute coronary syndrome, its role in perioperative myocardial infarction is unknown. What does this study add? Dual antiplatelet therapy use during perioperative myocardial infarction was not associated with a difference in myocardial infarction, stroke or mortality at 30 days. It was, however, associated with fewer re-hospitalizations at 30 days. How might this impact on clinical practice? Dual antiplatelet therapy may be a potential treatment option for perioperative myocardial infarction after CABG surgery. Further studies are needed to better understand treatment for this disease process., (Copyright © 2018. Published by Elsevier Inc.)

Background: The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known., Methods: We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute-sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained., Results: Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the troponin concentration used locally to diagnose myocardial infarction to the assay manufacturer-determined 99th percentile URL was <1 at 19 (6.6%) laboratories, equal to 1 at 91 (31.6%) laboratories, >1 to ≤5 at 101 (35.1%) laboratories, >5 to ≤10 at 34 (11.8%) laboratories, and >10 at 43 (14.9%) laboratories. The variability in troponin decision level for myocardial infarction relative to the assay 99th percentile URL was present for laboratories in and outside of the United States, as well as for high- and standard-sensitivity assays., Conclusions: There is substantial hospital-level variation in the troponin threshold used to diagnose myocardial infarction; only one-third of hospital laboratories currently follow the Universal Definition of Myocardial Infarction consensus recommendation for use of troponin concentration at the 99th percentile of a normal reference population as the decision level to diagnose myocardial infarction. This variability across laboratories has important implications for both the diagnosis of myocardial infarction in clinical practice as well as adjudication of myocardial infarction in clinical trials., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Clinical practice guidelines recommend admitting patients with stable non-ST-segment elevation acute coronary syndrome (NSTE ACS) to telemetry units, yet up to two-thirds of patients are admitted to higher-acuity critical care units (CCUs). The outcomes of patients with stable NSTE ACS initially admitted to a CCU vs a cardiology ward with telemetry have not been described., Methods: We used population-based data of 7,869 patients hospitalized with NSTE ACS admitted to hospitals in Alberta, Canada, between April 1, 2007, and March 31, 2013. We compared outcomes among patients initially admitted to a CCU (n=5,141) with those admitted to cardiology telemetry wards (n=2,728)., Results: Patients admitted to cardiology telemetry wards were older (median 69 vs 65years, P<.001) and more likely to be female (37.2% vs 32.1%, P<.001) and have a prior myocardial infarction (14.3% vs 11.5%, P<.001) compared with patients admitted to a CCU. Patients admitted directly to cardiology telemetry wards had similar hospital stays (6.2 vs 5.7days, P=.29) and fewer cardiac procedures (40.3% vs 48.5%, P<.001) compared with patients initially admitted to CCUs. There were no differences in the frequency of in-hospital mortality (1.3% vs 1.2%, adjusted odds ratio [aOR] 1.57, 95% CI 0.98-2.52), cardiac arrest (0.7% vs 0.9%, aOR 1.37, 95% CI 0.94-2.00), 30-day all-cause mortality (1.6% vs 1.5%, aOR 1.50, 95% CI 0.82-2.75), or 30-day all-cause postdischarge readmission (10.6% vs 10.8%, aOR 1.07, 95% CI 0.90-1.28) between cardiology telemetry ward and CCU patients. Results were similar across low-, intermediate-, and high-risk Duke Jeopardy Scores, and in patients with non-ST-segment myocardial infarction or unstable angina., Conclusions: There were no differences in clinical outcomes observed between patients with NSTE ACS initially admitted to a ward or a CCU. These findings suggest that stable NSTE ACS may be managed appropriately on telemetry wards and presents an opportunity to reduce hospital costs and critical care capacity strain., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Red blood cell distribution width (RDW) strongly predicts clinical outcomes among patients with coronary disease and heart failure. The factors underpinning this association are unknown., Methods: In 6,447 individuals enrolled in the Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) Study who had undergone coronary angiography between 2001 and 2007, we used Cox proportional hazards modeling to examine the adjusted association between RDW and death, and death or myocardial infarction (MI). Multiple linear regression using the R(2) model selection method was then used to identify clinical factors associated with variation in RDW., Results: Median follow-up was 4.2 (interquartile range 2.3-5.9) years, and the median RDW was 13.5% (interquartile range 12.9%-14.3%, clinical laboratory reference range 11.5%-14.5%). Red blood cell distribution width was independently associated with death (adjusted hazard ratio 1.13 per 1% increase in RDW, 95% CI 1.09-1.17), and death or MI (adjusted hazard ratio 1.12, 95% CI 1.08-1.16). Twenty-seven clinical characteristics and laboratory measures were assessed in the multivariable linear regression model; a final model containing 18 variables explained only 21% of the variation in RDW., Conclusions: Although strongly associated with death and death or MI, only one-fifth of the variation in RDW was explained by routinely assessed clinical characteristics and laboratory measures. Understanding the latent factors that explain variation in RDW may provide insight into its strong association with risk and identify novel targets to mitigate that risk., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: Non-ST-segment myocardial infarction (NSTEMI) can be complicated by high-degree atrioventricular (AV) block, asystole, or electromechanical dissociation (EMD), but these events are not well characterized in the contemporary era. This analysis assesses the incidence of and factors associated with these dysrhythmias in acute NSTEMIs., Methods: Patients with NSTEMI in the EARLY ACS, PLATO, and TRACER trials were included in the pooled cohort (N = 29,677). Logistic regression was used to identify factors associated with in-hospital high-degree AV block and asystole or EMD, and Kaplan-Meier methods were used to assess mortality., Results: High-degree AV block occurred in 112 (0.4%) patients, asystole in 157 (0.5%), and EMD in 38 (0.1%). Pacemakers were inserted in 241 patients (0.8%) during the index hospitalization: 30 (12%) for AV block. Among patients with high-degree AV block, we observed more frequent right coronary artery lesions (47% vs 29%). Age, diabetes, lower heart rate, and lower blood pressure were associated with high-degree AV block. Higher Killip class, ST-segment depression, prior myocardial infarction, and peripheral vascular disease were most strongly associated with asystole or EMD. Ten-day unadjusted survival was 90% for patients with high-degree AV block and 43% for those with asystole or EMD., Conclusions: Although high-degree AV block, asystole, and EMD were infrequent complications of NSTEMI, they were associated with substantial short-term mortality. Only 1 in 8 pacemakers placed in NSTEMI patients during the acute hospitalization was for high-degree AV block., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Female sex is an established risk factor for bleeding, which is an important safety end point in patients presenting with non-ST-segment elevation acute coronary syndromes (NSTE ACS). However, it is unknown whether the association between bleeding and mortality is modulated by sex in this patient population., Methods: We examined the interaction between sex and bleeding and 30-day mortality outcomes among 2,975 women and 6,431 men with high-risk NSTE ACS enrolled in the EARLY ACS trial. The Global Utilization of Strategies to Open Occluded Arteries (GUSTO) criteria were used to identify moderate or severe bleeds., Results: Women were older and had more comorbid disease compared with men. Bleeding rates were higher among women (8.2%) than among men (5.5%; P < .01). However, the association of bleeding and 30-day mortality was stronger among men (odds ratio 5.8, 95% CI 3.9-8.8) than among women (odds ratio 1.5, 95% CI 0.8-2.9; sex * bleeding interaction P < .01). Sex differences in the association of bleeding and mortality persisted in a landmark analysis of 120-hour survivors., Conclusions: In a contemporary high-risk NSTE ACS cohort, women had higher bleeding rates than did men. Paradoxically, the association between bleeding and mortality was worse among men than among women., (© 2013.)

Aims: In the EARLY ACS trial, routine early eptifibatide was not superior to delayed provisional use at percutaneous coronary intervention (PCI); however, among PCI-treated patients, numerically fewer ischemic end points occurred in the upstream eptifibatide group. We sought to further explore this finding using methods for examination of treatment effect in this postrandomization subgroup., Methods and Results: Of 9,406 patients in the EARLY ACS primary analysis cohort, 9,166 (97.4%) underwent coronary angiography. We used Cox proportional hazards regression modeling, with PCI as a time-dependent covariate, to examine the effect of routine early versus delayed provisional eptifibatide among 5,541 patients undergoing PCI and to explore the interaction between treatment with PCI and randomized treatment strategy. After multivariable adjustment, compared with delayed provisional use, routine early eptifibatide was associated with lower rate of 30-day death or myocardial infarction (MI) after PCI (hazard ratio [HR] 0.80, 95% CI 0.68-0.95) but not with medical management (HR 0.97, 95% CI 0.74-1.29); PCI × randomized treatment interaction term P = .24. Excluding PCI-related MI, the adjusted HR for 30-day death or MI for routine early eptifibatide versus delayed provisional use was 0.80 (95% CI 0.60-1.08) for post-PCI treatment and 1.01 (95% CI 0.79-1.34) for medical management; PCI × randomized treatment interaction term P = .28., Conclusions: Consistent with previous literature, upstream treatment with eptifibatide was associated with improved outcomes in high-risk non-ST-segment elevation acute coronary syndrome patients treated with PCI; however, a nonsignificant interaction term precludes a definite conclusion., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Women are at higher risk than men for bleeding and vascular complications after percutaneous coronary intervention (PCI). Compared with femoral access, radial access reduces these complications but may be more challenging in women because of higher rates of radial artery spasm, tortuosity, and occlusion as well as lower rates of procedure success. Whether the safety advantages of radial versus femoral access in women undergoing PCI are outweighed by reduced effectiveness has not been studied. The Study of Access site For Enhancement of PCI for Women is a prospective, randomized clinical trial comparing radial with femoral arterial access in women undergoing PCI. In conjunction with the US Food and Drug Administration's Critical Path Cardiac Safety Research Consortium, this study embeds the randomized clinical trial into the existing infrastructure of the National Cardiovascular Data Registry CathPCI Registry through the National Institute of Health's National Cardiovascular Research Infrastructure. The primary efficacy end point is a composite of bleeding (Bleeding Academic Research Consortium types 2, 3, or 5) or vascular complication requiring intervention occurring at 72 hours after PCI or by hospital discharge. The primary feasibility end point is procedure success. Secondary end points include procedure duration, contrast volume, radiation dose, quality of life, and a composite of 30-day death, vascular complication, or unplanned revascularization., (© 2013.)

Background: In 2010, after regulatory review of rosiglitazone licensing, the US Food and Drug Administration (FDA) requested a reevaluation of cardiovascular end points in the RECORD trial., Methods: Automated screening of the original clinical trial database and manual case report form review were performed to identify all potential cardiovascular and noncardiovascular deaths, and nonfatal myocardial infarction (MI) and stroke events. Search techniques were used to find participants lost to follow-up, and sites were queried for additional source documents. Suspected events underwent blinded adjudication using both original RECORD end point definitions and new FDA end point definitions, before analysis by the Duke Clinical Research Institute., Results: The reevaluation effort included an additional 328 person-years of follow-up. Automated screening identified 396 suspected deaths, 2,052 suspected MIs, and 468 suspected strokes. Manual review of documents by Duke Clinical Research Institute clinical events classification (CEC) coordinators identified an additional 31 suspected deaths, 49 suspected MIs, and 28 suspected strokes. There were 127 CEC queries issued requesting additional information on suspected deaths; 43 were closed with no site response, 61 were closed with a response that no additional data were available, and additional data were received for 23. Seventy CEC queries were issued requesting additional information for suspected MI and stroke events; 31 were closed with no site response, 20 were closed with a response that no additional data were available, and 19 resulted in additional data., Conclusions: Comprehensive procedures were used for rigorous event reascertainment and readjudication in a previously completed open-label, global clinical trial. These procedures used in this unique situation were consistent with other common approaches in the field, were enhanced to address the FDA concerns about the original RECORD trial results, and could be considered by clinical trialists designing event readjudication protocols for drug development programs that have been completed., (Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.)

Background: The US Food and Drug Administration (FDA) required a reevaluation of cardiovascular (CV) outcomes in the RECORD trial. This provided an opportunity to assess the implications of event adjudication by 2 groups and quantify the differences as well as to use new FDA end point definitions in development., Methods: Original data were used to systematically identify all potential deaths, myocardial infarctions (MIs), and strokes. Site investigators were approached for additional source documents and information about participants lost to follow-up. Suspected events were adjudicated using standard procedures, and the results were compared with the original trial outcomes., Results: Follow-up for mortality was 25,833 person-years, including an additional 328 person-years identified during the reevaluation effort. A total of 184 CV or unknown-cause deaths (88 rosiglitazone, 96 metformin/sulfonylurea), 128 participants with an MI (68 rosiglitazone, 60 metformin/sulfonylurea), and 113 participants with a stroke (50 rosiglitazone, 63 metformin/sulfonylurea) were included. The hazard ratio (HR) for rosiglitazone versus metformin/sulfonylurea for the end point of CV (or unknown cause) death, MI, or stroke was 0.95 (95% CI 0.78-1.17) compared with 0.93 (95% CI 0.74-1.15) for the original RECORD results. Treatment comparisons for MI (HR 1.13, 95% CI 0.80-1.59) and mortality (HR 0.86, 95% CI 0.68-1.08) were also the same compared with the original RECORD results. Sensitivity analyses were also consistent with the original RECORD results. Analyses using the FDA definitions showed similar results., Conclusions: Only a modest number of additional person-years of follow-up were ascertained from this reevaluation of CV end points in RECORD. Observed HRs and CIs from these analyses using the original RECORD or new FDA end point definitions showed similar treatment effects of rosiglitazone compared with the original RECORD results., (Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.)

Background: We examined the prevalence of undiagnosed diabetes or prediabetes and associations with ischemic outcomes among non-ST-segment elevation acute coronary syndrome (ACS) patients., Methods: We categorized 8795 EARLY ACS trial patients into one of the following groups: "known diabetes" (n = 2860 [32.5%]; reported on the case report form), "undiagnosed diabetes" (n = 1069 [12.2%]; no diabetes history and fasting glucose ≥126 mg/dL or hemoglobin A1c ≥6.5%), "prediabetes" (n = 947 [10.8%]; fasting glucose ≥110 to <126 mg/dL, or "normal" (n = 3919 [44.5%]). Adjusted associations of known diabetes, undiagnosed diabetes, and prediabetes (versus normal) with 30-day and 1-year outcomes were determined., Results: Undiagnosed diabetes was associated with greater 30-day death or myocardial infarction (MI) (ORadj 1.28, 95% CI 1.05-1.57), driven primarily by greater 30-day mortality (ORadj 1.65, 95% CI 1.09-2.48). Known diabetic patients had 30-day death or MI outcomes similar to those of normal patients, but 30-day mortality was higher (ORadj 1.40, 95% CI 1.01-1.93). Prediabetic patients had 30-day death or MI outcomes similar to those of normal patients. One-year mortality was greater among known diabetic patients (HRadj 1.38, 95% CI 1.13-1.67) but not among those with undiagnosed diabetes or prediabetes., Conclusions: Undiagnosed diabetes and prediabetes were common among high-risk non-ST-segment elevation ACS patients. Routine screening for undiagnosed diabetes may be useful since these patients seem to have worse short-term outcomes and deserve consideration of alternative management strategies., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Bleeding is a major limitation of antithrombotic therapy among invasively managed non-ST-segment elevation acute coronary syndromes (NSTE-ACS) patients; therefore, we examined the use of radial access and its association with outcomes among NSTE-ACS patients., Methods: Clinical characteristics and geographic variation in radial access were examined, as well as its association with bleeding, red blood cell transfusion and ischemic outcomes (96-hour death/myocardial infarction/recurrent ischemic/thrombotic bailout; 30-day death/myocardial infarction; 1-year death) in the EARLY versus delayed, provisional eptifibatide in acute coronary syndromes trial., Results: Of 9126 patients, 13.5% underwent radial-access catheterization. Female sex, age, weight, and prior revascularization were inversely associated with radial access, and its use varied widely by country (2%-97%). There were fewer GUSTO severe/moderate bleeds and red blood cell transfusions in the radial access group; however, it was attenuated after adjustment (odds ratio 0.73, 95% confidence intervals [CI] [0.50-1.06], P = .094 and 1.00 [0.71-1.40] P = .991). Ischemic outcomes did not differ by access site., Conclusions: In this post hoc analysis of a large clinical trial, there was significant international variation in use of radial access for NSTE-ACS patients undergoing invasive management, and it was preferentially used in those at lower risk for bleeding. Radial approach was not associated with a significant reduction in either bleeding or ischemic outcomes. Further study is needed to determine whether wider application of radial approach to acute coronary syndrome patients at high risk for bleeding improves overall outcomes., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Prior studies indicate that a subset of patients diagnosed as having ST-segment elevation myocardial infarction (STEMI) will have an initial non-diagnostic electrocardiogram (ECG) during evaluation. However, the timing of diagnostic ECG changes in this group is unknown. Our primary aim was to describe the timing of ECG diagnosis of STEMI in patients whose initial ECG was non-diagnostic. Secondarily, we sought to compare the delivery of American College of Cardiology/American Heart Association guidelines-based care and in-hospital outcomes in this group compared with patients diagnosed as having STEMI on initial ECG., Methods: We analyzed data from 41,560 patients diagnosed as having STEMI included in the National Cardiovascular Data Registry ACTION Registry-GWTG from January 2007 to December 2010. We divided this study population into 2 groups: those diagnosed on initial ECG (N = 36,994) and those with an initial non-diagnostic ECG that were diagnosed on a follow-up ECG (N = 4,566)., Results: In general, baseline characteristics and clinical presentations were similar between the 2 groups. For patients with an initial non-diagnostic ECG, 72.4% (n = 3,305) had an ECG diagnostic for STEMI within 90 minutes of their initial ECG. There did not appear to be significant differences in the administration of guideline-recommended treatments for STEMI, in-hospital major bleeding (P = .926), or death (P = .475) between these groups., Conclusions: In a national sample of patients diagnosed as having STEMI, 11.0% had an initial non-diagnostic ECG. Of those patients, 72.4% had a follow-up diagnostic ECG within 90 minutes of their initial ECG. There did not appear to be clinically meaningful differences in guidelines-based treatment or major inhospital outcomes between patients diagnosed as having STEMI on an initial ECG and those diagnosed on a follow-up ECG., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Although controversial, reducing low-density lipoprotein cholesterol (LDL-C) to target levels remains a common therapeutic goal after acute myocardial infarction (AMI). We sought to illuminate patient and provider characteristics associated with LDL-C goal nonattainment after AMI., Methods: In an observational registry of 24 US hospitals, we included 366 patients with AMI who had baseline LDL-C levels ≥100 mg/dL and underwent 6-month fasting LDL-C reassessment. Our primary outcome was failure to reach the guideline-recommended LDL-C goal of <100 mg/dL at 6 months post-AMI., Results: One in 3 patients with AMI with initially elevated LDL-C failed to attain LDL-C goal at 6 months. Compared with those who attained LDL-C goal, those who did not were more often discharged without a statin (21% vs 9%, P < .001), despite only 4% having documented contraindications. Patients not achieving LDL-C goal also more frequently discontinued statin use by 6 months (24% vs 6%, P < .001). Multivariable modeling (c index, 0.78) revealed the absence of a statin prescription at discharge and lack of persistence on statin therapy as the strongest independent factors associated with failure to reach LDL-C goal. Additional independent risk factors were patient report of not consistently adhering to prescribed medications, not participating in cardiac rehabilitation, nonwhite race, and lack of insurance., Conclusions: One-third of patients with AMI with baseline hyperlipidemia do not attain the LDL-C goal of <100 mg/dL at 6 months. Our findings support targeted interventions in the transition of AMI care to promote affordable statin prescription at discharge, medication persistence and adherence, and cardiac rehabilitation participation., (Copyright © 2013 Mosby, Inc. All rights reserved.)

The p38 mitogen-activated protein kinase (MAPK) is a nexus point in inflammation, sensing, and stimulating cytokine production and driving cell migration and death. In acute coronary syndromes, p38MAPK inhibition could stabilize ruptured atherosclerotic plaques, pacify active plaques, and improve microvascular function, thereby reducing infarct size and risk of subsequent cardiac events. The SOLSTICE trial is randomized, double-blind, placebo-controlled, parallel group, multicenter phase 2a study of 535 patients that evaluates the safety and efficacy of losmapimod (GW856553), a potent oral p38MAPK inhibitor, vs placebo in patients with non-ST-segment elevation myocardial infarction expected to undergo an invasive strategy. The coprimary end points are reduction in high-sensitivity C-reactive protein at 12 weeks and reduction in infarct size as assessed by troponin area under the curve at 72 hours. A key secondary end point is 72-hour and 12-week B-type natriuretic peptide levels as a measure of cardiac remodeling and ventricular strain. The primary safety assessments are serious and nonserious adverse events, results of liver function testing, and major adverse cardiac events. Cardiac magnetic resonance imaging (N = 117) and coronary flow reserve (N = 13) substudies will assess the effects of losmapimod on infarct size, myocardial function, and coronary vasoregulation. Information gained from the SOLSTICE trial will inform further testing of this agent in larger clinical trials., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Older patients with atrial fibrillation (AF) and coronary artery disease (CAD) face high risk of stroke and bleeding with antithrombotic therapy. Balancing safe and effective use of aspirin, clopidogrel, and warfarin in this population is important., Methods: From the Duke Databank for Cardiovascular Disease, we identified patients with AF ≥65 years old with angiographically confirmed CAD from 2000 to 2010. Antithrombotic use was described across age and Congestive heart failure, Hypertension, Age >75 years, Diabetes, prior Stroke/transient ischemic attack (CHADS(2)) stroke risk and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding scores. Death and the composite of death, myocardial infarction, and stroke by antithrombotic strategy were reported., Results: Of 2,122 patients ≥65 years old with AF and CAD, 477 (22.5%) were ≥80 years old; 1,133 (53.4%) had acute coronary syndromes. Overall rates of aspirin, clopidogrel, and warfarin use were 83.4%, 34.6%, and 38.9%, respectively. Compared with patients 65 to 79 years old, more patients ≥80 years old were at high stroke risk (CHADS(2) ≥2, 84.7% vs 57.8%) and high bleeding risk (ATRIA 5-10, 55.8% vs 23.3%). Warfarin use in both age groups increased with higher CHADS(2) scores and decreased with higher ATRIA scores. Of patients ≥80 years old with CHADS(2) ≥2, 150 (38.2%) received warfarin. Antithrombotic strategy was not associated with improved 1-year adjusted outcomes., Conclusions: Among older patients with AF and CAD, overall warfarin use was low. Patients ≥80 years old at highest stroke risk received warfarin in similar proportions to the overall cohort. Further investigation into optimizing antithrombotic strategies in this population is warranted., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Dose adjustment of renally excreted antithrombotic drugs is recommended for patients with reduced renal function. We examined the influence of dose modification on bleeding and efficacy., Methods: Based on initial study drug infusion rate, Early GP IIb/IIIa Inhibition in non-ST-segment elevation acute coronary syndromes (EARLY ACS) patients were categorized into groups: standard dose (2 μg/kg/min; estimated creatinine clearance [eCrCl] ≥50 ml/min), adjusted dose (1 μg/kg/min; eCrCl <50 ml/min, per protocol), excess dose (2 μg/kg/min; eCrCl <50 ml/min). We explored relationships among initial dosing, randomized treatment assignment, and bleeding and ischemic end points (96-h composite of death, myocardial infarction [MI], recurrent ischemia requiring urgent revascularization or thrombotic bailout, and 30-d death or MI)., Results: Of 8,708 patients with eCrCl and dosing data, 19% had eCrCl <50 ml/min. Of these, 13% received adjusted dose eptifibatide and 6% received an excess dose. Across all dosing groups, no significant reductions were found in ischemic end points between early versus delayed provisional eptifibatide (OR 1.14, 95% CI 0.80-1.65; OR 1.13, 95% CI 0.81-1.56, respectively, for 96-h and 30-d composite end points). Bleeding risk was not significantly increased in the early versus delayed provisional treatment group in either the adjusted (OR 1.50, 95% CI 0.95-2.39) or excess dose group (OR 1.67, 95% CI 0.85-3.39). There were no significant interactions between dose group and treatment strategy on bleeding or efficacy., Conclusion: Similar to observations in practice, despite guidelines recommendations and protocol guidance, 34% of EARLY ACS patients with reduced renal function failed to receive an appropriately adjusted study drug infusion. Use of an appropriately adjusted eptifibatide infusion was not associated with expected reductions in bleeding among patients with renal insufficiency., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Drug-induced cardiac toxicity is a recognized challenge in development and implementation of pharmacotherapy. Appropriate biomarkers are needed to detect these abnormalities early in development and to manage the risk of potentially cardiotoxic drugs or biologic agents. Circulating cardiac troponin (cTn) is the most widely used biomarker for detection of myocardial injury. Although most commonly used to detect myonecrosis in the setting of ischemia, cTns are also elevated with other acute and chronic disease processes, including heart failure, renal failure, sepsis, pulmonary embolic disease, and many others. High-sensitivity assays for both cTnI and cTnT are now available that achieve acceptable imprecision (coefficient of variation <10%) at the 99th percentile of a normal reference population. Even more sensitive assays are being developed that detect cTn in ranges that are near the level of normal cellular turnover (apoptosis). These properties of cTn and the continuing evolution of highly sensitive assays position cTn as a potentially uniquely informative marker for early detection of cardiac toxicity. This article summarizes collaborative discussions among key stakeholders in the Cardiac Safety Research Consortium about the use of cTn monitoring in drug development., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: We hypothesized that single-nucleotide polymorphisms (SNPs) associated with heightened in vitro platelet function during aspirin exposure (which we define as "laboratory aspirin resistance") would be associated with greater risk for death, myocardial infarction (MI) or stroke among patients with coronary artery disease regularly using aspirin., Methods: Duke Databank for Cardiovascular Disease patients with (n = 3,449, CATHeterization GENetics cohort) or without (n = 11,754, nongenetic cohort) banked DNA with ≥1 coronary stenosis >75% were followed up at 6 months, then annually for death, MI, or stroke occurring during periods of reported aspirin use. We evaluated associations of candidate SNPs from GNB3, PEAR1, ITGB3, VAV3, ITGA2, GPVI, PTGS1, F2R, THBS1, A2AR, and GP1BA with events during follow-up using Cox proportional hazards modeling adjusted for clinical characteristics associated with outcomes in the nongenetic cohort., Results: Over a median of 3.5 years, 2,762 (24%) nongenetic cohort patients and 648 (19%) CATHeterization GENetics cohort patients had the composite outcome during reported aspirin use. No candidate SNPs were significantly associated with death, MI, or stroke in either univariable or multivariable analyses. A prospective analysis demonstrated 80% to 88% power to detect a hazard ratio of ≥1.3 for minor allele carriers., Conclusion: Patients with angiographically significant coronary artery disease regularly using aspirin and carrying SNPs associated with laboratory aspirin resistance were not at higher risk for death, MI, or stroke. Using these SNPs to guide more aggressive antiplatelet therapy is not justified by these results. Direct extrapolation from in vitro findings to the clinical setting should be avoided., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Atrial fibrillation (AF) affects 2.5 million patients in the United States. The incidence of this condition increases with age, such that approximately 5% of people > 65 years of age have AF. Because of the lack of organized atrial contraction and thrombus formation in the left atrium, patients with AF are at increased risk of stroke. The estimated risk of stroke among all AF patients is 5% per year. Among patients without mitral stenosis, there is a graded relationship of stroke risk with the number of CHADS₂ risk factors. Warfarin is the recommended treatment for embolic stroke prophylaxis in AF in intermediate- to high-risk patients. However, elderly patients who are deemed to be at risk of falls are often not started on warfarin therapy secondary to a perceived higher risk of bleeding complications. These risks have been evaluated, but conclusive data regarding the risk-benefit trade-off are elusive. This review summarizes available data on the use of warfarin in elderly patients with AF, focusing on the risk of bleeding, and will specifically address the utility of falls risk assessment in the decision to initiate warfarin therapy for AF., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Major bleeding during an acute coronary syndrome (ACS) is associated with increased late ischemic events. Patients with bleeding are often discharged without antiplatelet therapy (AT). The association between discharge AT use and late ischemic outcomes among ACS patients with bleeding is uncertain., Methods: We examined discharge AT use among 8,582 ACS patients with in-hospital bleeding from a total of 26,451 patients enrolled in 4 randomized trials. After adjusting for the propensity to receive AT, we compared 6-month postdischarge outcomes between patients discharged with and those discharged without AT., Results: Almost 1 in 10 patients with bleeding was discharged without AT (n=826). Compared with those receiving discharge AT, those not receiving discharge AT had a higher risk of 6-month death, myocardial infarction, and stroke (14.3% vs 7.8%, propensity-adjusted hazard ratio [HR]=1.36, 95% confidence interval=1.01-1.85). Nonuse of AT at discharge was associated with worse outcomes among patients treated with percutaneous coronary intervention compared with those treated without it (adjusted HR=4.22 vs 1.13, interaction P=.0003). Discharge monotherapy was associated with worse outcomes than dual AT among patients receiving stents (adjusted HR=1.78, 95% CI=1.04-3.03)., Conclusions: Bleeding occurred commonly among patients with ACS. AT was often not used in these patients at discharge, and lack of discharge AT was associated with an increased risk of 6-month ischemic events. These data raise the possibility that lack of AT use among patients with in-hospital bleeding may contribute to their excess risk of long-term ischemic outcomes., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: Prior studies have demonstrated differences in adherence to non-ST-segment elevation acute coronary syndromes (NSTE ACS) guidelines-recommended therapies among patients managed conservatively without cardiac catheterization compared with those managed invasively. We evaluated the degree of yearly change in use of guidelines-recommended therapies for patients with NSTE ACS in CRUSADE stratified by use of cardiac catheterization and revascularization procedures., Methods: We analyzed data from 138,714 high-risk patients with NSTE ACS treated at 547 hospitals during the first 4 years of the CRUSADE initiative. Patients were categorized as no cardiac catheterization (29% of the total population), cardiac catheterization without revascularization (21%), percutaneous coronary intervention (40%), and coronary artery bypass graft surgery (11%). Composite guidelines adherence scores were used to compare yearly changes in use of guidelines-recommended therapies among the groups., Results: Although guidelines adherence improved in all 4 groups each year and was consistently highest in the percutaneous coronary intervention group, the adjusted yearly increase in the use of acute guidelines-recommended medications was highest in the no cardiac catheterization group, and the adjusted yearly increase in the use of discharge medications was highest in the coronary artery bypass graft surgery group., Conclusions: Improvements in the use of guidelines-recommended therapies were seen among all patients with NSTE ACS in CRUSADE over a 4-year period regardless of management strategy, and the trajectory of improvement in acute care was greatest in patients managed conservatively.

Background: Although adequate representation of specific subgroups (eg, women and the elderly) in randomized controlled trials (RCTs) has been under intense scrutiny, there are few data on representation by race., Methods: Using all RCTs cited by the 2007 American Heart Association guidelines for cardiovascular disease prevention in women (although trials were included whether or not there were female participants), we explored the extent to which information on race was reported in the baseline characteristics. Race/ethnicity categories were whites, blacks, Asians, Hispanics, and "others.", Results: Overall, 156 trials were analyzed. Demographic data on race/ethnicity were reported in 55 (35%) trials and increased significantly over time (1970s, 12.5%; 1980s, 25%; 1990s, 30.5%; 2000s, 46.2%; P for trend = .011). Among the 55 trials reporting any race/ethnicity information, trial inclusion of whites, blacks, Asians, Hispanics, and "others" was reported in 27%, 13%, 14%, 5%, and 10% of trials, respectively, and increased over time (P for trend < .05 for all). Trials enrolling subjects only in the United States or globally, including the US, were more likely to report race composition than trials that included no US sites (US only 64% vs global 62% vs non-US 21%, P < .01). Industry- and federal/foundation-funded RCTs reported race with similar frequency (industry 36% vs federal 34% vs both 24%, P = .44). When we isolated our analyses to trials that were funded by the National Institutes of Health, 12 (67%) of 18 RCTs reported race/ethnicity as a baseline characteristic., Conclusion: Although reporting the race/ethnic composition of study populations is increasing over time, two thirds of all RCTs supporting a recent American Heart Association () guideline failed to publish any information on race. A necessary first requirement in translating RCT evidence to patients of all races is information regarding racial demographics. Such information should be strongly encouraged in future publications.

Background: Short-term use of clopidogrel plus aspirin among patients with acute coronary syndrome reduces ischemic events, but concerns about coronary artery bypass graft (CABG) surgery-related bleeding limit its early use., Methods: Using data from 4,794 consecutive CABG procedures in the Duke Databank for Cardiovascular Disease (January 1999 to December 2003), we developed multivariable models for associations with CABG-related bleeding defined as reoperation for bleeding, red cell transfusion, and a composite of reoperation/transfusion/hematocrit drop>or=15%. We examined clopidogrel use

Background: Unfractionated heparin (UFH) is a mainstay of treatment for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), but the practice of weight-adjusted bolus and infusion dosing has not been carefully evaluated., Methods: Using data from 31,445 high-risk patients with NSTE ACS enrolled at 420 hospitals in the CRUSADE initiative, we evaluated initial UFH dosing relative to guideline recommendations and determined factors associated with excess weight-adjusted dosing and major bleeding, overall and among subgroups. Excess dose was defined as >70 U/kg for bolus or >15 U/kg per hour for infusion., Results: The most frequent bolus dose was 5,000 U (42.7%) and infusion dose was 1,000 U/h (46%). An excess weight-adjusted UFH bolus or infusion dose was administered 35% of the time. Factors strongly associated with excess weight-adjusted dosing were age (per 10-year increase) (odds ratio [OR] 1.11, 95% CI 1.08-1.15) and female sex (OR 1.45, 95% CI 1.33-1.59). Rate of major bleeding increased proportionally in relation to dose of UFH for both bolus and infusion, specifically when dose was above the recommended weight-adjusted range (>70 U/kg for bolus or >15 U/kg per hour for infusion). Both excess bolus (OR 1.03, 95% CI 1.00-1.06) and infusion (OR 1.16, 95% CI 1.05-1.28) were individually associated with increased bleeding. The relationship between weight-adjusted UFH dose and major bleeding did not vary independently by sex or age., Conclusions: In high-risk patients with NSTE ACS, initial UFH bolus and infusion dosing were frequently higher than recommended weight-adjusted ranges, particularly in patients with lower body weight. Excess bolus and infusion rate dosing was associated with more bleeding and was common among elderly and females. Attention to dosing by weight rather than standard bolus and infusion dosing should lead to improved safety in the use of UFH.

Objectives: To describe the association between transfusion and outcomes as a function of nadir hematocrit (HCT) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS)., Background: The adverse outcomes associated with transfusion in NSTE ACS is uncertain and may vary by nadir HCT of the transfused., Methods: Using data from 44242 patients with NSTE ACS in 400 US hospitals in the CRUSADE initiative (January 2004-December 2005), we describe blood transfusion as a function of nadir HCT and associated outcomes across nadir HCT groups (30%). We further explore patient and process variation across hospital quartiles defined by transfusion use., Results: Overall, 22.2% of patients with NSTE ACS are anemic and 10.4% receive a blood transfusion during their care. Likelihood of transfusion rose from 1% when nadir HCT was >30% to 70% when nadir HCT was 30% (adjusted OR 3.47 [2.30-5.23]) had higher mortality., Conclusion: Anemia and transfusion are common in the care of NSTE ACS. The observed association between transfusion and adverse outcomes is neutral in the nadir HCT range where transfusions are most often given and trends strongly to benefit when nadir HCT is

Background: Evidence-based medications (EBM) are underused in older patients despite potentially larger absolute benefits. Little is known about factors influencing prescribing in the elderly with acute coronary syndromes., Methods: Among the 15,904 patients from the Sibrafiban vs aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes (SYMPHONY) and second SYMPHONY trials, we examined the rates of use of EBM according to age (< 75 or > or = 75 years, and 3 subgroups of 5 year increments among patients > or = 75 years)., Results: Ninety-day mortality increased with age (< 75 years, 1.3%; > or = 75 to < 80 years, 4.4%; > or = 80 to < 85 years, 6.0%; > or = 85 years, 9.6%). Compared with subjects < 75 years (n = 14,043), acute EBM use was lower among patients > or = 75 years (n = 1794): aspirin (83% vs 85%), heparin (73% vs 78%), and beta-blockers (70% vs 76%). Similarly, discharge use of beta-blockers (69% vs 76%) and statins (28% vs 40%) was lower, although this was not the case for angiotensin-converting enzyme inhibitors (44% vs 41%). These patterns persisted among eligible patients. Beyond the age of 75 years, EBM use was not further influenced by age except for statins and angiotensin-converting enzyme inhibitors, which were used less frequently in those > or = 85 years. Among patients aged > or = 75 years, prediction for use of each EBM in multivariable modeling was modest (C indices, approximately 0.7); except for statins, increasing age did not predict lower EBM use., Conclusions: Despite higher mortality risk, EBM use was lower among older patients even considering eligibility. Among those aged > or = 75 years, age was no longer the major factor predicting EBM use. The modest C indices suggest other factors are associated with prescribing, underscoring the need for treatment algorithms and quality assurance measures in older patients.

Background: Although documented traditional cardiovascular risk factors (hypertension, diabetes, smoking, and dyslipidemia) increase the risk of developing coronary artery disease, their influence on the treatments and outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI) has not been fully elucidated., Methods: Using data from the CRUSADE Quality Improvement Initiative, we sought to characterize the effect that the absence of documented traditional risk factors has on inhospital treatments and outcomes in a population of patients with NSTEMI treated in routine practice. We compared clinical characteristics and inhospital outcomes according to the presence and number of risk factors in 74,220 patients with NSTEMI (defined as creatine kinase-MB and/or troponin I/T values above the local upper limit of normal) treated in 476 US hospitals from January 2001 through March 2004., Results: The 7755 (10.5%) patients with no documented traditional risk factors on admission were less likely to receive short-term guideline-recommended therapies and revascularization procedures. Despite a higher prevalence of normal left ventricular function and insignificant angiographic coronary artery disease, these patients had a slightly higher risk of adjusted inhospital mortality (odds ratio 1.15, 95% CI 1.03-1.29) compared with patients with any combination of risk factors., Conclusions: Patients without documented traditional cardiovascular risk factors represent 10.5% of the non-ST-segment elevation myocardial infarction population. Because the absence of documented traditional risk factors does not yield a favorable prognosis, further study is needed to delineate the effects of the interplay between novel and documented traditional risk factors and treatment differences on the outcomes of these patients.

Background: Unlike ST-segment elevation myocardial infarction, the degree of stenosis and physiology of ischemia varies in patients with non-ST-segment elevation myocardial infarction (NSTEMI). The prevalence, predictors, and outcomes of patients with NSTEMI who lack significant epicardial coronary artery disease (CAD) in routine clinical practice remain poorly characterized. We sought to determine the prevalence, predictors, and outcomes of patients with NSTEMI and insignificant CAD., Methods: We analyzed 38301 patients with NSTEMI in the CRUSADE quality improvement initiative who underwent cardiac catheterization to determine the prevalence and factors associated with insignificant CAD (all coronary stenoses <50%) and inhospital outcomes for patients with and without CAD. A multivariable model was used to determine the factors associated with insignificant CAD., Results: A total of 3306 (8.6%) of 38301 patients had insignificant CAD. The strongest multivariable predictors of insignificant CAD were female sex (odds ratio 2.8, 95% CI 2.6-3.1), younger age (odds ratio per 10-year decrease 1.5, 95% CI 1.5-1.6), and lack of current/recent smoking (odds ratio 1.9, 95% CI 1.7-2.0). Inhospital rates of death were 0.65% for patients with insignificant CAD compared with 2.36% for patients with CAD (P < .0001)., Conclusion: Insignificant CAD is present in 9% of patients with NSTEMI and is associated with a low incidence of adverse outcomes. The strongest predictors of insignificant CAD are female sex and younger age. These findings underscore the need for research to understand the pathophysiology of myocardial infarction in this population.

Background: We sought to assess the influence of emergency department (ED) structure and care processes on adherence to practice guidelines for the treatment of patients with non-ST-segment elevation acute coronary syndromes., Methods: We surveyed emergency physicians and nurses from 316 hospitals participating in the CRUSADE Quality Improvement Initiative and used multivariable modeling to correlate ED-specific characteristics with guidelines adherence., Results: Factors that were significantly associated with improved guidelines adherence included collaboration between emergency physicians and hospital administration, northeast region, adequate nursing support, use of locum tenens physicians, an independent ED (not a division of another clinical department), and use of a care algorithm for acute coronary syndromes., Conclusions: Quality improvement strategies that have the full support of hospital administration, focus on increasing collaboration between emergency physicians and other health care providers, and specified protocol-driven management algorithm may be the most successful methods for improving the care and outcomes of patients with non-ST-segment elevation acute coronary syndromes.

Background: Practice guidelines for patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) recommend targeting evidence-based therapies for the highest-risk patients. We characterized guideline adherence for NSTE ACS by risk status., Methods: We analyzed inhospital treatments and outcomes for 77760 patients with NSTE ACS (ischemic ST-segment changes and/or positive cardiac markers) included in the CRUSADE initiative from January 2001 to September 2003 at 457 US hospitals. Compliance with the American College of Cardiology/American Heart Association Class guideline recommendations for NSTE ACS was evaluated in subgroups of eligible patients without listed contraindications at increased risk for mortality and among risk categories designated by an adapted version of the PURSUIT risk model designed to predict inhospital mortality., Results: Inhospital mortality was increased in patients with diabetes mellitus (5.8% vs 4.3%), renal insufficiency (10.0% vs 3.9%), signs of congestive heart failure on presentation (10.6% vs 3.1%), and age > or = 75 years (8.6% vs 2.7%), compared with patients without these features. Use of guideline-recommended acute medications, invasive cardiac procedures, and discharge medications and interventions was significantly lower in patients with these high-risk features. Patients designated as high-risk for inhospital mortality were less likely to be treated with guideline-recommended therapies compared with low-risk and moderate-risk patients., Conclusions: Patients with NSTE ACS with the highest risk of mortality are less likely to receive guideline-recommended therapies and interventions. These findings highlight the need to clarify guideline recommendations for high-risk patients and to develop novel quality improvement approaches that target undertreated subgroups of patients with NSTE ACS.

Background: Troponin testing is useful for evaluating patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); however, a significant percentage of patients are troponin negative at presentation and develop late rise of the marker., Methods: Patients in the TIMI IIIB study were assessed with respect to their troponin I (TnI) status at presentation and 12 hours. Multivariable analysis identified independent clinical factors associated with TnI rise at 12 hours among subjects initially TnI negative. A score predicting late TnI rise in TIMI IIIB was developed using these factors and validated among patients in the GUSTO IIA study., Results: Of 1342 subjects in TIMI IIIB, 200 (14.9%) were negative at baseline, but developed an elevated TnI (> or = 0.4 ng/mL) at 12 hours. Six independent predictors of late TnI rise were identified: ST-segment deviation (odds ratio [OR] 3.52, 95% CI 2.38-5.23, P < .001), presentation < 8 hours from symptom onset (OR 2.91, 95% CI 1.92-4.40, P < .001), no prior percutaneous coronary intervention (OR 2.88, 95% CI 1.54-5.39, P = .001), no prior beta-blocker use (OR 1.74, 95% CI 1.15-2.63, P = .008), unheralded angina (OR 1.65, 95% CI 1.12-2.42, P = .01), and a history of myocardial infarction (OR 1.59, 95% CI 1.06-2.37, P = .02). ST deviation, presentation < 8 hours from symptoms, and no prior percutaneous coronary intervention were given a score of 2 points, whereas a score of 1 point was assigned to the other factors. Among baseline TnI-negative patients, a rising score was paralleled by an increasing prevalence of late TnI rise from 0% (with a score of 0) to 69% (with a score of 9) (P < .001). In confirmation, the score was able to similarly predict late troponin T rise among 855 patients in the GUSTO IIA study (P < .0001)., Conclusion: Development of late troponin rise is common in non-ST-segment elevation acute coronary syndromes. Six easily ascertained variables may be used to identify those at higher risk for late rise in troponin levels after an initially negative presentation.

Background: The degree to which elevated creatine kinase (CK)-MB in the presence of normal CK is predictive of outcome is not well understood despite having been studied for decades. This analysis examined whether normal CK with elevated CK-MB in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) is an independent predictor of worse outcomes. A concomitant goal was to contribute insight to the debate over how patients with NSTE ACS should be managed., Methods: Data for 25,960 patients from the GUSTO IIb, PARAGON A and B, and PURSUIT trials were analyzed. Of these patients, 6402 were excluded from primary analysis because of missing (unmeasured) biomarkers. Patients with complete laboratory data (n = 19,558) were grouped by CK and CK-MB results. To confirm the primary analysis results, data from patients with missing biomarkers were used in an imputation model., Results: Patients were categorized in 1 of 4 groups: normal CK + normal CK-MB; normal CK + elevated CK-MB; elevated CK + normal CK-MB; or elevated CK + elevated CK-MB. For the primary outcome, 180-day death, or myocardial infarction, Kaplan-Meier estimates were 14.9%, 20.8%, 14.5%, and 18.2%, respectively. Regardless of total CK, elevated CK-MB was associated with a 25% to 49% increased relative risk of worse outcomes. Findings from the analyses were verified by the multivariable model., Conclusions: CK-MB remains a reliable marker for myocardial necrosis and a strong predictor of worse prognosis. All patients with ACS should have CK-MB measurement to search for cardiac ischemia. Patients with elevated CK-MB should receive aggressive management commensurate with their increased risks.

Background: Hypertension affects 1 billion individuals worldwide and is an independent risk factor for death after acute coronary syndromes (ACS)., Methods: We examined the prevalence and medical treatment of hypertension among 15,904 ACS patients randomized in the SYMPHONY and 2nd SYMPHONY trials. Analyses were performed overall and according to sex for the United States and across international practice. Multivariable models identified factors associated with use of antihypertensive medication classes and examined the association of hypertension and sex with mortality., Results: In the United States, hypertension was more prevalent in women than in men, overall (63% vs 50%) and within every decile of age. Hypertensive women more often received calcium-channel blockers (35% vs 30%) and diuretics (33% vs 19%) and less often received beta-blockers (51% vs 57%). Angiotensin-converting enzyme inhibitor use was similar (35% vs 34%). Women received multiple agents more frequently than did men: 2 agents, 35% vs 30%; > or = 3 agents, 16% vs 13%. Female sex independently predicted drug-class use only for diuretics. Mortality was higher in hypertensive women than in hypertensive men; after multivariable adjustment, mortality was similar without evidence of a differential association between hypertension and mortality according to sex. Although there was international variation in the use of individual classes of agents, the overall findings by sex were similar across regions., Conclusion: Hypertension is more prevalent in women than in men with ACS, and its medical management varies by sex, but its association with mortality is similar. Opportunities exist to improve medical therapy and outcomes in women with hypertension.