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In this Emergency Medicine Cardiac Research and Education Group (EMCREG)-International Proceedings Monograph from the October 20, 2018, EMCREG-International Multidisciplinary Consensus Panel on Management of Severe Bleeding in Patients Treated With Oral Anticoagulants held in Orlando, FL, you will find a detailed discussion regarding the treatment of patients requiring anticoagulation and the reversal of anticoagulation for patients with severe bleeding. For emergency physicians, critical care physicians, hospitalists, cardiologists, internists, surgeons, and family physicians, the current approach and disease indications for treatment with anticoagulants such as coumadin, factor IIa, and factor Xa inhibitors are particularly relevant. When a patient treated with anticoagulants presents to the emergency department, intensive care unit, or operating room with severe, uncontrollable bleeding, achieving rapid, controlled hemostasis is critically important to save the patient's life. This EMCREG-International Proceedings Monograph contains multiple sections reflecting critical input from experts in Emergency Cardiovascular Care, Prehospital Emergency Medical Services, Emergency Medicine Operations, Hematology, Hospital Medicine, Neurocritical Care, Cardiovascular Critical Care, Cardiac Electrophysiology, Cardiology, Trauma and Acute Care Surgery, and Pharmacy. The first section provides a description of the current indications for the treatment of patients using oral anticoagulants including coumadin, the factor IIa (thrombin) inhibitor dabigatran, and factor Xa inhibitors such as apixaban and rivaroxaban. In the remaining sections, the treatment of patients presenting to the hospital with major bleeding becomes the focus. The replacement of blood components including red blood cells, platelets, and clotting factors is the critically important initial treatment for these individuals. Reversing the anticoagulated state is also necessary. For patients treated with coumadin, infusion of vitamin K helps to initiate the process of protein synthesis for the vitamin K-dependent coagulation proteins II, VII, IX, and X and the antithrombotic protein C and protein S. Repletion of clotting factors for the patient with 4-factor prothrombin complex concentrate, which includes factors II (prothrombin), VII, IX, and X and therapeutically effective concentrations of the regulatory proteins (protein C and S), provides real-time ability to slow bleeding. For patients treated with the thrombin inhibitor dabigatran, treatment using the highly specific, antibody-derived idarucizumab has been demonstrated to reverse the hypocoagulable state of the patient to allow blood clotting. In May 2018, andexanet alfa was approved by the US Food and Drug Administration to reverse the factor Xa anticoagulants apixaban and rivaroxaban in patients with major bleeding. Before the availability of this highly specific agent, therapy for patients treated with factor Xa inhibitors presenting with severe bleeding usually included replacement of lost blood components including red blood cells, platelets, and clotting factors and 4-factor prothrombin complex concentrate, or if not available, fresh frozen plasma. The evaluation and treatment of the patient with severe bleeding as a complication of oral anticoagulant therapy are discussed from the viewpoint of the emergency physician, neurocritical and cardiovascular critical care intensivist, hematologist, trauma and acute care surgeon, hospitalist, cardiologist, electrophysiologist, and pharmacist in an approach we hope that the reader will find extremely practical and clinically useful. The clinician learner will also find the discussion of the resumption of oral anticoagulation for the patient with severe bleeding after effective treatment important because returning the patient to an anticoagulated state as soon as feasible and safe prevents thrombotic complications. Finally, an EMCREG-International Severe Bleeding Consensus Panel algorithm for the approach to management of patients with life-threatening oral anticoagulant-associated bleeding is provided for the clinician and can be expanded in size for use in a treatment area such as the emergency department or critical care unit.

Professional society guidelines suggest early stress testing (within 72 hours) after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS). However, there is increasing concern that current practice results in over-testing without evidence of benefit. We test the hypothesis that early stress testing improves outcomes.We analyzed prospectively collected data from 9 EDs on patients with suspected ACS, 1999-2001. We excluded patients with an ED diagnosis of ACS. The primary outcome was 30-day major adverse cardiac events (MACEs), including all-cause death, acute myocardial infarction, and revascularization. We used the HEART score to determine pretest ACS risk (low, intermediate, and high). To mitigate potential confounding, patients with and without early stress testing were matched within pretest risk strata in a 1:2 ratio using propensity scores.Of 7127 potentially eligible patients, 895 (13%) received early stress testing. The analytic cohort included 895 patients with early stress testing matched to 1790 without early stress testing. The overall 30-day MACE rate in both the source and analytic population was 3%. There were no baseline imbalances after propensity score matching (P0.1 for more than 30 variables). There was no association between early stress testing and 30-day MACE [odds ratio, 1.0; 95% confidence interval (CI), 0.6-1.7]. There was no effect modification by pretest risk (low: odds ratio, 1.0; 95% CI, 0.2-3.7; intermediate: 1.2; 95% CI, 0.6-2.6; high: 0.4; 95% CI, 0.1-1.6).Early stress testing is not associated with reduced MACE in patients evaluated for suspected ACS. Early stress testing may have limited value in populations with low MACE rate.

ACADEMIC EMERGENCY MEDICINE 2012; 19:153–160 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: ST-segment elevation myocardial infarction (STEMI) care is time-dependent. Many STEMI patients require interhospital helicopter transfer for percutaneous coronary intervention (PCI) if ground emergency medical services (EMS) initially transport the patient to a non-PCI center. This investigation models potential time savings of ground EMS requests for helicopter EMS (HEMS) transport of a STEMI patient directly to a PCI center, rather than usual transport to a local hospital with subsequent transfer. Methods: Data from a multicenter retrospective chart review of STEMI patients transferred for primary PCI by a single HEMS agency over 12 months were used to model medical contact to balloon times (MCTB) for two scenarios: a direct-to-scene HEMS response and hospital rendezvous after ground EMS initiation of transfer. Results: Actual MCTB median time for 36 hospital-initiated transfers was 160 minutes (range = 116 to 321 minutes). Scene response MCTB median time was estimated as 112 minutes (range = 69 to 187 minutes). The difference in medians was 48 minutes (95% confidence interval [CI] = 33 to 62 minutes). Hospital rendezvous MCTB median time was estimated as 113 minutes (range = 74 to 187 minutes). The difference in medians was 47 minutes (95% CI = 32 to 62 minutes). No patient had an actual MCTB time of less than 90 minutes; in the scene response and hospital rendezvous scenarios, 2 of 36 (6%) and 3 of 36 (8%), respectively, would have had MCTB times under 90 minutes. Conclusions: In this setting, ground EMS initiation of HEMS transfers for STEMI patients has the potential to reduce MCTB time, but most patients will still not achieve MCTB time of less than 90 minutes.

ACADEMIC EMERGENCY MEDICINE 2011; 18:613–618 © 2011 by the Society for Academic Emergency Medicine Abstract Objectives: Risk stratification of patients with potential acute coronary syndrome (ACS) is difficult. Patients with prior revascularization are considered higher risk, but they can also have symptoms from noncardiac causes. This study evaluated whether the presenting clinical characteristics were predictive of an increased risk of 30-day cardiovascular events in patients with prior revascularization presenting to the emergency department (ED) with symptoms of potential ACS. Methods: This was a secondary analysis of the DISPO-ACS study, a 2000-patient, four-site, randomized controlled trial of patients presenting with potential ACS. Process outcomes were evaluated using point-of-care cardiac markers compared to standard laboratory-based markers. Data included demographics, history, presenting symptoms, laboratory and electrocardiogram (ECG) results, hospital course, and 30-day cardiovascular events (death, acute myocardial infarction [AMI], revascularization). The association between presenting characteristics and 30-day cardiovascular events was assessed using univariable analysis and logistic regression; odds ratios (ORs) with 95% confidence intervals (CIs) are given. Results: Of 2,000 patients enrolled, 611 had prior revascularization (538 percutaneous coronary intervention [PCI], 232 coronary artery bypass graft [CABG], 159 both). The mean (±SD) age was 66 (±14) years, 44% were female, and 22% were black. By 30 days, 101 patients (17%) had cardiovascular events (81 during the index visit, 20 during follow-up). There were four deaths, 28 AMIs, and 67 revascularizations within 30 days; 20 patients had multiple endpoints. Being male (OR = 1.67, 95% CI = 1.07 to 2.62) or nonblack (OR = 1.95, 95% CI = 1.07 to 3.56) or having a family history of coronary artery disease (CAD; OR = 2.09, 95% CI = 1.32 to 3.3), elevated lipids (OR = 1.71, 95% CI = 1.04 to 2.82), prior AMI (OR = 1.79, 95% CI = 1.16 to 2.76), abnormal ECG on arrival (OR = 2.1, 95% CI = 1.33 to 3.34), and a positive initial troponin (OR = 14.7, 95% CI = 6.8 to 32.2) were predictive of cardiovascular events. The multivariable model found family history of CAD (OR = 2.06, 95% CI = 1.26 to 3.36), abnormal initial ECG (OR = 1.89, 95% CI = 1.16 to 3.09), and positive initial troponin (OR = 13.3, 95% CI = 5.9 to 29.6) remained predictive of 30-day cardiovascular events. Conclusions: In patients with prior revascularization, the initial ECG and early cardiac marker elevations, but not clinical presentation, predict odds of 30-day death, AMI, or revascularization.

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%, P trend = .01) and among the elderly (65.6%-52.1%, P trend P trend P trend = .02), but declines among women (14.4%-11.5%, P trend = .08) and the elderly (17.1%-11.0%, P trend = .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.

With a prevalence of 5 800 000 (≈2% of the entire populace) in 2009 and an estimated yearly incidence of 550 000, the burden of heart failure (HF) in the United States is tremendous.1 Although HF is largely a condition defined by chronic debility, virtually all patients experience, at some point, acute symptoms that trigger a visit to the emergency department (ED). These symptoms may vary in severity but, for the most part, they necessitate early intervention, often with intravenous medication and, less frequently, respiratory support. As shown by combined data from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS), this is a common occurrence; there are nearly 658 000 annual ED encounters primarily for acute HF in the United States—a figure that represents almost 20% of the total HF-specific ambulatory care delivered each year.2 It is noteworthy that few settings other than the ED can offer open access to treatment or provide the level and intensity of care required to effectively manage the acute phase of decompensation, also referred to as episodes of acute heart failure syndromes (AHFS). Nearly 80% of those treated for AHFS in the ED are ultimately admitted to the hospital and, accordingly, the ED serves as the principal portal of entry for hospitalized AHFS patients.34 The ED therefore plays a unique role in the continuum of AHFS treatment, functioning for most patients as the initial point of definitive healthcare contact, the location where primary stabilization is achieved, and the site where disposition decisions are generally made.4 Whereas the ED is a pivotal place for the vast majority of hospitalized patients with acute HF, the evidence base on which this foundation of acute care is built is astonishingly thin. The purpose of this …

TdP is an uncommon but potentially fatal arrhythmia that can be caused by drugs that cause selective prolongation of action potential durations in certain layers of the ventricular myocardium, which creates dispersion of repolarization and a long, distorted QT-U interval on the ECG. A summary of key points to remember is provided in Table 3. Table 3 Summary of Key Points For patients who receive QT-prolonging drugs in hospital units with continuous ECG monitoring, TdP should be avoidable if there is an awareness of individual risk factors and the ECG signs of drug-induced LQTS. Particularly important are the ECG risk factors for TdP, including marked QTc prolongation to >500 ms (with the exception of amiodarone- or verapamil-induced QT prolongation), marked QT-U prolongation and distortion after a pause, onset of ventricular ectopy and couplets, macroscopic T-wave alternans, or episodes of polymorphic ventricular tachycardia that are initiated with a short-long-short R-R cycle sequence (typically, PVC– compensatory pause–PVC). Recognition of these ECG harbingers of TdP allows for treatment with intravenous magnesium, removal of the offending agent, and correction of electrolyte abnormalities and other exacerbating factors, including the prevention of bradycardia and long pauses with temporary pacing if necessary.

Objective We compared the performance characteristics of the 12-lead electrocardiography (ECG) with body surface mapping (BSM) in patients presenting for evaluation of symptoms suggestive of acute coronary syndromes. Methods The diagnostic test characteristics (sensitivity, specificity, likelihood ratios, and predictive values) for 12-lead ECG and BSM were computed using 3 different criterion standards. Results Of the 150 patients enrolled, 19 were positive for acute coronary syndromes using the criterion standard of cardiac troponin T >0.1 ng/mL, percutaneous coronary intervention, more than 70% stenosis, abnormal noninvasive testing, and coronary artery bypass graft. Changes not known to be old on ECG and BSM had sensitivities of 10.5 (95% confidence interval [CI 95 ], 1.8-34.5) and 15.8 (CI 95 , 4.2-40.5), and specificities of 90.1 (CI 95 , 83.3-94.4) and 86.3 (CI 95 , 78.9-91.4), respectively. Conclusion In this emergency department population, both the BSM and the 12-lead ECG exhibited similar test characteristics.

Background Acute treatment is associated with improved in-hospital outcomes for patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS). Hypothesis Patients who receive appropriate acute treatment are more likely to receive guideline-recommended therapy at hospital discharge. Methods Use of aspirin (ASA), β-blockers, and clopidogrel was evaluated in the first 24 hours and upon hospital discharge according to the 2002 American College of Cardiology/American Heart Association (ACC AHA) guidelines for NSTE ACS. We compared the relationship between 3 groups: (1) ASA therapy given in the emergency department (ED); (2) ASA therapy not given in the ED, but within the first 24 hours; and (3) no acute ASA treatment. The ASA data set includes 10, 468 high risk patients with positive cardiac biomarkers or ischemic ST-segment changes on ECG from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) Quality Improvement Initiative. β-Blocker therapy was evaluated in 11, 838 and clopidogrel treatment in 17, 513 patients presenting to over 345 US hospitals. Results Patients who received acute ASA in the ED, ASA in the first 24 hours but not in the ED, and patients who did not receive ASA therapy within 24 hours had discharge ASA treatment rates of 91.8%, 91.4%, and 55.6%, respectively (P < 0.0001). Patients eligible for β-blocker and clopidogrel therapy had discharge β-blocker treatment rates of 91.1%, 92.4%, and 46.6% (P < 0.0001), and discharge clopidogrel treatment rates of 86.6%, 92.4%, and 38.5% (P < 0.0001), respectively. Conclusions Acute treatment for NSTE ACS in-hospital is associated with appropriate treatment on hospital discharge. This link between early treatment and discharge therapy may lead to new approaches ensuring the delivery of high-quality, guideline-based care for patients with NSTE ACS. Copyright © 2009 Wiley Periodicals, Inc.

Background— The risks of late stent thrombosis with drug-eluting stents (DES) were intensely debated after the presentation of a number of studies highlighting this issue in September 2006. We evaluated trends in the use of DES for patients with non–ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) from 2006 to 2008. Methods and Results— Temporal patterns of DES use were examined among non–ST-elevation myocardial infarction patients in the Can Rapid risk stratification of Unstable angina patients Supress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE; January 2006 to December 2006) and Acute Coronary Treatment and Intervention Outcomes Network–Get With The Guidelines (ACTION–GWTG; January 2007 to June 2008) registries to determine how practice patterns changed for patients with acute myocardial infarction undergoing PCI. Among the 54 662 patients analyzed, the percentage of patients undergoing PCI by quarter varied from 54% to 58% during the analysis time period. More than 90% of patients undergoing PCI received a DES in the first 3 quarters of 2006 before the public debate about the risks of DES began. Thereafter, the use of DES for PCI patients declined during the fourth quarter of 2006 through the first quarter of 2007 (82% to 67%), gradually declined during quarters 2 to 4 of 2007 (63% to 63% to 59%) but then slightly increased from the first to second quarter of 2008 (58% to 60%). Hospital characteristics did not seem to correlate with temporal changes in DES use, but by the last 2 quarters of the study period, patient characteristics such as white race, hypertension, diabetes mellitus, and private or managed care insurance were more common among patients who received a DES compared with the beginning 2 quarters of the study period. Conclusions— These findings highlight how rapidly treatment decisions in contemporary practice can be affected by public debate related to scientific presentations and publications.

Objectives: The value of unstructured physician estimate of risk for disease processes, other than acute coronary syndrome (ACS), has been demonstrated. The authors sought to evaluate the predictive value of unstructured physician estimate of risk for ACS in emergency department (ED) patients without obvious initial evidence of a cardiac event. Methods: This was a post hoc secondary analysis of the Internet Tracking Registry for Acute Coronary Syndromes (i*trACS), a prospectively collected multicenter data registry of patients over the age of 18 years presenting to the ED with symptoms of ACS between 1999 and 2001. In this registry, following patient history, physical exam, and electrocardiogram (ECG), the unstructured treating physician estimate of risk was recorded. A 30-day follow-up and a medical record review were used to determine rates of adverse cardiac events, death, myocardial infarction (MI), or revascularization procedure. The analysis included all patients with nondiagnostic ECG changes, normal initial biomarkers, and a non-MI initial impression from the registry and excluded those without complete data or who were lost to follow-up. Data were stratified by unstructured physician risk estimate: noncardiac, low risk, high risk, or unstable angina. Results: Of 15,608 unique patients in the registry, 10,145 met inclusion ⁄exclusion criteria. Patients were defined as having unstable angina in 6.0% of cases; high risk, 23.5% of cases; low risk, 44.2%; and noncardiac, 26.3% of cases. Adverse cardiac event rates had an inverse relationship, decreasing from 22.0% (95% confidence interval [CI] = 18.8% to 25.6%) for unstable angina, 10.2% (95% CI = 9.0% to 11.5%) for those stratified as high risk, 2.2% (95% CI = 1.8% to 2.6%) for low risk, and to 1.8% (95% CI = 1.4% to 2.4%) for noncardiac. The relative risk (RR) of an adverse cardiac event for those with an initial label of unstable angina compared to those with a low-risk designation was 10.2 (95% CI = 8.0 to 13.0). The RR of an event for those with a high-risk initial impression compared to those with a low-risk initial impression was 4.7 (95% CI = 3.8 to 5.9). The risk of an event among those with a low-risk initial impression was the same as for those with a noncardiac initial impression (RR = 0.83, 95% CI = 0.6 to 1.2). Conclusions: In ED patients without obvious initial evidence of a cardiac event, unstructured emergency physician (EP) estimate of risk correlates with adverse cardiac outcomes. ACADEMIC EMERGENCY MEDICINE 2009; 16:740‐748 a 2009 by the Society for Academic Emergency

Background The long-term benefits of coronary revascularization are proportional to the severity of underlying coronary artery disease (CAD). We sought to identify patients with a greater probability of severe CAD to target those who could receive the greatest benefit from revascularization. Methods We used multivariable logistic generalized estimating equations modeling to identify clinical factors associated with severe CAD in 83,490 patients, without prior bypass surgery, who underwent coronary angiography after presenting with non–ST-segment elevation acute coronary syndromes enrolled in CRUSADE. We then compared actual patterns of cardiac catheterization use relative to patients' probability of severe CAD in those who underwent catheterization and those who did not. Results Independent factors associated with severe CAD included older age, male sex, diabetes, no prior percutaneous coronary intervention, signs or history of heart failure, prior myocardial infarction, ST-segment depression, and family history of CAD. Cardiac catheterization rates were inversely related to the probability of severe CAD as estimated by the model. Conclusions There is a misalignment in the use of cardiac catheterization in patients with non–ST-segment elevation acute coronary syndromes relative to their predicted probability of severe CAD. The use of catheterization appears to target patients who would derive less benefit from revascularization. Further quality improvement efforts should promote appropriate use of cardiac catheterization procedures among patients with the greatest potential benefit.

Study objective Since 2003, the Society of Chest Pain Centers (SCPC) has provided hospital accreditation for acute coronary syndrome care processes. Our objective is to evaluate the association between SCPC accreditation and adherence to the American College of Cardiology/American Heart Association (ACC/AHA) evidence-based guidelines for non–ST-segment elevation myocardial infarction (NSTEMI). The secondary objective is to describe the clinical outcomes and the association with accreditation. Methods We conducted a secondary analysis of data from patients with NSTEMI enrolled in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines (CRUSADE) quality improvement initiative in 2005. The analysis explored differences between SCPC-accredited and nonaccredited hospitals in evidence-based therapy given within the first 24 hours (including aspirin, β-blocker, glycoprotein IIb/IIIa inhibitors, heparin, and ECG within 10 minutes). Results Of 33,238 patients treated at 21 accredited hospitals and 323 nonaccredited hospitals, those at SCPC-accredited centers (n=3,059) were more likely to receive aspirin (98.1% versus 95.8%; odds ratio [OR] 1.73; 95% confidence interval [CI] 1.06 to 2.83) and β-blockers (93.4% versus 90.6%; OR 1.68; 95% CI 1.04 to 2.70) within 24 hours than patients at non-SCPC-accredited centers (n=30,179). No difference was observed in obtaining a timely ECG (40.4% versus 35.2%; OR 1.28; 95% CI 0.98 to 1.67), administering a glycoprotein IIb/IIIa inhibitor (OR 1.30; 95% CI 0.93 to 1.80), or administering heparin (OR 1.12; 95% CI 0.74 to 1.70). Also, there was no significant difference in risk-adjusted mortality for patients treated at SCPC hospitals versus nonaccredited hospitals (3.4% versus 3.5%; adjusted OR 1.17; 95% CI 0.88 to 1.55). Conclusion SCPC-accredited hospitals had higher NSTEMI ACC/AHA evidence-based guideline adherence in the first 24 hours of care on 2 of the 5 measures. No difference in outcomes was observed. Further studies are needed to better understand the association between SCPC accreditation and improved care for patients with acute coronary syndrome.

To evaluate how enoxaparin is dosed in contemporary clinical practice as a function of patients' total body weight (TBW) and body mass index (BMI), and to determine any association between dose and major bleeding.Retrospective cohort study.The Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology-American Heart Association Guidelines (CRUSADE) national quality improvement initiative database.A total of 19,061 patients enrolled in the CRUSADE initiative between January 1, 2004, and March 31, 2006, who received enoxaparin for the initial treatment of non-ST-segment elevation acute coronary syndromes.Demographic and clinical data, enoxaparin doses, and frequency of major bleeding unrelated to coronary artery bypass graft (CABG) surgery were compared among patient groups stratified by TBW(or = 100, 101-120, 121-150, and150 kg). Adjusted odds ratios (OR) of major bleeding unrelated to CABG surgery were calculated with each dose increase of 0.25 mg/kg stratified by BMI (18.5, 18.5-24.9, 25.0-29.9, andor = 30 kg/m(2)), as well as for patients receiving a reduced dose (0.95 mg/kg) compared with those receiving a recommended dose (0.95-1.05 mg/kg), stratified by TBW. An inverse association was noted between enoxaparin dose and patient weight. Median initial doses were 1 mg/kg in those weighing 100 kg or less, 0.96 mg/kg in those 101-120 kg, 0.92 mg/kg in those 121-150 kg, and 0.65 mg/kg in those weighing more than 150 kg (p0.0001 foror = 100 kg vs150 kg). Up to 80% of patients weighing more than 150 kg received an initial enoxaparin dose below the recommended dose. In contrast to patients with normal body weight, those weighing more than 150 kg who received a recommended dose of enoxaparin had a higher bleeding risk relative to those who received a lower dose (adjusted OR 2.42, 95% confidence interval 0.70-8.37).Clinicians tend to use reduced weight-based doses of enoxaparin in overweight and obese patients. Although data are limited, use of the recommended enoxaparin dose of 1 mg/kg is associated with a higher bleeding risk in those weighing more than 150 kg. Thus, further study of enoxaparin dosing in very obese patients with non-ST-segment elevation acute coronary syndromes is warranted.

Background— Prior studies examining thrombocytopenia among patients with acute coronary syndromes (ACS) evaluated highly selected patients in a clinical trial setting using varying definitions of thrombocytopenia. The incidence, severity, and prognostic significance of acquired thrombocytopenia during ACS in community practice have not been well defined. Methods and Results— We examined 36 182 patients with non–ST-segment elevation ACS enrolled at 379 US hospitals participating in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) quality improvement initiative between June 2004 and December 2006. Patients with baseline platelet counts 9 /L were excluded. Overall, 4697 patients (13%) developed new thrombocytopenia, defined as nadir platelet count 9 /L (referenced lower limit of normal), during their ACS hospitalization. Risks of in-hospital mortality and bleeding correlated directly with severity of thrombocytopenia; even mild thrombocytopenia (nadir 100 to 149×10 9 /L) was associated with increased risks of mortality (adjusted odds ratio [OR], 2.01; 95% CI, 1.69 to 2.38) and bleeding (adjusted OR, 3.76; 95% CI, 3.43 to 4.12). Each 10% drop in platelet count was associated with increased mortality and bleeding risks (adjusted ORs, 1.39 [95% CI, 1.33 to 1.46] and 1.89 [95% CI, 1.83 to 1.95], respectively). A ≥50% drop in platelet count was associated with higher risk of adverse outcomes regardless of the nadir count. A novel combined definition of acquired thrombocytopenia—nadir 9 /L or platelet count drop ≥50%—identifies a population of ACS patients at higher risk of mortality and major bleeding (adjusted ORs, 2.58 [95% CI, 2.23 to 2.98] and 4.32 [95% CI, 3.97 to 4.70], respectively). Conclusions— Thrombocytopenia, a common complication of ACS, is associated with increased mortality and bleeding risks. Even mild thrombocytopenia or a platelet count drop ≥50% in the setting of normal nadir values is clinically significant. Application of a combined definition for thrombocytopenia using both absolute and relative thresholds permits increased sensitivity for patients at high risk of adverse outcomes.

Objectives This study sought to determine the association of pre-hospital electrocardiograms (ECGs) and the timing of reperfusion therapy for patients with ST-segment elevation myocardial infarction (STEMI). Background Pre-hospital ECGs have been recommended in the management of patients with chest pain transported by emergency medical services (EMS). Methods We evaluated patients with STEMI from the NCDR (National Cardiovascular Data Registry) ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were transported by EMS from January 1, 2007, through December 31, 2007. Patients were stratified by the use of pre-hospital ECGs, and timing of reperfusion therapy was compared between the 2 groups. Results A total of 7,098 of 12,097 patients (58.7%) utilized EMS, and 1,941 of these 7,098 EMS transport patients (27.4%) received a pre-hospital ECG. Among the EMS transport population, primary percutaneous coronary intervention was performed in 92.1% of patients with a pre-hospital ECG versus 86.3% with an in-hospital ECG, whereas fibrinolytic therapy was used in 4.6% versus 4.2% of patients. Median door-to-needle times for patients receiving fibrinolytic therapy (19 min vs. 29 min, p = 0.003) and median door-to-balloon times for patients undergoing primary percutaneous coronary intervention (61 min vs. 75 min, p Conclusions Only one-quarter of these patients transported by EMS receive a pre-hospital ECG. The use of a pre-hospital ECG was associated with a greater use of reperfusion therapy, faster reperfusion times, and a suggested trend for a lower risk of mortality.

Although current guidelines recommend early initiation of clopidogrel in patients with non-ST-segment elevation myocardial infarction (NSTEMI), the degree to which it has been adopted in clinical practice remains unclear. We sought to determine patterns of early (24 hours of arrival) clopidogrel use and its association with clinical outcomes in patients with NSTEMI not undergoing early percutaneous intervention (PCI).Using data from the CRUSADE initiative, after the exclusion of patients who underwent PCI within 24 hours of arrival, we studied trends in early clopidogrel use among 93,045 patients with NSTEMI. Multivariable logistic regression models were used to determine the association between early clopidogrel treatment and inhospital outcomes.A total of 38.6% of the NSTEMI patients not undergoing PCI within 24 hours of arrival received early clopidogrel. Adjusted inhospital mortality rate was lower in the early clopidogrel group compared to the group that did not receive it on admission (odds ratio 0.68, 95% CI 0.61-0.77). The rate of major bleeding in patients not undergoing coronary artery bypass surgery was similar among the groups treated with and without early clopidogrel (9.5% vs 9.5%, P = .90).Until recently, up to 50% of NSTEMI patients in contemporary practice in the United States not undergoing PCI within 24 hours of arrival in the United States are not treated according to guideline recommendations. Among a high-risk NSTEMI population not undergoing PCI within 24 hours of arrival, the nonrandomized short-term use of clopidogrel is associated with a lower risk of inhospital mortality without an increased risk of major bleeding.

Background Although the use of heparin with fibrinolytics is associated with more rapid ST-segment resolution and increased infarct-related artery patency among patients with ST-segment elevation myocardial infarction (STEMI), its associated increase in bleeding risk is well documented and might be augmented by excess heparin dosing. Methods We sought to characterize the incidence and associated bleeding risk of excess heparin dosing among patients with STEMI treated with fibrinolysis who were enrolled in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines initiative. Excess dosing was defined as a bolus more than 60 U/kg or an infusion more than 12 U/kg/h per American College of Cardiology/American Heart Association guidelines and was further stratified into major and mild excess (major defined as a bolus>70 U/kg or infusion >15 U/kg/h). Results Among 964 fibrinolytic-treated patients with STEMI, 758 (79%) received adjunctive unfractionated heparin therapy. Of these, 368 patients (49%) received excess dosing of unfractionated heparin and 137 patients (18%) received major excess heparin dosing. Factors significantly associated with excess dosing included low body weight and female sex. Patients who received major excess dosing had higher unadjusted rates of major bleeding (19.2% vs 12.4%, P =.004) and transfusion (13.5% vs 4.7%, P =.0002) than patients without excess dosing. After adjustment, a trend persisted for the association with higher transfusion risk (odds ratio 1.39 [0.61-3.14]). Conclusion Approximately half of fibrinolytic-treated patients with STEMI in contemporary practice received an excess dose of unfractionated heparin. Careful attention to dosing is needed to limit the compounded bleeding risk when heparin is added to fibrinolytic therapy.

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.

Background Practice guidelines for non–ST-segment elevation acute coronary syndromes (NSTE ACS) recommend early invasive management (cardiac catheterization and revascularization within 48 hours of hospital presentation) for high-risk patients, but interhospital transfer is necessary to provide rapid access to revascularization procedures for patients who present to community hospitals without revascularization capabilities. Methods We analyzed patterns and factors associated with interhospital transfer among 19,238 patients with NSTE ACS (positive cardiac markers and/or ischemic ST-segment changes) from 124 community hospitals without revascularization capabilities in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines quality improvement initiative from January 2001 through June 2004. Results Less than half of the patients (46.3%) admitted to community hospitals were transferred to tertiary hospitals, and fewer (20%) were transferred early (within 48 hours of presentation). Early transfer rates increased by 16% over 10 quarters in patients with a predicted low or moderate risk of inhospital mortality, compared with 5% in high-risk patients. By the last quarter of the analysis, 41.4% of low-risk patients were transferred early versus 12.5% of high-risk patients. Factors significantly associated with early transfer included younger age, lack of prior heart failure, cardiology inpatient care, and ischemic ST-segment electrocardiographic changes. Among patients who were not transferred, 29% had no further risk stratification performed with stress testing, ejection fraction measurement, or diagnostic cardiac catheterization (at hospitals with catheterization laboratories). Conclusions Most patients with NSTE ACS presenting to community hospitals without revascularization capabilities are not rapidly transferred to tertiary hospitals, and lower-risk patients appear to be preferentially transferred early. Further investigation is needed to determine if improved risk-based triage at community hospitals can optimize transfer decision making for high-risk patients with NSTE ACS.

The goals of the present article are to provide a critical review of the literature on cocaine-associated chest pain and myocardial infarction (MI) and to give guidance for diagnostic and therapeutic interventions. Classification of recommendations and levels of evidence are expressed in the American College of Cardiology/American Heart Association (ACC/AHA) format as follows: The Writing Committee conducted a comprehensive search of the medical literature concerning cocaine-associated chest pain and MI. The literature search included English-language publications on humans and animals from 1960 to 2007. In addition to broad-based searching concerning cocaine, specific targeted searches were performed on cocaine and the following topics: MI, chest pain, emergency department (ED), aspirin, nitroglycerin, calcium channel blocker, benzodiazepine, thrombolytics, phentolamine, heparin, primary angioplasty, ECG, and stress testing. Literature citations were generally limited to published articles listed in Index Medicus. The article was reviewed by 4 outside reviewers nominated by the AHA. Cocaine is the second most commonly used illicit drug in the United States, with only marijuana …

Aims To examine treatment patterns and outcomes of patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) receiving long-term warfarin anticoagulation. Methods and results We examined acute medication and invasive cardiac procedure use and in-hospital outcomes among 101 078 patients with NSTE ACS included in the CRUSADE registry. On admission, 7201 patients (7%) were on home warfarin therapy. Compared with non-anticoagulated patients, these patients were older and had more comorbidities, but were less likely to receive acute antiplatelet and antithrombin medications. Patients on warfarin were also less likely to undergo coronary angiography (adjusted OR 0.77, 95% CI 0.70–0.86) and percutaneous coronary intervention (adjusted OR 0.80, 95% CI 0.75–0.86), and had longer waiting times for these procedures when performed. Although patients on warfarin had higher rates of death and major bleeding compared with non-anticoagulated patients, these differences were no longer significant after multivariable adjustment [ORs 0.90 (95% CI 0.80–1.02) and 1.02 (95% CI 0.93–1.11)]. Among patients on warfarin, however, early use of antiplatelet medications was associated with increased transfusion risk. Conclusion Despite higher-risk characteristics, warfarin-anticoagulated patients are often more conservatively managed, as early use of antithrombotic therapies may be associated with increased bleeding. Further investigation is needed to determine the optimal choice of therapies for this population.

Objectives Our purpose was to compare formulae for estimating glomerular filtration rate (GFR) in non–ST-segment elevation acute coronary syndromes (NSTE ACS) patients. Background Assessment of GFR is important for antithrombotic dose adjustment in NSTE ACS patients. Methods We assessed estimated glomerular filtration rate (eGFR) with Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD) formulae in 46,942 NSTE ACS patients from 408 CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines) hospitals. Formula agreement was shown continuously and by chronic kidney disease (CKD) stages. We determined in-hospital outcomes and the association between antithrombotic dose adjustment and bleeding for moderate CKD as determined by each formula. Results The median (interquartile range [IQR]) eGFR was 53.2 ml/min (34.7, 75.1 ml/min) by C-G and 65.8 ml/min (47.6, 83.5 ml/min) by MDRD. The mean eGFR was higher with MDRD (∼9.1 ml/min), but this difference was greater in age, weight, and gender subgroups. Chronic kidney disease classification differed in 20% of the population and altered when antithrombotic dose adjustment was required by C-G versus MDRD (eptifibatide: 45.7% vs. 27.3%; enoxaparin: 19.0% vs. 9.6%). Conclusions Important CKD disagreements occur in ∼20% of acute coronary syndrome patients, affecting dosing adjustments in those already susceptible to bleeding. Dosing based on C-G formula is preferable, particularly in the small, female, or elderly patient.

BACKGROUND: The prognostic value of cardiac troponins (cTn) in patients with non‐ST‐segment elevation acute coronary syndromes (NSTE ACS) and chronic kidney disease (CKD) is debated. HYPOTHESIS: We tested the performance of cTnI and cTnT for risk stratification in patients with CKD and evaluated the prognostic significance of cTnI and cTnT elevations by their magnitude across the range of CKD severity. METHODS: We examined correlations among cTn elevation, CKD, and in‐hospital mortality in 31,586 high‐risk patients with NSTE ACS included in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines initiative (CRUSADE). Cardiac tropinins I and T levels were categorized as ratios of each site's upper limit of normal (ULN) for myocardial necrosis: normal (cTn ratio ⩽1 × ULN), mild (cTn ratio > 1–3 × ULN), and major (cTn ratio > 3 × ULN) elevation. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease equation. Stages of CKD were categorized as normal to mild (eGFR > 60 mL/min), moderate (eGFR 30–60 mL/min), or severe (eGFR < 30 mL/min). RESULTS: Mortality increased more steeply across CKD stages (2.0%–12.9%) than across cTn ratio categories (2.7%–5.4%). In normal or mild CKD, mortality was low regardless of cTn elevations. In moderate CKD, mortality increased incrementally with cTnI (3.3% versus 5.4% versus 7.4%) and cTnT (3.7% versus 5.3% versus 7.3%) elevation. Among severe CKD patients, only major cTn elevations further distinguished risk (cTnI: 10.1% versus 9.7% versus 14.6%; cTnT: 7.0% versus 5.7% versus 14.0%). CONCLUSIONS: In patients with CKD, cTnI and cTnT perform equally in differentiating short‐term prognosis following NSTE ACS; however, the prognostic impact of cTn is dependent upon the degree of CKD severity. Copyright © 2008 Wiley Periodicals, Inc.

Hospitals are under increasing pressure to improve their quality of care. However, a key question remains: how can hospitals best design and implement successful quality improvement (QI) programs? Hospitals currently employ a variety of QI initiatives but have little empirical evidence on which to base their quality efforts.We designed and applied a hospital cross-sectional survey to 212 hospitals participating in CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines), a voluntary QI initiative of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). We factor analysis and an ordinary least squares regression model to determine the key hospital factors most associated with unexpected improvements in institutional QI in the treatment of NSTE ACS.From 2002 to 2004, the following factors had a significant association with unexpected increases in the 2004 QI in NSTE ACS treatment: the use of CRUSADE QI tools, clinical commitment to quality by a cardiology coadvocate, institutional financial commitment to quality, and barriers to QI related to resource availability and cultural resistance to change (all P.10). Of these factors, optimal use of CRUSADE QI tools was associated with the highest absolute improvement in process adherence score relative to other factors.We identified several institutional factors associated with improved quality of care in the treatment of high-risk NSTE ACS. We hope that this evidence-based framework will help guide the development and implementation of future QI programs in order to improve the institutional quality of care for NSTE ACS.

Elevated B-type natriuretic peptide (BNP) levels are associated with increased risk for mortality in patients with non–ST-segment-elevation (NSTE) acute coronary syndromes (ACS). However, the optimal use of BNP measurement for the risk stratification of these patients remains unclear. This study was conducted to analyze patterns of, and factors associated with, BNP measurement in patients with NSTE ACS from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines? (CRUSADE) quality improvement initiative from 2003 through 2006. The association of degree of BNP elevation with in-hospital mortality in patients with measured BNP levels across risk categories was also analyzed. A total of 16,323 of 77,071 patients (21.2%) from 486 hospitals had BNP levels measured; the rate of BNP measurement by quarter increased from 5.1% to 27.7% during this analysis. Factors most strongly associated with BNP measurement included signs of heart failure on presentation, older age, previous heart failure, faster presenting heart rate, and higher body mass index. The adjusted risk for mortality was higher in patients who had BNP levels measured than in those who did not (adjusted odds ratio 1.14, 95% confidence interval 1.03 to 1.25). In patients with BNP levels measured, a higher degree of BNP elevation was associated with incrementally higher in-hospital mortality rates across risk categories. BNP levels were measured in approximately 1/5 of patients with NSTE ACS in contemporary practice. BNP was most frequently measured in patients presenting with high-risk characteristics, but the association of incremental increases in BNP levels with higher mortality rates was similar across risk categories. In conclusion, more widespread measurement of BNP levels for risk stratification of patients with NSTE ACS may be warranted.

Myocardial infarction is a major cause of death and disability worldwide. Coronary atherosclerosis is a chronic disease with stable and unstable periods. During unstable periods with activated inflammation in the vascular wall, patients may develop a myocardial infarction. Myocardial infarction may be a minor event in a lifelong chronic disease, it may even go undetected, but it may also be a major catastrophic event leading to sudden death or severe hemodynamic deterioration. A myocardial infarction may be the first manifestation of coronary artery disease, or it may occur, repeatedly, in patients with established disease. Information on myocardial infarction attack rates can provide useful data regarding the burden of coronary artery disease within and across populations, especially if standardized data are collected in a manner that demonstrates the distinction between incident and recurrent events. From the epidemiological point of view, the incidence of myocardial infarction in a population can be used as a proxy for the prevalence of coronary artery disease in that population. Furthermore, the term myocardial infarction has major psychological and legal implications for the individual and society. It is an indicator of one of the leading health problems in the world, and it is an outcome measure in clinical trials and observational studies. With these perspectives, myocardial infarction may be defined from a number of different clinical, electrocardiographic, biochemical, imaging, and pathological characteristics. In the past, a general consensus existed for the clinical syndrome designated as myocardial infarction. In studies of disease prevalence, the World Health Organization (WHO) defined myocardial infarction from symptoms, ECG abnormalities, and enzymes. However, the development of more sensitive and specific serological biomarkers and precise imaging techniques allows detection of ever smaller amounts of myocardial necrosis. Accordingly, current clinical practice, health care delivery systems, as well as epidemiology and clinical trials all require a …

We evaluate the association of emergency department (ED) length of stay with use of guideline-recommended therapies for acute treatments and clinical outcomes. Prolonged ED stays often reflect ED crowding or limited hospital capacity. We hypothesized that patients with non-ST-segment-elevation myocardial infarction who have ED stays of greater than 8 hours may have lower quality of care and worse outcomes.Using a secondary analysis of data from an observational registry (Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC/AHA Guidelines, CRUSADE), we compared rates of use of 5 individual acute (24 hours) guideline-recommended therapies in patients with non-ST-segment-elevation myocardial infarction according to ED length of stay. Patients were grouped by length of stay (short [4 hours], average [4 to 8 hours], or long [8 hours]). Multivariable analyses were used to determine independent association of ED length of stay with acute medications and inhospital outcomes (death and myocardial infarction).This analysis included 42,780 patients with non-ST-segment-elevation myocardial infarction. The median ED length of stay was 4.3 hours (25th to 75th percentile 2.9, 6.3); 15% of patients stayed longer than 8 hours. Patients who had long ED stays were more likely to be women and nonwhite and less likely to have health maintenance organization or private insurance. After adjustment, patients with long ED stays less often received guideline-recommended acute myocardial infarction therapies. Although risk-adjusted inhospital mortality rates were similar among groups, the rate of recurrent myocardial infarction increased among patients with long ED stays (odds ratio 1.23; 95% confidence interval 1.01 to 1.48) compared with those with average ED length of stay.For patients with non-ST-segment-elevation myocardial infarction, long ED stays were associated with decreased use of guideline-recommended therapies and a higher risk of recurrent myocardial infarction. However, there was no observed difference in mortality. Factors associated with prolonged ED length of stay should be evaluated to optimize treatments and outcomes of patients with non-ST-segment-elevation myocardial infarction.

Practice guidelines support an early invasive strategy in patients with non-ST segment elevation acute coronary syndromes, particularly in those at higher risk.To compare North American rates of invasive cardiac procedure use stratified by risk.Use of invasive cardiac procedures and other care patterns in patients with non-ST segment elevation acute coronary syndromes from the United States (US) Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) National Quality Improvement Initiative (n=88,097; 465 hospitals) and Canadian ACS Registries I (n=1270; 51 hospitals) and II (n=1473; 36 hospitals) were compared after dividing patients into different risk categories based on predicted risk of in-hospital mortality.While the overall use of invasive procedures was higher in the US, high-risk patients were least likely to undergo coronary angiography (41% versus 64% in Canada [P0.0001] and 53% versus 76% in the United States [P0.0001]) and percutaneous coronary intervention (14% versus 32% in Canada [P0.0001] and 28% versus 51% in the US [P0.0001]) compared with low-risk patients in both countries, and had longer median waiting times for these procedures (120 h versus 96 h in Canada [P0.0001] and 34 h versus 23 h in the US [P0.0001] for coronary angiography).The inverse relationship between risk level and the use of invasive cardiac procedures for patients in the US and Canada suggests that a risk stratification-guided approach for triaging patients to an early invasive management strategy is paradoxically used. This incongruous relationship holds true regardless of resource availability or overall rates of cardiac catheterization.

Objectives We sought to determine whether for-profit status influenced hospitals’ care or outcomes among non–ST-segment elevation myocardial infarction (NSTEMI) patients. Background While for-profit hospitals potentially have financial incentives to selectively care for younger, healthier patients, perform highly reimbursed procedures, reduce costs by limiting access to expensive medications, and encourage shorter in-patient length of stay, there are limited data available to investigate these issues objectively. Methods Using data from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines) Initiative, we investigated whether for-profit status influenced hospitals’ patient case mix, care, or outcomes among 145,357 patients with NSTEMI treated between January 1, 2001, and December 31, 2005, at 532 U.S. hospitals. Impact of for-profit status on care and outcomes was analyzed overall and after adjustment for clinical and facility factors using regression modeling. Results Patients (n = 11,658) treated at 58 for-profit hospitals were of similar age and gender, but were more likely to be nonwhite (black, Asian, Hispanic, and other) and have health maintenance organization/private insurance, diabetes mellitus, congestive heart failure, hypertension, and renal insufficiency compared with 133,699 patients treated at 474 nonprofit hospitals. For-profit hospitals were less likely to use discharge beta-blockers, but all other treatments were similar including the use of interventional procedures (cardiac catheterization and revascularization procedures) compared with nonprofit centers. In-hospital length of stay and mortality were also similar by hospital type. Conclusions We found no evidence that for-profit hospitals selectively treat less sick patients, provide less evidence-based care, limit in-hospital stays, or have patients with worse acute outcomes than nonprofit centers.

[Graphic][1] Myocardial infarction is a major cause of death and disability worldwide. Coronary atherosclerosis is a chronic disease with stable and unstable periods. During unstable periods with activated inflammation in the vascular wall, patients may develop a myocardial infarction. Myocardial infarction may be a minor event in a lifelong chronic disease, it may even go undetected, but it may also be a major catastrophic event leading to sudden death or severe haemodynamic deterioration. A myocardial infarction may be the first manifestation of coronary artery disease, or it may occur, repeatedly, in patients with established disease. Information on myocardial infarction attack rates can provide useful data regarding the burden of coronary artery disease within and across populations, especially if standardized data are collected in a manner that demonstrates the distinction between incident and recurrent events. From the epidemiological point of view, the incidence of myocardial infarction in a population can be used as a proxy for the prevalence of coronary artery disease in that population. Furthermore, the term myocardial infarction has major psychological and legal implications for the individual and society. It is an indicator of one of the leading health problems in the world, and it is an outcome measure in clinical trials and observational studies. With these perspectives, myocardial infarction may be defined from a number of different clinical, electrocardiographic, biochemical, imaging, and pathological characteristics. In the past, a general consensus existed for the clinical syndrome designated as myocardial infarction. In studies of disease prevalence, the World Health Organization (WHO) defined myocardial infarction from symptoms, ECG abnormalities, and enzymes. However, the development of more sensitive and specific serological biomarkers and precise imaging techniques allows detection of ever smaller amounts of myocardial necrosis. Accordingly, current clinical practice, health care delivery systems, as well as epidemiology and clinical trials all require a … [1]: /embed/inline-graphic-1.gif

ObjectivesTo describe the evaluation and outcomes of elder patients with suspected acute coronary syndromes (ACS) presenting to the emergency department (ED). MethodsThis was a post hoc analysis of the Internet Tracking Registry for Acute Coronary Syndromes (i∗trACS) registry, which had 17,713 ED visits for suspected ACS. First visits from the United States with nonmissing patient demographics, 12-lead electrocardiogram results, and clinical history were included in the analysis. Those who used cocaine or amphetamines or left the ED against medical advice were excluded. Elder was defined as age 75 years or older. ACS was defined by 30-day revascularization, Diagnosis-related Group codes, or death within 30 days with positive cardiac biomarkers at index hospitalization. Multivariable logistic regression analyses were performed to determine the association between being elder and 1) 30-day all-cause mortality, 2) ACS, 3) diagnostic tests ordered, and 4) disposition. Multivariable logistic regression was also performed to determine which clinical variables were associated with ACS in elder and nonelder patients. ResultsA total of 10,126 patients with suspected ACS presenting to the ED were analyzed. For patients presenting to the ED, being elder was independently associated with ACS and all-cause 30-day mortality, with adjusted odds ratios of 1.8 (95% confidence interval [CI] = 1.5 to 2.2) and 2.6 (95% CI = 1.6 to 4.3), respectively. Elder patients were more likely to be admitted to the hospital (adjusted odds ratio, 2.2; 95% CI = 1.8 to 2.6), but there were no differences in the rates of cardiac catheterization and noninvasive stress cardiac imaging. Different clinical variables were associated with ACS in elder and nonelder patients. Chest pain as chief complaint, typical chest pain, and previous history of coronary artery disease were significantly associated with ACS in nonelder patients but were not associated with ACS in elder patients. Male gender and left arm pain were associated with ACS in both elder and nonelder patients. ConclusionsElder patients who present to the ED with suspected ACS represent a population at high risk for ACS and 30-day mortality. Elders are more likely to be admitted to the hospital, but despite an increased risk for adverse events, they have similar odds of receiving a diagnostic test, such as stress cardiac imaging or cardiac catheterization, compared with nonelder patients. Different clinical variables are associated with ACS, and clinical prediction rules utilizing presenting symptoms should consider the effect modification of age.

Background— Age is an important determinant of outcomes for patients with acute coronary syndromes. However, community practice reveals a disproportionately lower use of cardiovascular medications and invasive treatment even among elderly patients who would stand to benefit. Limited trial data are available to guide care of older adults, which results in uncertainty about benefits and risks, particularly with newer medications or invasive treatments and in the setting of advanced age and complex health status. Methods and Results— Part II of this American Heart Association scientific statement summarizes evidence on presentation and treatment of ST-segment–elevation myocardial infarction in relation to age ( Conclusions— Few trials have adequately described treatment effects in older patients with ST-segment–elevation myocardial infarction. In the future, absolute and relative risks for efficacy and safety in age subgroups should be reported, and trials should make efforts to enroll the elderly in proportion to their prevalence among the treated population. Outcomes of particular relevance to the older adult, such as quality of life, physical function, and independence, should also be evaluated, and geriatric conditions unique to this age group, such as frailty and cognitive impairment, should be considered for their influence on care and outcomes. With these efforts, treatment risks can be minimized, and benefits can be placed within the health context of the elderly patient.

Background— Age is an important determinant of outcomes for patients with acute coronary syndromes (ACS); however, community practice reveals a disproportionately lower use of cardiovascular medications and invasive treatment even among elderly patients with ACS who would stand to benefit. Reasons include limited trial data to guide the care of older adults and uncertainty about benefits and risks, particularly with newer medications or invasive treatments and in the setting of advanced age or complex health status. Methods and Results— This 2-part American Heart Association scientific statement summarizes evidence on patient heterogeneity, clinical presentation, and treatment of non–ST-elevation ACS in relation to age ( Conclusions— Although a few recent trials have described treatment effects in older patients, others continue to exclude patients on the basis of age. Going forward, prospective trials should enroll elderly subjects proportionate to their prevalence among the treated population to define risk and benefit. Findings from age subgroup analyses should be reported in a consistent manner across trials, including absolute and relative risks for efficacy and safety. Outcomes of particular relevance to the elderly, such as quality of life, physical function, and independence, should also be considered. Creatinine clearance should be calculated for every elderly patient to enable appropriate dosing. In addition, physicians need an understanding of conditions unique to older patients (eg, frailty, cognitive impairment) that influence treatment goals and outcomes. With these efforts, treatment risks can be minimized, and benefits can be placed in the health context of the elderly patient with ACS.

Since the introduction of drug-eluting stents (DESs), patterns of revascularization strategies for patients with non-ST-segment elevation acute coronary syndromes have not been assessed. We studied 82,924 patients from the CRUSADE Initiative who presented with non-ST-segment elevation acute coronary syndromes and underwent coronary angiography at 365 United States hospitals that had capabilities for surgical (coronary artery bypass grafting [CABG]) and percutaneous (percutaneous coronary intervention [PCI]) revascularization from January 2002 to June 2005. Temporal trends in the use of PCI, CABG, and medical management without revascularization were analyzed with respect to the introduction of DESs. In total, 73,577 patients (89%) had50% stenosis inor =1 coronary artery, and there was a significant increase in the use of PCI (vs CABG or medical management without revascularization) during the study period (38.3% vs 52.5%). By quarter 2 of 2005, 80% of patients who underwent PCI received a DES. In total, 18,462 of 25,068 patients (73.6%) with 3-vessel disease (3VD) underwent revascularization and use of CABG decreased for these patients (48.9% to 39.9%, p0.001), whereas use of PCI increased (51.1% to 60.1%, p0.001). Factors significantly associated with use of PCI for patients with 3VD who underwent any revascularization included previous PCI, previous CABG, cardiology inpatient care, care at an academic hospital, renal insufficiency, and previous congestive heart failure. In conclusion, coinciding with the introduction of DESs, there has been a significant increase in the use of PCI and, in those patients with 3VD, a decrease in the use of CABG with a shift toward increasing use of PCI. Long-term implications of this shift remain uncertain, especially in patients with 3VD.

Previous studies of non-ST-segment elevation acute coronary syndromes (NSTE ACSs) complicated by heart failure (HF) have focused primarily on patients with left ventricular systolic dysfunction defined by an ejection fraction (EF)40%. Little is known about HF with preserved systolic function (EFor =40%) in the NSTE ACS population. We identified high-risk patients with NSTE ACS (ischemic electrocardiographic changes and/or positive cardiac markers) from the CRUSADE quality improvement initiative who had an EF recorded and who had information on HF status. Management and outcomes were analyzed and compared based on the presence or absence of HF and whether left ventricular EF wasor =40%. Of 94,558 patients with NSTE ACS, 21,561 (22.8%) presented with signs of HF, and most had HF with preserved systolic function (n = 11,860, 55%). Mortality rates were 10.7% for HF/systolic dysfunction, 5.8% for HF/preserved systolic function, 5.7% for no HF/systolic dysfunction, and 1.5% for no HF/preserved systolic function. Use of guideline-recommended medical therapies and interventions was frequently significantly lower in those with HF regardless of EF compared with those without HF, except for use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. In conclusion, NSTE ACS complicated by HF with preserved systolic function is common and associated with a 2.3-fold higher mortality compared with NSTE ACS without HF or systolic dysfunction. Guideline-recommended therapies and interventions are under-utilized in patients with NSTE ACS and HF, with and without preserved systolic function, compared with those without HF.

Objectives The goal of this work was to explore the treatment and outcomes of patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) age ≥90 years. Background The elderly are often excluded from clinical trials of NSTE-ACS and are underrepresented in clinical registries. Methods We used data from the CRUSADE registry to study 5,557 patients with NSTE-ACS age ≥90 years and compared their baseline characteristics, treatment patterns, and in-hospital outcomes with a cohort age 75 to 89 years (n = 46,270). Results Although both groups had much in common, compared with the younger elderly, the older elderly were less likely to be diabetic, smokers, or obese. Among patients without contraindications, the older elderly were less likely to receive glycoprotein IIb/IIIa inhibitors and statins during the first 24 h and were less likely to undergo cardiac catheterization within 48 h. The older elderly were more likely to die (12.0% vs. 7.8%) and experienced more frequent adverse events (26.8% vs. 21.3%) during the hospitalization—differences that persisted after adjustment for baseline patient and hospital characteristics. Increasing adherence to guideline-recommended therapies was associated with both increased bleeding and a graded reduction in risk-adjusted in-hospital mortality across both age groups. Conclusions In this large population of nonagenarians and centenarians with NSTE-ACS, increasing adherence to guideline-recommended therapies was associated with decreased mortality. These findings reinforce the importance of optimizing care patterns for even the oldest patients with NSTE-ACS, while examining novel approaches to reduce the risk of bleeding in this rapidly expanding patient population.

Background Dyslipidemia is not routinely evaluated in emergency department (ED) patients. We hypothesized that many ED patients would qualify for lipid therapy and that methods of follow-up for patients would not achieve adequate treatment goals. Methods We performed an observational study of ED patients with symptoms consistent with acute coronary syndrome (ACS). Lipid profiles and data about coronary heart disease risk factors were obtained. The National Institutes of Health/National Cholesterol Education Program guidelines were used to determine whether patients qualified for drug therapy. Six-week and 6-month follow-ups were performed. Results Three hundred ninety-four patients presenting to the ED with possible ACS were enrolled in the study; 47 patients were subsequently excluded. The remaining 347 included patients who were 63.7% African American and 53.6% female. Proportions of patients with low-density lipoprotein ≥130 and ≥160 were 30.8% and 10.1%, respectively. Fifty-seven (16.4%, 95% CI 12.9%-20.7%) qualified for immediate drug therapy. Of the 44 patients meeting treatment criteria for whom follow-up was obtained, only 1 (2.3%) had received lipid-lowering medications with outpatient referral within 6 weeks. At 6 months, 4 (9.5%) of 42 patients with follow-up had received lipid-lowering therapies. Conclusions Dyslipidemia meeting criteria for therapy is present in a significant proportion of ED patients. Most of these patients do not get appropriately treated on medical follow-up. Our study suggests that lipid screening and subsequent appropriate lipid-lowering therapy could be considered for ED patients with possible ACS.

We evaluated temporal trends in the use of early (

Background— Glycoprotein (GP) IIb/IIIa inhibitors are beneficial in patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS); their safe use in women, however, remains a concern. The contribution of dosing to the observed sex-related differences in bleeding is unknown. Methods and Results— We explored the relationship between patient sex, GP IIb/IIIa inhibitor use, dose, and bleeding in 32 601 patients with NSTE ACS across 400 CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) hospitals, of whom 18 436 were treated. GP IIb/IIIa inhibitor dose was defined as excessive if not reduced when creatinine clearance was P P P Conclusions— Women experience more bleeding than men whether or not they are treated with GP IIb/IIIa inhibitors; however, because of frequent excessive dosing in women, up to one fourth of this sex-related risk difference in bleeding is avoidable. Appropriate dosing will improve care of all patients with NSTE ACS, with a particular benefit for women.

We assessed the hypothesis that emergency department point-of-care (POC) testing for myoglobin and cardiac troponin T (cTnT) reduces the time to result with no reduction in diagnostic accuracy for acute coronary syndrome (ACS) compared with standard-of-care local laboratory (LL) tests for c

In the case of non-ST-segment elevation acute coronary syndromes (NSTE-ACSs), the acute use of certain antiplatelet agents is complicated by concerns about perioperative bleeding risks in patients requiring coronary artery bypass grafting (CABG) during the index hospitalization. As a result, clinicians often withhold potentially useful agents, such as clopidogrel, before determining patients' coronary anatomy. An accurate predictive model could allow for a better balance of this safety concern with the demonstrated benefits of agents such as clopidogrel. To create an accurate decision-making tool that would assess, at hospital presentation, the need for CABG in patients with NSTE-ACSs, we studied 61,974 high-risk patients with NSTE-ACS admitted to 311 CABG-capable hospitals participating in Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) from 2001 to 2003. A total of 8,395 patients (14%) underwent CABG during their initial hospital stay. A multivariate model was developed and identified 13 presenting clinical characteristics significantly associated with the likelihood of CABG (previous CABG, male gender, previous heart failure, diabetes, hyperlipidemia, renal insufficiency, ST depression and transient ST elevation, ageor = 75 years, previous percutaneous coronary intervention, family history of coronary artery disease, hypertension, trends in CABG rates, and previous stroke). This model had only modest predictive accuracy and calibration (c-index = 0.67). In conclusion, although certain presenting clinical features are associated with an increased likelihood of CABG in patients with NSTE-ACSs during the index hospitalization, it remains difficult to reliably identify, before diagnostic angiography, those who will subsequently undergo surgical revascularization.

Although obesity is a known risk factor for coronary artery disease, its impact on the presentation, treatment, and outcome of patients with acute coronary syndromes (ACS) has not been well studied.Using data from the CRUSADE Initiative, we compared inhospital treatments and clinical outcomes of 80845 patients with high-risk non-ST-segment elevation (NSTE) ACS (positive cardiac markers and/or ischemic ST-segment changes) to determine whether there was an association with body mass index (BMI [kg/m2]). Patient weights were categorized according to World Health Organization classifications: Underweight (BMI18.5), Normal range (BMI 18.5-24.9), Overweight (BMI 25-29.9), Obese Class I (BMI 30-34.9), Obese Class II (BMI 35-39.9), and Extremely Obese (BMI =40).Most (70.5%) of the CRUSADE patients were classified as overweight or obese; these patients were younger and more likely to present with comorbid conditions, including diabetes mellitus, hypertension, and hyperlipidemia. Medications given during the first 24 hours and invasive cardiac procedures recommended by the American College of Cardiology/American Heart Association guidelines for NSTE ACS were more commonly used in these patients. The incidence of death and death and reinfarction, adjusted for covariates, were generally lower in overweight and obese patients, compared with normal-weight patients, but higher in underweight and extremely obese patients.Most patients with NSTE ACS are overweight or obese. These patients receive more aggressive treatment, and, except for the extremely obese, have less adverse outcomes compared with underweight and normal-weight patients. Although obesity appears to be a risk factor for developing ACS at a younger age, it also appears to be associated with more aggressive ACS management and, ultimately, improved outcomes.

Data regarding the management of non-ST-segment elevation acute coronary syndromes (NSTE ACS) in Hispanic patients, the largest and fastest-growing minority in the United States, are scarce.We sought to describe the clinical characteristics, process of care, and outcomes of Hispanics presenting with NSTE ACS at US hospitals. We compared baseline characteristics, resource use, and inhospital mortality among 3936 Hispanics and 90280 non-Hispanic whites with NSTE ACS from the CRUSADE Quality Improvement Initiative.The regional distribution of Hispanics in CRUSADE paralleled that in the US Census. Hispanics were younger (65 vs 70 years, P.0001) and had less hyperlipidemia (45.4% vs 49.0%, P.0001) but were more likely to be hypertensive (72.2% vs 67.9%, P.0001) and diabetic (46.5% vs 30.9%, P.0001). Hispanics were also more likely to be uninsured (12.5% vs 5.1%, P.001). During hospitalization, Hispanics were more often managed conservatively, undergoing stress tests more frequently (13.0% vs 10.1%, P.0001), with less use of cardiac catheterization within 48 hours (48.7% vs 55.5%, P.0001) or percutaneous coronary intervention (39.6% vs 46.4%, P.0001) at any time. Hispanics received similar discharge treatments but were less frequently referred for cardiac rehabilitation (38.5% vs 49.2%, P.0001). Adjusted inhospital mortality was similar in both groups (odds ratio 0.87, 95% CI 0.72-1.05).Although hispanics have a different risk factor profile and are treated less aggressively during hospitalization when they present with NSTE ACS, these treatment differences do not appear to affect inhospital outcomes. Further research is warranted to explore the long-term consequences of these findings.

Both heparin and glycoprotein (GP) IIb/IIIa inhibitor therapy and early invasive management strategies are recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the treatment of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). However, controversy exists about which form of heparin-unfractionated (UF) or low-molecular-weight (LMW)-is preferable. We sought to compare the efficacy and safety of these treatment strategies in a large contemporary population of patients with NSTE ACS.Using data from the CRUSADE Initiative, we evaluated LMWH and UFH in high-risk NSTE ACS patients (positive cardiac markers and/or ischemic ST-segment changes) who had received early (24 hours) GP IIb/IIIa inhibitor therapy and underwent early invasive management. In-hospital outcomes were compared among treatment groups.From a total of 11,358 patients treated at 407 hospitals in the US from January 2002-June 2003, 6881 (60.6%) received UFH and 4477 (39.4%) received LMWH. Patients treated with UFH were more often admitted to a cardiology inpatient service (73.6% vs. 65.5%, P0.0001) and more frequently underwent diagnostic catheterization (91.8% vs. 85.9%, P0.0001) and percutaneous coronary intervention (PCI) (69.7% vs. 56.9%, P0.0001) than patients treated with LMWH. The point estimate of the adjusted risk of in-hospital death or reinfarction was slightly lower among patients treated with LMWH (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.67-0.99) and the risk of red blood cell transfusion was similar (OR 1.01, 95% CI 0.89-1.15). Among patients who underwent PCI within 48 hours, adjusted rates of death (OR 1.14, 95% CI 0.71-1.85), death or reinfarction (OR 0.93, 0.67-1.31), and transfusion (OR 1.16, 0.89-1.50) were similar. Patients who underwent PCI more than 48 hours into hospitalization had reduced rates of death (OR 0.64, 0.46-0.88), death or reinfarction (OR 0.57, 0.44-0.73), and transfusion (OR 0.66, 0.52-0.84).In routine clinical practice, patients treated with GP IIb/IIIa inhibitors have slightly improved outcomes and similar bleeding risks with LMWH than with UFH. These findings are consistent with current ACC/AHA guidelines but raise important questions about the safety and effectiveness of antithrombotic therapy in real-world clinical practice. Using data from the CRUSADE Initiative, we evaluated low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in high-risk patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) who received early (24 hours) glycoprotein (GP) IIb/IIIa inhibitors and early invasive management. In-hospital outcomes were compared among treatment groups. LMWH was associated with slightly improved clinical outcomes and similar rates of transfusion compared with UFH. Our results support the current ACC/AHA guidelines recommendations but raise concerns about the safety and efficacy of UFH in the setting of background use of upstream GP IIb/IIIa inhibitors for patients with NSTE ACS in routine clinical practice.