Management of Severe Bleeding in Patients Treated With Oral Anticoagulants: Proceedings Monograph From the Emergency Medicine Cardiac Research and Education Group-International Multidisciplinary Severe Bleeding Consensus Panel October 20, 2018.

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.

Association of Early Stress Testing with Outcomes for Emergency Department Evaluation of Suspected Acute Coronary Syndrome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (P > 0.1 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). CONCLUSIONS: 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.

Self-reported cocaine use, emergency physician testing and outcomes in suspected acute coronary syndromes: a nested matched case-control study.

OBJECTIVES: The primary purpose was to compare the odds of acute coronary syndrome-pertinent diagnostic testing between self-reported cocaine users and non-users at the turn of the century. The secondary purpose was to compare the odds of acute coronary syndrome outcomes between cocaine users and non-users. DESIGN: Nested matched case-control study using data from the Internet Tracking Registry of Acute Coronary Syndromes. SETTING: Extracted data of patients from eight US institutions composed of six academic and two community hospitals, with census varying between 10 000 and 160 000 visits per year. PARTICIPANTS: 249 cases of self-reported cocaine users and 249 matched controls. Matching was based on age, race, sex and any history of known coronary artery disease. Exclusion criteria were new ST elevations on initial ECG and initial physician impression of acute myocardial infarction. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the conditional odds of undergoing non-invasive and invasive testing for coronary artery disease. Secondary outcome was the occurrences of adverse cardiac outcomes within 30 days. RESULTS: Cocaine users underwent diagnostic testing at similar rates compared with non-users (9.6% vs 8.0%, OR 1.24, CI 0.65 to 2.34). Adverse cardiovascular outcomes occurred in four (1.6%) cocaine users and in seven (2.8%) controls. CONCLUSIONS: There was no increase in tendency for testing associated with self-reported history of cocaine use between 1999 and 2001. This suggests that even 10 years ago, cocaine use already had only a limited role in the Emergency Department (ED) physician's decision-making process. Similar data analyses of detailed registries can offer important contextual information that can better direct resources for future comparative effectiveness research.

Polyvascular disease and long-term cardiovascular outcomes in older patients with non-ST-segment-elevation myocardial infarction.

BACKGROUND: The impact of polyvascular disease (peripheral arterial disease [PAD] and cerebrovascular disease [CVD]) on long-term cardiovascular outcomes among older patients with acute myocardial infarction has not been well studied. METHODS AND RESULTS: Patients with non-ST-segment-elevation myocardial infarction aged ≥65 years from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines) registry who survived to hospital discharge were linked to longitudinal data from the Centers for Medicare & Medicaid Services (n=34 205). All patients were presumed to have coronary artery disease (CAD) and were classified into the following 4 groups: 10.7% with prior CVD (CAD+CVD group); 11.5% with prior PAD (CAD+PAD); 3.1% with prior PAD and CVD (CAD+PAD+CVD); and 74.7% with no polyvascular disease (CAD alone). Cox proportional hazards modeling was used to examine the hazard of long-term mortality and composite of death or readmission for myocardial infarction or stroke (median follow-up, 35 months; interquartile range, 17-49 months). Compared with the CAD alone group, patients with polyvascular disease had greater comorbidities, were less likely to undergo revascularization, and received less often recommended discharge interventions. Three-year mortality rates increased with number of arterial bed involvement as follows: 33% for CAD alone, 49% for CAD+PAD, 52% for CAD+CVD, and 59% for CAD+PAD+CVD. Relative to the CAD alone group, patients with all 3 arterial beds involved had the highest risk of long-term mortality (adjusted hazard ratio [95% CI], 1.49 [1.38-1.61]; CAD+CVD, 1.38 [1.31-1.44]; CAD+PAD, 1.29 [1.23-1.35]). Similarly, the risk of long-term composite ischemic events was highest among patients in the CAD+PAD+CVD group. CONCLUSIONS: Among older patients with non-ST-segment-elevation myocardial infarction, those with polyvascular disease have substantially higher long-term risk for recurrent events or death. Future studies targeting greater adherence to secondary prevention strategies and novel therapies are needed to help to reduce long-term cardiovascular events in this vulnerable population.

Ground emergency medical services requests for helicopter transfer of ST-segment elevation myocardial infarction patients decrease medical contact to balloon times in rural and suburban settings.

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.

Predicting long-term mortality in older patients after non-ST-segment elevation myocardial infarction: the CRUSADE long-term mortality model and risk score.

OBJECTIVES: We sought to develop a long-term mortality risk prediction model and a simplified risk score for use in older patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: Limited data are available regarding long-term mortality rates and concomitant risk predictors after acute myocardial infarction in contemporary community practice. METHODS: From the CRUSADE registry, a total of 43,239 (NSTEMI) patients aged ≥65 years treated at 448 hospitals in the United States from 2003 to 2006 were linked to Centers for Medicare and Medicaid Services data to track longitudinal all-cause mortality (median follow-up 453 days). Cox proportional hazard modeling was used to determine baseline independent demographic, clinical, and laboratory variables associated with long-term mortality. A simplified long-term mortality risk score was subsequently developed from these results. RESULTS: The median age of this population was 77 years, and mortality rates at 1, 2, and 3 years were 24.4%, 33.2%, and 40.3%, respectively. We identified 22 variables independently associated with long-term mortality in a full model (c-statistic 0.754 in the derivation sample and 0.744 in the validation sample). The CRUSADE long-term mortality risk score was limited to the 13 most clinically and statistically significant variables from the full model yet retained comparable discrimination in the derivation and validation samples (c-statistics 0.734 and 0.727, respectively) and had good calibration across the risk spectra. CONCLUSIONS: Older patients face substantial long-term mortality risks after NSTEMI that can be accurately predicted from baseline characteristics. These prognostic estimates may support informed treatment decision-making and comparison of long-term provider outcomes.

Predictors of 30-day cardiovascular events in patients with prior percutaneous coronary intervention or coronary artery bypass grafting.

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.

Reperfusion is delayed beyond guideline recommendations in patients requiring interhospital helicopter transfer for treatment of ST-segment elevation myocardial infarction.

STUDY OBJECTIVE: Early reperfusion portends better outcomes for ST-segment elevation myocardial infarction (STEMI) patients. This investigation estimates the proportions of STEMI patients transported by a hospital-based helicopter emergency medical services (EMS) system who meet the goals of 90-minute door-to-balloon time for percutaneous coronary intervention or 30-minute door-to-needle time for fibrinolysis. METHODS: This was a multicenter, retrospective chart review of STEMI patients flown by a hospital-based helicopter service in 2007. Included patients were transferred from an emergency department (ED) to a cardiac catheterization laboratory for primary or rescue percutaneous coronary intervention. Out-of-hospital, ED, and inpatient records were reviewed to determine door-to-balloon time and door-to-needle time. Data were abstracted with a priori definitions and criteria. RESULTS: There were 179 subjects from 16 referring and 6 receiving hospitals. Mean age was 58 years, 68% were men, and 86% were white. One hundred forty subjects were transferred for primary percutaneous coronary intervention, of whom 29 had no intervention during catheterization. For subjects with intervention, door-to-balloon time exceeded 90 minutes in 107 of 111 cases (97%). Median door-to-balloon time was 131 minutes (interquartile range 114 to 158 minutes). Thirty-nine subjects (21%) received fibrinolytics before transfer, and 19 of 39 (49%) received fibrinolytics within 30 minutes. Median door-to-needle time was 31 minutes (interquartile range 23 to 45 minutes). CONCLUSION: In this study, STEMI patients presenting to non-percutaneous coronary intervention facilities who are transferred to a percutaneous coronary intervention-capable hospital by helicopter EMS do not commonly receive fibrinolysis and rarely achieve percutaneous coronary intervention within 90 minutes. In similar settings, primary fibrinolysis should be considered while strategies to reduce the time required for subsequent interventional care are explored.

Outcomes associated with small changes in normal-range cardiac markers.

INTRODUCTION: Troponin concentrations rising above an institutional cutpoint are used to define acute myocardial necrosis, yet it is uncertain what outcomes are associated with fluctuations in troponin that do not exceed this level. We evaluate the association between troponin fluctuations below an institutional upper limit of normal and acute coronary syndrome (ACS). MATERIALS AND METHODS: This was a post hoc analysis of the Internet tracking registry of ACS (i*trACS), which describes patients presenting to emergency departments (EDs) with suspected ACS across the spectrum of risk. Patients were included in this registry if they were at least 18 years old and had suspected ACS at the time of their ED visit. Inclusions in this analysis required that patients had at least 1 cardiac marker (creatine kinase-MB [CK-MB], troponin T, or troponin I) drawn twice within 6 hours of presentation, with both measures being below the institution's upper limit of normal. A marker change was defined as either an increase or decrease that exceeded 15% of the institutional upper limit of normal. Acute coronary syndrome was defined as a positive stress test, documented myocardial infarction, coronary revascularization, or death within 30 days of their ED admission. RESULTS: Of 17,713 patient visits, 2162 met inclusion and exclusion criteria. There were 1872 patient visits with 2 troponin results and 1312 with 2 CK-MB results. Patient visits with increasing troponin had increased odds of ACS compared with those with stable troponin levels (odds ratio, 3.6; 95% confidence interval, 1.4-9.2). Changing CK-MB and decreasing troponin were not associated with increased odds of ACS. CONCLUSIONS: Small increases in troponin concentration below the upper limit of normal are associated with increased odds of ACS.

Changes in glycoprotein IIb/IIIa inhibitor excess dosing with site-specific safety feedback in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) initiative.

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

Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: results from the Medications ApplIed aNd SusTAINed Over Time (MAINTAIN) registry.

BACKGROUND: Current American College of Cardiology/American Heart Association guidelines recommend initiation or intensification of statin therapy to achieve low-density lipoprotein cholesterol (LDL-C) goals after an acute coronary syndrome (ACS), yet little is known about the actual practice of intensifying lipid-lowering (LL) therapy and LDL-C achievement from hospital admission to 1-year follow-up. METHODS: The MAINTAIN registry enrolled ACS patients from January 2006 through September 2007, collecting data on statin formulation, dose, and lipid profiles at both baseline and 12 months. Statin intensity (estimated LDL-C lowering) was categorized by formulation and dose as either moderate (<40%) or intensive (≥40%). In-hospital LL intensification is described and LDL goal attainment is reported for patients with complete baseline and 12-month lipid panels. RESULTS: Of the 788 patients without contraindications to LL, 40% were on LL therapy before admission, and 89% at discharge. Among patients on LL therapy with LDL-C>100 mg/dL at admission, only 37% (n=38) had their LL therapy intensified. Among 382 patients with 12 months of data, 89% (n=341) were discharged on a statin. Of these, 89% were still on a statin at 12-month follow-up. A LDL-C goal of ≤100 mg/dL was achieved in 71% of patients, but the optional LDL-C goal≤70 mg/dL was achieved in only 31%. CONCLUSIONS: Most high-risk ACS patients are prescribed statin therapy at hospital discharge and remain on therapy at 12-month follow-up. Despite this, the LDL-C goal of ≤70 mg/dL is achieved in a small minority. There is substantial opportunity to intensify LL therapy after ACS to achieve guideline LDL-C goals and prevent future morbidity and mortality.

Influence of transfer-in rates on quality of care and outcomes at receiving hospitals in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND: Patients with non-ST-segment elevation myocardial infarction (NSTEMI) are frequently transferred to tertiary hospitals for angiography and/or revascularization from hospitals lacking such capabilities. Given that patients who undergo invasive cardiac procedures are younger and have fewer comorbidities compared with those managed medically, the relative proportion of transfer-in patients at tertiary hospitals may influence comparisons of quality and guidelines adherence. METHODS: We evaluated 142,092 NSTEMI patients treated at 396 revascularization-capable sites in the CRUSADE National Quality Improvement Initiative from 2001 to 2006. Transfer-in patients were included if they arrived at the receiving hospital after their first presentation to a different hospital. Hospitals were categorized into tertiles based upon their transfer-in rates (low, intermediate, and high) and adherence to practice guidelines recommendations for NSTEMI. In-hospital clinical outcomes were compared across hospital tertiles. RESULTS: Acute and discharge composite guidelines adherence scores improved at hospitals with an increasing proportion of transfer-in patients, both for transferred as well as for directly admitted patients. These better adherence scores were inversely associated with overall mortality, with the lowest mortality observed in patients at hospitals with the highest transfer-in rates. However, once adjusted for baseline confounders, the mortality rates for patients in the hospitals in the highest transfer-in tertile did not differ significantly compared with the sites in the lowest transfer-in tertile (odds ratio 1.02, 95% CI 0.90-1.16). CONCLUSIONS: Our findings show that the proportion of NSTEMI patients transferred into revascularization-capable hospitals varies significantly. Hospitals with a higher proportion of transfer-in patients tend to provide higher overall quality of NSTE acute coronary syndrome care; they also have lower overall in-hospital mortality, which may, in part, be related to the lower-risk baseline characteristics of patients at these hospitals.

Implications and reasons for the lack of use of reperfusion therapy in patients with ST-segment elevation myocardial infarction: findings from the CRUSADE initiative.

BACKGROUND: Prompt reperfusion for patients with ST-segment elevation myocardial infarction (STEMI) is a class I guideline recommendation and has been shown to reduce mortality. However, many STEMI patients in contemporary practice still do not receive any form of reperfusion therapy. METHODS: We evaluated 8,578 patients with STEMI from 226 US hospitals participating in the CRUSADE quality improvement initiative from September 2004 to December 2006 to determine the proportion of eligible patients who received an attempt at reperfusion therapy and factors associated with lack of reperfusion among patients without a contraindication to reperfusion. STEMI patients were classified into 3 groups: (1) patients eligible for reperfusion and for whom reperfusion was attempted; (2) patients eligible for reperfusion and for whom reperfusion was not attempted; and (3) patients who were ineligible for reperfusion because of identified contraindications. We compared patient characteristics, treatments, and outcomes among the groups and identified factors independently associated with lack of reperfusion use among eligible patients. RESULTS: Of the 8,578 patients with STEMI, 881 patients (10.3%) had a documented contraindication to reperfusion, 7,080 (82.5%) received fibrinolysis or underwent an attempt at primary percutaneous coronary intervention, and 617 reperfusion-eligible patients (7.2%) had no attempt to administer reperfusion. Primary reasons for contraindications were identified as absence of an ischemic indication (n = 474; 53.8%), bleeding risk (n = 147; 16.7%), patient-related reasons (n = 223; 25.3%), and other (n = 37; 4.2%). The strongest factors associated with not attempting reperfusion among the reperfusion-eligible population were older age, heart failure at presentation, noncardiac surgical center, prior stroke, and female sex. Compared with patients receiving an attempt at reperfusion, adjusted in-hospital mortality rates were higher for patients with a documented reperfusion contraindication (adjusted odds ratio 1.77, 95% CI 1.28-2.45) and in eligible patients who did not receive reperfusion (adjusted odds ratio 1.64, 95% CI 1.07-2.50). CONCLUSIONS: More than 7% of STEMI patients without a reperfusion contraindication did not have an attempt to administer reperfusion therapy, and this was associated with greater in-hospital mortality. Age, sex, and comorbidity were factors related to lack of attempting reperfusion among apparently eligible patients. Quality improvement efforts should focus on maximizing reperfusion use among all eligible STEMI patients and in addressing the processes by which contraindications are defined, clinically determined, and reported.

Influence of clinical trial participation on subsequent antithrombin use.

BACKGROUND: Results from the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial showed that the low-molecular-weight heparin (LMWH) enoxaparin was non-inferior compared with unfractionated heparin (UFH) in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) managed invasively. HYPOTHESIS: We explored the influence of SYNERGY trial site participation on subsequent patterns of heparin use for NSTE-ACS patients treated in routine practice. METHODS: We examined temporal patterns of LMWH use compared with UFH use among 122 764 patients with NSTE-ACS 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 between January 1, 2002 and June 30, 2006, to determine whether site participation in SYNERGY influenced the type of heparin used before and after publication of the SYNERGY results in July 2004. RESULTS: A total of 118 out of 388 (30%) U.S. hospitals participating in CRUSADE simultaneously participated in SYNERGY. SYNERGY sites in the CRUSADE registry were more likely to have a teaching affiliation and have more hospital beds than non-SYNERGY centers in the registry. There was no difference in the proportion of patients treated with LMWH at SYNERGY and non-SYNERGY sites prior to July 2004 compared with after July 2004. However, at SYNERGY sites, there was a slight decrease in the proportion of patients treated with both UFH and LMWH within 24 hours of presentation. CONCLUSIONS: The results of the SYNERGY trial did not appear to influence temporal patterns of LMWH use at sites in the CRUSADE registry. Furthermore, site participation in the SYNERGY trial did not alter patterns of LMWH use for NSTE-ACS after publication of the trial results in July 2004.