Methods of the PivotaL triAl of the Atellica VTLi point of care emergencY dePartment high sensitivity troponin evalUationS.

BACKGROUND: The Atellica® VTLi point-of-care (POC) High Sensitivity Cardiac Troponin-I (hs-cTnI) assay is intended for use as an aid in the diagnosis of myocardial infarction (MI). Our primary objective is to assess its diagnostic performance in patients presenting with suspected acute coronary syndrome (ACS). METHODS: This prospective observational study will enrol ∼1500 patients at ∼20 U.S. Emergency Departments. After informed consent, adults (>21 years of age) with suspected ACS, and no prior enrollment in this study, will provide a fingerstick and venous blood sample within 2 h of ED presentation, >2 to ≤4 h, and >4 to ≤9 h (max. blood draw = 60 mL). HEART and EDACS scores will be prospectively documented. Patients without the first blood draw may be enrolled if the second draw was obtained. Capillary and venous whole blood will undergo Atellica VTLi assay testing, with remaining venous sample processed to plasma and run. All results will be blinded to the clinical care team. Site operators will undergo a 3-day familiarization period. Quality control testing will be performed daily. At 30 ± 3 days, patient mortality status, major adverse cardiac events, and rehospitalizations will be determined. A clinical endpoint adjudication committee, blinded to hs-cTnI VTLi result, will define the final diagnosis. Sensitivity, specificity, and predictive values will describe the assay performance. RESULTS: We expect study completion within 114 weeks of enrollment of the first patient. CONCLUSIONS: It is anticipated that the Atellica VTLi hs-cTnI assay validation study will define a performance equivalent to lab-based hs-cTnI, with results within ∼8 min at the point of care.

First-Dose Efficacy of Methylnaltrexone in Patients with Severe Medical Illness and Opioid-Induced Constipation: A Pooled Analysis.

BACKGROUND: Opioid-induced constipation (OIC) is a frequent consequence of opioid analgesia that may increase patient risk for emergency department visits and hospitalization. Methylnaltrexone is a peripherally acting µ-opioid receptor antagonist indicated for the treatment of OIC. OBJECTIVE: To assess the safety and efficacy of a single methylnaltrexone dose. METHODS: Results were pooled from three randomized, placebo-controlled methylnaltrexone (MNTX) studies in opioid-treated patients with advanced illness and OIC, despite treatment with conventional laxatives. Baseline assessments included demographics, disease/treatment characteristics, and functional levels. Efficacy endpoints included rescue-free laxation (RFL) rates within 4 and 24 h, time to first RFL, pain score change, and adverse events (AEs) after a single MNTX dose or placebo. RESULTS: The analysis included 281 patients receiving MNTX and 237 receiving placebo. Mean age was 66.2 years for MNTX and 65.8 for placebo; ∼50% were men. The most frequent primary diagnosis was cancer (MNTX = 70.5%; placebo = 66.2%) and most (∼98%) were receiving at least one laxative at baseline. RFL occurred in 61.4% vs. 16.0%, and 72.1% vs. 40.1% MNTX vs. placebo patients, within 4 and 24 h of the initial dose, respectively. Relative to placebo, MNTX use reduced the time to first RFL, with most MNTX-treated patients achieving RFL within 2 h. Baseline and posttreatment pain scores were similar (p = 0.9556 vs. placebo for current and worst pain change from baseline), demonstrating that MNTX did not negatively affect opioid analgesia. Most AEs were gastrointestinal related and dissipated by the second dose. CONCLUSIONS: Methylnaltrexone provides early RFL without compromising analgesia in patients receiving chronic opioid therapy.

Oral Antiplatelet Therapy Administered Upstream to Patients With NSTEMI.

OBJECTIVE: To describe from a noninterventional registry (Utilization of Ticagrelor in the Upstream Setting for Non-ST-Segment Elevation Acute Coronary Syndrome), the short-term ischemic and hemorrhagic outcomes in patients with non-ST elevation myocardial infarction (MI) are managed with a loading dose (LD) of a P2Y12 inhibitor (P2Y12i) given at least 4 hours before diagnostic angiography and delineation of coronary anatomy. Prior data on the effects of such "upstream loading" have been inconsistent. METHODS: In 53 US hospitals, we evaluated the in-hospital care and outcomes of patients with confirmed non-ST elevation MI managed with an interventional strategy and loaded upstream (at least 4 h before diagnostic angiography) with oral P2Y12i therapy. Patients entered into the database were grouped into 1 of 4 cohorts for analysis: (1) overall cohort, (2) thienopyridine (clopidogrel or prasugrel) load, (3) ticagrelor load, and (4) ticagrelor-consistent. The fourth cohort is a subset of cohort 3 that received ticagrelor throughout the index hospital stay and at discharge. We evaluated in-hospital clinical course and ischemic and bleeding outcomes in all patients and also 30-day outcomes in the ticagrelor-consistent cohort. RESULTS: A total of 3355 patients were enrolled, of whom 1087 had 30-day follow-up. The mean (±SD) age was 63.3 ± 12.5 years, and 62.6% were male. Thrombolysis in MI and Global Registry of Acute Coronary Events scores placed these patients in the intermediate risk range, and CRUSADE scores were in the moderate risk range. The LD in Utilization of Ticagrelor in the Upstream Setting for Non-ST-Segment Elevation Acute Coronary Syndrome was clopidogrel in 45.6%, ticagrelor in 53.6%, and prasugrel in 0.8%. The median upstream interval (LD to angiography) was 17:27 hours and did not change appreciably over the course of the data collection period (2/15-10/19). Access was radial in 48.6% and femoral in 51.4%. Postangiography management was medical only in 32.3%, percutaneous coronary intervention in 59.4%, and coronary artery bypass grafting in 8.3%. Median length of stay was 2.7 days, and median time from angiography to coronary artery bypass grafting was 3.6 days. In-hospital mortality was 0.51%, and major bleeding (thrombolysis in MI) was 0.24%; the in-hospital major adverse cardiovascular events rate was 0.7%, and stent thrombosis occurred in 0.18%. No significant differences were seen between the ticagrelor and clopidogrel cohorts in hospital, but 16% received more than 1 P2Y12i in-hospital. On follow-up (93.2% response), 86.7% of patients reported taking ticagrelor as directed. CONCLUSIONS: Upstream loading of P2Y12i was associated with very low rates of bleeding and short length of stay in a large cohort of non-ST elevation MI (NSTEMI) patients managed invasively.

Management of Nonpregnant Women Presenting to the Emergency Department With Iron Deficiency Anemia Caused by Uterine Blood Loss: A Retrospective Cohort Study.

BACKGROUND: Women with abnormal uterine bleeding are commonly encountered in the emergency department (ED). Contemporary management of severe iron deficiency anemia (IDA) in this setting may be inadequate and expose patients to unnecessary blood transfusions. OBJECTIVE: We sought to describe the characteristics and management of women presenting to the ED with moderate to severe anemia caused by uterine bleeding. We hypothesized that blood transfusions were frequently administered to stable patients without severe symptoms or active bleeding. METHODS: This is a retrospective cohort study of women presenting to the ED from October 31, 2018 to March 31, 2019 with IDA from uterine bleeding. Eligible subjects were adult females with IDA caused by uterine blood loss, hemoglobin ≤10 g/dL, and who were discharged from the ED. RESULTS: One hundred twenty-seven encounters (117 unique patients, mean 40 years of age) met the eligibility criteria. No patients were hemodynamically unstable and clinically significant active bleeding was rare (6%). Blood transfusion was administered during 70 (55%) encounters, with ≥2 units given to more than half (53%) of those transfused. Subsequent ED visits (14%) and transfusions (16%) during the follow-up period were common. CONCLUSION: In this cohort of adult females with moderate to severe IDA caused by uterine bleeding, blood transfusion was often administered in the absence of hemodynamic instability or active hemorrhage, iron deficiency was inadequately treated, and a high rate of subsequent transfusions occurred. Future studies should investigate optimal indications for transfusion and emphasize adequate iron supplementation.

Anticoagulant Reversal Strategies in the Emergency Department Setting: Recommendations of a Multidisciplinary Expert Panel.

Bleeding is the most common complication of anticoagulant use. The evaluation and management of the bleeding patient is a core competency of emergency medicine. As the prevalence of patients receiving anticoagulant agents and variety of anticoagulants with different mechanisms of action, pharmacokinetics, indications, and corresponding reversal agents increase, physicians and other clinicians working in the emergency department require a current and nuanced understanding of how best to assess, treat, and reverse anticoagulated patients. In this project, we convened an expert panel to create a consensus decision tree and framework for assessment of the bleeding patient receiving an anticoagulant, as well as use of anticoagulant reversal or coagulation factor replacement, and to address controversies and gaps relevant to this topic. To support decision tree interpretation, the panel also reached agreement on key definitions of life-threatening bleeding, bleeding at a critical site, and emergency surgery or urgent invasive procedure. To reach consensus recommendations, we used a structured literature review and a modified Delphi technique by an expert panel of academic and community physicians with training in emergency medicine, cardiology, hematology, internal medicine/thrombology, pharmacology, toxicology, transfusion medicine and hemostasis, neurology, and surgery, and by other key stakeholder groups.

Idarucizumab for Reversal of Dabigatran in Early/Emergency Surgeries: A Case Series.

BACKGROUND: Idarucizumab is a humanized, monoclonal antibody fragment used specifically to reverse the anticoagulant effects of dabigatran. CASE REPORTS: We discuss 4 cases of patients who were treated with idarucizumab to reverse dabigatran before early/emergency surgery. Two of the patients had subdural hematomas, 1 had a splenic laceration, and 1 had Fournier gangrene. All patients received 5 g of idarucizumab before surgery. Intraoperative blood loss in all patients was normal, no adverse events were reported, and the patients recovered normally. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The case reports presented provide detailed, practical, real-world experience beyond that reported in other case reports and the Reversal Effects of Idarucizumab on Active Dabigatran study. This can help guide clinicians on how idarucizumab can reverse the anticoagulant effect of dabigatran in emergency situations, including patients with subdural hematoma. Our experience suggests that idarucizumab may be a safe and effective antidote to the effects of dabigatran in real-life bleeding situations involving early or emergency surgeries.

Identification and Management of Iron Deficiency Anemia in the Emergency Department.

BACKGROUND: Iron deficiency anemia is the most common hematologic disorder in the United States and worldwide. Yet, clinical guidelines for the identification and management of this disorder in the emergency department are lacking. OBJECTIVE OF REVIEW: This clinical review examines strategies for identifying and treating iron deficiency anemia in the emergency department, with a focus on the role of oral iron therapy, intravenous iron therapy, as well as red blood cell transfusion. The article highlights both the available evidence on this topic and the need for future research. DISCUSSION: The diagnosis of iron deficiency anemia has important clinical implications and, although testing is generally straightforward, it may be under-recognized. The scant literature available describing emergency department practice patterns for iron deficiency anemia suggests there is room for improvement. In particular, intravenous iron may be underutilized and red blood cell transfusions administered too liberally. CONCLUSIONS: Iron deficiency anemia is common and many patients can be treated effectively with oral iron. For selected patients with moderate-to-severe iron deficiency anemia, intravenous iron is safe and more effective than oral iron. Red blood cell transfusions should be used rarely for hemodynamically stable patients with iron deficiency irrespective of hemoglobin levels.

Cost and inpatient burden of peripheral artery disease: Findings from the National Inpatient Sample.

BACKGROUND AND AIMS: We aimed to examine the prevalence, demographics, clinical outcomes and economic burden of hospitalizations for patients with PAD. METHODS: Using the National Inpatient Sample, we retrospectively evaluated patients hospitalized with PAD in 2014. Hospitalizations in patients with PAD were identified by the presence of an International Classification of Diseases-9th Revision (ICD-9) diagnosis code of 440.20-440.24. We calculated hospitalization rates/100,000 patients, the proportion of hospitalizations with a major adverse limb event (MALE), as well as minor amputation, mortality, median (interquartile range) length-of-stay (LOS) and treatment costs (in 2017 US$). A separate analysis of hospitalizations of patients with clinical limb ischemia defined as Fontaine class III or IV PAD (440.22, resting pain; 440.23-440.24, ulcers or gangrene) was also performed. RESULTS: We identified 286,160 hospitalizations for patients with PAD. The rate of hospitalizations for PAD was 89.5/100,000, with 137,050 (or 45%) of these having Fontaine class III-IV disease. The proportion of hospitalizations resulting in MALE, major or minor lower extremity amputation or in-hospital death was 45.8%, 8.9%, 8.2% and 3.1%, respectively. Median hospital LOS was 5 (3, 9) days and costs were $15,755 ($8972, $27,800), resulting in an annual cost burden for hospitalization of patients with PAD of ∼$6.31 billion. In hospitalizations of Fontaine class III-IV PAD, MALE, major and minor amputation and death occurred in 60.9%, 16.8%, 15.8% and 3.3% of cases, respectively. Median LOS and costs were 7 (4, 11) days and $18,984 ($10,913, $31,816). CONCLUSIONS: Hospitalizations of patients with PAD represent a substantial medical and financial burden for patients and the US healthcare system.

Inflammatory Biomarkers and Clinical Judgment in the Emergency Diagnosis of Urgent Abdominal Pain.

BACKGROUND: The early diagnosis of urgent abdominal pain (UAP) is challenging. Most causes of UAP are associated with extensive inflammation. Therefore, we hypothesized that quantifying inflammation using interleukin-6 and/or procalcitonin would provide incremental value in the emergency diagnosis of UAP. METHODS: This was an investigator-initiated prospective, multicenter diagnostic study enrolling patients presenting to the emergency department (ED) with acute abdominal pain. Clinical judgment of the treating physician regarding the presence of UAP was quantified using a visual analog scale after initial clinical and physician-directed laboratory assessment, and again after imaging. Two independent specialists adjudicated the final diagnosis and the classification as UAP (life-threatening, needing urgent surgery and/or hospitalization for acute medical reasons) using all information including histology and follow-up. Interleukin-6 and procalcitonin were measured blinded in a central laboratory. RESULTS: UAP was adjudicated in 376 of 1038 (36%) patients. Diagnostic accuracy for UAP was higher for interleukin-6 [area under the ROC curve (AUC), 0.80; 95% CI, 0.77-0.82] vs procalcitonin (AUC, 0.65; 95% CI, 0.62-0.68) and clinical judgment (AUC, 0.69; 95% CI, 0.65-0.72; both P < 0.001). Combined assessment of interleukin-6 and clinical judgment increased the AUC at presentation to 0.83 (95% CI, 0.80-0.85) and after imaging to 0.87 (95% CI, 0.84-0.89) and improved the correct identification of patients with and without UAP (net improvement in mean predicted probability: presentation, +19%; after imaging, +15%; P < 0.001). Decision curve analysis documented incremental value across the full range of pretest probabilities. A clinical judgment/interleukin-6 algorithm ruled out UAP with a sensitivity of 97% and ruled in UAP with a specificity of 93%. CONCLUSIONS: Interleukin-6 significantly improves the early diagnosis of UAP in the ED.

Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

BACKGROUND: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. AIMS: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. METHODS: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. RESULTS: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. CONCLUSIONS: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.

A post-marketing assessment of major bleeding in total hip and total knee replacement surgery patients receiving rivaroxaban.

BACKGROUND: Rivaroxaban is a novel oral anticoagulant indicated for prophylaxis against deep vein thrombosis and pulmonary embolism in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery. OBJECTIVE: To evaluate major bleeding (MB) in THR/TKR patients receiving post-operative rivaroxaban. METHODS: Electronic medical records of nearly 10 million US Department of Defense (DoD) beneficiaries were queried from 1 January 2013 through 30 June 2015. Using the validated Cunningham case-finding algorithm, post-surgical MB events in rivaroxaban users were identified and analyzed. The incidence of MB was determined, and descriptive statistics were used to compare patient characteristics and other covariates in those with and without MB. Two additional methods were used to explore and identify bleeding cases that were not considered MB events per the study case-finding algorithm. RESULTS: A total of 12,429 patients received THR and/or TKR surgery, and were post-operatively prescribed rivaroxaban. Nine patients had MB, yielding an incidence proportion of 0.07% (95% CI 0.02-0.13). The alternative case-finding methods found bleeding incidences of 0.46% and 0.21%, though it is not clear whether these are clinical MB cases, since the alternative methods were not validated. CONCLUSIONS: The incidence of MB in this retrospective analysis is lower than that observed in the clinical trials of rivaroxaban. Whether this is due to lower real-world MB rates or challenges with case-finding algorithms is unclear.

Discharge or admit? Emergency department management of incidental pulmonary embolism in patients with cancer: a retrospective study.

BACKGROUND: Hospitalization and early anticoagulation therapy remain standard care for patients who present to the emergency department (ED) with pulmonary embolism (PE). For PEs discovered incidentally, however, optimal therapeutic strategies are less clear-and all the more so when the patient has cancer, which is associated with a hypercoagulable state that exacerbates the threat of PE. METHODS: We conducted a retrospective review of a historical cohort of patients with cancer and incidental PE who were referred for assessment to the ED in an institution whose standard of care is outpatient treatment of selected patients and use of low-molecular-weight heparin for anticoagulation. Eligible patients had received a diagnosis of incidental PE upon routine contrast enhanced chest CT for cancer staging. Survival data was collected at 30 days and 90 days from the date of ED presentation and at the end of the study. RESULTS: We identified 193 patients, 135 (70%) of whom were discharged and 58 (30%) of whom were admitted to the hospital. The 30-day survival rate was 92% overall, 99% for the discharged patients and 76% for admitted patients. Almost all (189 patients, 98%) commenced anticoagulation therapy in the ED; 170 (90%) of these received low-molecular-weight heparin. Patients with saddle pulmonary artery incidental PEs were more likely to die within 30 days (43%) than were those with main or lobar (11%), segmental (6%), or subsegmental (5%) incidental PEs. In multivariate analysis, Charlson comorbidity index (age unadjusted), hypoxemia, and incidental PE location (P = 0.004, relative risk 33.5 (95% CI 3.1-357.4, comparing saddle versus subsegmental PE) were significantly associated with 30-day survival. Age, comorbidity, race, cancer stage, tachycardia, hypoxemia, and incidental PE location were significantly associated with hospital admission. CONCLUSIONS: Selected cancer patients presenting to the ED with incidental PE can be treated with low-molecular-weight heparin anticoagulation and safely discharged. Avoidance of unnecessary hospitalization may decrease in-hospital infections and death, reduce healthcare costs, and improve patient quality of life. Because the natural history and optimal management of this condition is not well described, information supporting the creation of straightforward evidence-based practice guidelines for ED teams treating this specialized patient population is needed.

Observation management of pulmonary embolism and agreement with claims-based and clinical risk stratification criteria in United States patients: a retrospective analysis.

BACKGROUND: Guidelines suggest observation stays are appropriate for pulmonary embolism (PE) patients at low-risk for early mortality. We sought to assess agreement between United States (US) observation management of PE and claims-based and clinical risk stratification criteria. METHODS: Using US Premier data from 11/2012 to 3/2015, we identified adult observation stay patients with a primary diagnosis of PE, ≥1 PE diagnostic test claim and evidence of PE treatment. The proportion of patients at high-risk was assessed using the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) equation and high-risk characteristics (age > 80 years, heart failure, chronic lung disease, renal or liver disease, high-risk for bleeding, cancer or need for thrombolysis/embolectomy). RESULTS: We identified 1633 PE patients managed through an observation stay. Despite their observation status, IMPACT classified 46.4% as high-risk for early mortality and 33.3% had ≥1 high-risk characteristic. Co-morbid heart failure, renal or liver disease, high-risk for major bleeding, cancer and hemodynamic instability were low (each <4.5%), but 7.8% were >80 years-of-age and 19.4% had chronic lung disease. CONCLUSION: Many PE patients selected for management in observation stay units appeared to have clinical characteristics suggestive of higher-risk for mortality based upon published claims-based and clinical risk stratification criteria.

External Validation of the Hestia Criteria for Identifying Acute Pulmonary Embolism Patients at Low Risk of Early Mortality.

INTRODUCTION: There are limited studies evaluating the ability of the Hestia criteria to accurately identify patients with acute pulmonary embolism (PE) at low risk of early mortality. We sought to externally validate the Hestia criteria for predicting in-hospital and 30-day post-PE mortality. METHODS: We retrospectively identified consecutive, adult, objectively confirmed PE patients presenting to the emergency department at our institution from November 21, 2010, to January 31, 2014. We ascertained the total number of Hestia criteria met for each patient, calculated the proportion of patients categorized as low risk (ie, no Hestia criteria met), and determined the accuracy of the Hestia criteria for predicting in-hospital and 30-day all-cause mortality. Mortality was determined through Social Security Death Index searches. RESULTS: A total of 577 patients with PE were included, of which 19 (3.3%) and 35 (6.6%) died in hospital or within 30 days of presentation. Both in-hospital and 30-day case fatality rates rose as the number of Hestia criteria increased. One-hundred forty nine (25.8%) patients were classified as low risk for early mortality, and none of these patients died within 30 days (negative predictive values of 100%). The Hestia criteria had excellent sensitivity (100%, 95% confidence interval [CI] = 79.1%-100% and 100%, 95% CI = 87.7%-100%) for predicting in-hospital and 30-day mortality but low specificity (<27.5% for both). The c-statistics for in-hospital and 30-day mortality were 83.5%, 95% CI = 77.1%-89.9% and 78.5%, 95% CI = 71.9%-85.1%. The predictive accuracy of the Hestia criteria remained acceptable in patients >80 years of age, with active cancer or chronic cardiopulmonary disease. CONCLUSION: The Hestia criteria have an acceptable predictive accuracy to identify patients with PE at low risk for in-hospital or 30-day mortality.

Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians.

Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)-dabigatran, rivaroxaban, apixaban, and edoxaban-have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed.

Temporal trends for secondary prevention measures among patients hospitalized with coronary artery disease.

BACKGROUND: Prior studies have noted that in-hospital adherence to secondary prevention measures varied among patients undergoing coronary artery bypass graft surgery, percutaneous coronary revascularization, or no intervention. We sought to study contemporary temporal trends in the in-hospital management of patients with coronary artery disease. METHODS: By using data from the Get With The Guidelines-Coronary Artery Disease registry, we compared adherence to 6 performance measures (aspirin within 24 hours, discharge on aspirin, discharge on beta-blockers, patients with low ejection fraction discharged on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, smoking cessation counseling, and use of lipid-lowering medications) in eligible patients with coronary artery disease who underwent coronary artery bypass graft surgery, percutaneous coronary intervention, or no intervention between 2003 and 2008. RESULTS: A total of 113,971 patients with coronary artery disease were treated at 193 hospitals. Overall adherence to all 6 quality of care measures improved over time in all 3 treatment groups, but was highest at all time periods in the percutaneous coronary intervention group compared with the coronary artery bypass graft surgery group, whereas the no intervention group had the lowest use of prevention measures at all time points (P < .0001). Likewise, 100% adherence to all 6 measures was superior in the percutaneous coronary intervention group at all time points (P < .0001). On multivariable adjustment for case-mix of patients, the majority of these differences persisted. CONCLUSIONS: Over the last decade, overall adherence with secondary prevention measures improved significantly in patients hospitalized with coronary artery disease regardless of revascularization strategy. However, there still exist select opportunities for improving adherence, particularly among patients undergoing coronary artery bypass graft surgery or no intervention.

Managing bleeding and emergency reversal of newer oral anticoagulants: a review for primary care providers.

The therapeutic landscape for anticoagulation management is undergoing a shift from the use of traditional anticlotting agents such as heparins and warfarin as the only options to the growing adoption of newer target-specific oral anticoagulants (TSOACs) with novel mechanisms of action. Dabigatran, the first TSOAC approved for use in the United States, is a direct competitive inhibitor of thrombin. It has predictable kinetics, with an elimination half-life of 12 to 17 hours in healthy volunteers. Apixaban and rivaroxaban are selective inhibitors of factor Xa, and also display first-order kinetics. In younger healthy individuals, apixaban has an apparent half-life of approximately 12 hours, whereas rivaroxaban has an elimination half-life of 5 to 9 hours. Understanding the pharmacologic properties of these newer drugs can lead to better insights regarding their respective safety and efficacy profiles and their application in clinical practice. Laboratory assessments have been developed to measure the anticoagulant efficacy of these newer agents. However, the results of these tests can be highly variable, and are therefore not always useful for monitoring the anticoagulation effects of these agents. In addition, several strategies have been documented for the potential reversal of the anticoagulant effects of these drugs, from the temporary discontinuation of an agent before elective surgery to suggested emergency procedures in the case of major bleeding events. New, specific reversal agents for dabigatran, apixaban, and rivaroxaban are currently being developed, and dabigatran has received fast-track designation from the US Food and Drug Administration. Until comprehensive clinical guidelines are developed, institutions involved in emergency care should establish their own procedures for the management of patients undergoing anticoagulation who require emergency treatment. These protocols should include appropriate laboratory testing to assess anticoagulant activity as part of the inpatient workup if time allows, and the potential use of hemodialysis, prohemostatic agents, and reversal agents when available.

Novel biomarkers in acute heart failure: MR-pro-adrenomedullin.

First isolated from human pheochromocytoma cells, adrenomedullin (ADM) is a peptide hormone with natriuretic, vasodilatory, and hypotensive effects mediated by cyclic adenosine monophosphate (cAMP), nitric oxide, and renal prostaglandin systems. ADM expression occurs in many tissues and organ systems, including cardiovascular, renal, pulmonary, cerebrovascular, gastrointestinal, and endocrine tissues where it acts as a circulating hormone and a local autocrine and paracrine hormone. ADM plasma concentrations are increased in hypertension, chronic renal disease, and heart failure. As ADM is unstable in vitro, it is necessary to measure its mid-regional pro-hormone fragment, the levels of which correspond to ADM concentration (MR-proADM). The prognostic potential of MR-proADM was recently demonstrated in the Biomarkers in Acute Heart Failure (BACH) trial. In this trial of 568 acute heart failure patients, MR-proADM was superior to both brain natriuretic peptide (BNP) and NT-proBNP in predicting mortality within 14 days. MR-proADM also provided significant additive incremental predictive value for 90-day mortality when added to BNP and NT-proBNP.

Temporal trends in clinical characteristics of patients without known cardiovascular disease with a first episode of myocardial infarction.

BACKGROUND: Recent initiatives have focused on primary prevention to delay time to first myocardial infarction (MI). The aim of this study was to evaluate the change in risk factor profile over time in patients without known cardiovascular disease presenting with first MI. METHODS: In the American Heart Association's Get With The Guidelines-Coronary Artery Disease national registry, 100,884 patients without known cardiovascular disease presenting with acute MI from 408 hospitals were evaluated between 2002 and 2008. The time trends of the proportion of patients with cardiovascular risk factors (nonmodifiable: age >45 years for men or >55 years for women, male sex, modifiable: diabetes mellitus, hypertension, hyperlipidemia, tobacco use) were analyzed. Analyses were stratified by non-ST-segment elevation MI (NSTEMI) versus ST-segment elevation MI (STEMI). RESULTS: The proportion of patients with ≥3 of 6 traditional risk factors slightly decreased over time in the NSTEMI (69.5%-66.8%, P < .0001) and STEMI (68.9%-66.4%, P < .0001) cohorts. The proportion of patients with ≥2 of 4 modifiable risk factors increased from 52% to 59% and then declined to 52.1% (P < .0001) in the NSTEMI cohort but declined slightly in the STEMI cohort (50.9%-47.3%, P < .0001). After adjusting for age and gender, the time trend of proportion with diabetes mellitus, hypertension, and tobacco use declined in both cohorts. However, the proportion of patients with hyperlipidemia remained similar. CONCLUSIONS: Although risk factor profiles in patients presenting with first MI have shown improvements over time, the changes are modest.