Systems of Care for ST-Segment-Elevation Myocardial Infarction: A Policy Statement From the American Heart Association.

The introduction of Mission: Lifeline significantly increased timely access to percutaneous coronary intervention for patients with ST-segment-elevation myocardial infarction (STEMI). In the years since, morbidity and mortality rates have declined, and research has led to significant developments that have broadened our concept of the STEMI system of care. However, significant barriers and opportunities remain. From community education to 9-1-1 activation and emergency medical services triage and from emergency department and interfacility transfer protocols to postacute care, each critical juncture presents unique challenges for the optimal care of patients with STEMI. This policy statement sets forth recommendations for how the ideal STEMI system of care should be designed and implemented to ensure that patients with STEMI receive the best evidence-based care at each stage in their illness.

Variation in Post-Cardiac Arrest Care Within a Regional EMS System.

Objective: Within Emergency Medical Systems (EMS) regional systems, there may be significant differences in the approach to patient care despite efforts to promote standardization. Identifying hospital-level factors that contribute to variations in care can provide opportunities to improve patient outcomes. The purpose of this analysis was to evaluate variation in post-cardiac arrest care within a large EMS system and explore the contribution of hospital-level factors. Methods: This was a retrospective analysis from a regional cardiac system serving over 10 million persons. Patients with out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC) are transported to 36 cardiac arrest centers with 24/7 emergent coronary angiography (CAG) capabilities and targeted temperature management (TTM) policies based on regional guidelines. We included adult patients ≥18 years with non-traumatic OHCA from 2016-2018. Patients with a Do-Not-Resuscitate order and those who died in the emergency department (ED) were excluded. For the TTM analysis, we also excluded patients who were alert in the ED. The primary outcome was receiving CAG or TTM after cardiac arrest. The secondary outcome was neurologic recovery (dichotomized to define a "good" outcome as cerebral performance category (CPC) 1 or 2). We used generalized estimating equations including patient-level factors (age, sex, witnessed arrest, initial rhythm) and hospital-level factors (academic status, hospital size based on licensed beds, annual OHCA patient volume) to estimate the odds ratios associated with these variables. Results: There were 7831 patients with OHCA during the study period; 4694 were analyzed for CAG and 3903 for TTM. The median and range for treatment with CAG and TTM after OHCA was 23% (12-49%) and 58% (17-92%) respectively. Hospital size was associated with increased likelihood of CAG, adjusted odds ratio 1.71, 95% CI 1.05-2.86, p = 0.03. Academic status approached significance in its association with TTM, adjusted odds ratio 1.69, 95% CI 0.98-2.91, p = 0.06. Overall, 28% of patients survived with good neurologic outcome, ranging from 17 to 43% across hospitals. Conclusion: Within this regional cardiac system, there was significant variation in use of CAG and TTM after OHCA, which was not fully explained by patient-level factors. Hospital size was associated with increased CAG.

Prehospital Predictors of Atypical STEMI Symptoms.

Introduction: Rapid prehospital identification of patients with ST-elevation myocardial infarction (STEMI) is a critical step to reduce time to treatment. Broad screening with field 12-lead ECGs can lead to a high rate of false positive STEMI activations due to low prevalence. One strategy to reduce false positive STEMI interpretations is to limit acquisition of 12-lead ECGs to patients who have symptoms strongly suggestive of STEMI, but this may delay care in patients who present atypically and lead to disparities in populations with more atypical presentations. We sought to assess patient factors associated with atypical STEMI presentation.Methods: We retrospectively analyzed consecutive adult patients for whom Los Angeles Fire Department paramedics obtained a field 12-lead ECG from July 2011 through June 2012. The regional STEMI receiving center registry was used to identify patients with STEMI. Patients were designated as having typical symptoms if paramedics documented provider impressions of chest pain/discomfort, cardiac arrest, or cardiac symptoms, otherwise they were designated as having atypical symptoms. We utilized logistic regression to determine patient factors (age, sex, race) associated with atypical STEMI presentation.Results: Of the 586 patients who had STEMI, 70% were male, 43% White, 16% Black, 20% Hispanic, 5% Asian and 16% were other or unspecified race. Twenty percent of STEMI patients (n = 117) had atypical symptoms. Women who had STEMI were older than men (74 years [IQR 62-83] vs. 60 years [IQR 53-70], p < 0.001). Univariate predictors of atypical symptoms were older age and female sex (p < 0.0001), while in multivariable analysis older age [odd ratio (OR) 1.05 per year, [95%CI 1.04-1.07, p < 0.0001] and black race (OR vs White 2.18, [95%CI 1.20-3.97], p = 0.011) were associated with atypical presentation.Conclusion: Limiting prehospital acquisition of 12-lead ECGs to patients with typical STEMI symptoms would result in one in five patients with STEMI having delayed recognition, disproportionally impacting patients of older age, women, and Black patients. Age, not sex, may be a better predictor of atypical STEMI presentation.

Treatment Time and In-Hospital Mortality Among Patients With ST-Segment Elevation Myocardial Infarction, 2018-2021.

Importance: Recognizing the association between timely treatment and less myocardial injury for patients with ST-segment elevation myocardial infarction (STEMI), US national guidelines recommend specific treatment-time goals. Objective: To describe these process measures and outcomes for a recent cohort of patients. Design, Setting, and Participants: Cross-sectional study of a diagnosis-based registry between the second quarter of 2018 and the third quarter of 2021 for 114 871 patients with STEMI treated at 648 hospitals in the Get With The Guidelines-Coronary Artery Disease registry. Exposures: STEMI or STEMI equivalent. Main Outcomes and Measures: Treatment times, in-hospital mortality, and adherence to system goals (75% treated ≤90 minutes of first medical contact if the first hospital is percutaneous coronary intervention [PCI]-capable and ≤120 minutes if patients require transfer to a PCI-capable hospital). Results: In the study population, median age was 63 (IQR, 54-72) years, 71% were men, and 29% were women. Median time from symptom onset to PCI was 148 minutes (IQR, 111-226) for patients presenting to PCI-capable hospitals by emergency medical service, 195 minutes (IQR, 127-349) for patients walking in, and 240 minutes (IQR, 166-402) for patients transferred from another hospital. Adjusted in-hospital mortality was lower for those treated within target times vs beyond time goals for patients transported via emergency medical services (first medical contact to laboratory activation ≤20 minutes [in-hospital mortality, 3.6 vs 9.2] adjusted OR, 0.54 [95% CI, 0.48-0.60], and first medical contact to device ≤90 minutes [in-hospital mortality, 3.3 vs 12.1] adjusted OR, 0.40 [95% CI, 0.36-0.44]), walk-in patients (hospital arrival to device ≤90 minutes [in-hospital mortality, 1.8 vs 4.7] adjusted OR, 0.47 [95% CI, 0.40-0.55]), and transferred patients (door-in to door-out time <30 minutes [in-hospital mortality, 2.9 vs 6.4] adjusted OR, 0.51 [95% CI, 0.32-0.78], and first hospital arrival to device ≤120 minutes [in-hospital mortality, 4.3 vs 14.2] adjusted OR, 0.44 [95% CI, 0.26-0.71]). Regardless of mode of presentation, system goals were not met in most quarters, with the most delayed system performance among patients requiring interhospital transfer (17% treated ≤120 minutes). Conclusions and Relevance: This study of patients with STEMI included in a US national registry provides information on changes in process and outcomes between 2018 and 2021.

Causes of Prehospital Misinterpretations of ST Elevation Myocardial Infarction.

OBJECTIVES: To determine the causes of software misinterpretation of ST elevation myocardial infarction (STEMI) compared to clinically identified STEMI to identify opportunities to improve prehospital STEMI identification. METHODS: We compared ECGs acquired from July 2011 through June 2012 using the LIFEPAK 15 on adult patients transported by the Los Angeles Fire Department. Cases included patients ≥18 years who received a prehospital ECG. Software interpretation of the ECG (STEMI or not) was compared with data in the regional EMS registry to classify the interpretation as true positive (TP), true negative (TN), false positive (FP), or false negative (FN). For cases where classification was not possible using registry data, 3 blinded cardiologists interpreted the ECG. Each discordance was subsequently reviewed to determine the likely cause of misclassification. The cardiologists independently reviewed a sample of these discordant ECGs and the causes of misclassification were updated in an iterative fashion. RESULTS: Of 44,611 cases, 50% were male (median age 65; inter-quartile range 52-80). Cases were classified as 482 (1.1%) TP, 711 (1.6%) FP, 43371 (97.2%) TN, and 47 (0.11%) FN. Of the 711 classified as FP, 126 (18%) were considered appropriate for, though did not undergo, emergent coronary angiography, because the ECG showed definite (52 cases) or borderline (65 cases) ischemic ST elevation, a STEMI equivalent (5 cases) or ST-elevation due to vasospasm (4 cases). The sensitivity was 92.8% [95% CI 90.6, 94.7%] and the specificity 98.7% [95% CI 98.6, 98.8%]. The leading causes of FP were ECG artifact (20%), early repolarization (16%), probable pericarditis/myocarditis (13%), indeterminate (12%), left ventricular hypertrophy (8%), and right bundle branch block (5%). There were 18 additional reasons for FP interpretation (<4% each). The leading causes of FN were borderline ST-segment elevations less than the algorithm threshold (40%) and tall T waves reducing the ST/T ratio below threshold (15%). There were 11 additional reasons for FN interpretation occurring ≤3 times each. CONCLUSION: The leading causes of FP automated interpretation of STEMI were ECG artifact and non-ischemic causes of ST-segment elevation. FN were rare and were related to ST-segment elevation or ST/T ratio that did not meet the software algorithm threshold.

The effect of high-risk ST elevation myocardial infarction transfer patients on risk-adjusted in-hospital mortality: A report from the American Heart Association Mission: Lifeline program.

BACKGROUND: Hospital mortality is an important quality measure for acute myocardial infarction care. There is a concern that despite risk adjustment, percutaneous coronary intervention hospitals accepting a greater volume of high-risk ST elevation myocardial infarction (STEMI) transfer patients may have their reported mortality rates adversely affected. METHODS: The STEMI patients in the National Cardiovascular Data RegistryAcute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines from April 2011 to December 2013 were included. High-risk STEMI was defined as having either cardiogenic shock or cardiac arrest on first medical contact. Receiving hospitals were divided into tertiles based on the ratio of high-risk STEMI transfer patients to the total number of STEMI patients treated at each hospital. Using the Action Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines in-hospital mortality risk model, we calculated the difference in risk-standardized in-hospital mortality before and after excluding high-risk STEMI transfers in each tertile. RESULTS: Among 119,680 STEMI patients treated at 539 receiving hospitals, 37,028 (31%) were transfer patients, of whom 4,500 (12%) were highrisk. The proportion of high-risk STEMI transfer patients ranged from 0% to 12% across hospitals. Unadjusted mortality rates in the low-, middle-, and high-tertile hospitals were 6.0%, 6.0%, and 5.9% among all STEMI patients and 6.0%, 5.5%, and 4.6% after excluding high-risk STEMI transfers. However, risk-standardized hospital mortality rates were not significantly changed after excluding high-risk STEMI transfer patients in any of the 3 hospital tertiles (low, -0.04%; middle, -0.05%; and high, 0.03%). CONCLUSIONS: Risk-adjusted in-hospital mortality rates were not adversely affected in STEMI-receiving hospitals who accepted more high-risk STEMI transfer patients when a clinical mortality risk model was used for risk adjustment.

A Decade of Progress in Regional ST-Segment Elevation Myocardial Infarction Systems of Care: A Tale of Two Cities.

Over the past 20 years, care for patients with ST-elevation myocardial infarction (STEMI) has rapidly evolved, not just in terms of how patients are treated, but where patients are treated. The advent of regional STEMI systems of care has decreased the number of "eligible but untreated" patients while improving access to primary percutaneous coronary intervention for patients. These regional STEMI systems of care have consistently demonstrated that rapid transport of STEMI patients is safe and effective, and have shown marked improvements in a variety of clinical outcomes. However, no two STEMI systems are alike, and each must be tailored to the unique geographic, political, and socioeconomic challenges of the region. This article takes an in-depth look at two of the earliest STEMI systems within the United States: the Minneapolis Heart Institute and the Los Angeles County STEMI receiving network.

Therapeutic Hypothermia After Resuscitation From a Non-Shockable Rhythm Improves Outcomes in a Regionalized System of Cardiac Arrest Care.

OBJECTIVE: Therapeutic hypothermia (TH) improves neurologic outcome in patients resuscitated from ventricular fibrillation. The purpose of this study was to evaluate TH effects on neurologic outcome in patients resuscitated from a non-shockable out-of-hospital cardiac arrest rhythm. DESIGN AND SETTING: This is a retrospective cohort study of data reported to a registry in an emergency medical system in a large metropolitan region. Patients achieving field return of spontaneous circulation are transported to designated hospitals with TH protocols. PATIENTS: Patients with an initial non-shockable rhythm were identified. Patients were excluded if awake in the Emergency Department or if TH was withheld due to preexisting coma or death prior to initiation. The decision to initiate TH was determined by the treating physician. MEASUREMENTS: The primary outcome was survival with good neurologic outcome defined by a cerebral performance category of 1 or 2. MAIN RESULTS: Of the 2772 patients treated for cardiac arrest during the study period, there were 1713 patients resuscitated from cardiac arrest with an initial non-shockable rhythm and 1432 patients met inclusion criteria. The median age was 69 years [IQR 59-82]; 802 (56%) male. TH was induced in 596 (42%) patients. Survival with good neurologic outcome was 14% in the group receiving TH, compared with 5% in those not treated with TH (risk difference = 8%, 95% CI 5-12%). The adjusted OR for a CPC 1 or 2 with TH was 2.9 (95% CI 1.9-4.4). CONCLUSION: Analyzing the data collected from the registry of the standard practice in a large metropolitan region, TH is associated with improved neurologic outcome in patients resuscitated from initial non-shockable rhythms in a regionalized system for post-resuscitation care.

Current State of ST-Segment Myocardial Infarction: Evidence-based Therapies and Optimal Patient Outcomes in Advanced Systems of Care.

Advances in reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) provide optimal patient outcomes. Reperfusion therapies, including contemporary primary percutaneous coronary intervention, represent decades of clinical evidence development in large clinical trials and national databases. However, rapid identification of STEMI and guideline-directed management of patients across broad populations have been best achieved in advanced systems of care. Current outcomes in STEMI reflect the evolution of both clinical data and idealized health care delivery networks.

The Utility of Prehospital ECG Transmission in a Large EMS System.

BACKGROUND: Prehospital identification of STEMI and activation of the catheterization lab can improve door-to-balloon (D2B) times but may lead to decreased specificity and unnecessary resource utilization. The purpose of this study was to examine the effect of electrocardiogram (ECG) transmission on false-positive (FP) cath lab activations and time to reperfusion. METHODS: This is a retrospective cohort from a registry in a large metropolitan area with regionalized cardiac care and emergency medical services (EMS) with ECG transmission capabilities. Thirty-four designated STEMI receiving centers (SRC) contribute to this registry, from which patients with a prehospital ECG software interpretation of myocardial infarction (MI) indicated by ****Acute MI****, or manufacturer equivalent, were identified between April 2011 and September 2013. Frequency of FP field activations (defined as not resulting in emergent percutaneous coronary intervention [PCI] or referral for CABG during hospital admission) for patients with ECG transmission received by the SRC was compared to a reference group without successful ECG transmission. FP field activations were compared to the baseline frequency of FP ED activations. We hypothesized that successful transmission would reduce FP field activation to ED activation levels. Door-to-balloon and first medical contact-to-balloon (FMC2B) times were compared. The protocol for field cath lab activation varied by institution. RESULTS: There were 7,768 patients presenting with a prehospital ECG indicating MI. The ECG was received by the SRC for 2,156 patients (28%). Regardless of transmission, the cath lab was activated 77% of the time; this activation occurred from the field in 73% and 74% of the activations in the transmission and reference group, respectively. The overall proportion of FP activation was 57%. Among field activations, successful ECG transmission reduced the FP activation rate compared to without ECG transmission, 55% vs. 61% (RD = -6%, 95%CI -9, -3%). This led to an overall system reduction in FP activations of 5% (95%CI 2, 8%). ECG transmission had no effect on D2B and FMC2B time. CONCLUSION: Prehospital ECG transmission is associated with a small reduction in false-positive field activations for STEMI and had no effect on time to reperfusion in this cohort.

Emergency department bypass for ST-Segment-elevation myocardial infarction patients identified with a prehospital electrocardiogram: a report from the American Heart Association Mission: Lifeline program.

BACKGROUND: For patients identified before hospital arrival with ST-segment-elevation myocardial infarction, bypassing the emergency department (ED) with direct transport to the catheterization laboratory may shorten reperfusion times. METHODS AND RESULTS: We studied 12 581 ST-segment-elevation myocardial infarction patients identified with a prehospital ECG treated at 371 primary percutaneous coronary intervention-capable US hospitals participating in the Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines, including those participating in the American Heart Association Mission: Lifeline program from 2008 to 2011. Reperfusion times with primary percutaneous coronary intervention and in-hospital mortality rates were compared between patients undergoing ED evaluation and those bypassing the ED. ED bypass occurred in 1316 patients (10.5%). These patients had a lower frequency of heart failure and shock on presentation and nonsystem reasons for delay in percutaneous coronary intervention. ED bypass occurred more frequently during working hours compared with off-hours (18.3% versus 4.3%); ED bypass rate varied significantly across hospitals (median, 3.3%; range, 0%-71%). First medical contact to device activation time was shorter (median, 68 minutes [interquartile range, 54-85 minutes] versus 88 minutes [interquartile range, 73-106 minutes]; P<0.0001) and achieved within 90 minutes more frequently (80.7% versus 53.7%; P<0.0001) with ED bypass. The unadjusted in-hospital mortality rate was lower among ED bypass patients (2.7% versus 4.1%; P=0.01), but the adjusted mortality risk was similar (adjusted odds ratio, 0.69; 95% confidence interval, 0.45-1.03; P=0.07). CONCLUSIONS: Among ST-segment-elevation myocardial infarction patients identified with a prehospital ECG, the rate of ED bypass varied significantly across US hospitals, but ED bypass occurred infrequently and was mostly isolated to working hours. Because ED bypass was associated with shorter reperfusion times and numerically lower mortality rates, further exploration of and advocacy for the implementation of this process appear warranted.

Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data.

BACKGROUND: Cangrelor is a potent, rapid-acting, reversible intravenous platelet inhibitor that was tested for percutaneous coronary intervention (PCI) in three large, double-blind, randomised trials. We did a pooled analysis of data from three trials that assessed the effectiveness of cangrelor against either clopidogrel or placebo in PCI. METHODS: This prespecified, pooled analysis of patient-level data from three trials (CHAMPION-PCI, CHAMPION-PLATFORM, and CHAMPION-PHOENIX) compared cangrelor with control (clopidogrel or placebo) for prevention of thrombotic complications during and after PCI. Trial participants were patients undergoing PCI for ST-elevation myocardial infarction (11.6%), non-ST-elevation acute coronary syndromes (57.4%), and stable coronary artery disease (31.0%). Efficacy was assessed in the modified intention-to-treat population of 24,910 patients, with a prespecified primary efficacy composite of death, myocardial infarction, ischaemia-driven revascularisation, or stent thrombosis at 48 h. The primary safety outcome was non-coronary artery bypass graft-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe or life-threatening bleeding at 48 h. FINDINGS: Cangrelor reduced the odds of the primary outcome by 19% (3.8% for cangrelor vs 4.7% for control; odds ratio [OR] 0.81, 95% CI 0.71-0.91, p=0.0007), and stent thrombosis by 41% (0.5% vs 0.8%, OR 0.59, 95% CI 0.43-0.80, p=0.0008). Cangrelor reduced the odds of the secondary triple composite (all-cause death, myocardial infarction, or ischaemia-driven revascularisation at 48 h) by 19% (3.6% vs 4.4%, OR 0.81, 95% CI 0.71-0.92, p=0.0014). Efficacy outcomes were consistent across the trials and main patient subsets. These benefits were maintained at 30 days. There was no difference in the primary safety outcome (0.2% in both groups), in GUSTO moderate bleeding (0.6% vs 0.4%), or in transfusion (0.7% vs 0.6%), but cangrelor increased GUSTO mild bleeding (16.8% vs 13.0%, p<0.0001). INTERPRETATION: Compared with control (clopidogrel or placebo), cangrelor reduced PCI periprocedural thrombotic complications, at the expense of increased bleeding. FUNDING: The Medicines Company.

Survival and neurologic outcome after out-of-hospital cardiac arrest: results one year after regionalization of post-cardiac arrest care in a large metropolitan area.

BACKGROUND: Post-resuscitation care of cardiac arrest patients at specialized centers may improve outcome after out-of-hospital cardiac arrest (OOHCA). This study describes experience with regionalized care of resuscitated patients. METHODS: Los Angeles (LA) County established regionalized cardiac care in 2006. Since 2010, protocols mandate transport of nontraumatic OOHCA patients with field return of spontaneous circulation (ROSC) to a STEMI Receiving Center (SRC) with a hypothermia protocol. All SRC report outcomes to a registry maintained by the LA County Emergency Medical Services (EMS) Agency. We report the first year's data. The primary outcome was survival with good neurologic outcome, defined by a Cerebral Performance Category (CPC) score of 1 or 2. RESULTS: The SRC treated 927 patients from April 2011 through March 2012 with median age 67; 38% were female. There were 342 patients (37%) who survived to hospital discharge. CPC scores were unknown in 47 patients. Of the 880 patients with known CPC scores, 197 (22%) survived to hospital discharge with a CPC score of 1 or 2. The initial rhythm was VF/VT in 311 (34%) patients, of whom 275 (88%) were witnessed. For patients with an initial shockable rhythm, 183 (59%) survived to hospital discharge and 120 (41%) had survival with good neurologic outcome. Excluding patients who were alert or died in the ED, 165 (71%) patients with shockable rhythms received therapeutic hypothermia (TH), of whom 67 (42%) had survival with good neurologic outcome. Overall, 387 patients (42%) received TH. In the TH group, the adjusted OR for CPC 1 or 2 was 2.0 (95%CI 1.2-3.5, p = 0.01), compared with no TH. In contrast, the proportion of survival with good neurologic outcome in the City of LA in 2001 for all witnessed arrests (irrespective of field ROSC) with a shockable rhythm was 6%. CONCLUSION: We found higher rates of neurologically intact survival from OOHCA in our system after regionalization of post-resuscitation care as compared to historical data.

Association of the COVID-19 Pandemic on Treatment Times for ST-Elevation Myocardial Infarction: Observations from the Los Angeles County Regional System.

Previous studies have documented longer treatment times and worse outcomes for patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) during the COVID-19 pandemic. The objective of the present study was to evaluate the impact of the COVID-19 pandemic on treatment times and outcomes for patients with STEMI who underwent primary PCI within a regional system of care. This was a retrospective study using data from the Los Angeles County Emergency Medical Services Agency. Data on the emergency medical service activations were abstracted for patients with STEMI from March 19, 2020 to January 31, 2021, during the COVID-19 pandemic and for the same interval the previous year. All adult patients (≥18 years) with STEMI who underwent emergent coronary angiography were included. The primary end point was the first medical contact (FMC) to device time. The secondary end points included treatment time intervals, vascular complications, need for emergent coronary artery bypass surgery, length of hospital stay, and in-hospital mortality. During the study period, 3,017 patients underwent coronary angiography for STEMI, 1,893 patients pre-COVID-19 and 1,124 patients during COVID-19 (40% lower). A total of 2,334 patients (77%) underwent PCI. During the COVID-19 period, rates of PCI were significantly lower compared with the control period (75.1% vs 78.7%, p = 0.02). FMC to device time was shorter during the COVID-19 period compared with the control period (median 77.0 vs 81.0 minutes, p = 0.004). For patients with STEMI complicated by out-of-hospital cardiac arrest, FMC to device time was similar during the COVID-19 period compared with the control period (median 95.0 [33.0] vs 100.0 [40.0] minutes, p = 0.34). Vascular complications, the need for emergent bypass surgery, length of hospital stay, and in-hospital mortality were similar between the periods. In conclusion, in this large regional system of care, we found a relatively small but significant decrease in treatment times, yet overall, similar clinical outcomes for patients with STEMI who underwent primary PCI and were treated during the COVID-19 period compared with a control period. These findings suggest that mature cardiac systems of care were able to maintain efficient care despite the challenges of the COVID-19 pandemic.

Anticoagulation with otamixaban and ischemic events in non-ST-segment elevation acute coronary syndromes: the TAO randomized clinical trial.

IMPORTANCE: The optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial. OBJECTIVE: To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, active-controlled superiority trial that enrolled 13,229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013. A planned interim analysis was conducted for otamixaban dose selection. INTERVENTIONS: Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide. The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7. RESULTS: Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16]; P = .93). There were no differences for the secondary end points, including procedural thrombotic complications. The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78]; P < .001). Results were consistent across prespecified subgroups. CONCLUSIONS AND RELEVANCE: Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01076764.

Platelet inhibition with cangrelor in patients undergoing PCI.

BACKGROUND: Cangrelor, a nonthienopyridine adenosine triphosphate analogue, is an intravenous blocker of the adenosine diphosphate receptor P2Y(12). This agent might have a role in the treatment of patients who require rapid, predictable, and profound but reversible platelet inhibition. METHODS: We performed a large-scale international trial comparing cangrelor with 600 mg of oral clopidogrel administered before percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. The primary efficacy end point was a composite of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. RESULTS: We enrolled 8877 patients, and 8716 underwent PCI. At 48 hours, cangrelor was not superior to clopidogrel with respect to the primary composite end point, which occurred in 7.5% of patients in the cangrelor group and 7.1% of patients in the clopidogrel group (odds ratio, 1.05; 95% confidence interval [CI], 0.88 to 1.24; P=0.59). Likewise, cangrelor was not superior at 30 days. The rate of major bleeding (according to Acute Catheterization and Urgent Intervention Triage Strategy criteria) was higher with cangrelor, a difference that approached statistical significance (3.6% vs. 2.9%; odds ratio, 1.26; 95% CI, 0.99 to 1.60; P=0.06), but this was not the case with major bleeding (according to the Thrombolysis in Myocardial Infarction criteria) or severe or life-threatening bleeding (according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria). A secondary exploratory end point of death from any cause, Q-wave myocardial infarction, or ischemia-driven revascularization showed a trend toward a reduction with cangrelor, but it was not significant (0.6% vs. 0.9%; odds ratio, 0.67; 95% CI, 0.39 to 1.14; P=0.14). CONCLUSIONS: Cangrelor, when administered intravenously 30 minutes before PCI and continued for 2 hours after PCI, was not superior to an oral loading dose of 600 mg of clopidogrel, administered 30 minutes before PCI, in reducing the composite end point of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. (ClinicalTrials.gov number, NCT00305162.)

Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials.

Cangrelor is an intravenous antagonist of the P2Y(12) receptor characterized by rapid, potent, predictable, and reversible platelet inhibition. However, cangrelor was not superior to clopidogrel in reducing the incidence of ischemic events in the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. A prospectively designed platelet function substudy was performed in a selected cohort of patients to provide insight into the pharmacodynamic effects of cangrelor, particularly in regard to whether cangrelor therapy may interfere with the inhibitory effects of clopidogrel. This pre-defined substudy was conducted in a subset of patients from the CHAMPION-PCI trial (n = 230) comparing cangrelor with 600 mg of clopidogrel administered before percutaneous coronary intervention (PCI) and from the CHAMPION-PLATFORM trial (n = 4) comparing cangrelor at the time of PCI and 600 mg clopidogrel given after the PCI. Pharmacodynamic measures included P2Y12 reaction units (PRU) assessed by VerifyNow P2Y12 testing (primary endpoint marker), platelet aggregation by light transmittance aggregometry following 5 and 20 µmol/L adenosine diphosphate stimuli, and markers of platelet activation determined by flow cytometry. The primary endpoint was the percentage of patients who achieved <20 % change in PRU between baseline and >10 h after PCI. The main trial was stopped early limiting enrollment in the platelet substudy. A total of 167 patients had valid pharmacodynamic assessments for the primary endpoint. The percent of individuals achieving <20 % change in PRU between baseline and >10 h after PCI was higher with cangrelor + clopidogrel (32/84, 38.1 %) compared with placebo + clopidogrel (21/83, 25.3 %), but this was not statistically significant (difference:12.79 %, 95 % CI: -1.18 %, 26.77 %;p = 0.076). All pharmacodynamic markers as well as the prevalence of patients with high on-treatment platelet reactivity were significantly lower in patients treated with cangrelor. A rapid platelet inhibitory effect was achieved during cangrelor infusion and a rapid offset of action after treatment discontinuation. This CHAMPION platelet function substudy represents the largest pharmacodynamic experience with cangrelor, demonstrating its potent P2Y(12) receptor inhibitory effects, and rapid onset/offset of action. Although there was no significant pharmacodynamic interaction when transitioning to clopidogrel therapy, further studies are warranted given that enrollment in this study was limited due to premature interruption of the main trial.

Emergency Interhospital Transfer of Patients With ST-Segment-Elevation Myocardial Infarction: Call 9-1-1-The American Heart Association Mission: Lifeline Program.

The American Heart Association Mission: Lifeline program objectives are to improve the quality of care and outcomes for patients with ST-segment-elevation myocardial infarction. Every minute of delay in treatment adversely affects 1-year mortality. Transfer of patients safely and timely to hospitals with primary percutaneous coronary intervention capability is needed to improve outcomes. But treatment times continue to show delays, especially during interhospital transfers. A simple 3-step process of an interhospital "Call 9-1-1" protocol may expedite this process. This STAT TRANSFER process uses a systems approach that considers diverse ways in which patients access care, how EMS responds and determines destinations, how referring hospital transfers are performed, urban and rural differences, and how receiving hospitals prepare for an incoming patient with ST-segment-elevation myocardial infarction. This initiative suggests a strategy to reduce variability in interhospital transfer times using a STAT TRANSFER and a Call 9-1-1 process in a system of care that involves all stakeholders.

Number of coronary heart disease risk factors and mortality in patients with first myocardial infarction.

CONTEXT: Few studies have examined the association between the number of coronary heart disease risk factors and outcomes of acute myocardial infarction in community practice. OBJECTIVE: To determine the association between the number of coronary heart disease risk factors in patients with first myocardial infarction and hospital mortality. DESIGN: Observational study from the National Registry of Myocardial Infarction, 1994-2006. PATIENTS: We examined the presence and absence of 5 major traditional coronary heart disease risk factors (hypertension, smoking, dyslipidemia, diabetes, and family history of coronary heart disease) and hospital mortality among 542,008 patients with first myocardial infarction and without prior cardiovascular disease. MAIN OUTCOME MEASURE: All-cause in-hospital mortality. RESULTS: A majority (85.6%) of patients who presented with initial myocardial infarction had at least 1 of the 5 coronary heart disease risk factors, and 14.4% had none of the 5 risk factors. Age varied inversely with the number of coronary heart disease risk factors, from a mean age of 71.5 years with 0 risk factors to 56.7 years with 5 risk factors (P for trend < .001). The total number of in-hospital deaths for all causes was 50,788. Unadjusted in-hospital mortality rates were 14.9%, 10.9%, 7.9%, 5.3%, 4.2%, and 3.6% for patients with 0, 1, 2, 3, 4, and 5 risk factors, respectively. After adjusting for age and other clinical factors, there was an inverse association between the number of coronary heart disease risk factors and hospital mortality adjusted odds ratio (1.54; 95% CI, 1.23-1.94) among individuals with 0 vs 5 risk factors. This association was consistent among several age strata and important patient subgroups. CONCLUSION: Among patients with incident acute myocardial infarction without prior cardiovascular disease, in-hospital mortality was inversely related to the number of coronary heart disease risk factors.

Sex Differences in Ischemic and Bleeding Outcomes in Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Insights From the TAO Trial.

BACKGROUND: Previous studies have observed poorer outcomes in females with myocardial infarction, but older age and lower use of percutaneous coronary intervention in females are factors that potentially explain the worse outcome. This study sought to determine if female sex is an independent factor of ischemic and bleeding outcomes in non-ST-segment-elevation acute coronary syndrome treated with a systematic invasive approach. METHODS: The TAO trial (Treatment of Acute Coronary Syndrome With Otamixaban) randomized patients with non-ST-segment-elevation acute coronary syndrome treated invasively to heparin plus eptifibatide versus otamixaban. In this post hoc analysis, the primary ischemic end point (all-cause death, myocardial infarction within 180 days) and the primary safety end point (Thrombolysis in Myocardial Infarction major or minor bleeding within 30 days) were analyzed according to sex. RESULTS: Of 13 229 randomized patients, 3980 (30.1%) were females and 9249 (69.9%) were males. Females were older (64.8±11.0 versus 60.7±11.1 years), had more comorbidities, received less peri-procedural antithrombotic therapy, and underwent less frequently revascularization. Overall, females experienced a higher risk of ischemic (10.2% versus 9.1%; odds ratio [OR], 1.15 [1.01-1.30]) and bleeding events (4.2% versus 3.4%; OR, 1.23 [1.02-1.49]) than males. After multivariate analysis, the risk of ischemic outcomes (OR, 1.04 [0.90-1.19]), death (OR, 1.00 [0.75-1.23]), or bleeding (OR, 1.05 [0.85-1.28]), were similar between females and males. Only, noncoronary artery bypass graft related Thrombolysis in Myocardial Infarction major bleeding were increased in females (OR, 1.69 [1.11-2.56]). CONCLUSIONS: In patients with non-ST-segment-elevation acute coronary syndrome with systematic invasive management, ischemic outcomes, bleeding events, and mortality were higher in females. After multivariate analyses, female sex was not an independent predictor of ischemic and bleeding events although noncoronary artery bypass graft related Thrombolysis in Myocardial Infarction major bleeding was higher in females. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01076764.