ACCF/AHA Guideline Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0b013e3182742cf6 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American College of Emergency Physicians and Society for Cardiovascular Angiography and Interventions WRITING COMMITTEE MEMBERS* Patrick T. O Gara, MD, FACC, FAHA, Chair ; Frederick G. Kushner, MD, FACC, FAHA, FSCAI, Vice Chair* ; Deborah D. Ascheim, MD, FACC ; Donald E. Casey, Jr, MD, MPH, MBA, FACP, FAHA ; Mina K. Chung, MD, FACC, FAHA* ; James A. de Lemos, MD, FACC ; Steven M. Ettinger, MD, FACC* ; James C. Fang, MD, FACC, FAHA ; Francis M. Fesmire, MD, FACEP* ; Barry A. Franklin, PhD, FAHA ; Christopher B. Granger, MD, FACC, FAHA* ; Harlan M. Krumholz, MD, SM, FACC, FAHA* ; Jane A. Linderbaum, MS, CNP-BC ; David A. Morrow, MD, MPH, FACC, FAHA* ; L. Kristin Newby, MD, MHS, FACC, FAHA* ; Joseph P. Ornato, MD, FACC, FAHA, FACP, FACEP* ; Narith Ou, PharmD ; Martha J. Radford, MD, FACC, FAHA ; Jacqueline E. Tamis-Holland, MD, FACC ; Carl L. Tommaso, MD, FACC, FAHA, FSCAI#; Cynthia M. Tracy, MD, FACC, FAHA ; Y. Joseph Woo, MD, FACC, FAHA ; David X. Zhao, MD, FACC* ACCF/AHA TASK FORCE MEMBERS Jeffrey L. Anderson, MD, FACC, FAHA, Chair; Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair; Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect; Nancy M. Albert, PhD, CCNS, CCRN, FAHA; Ralph G. Brindis, MD, MPH, MACC; Mark A. Creager, MD, FACC, FAHA; David DeMets, PhD; Robert A. Guyton, MD, FACC, FAHA; Judith S. Hochman, MD, FACC, FAHA; Richard J. Kovacs, MD, FACC; Frederick G. Kushner, MD, FACC, FAHA**; E. Magnus Ohman, MD, FACC; William G. Stevenson, MD, FACC, FAHA; Clyde W. Yancy, MD, FACC, FAHA** *Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. ACCF/AHA representative. ACP representative. ACCF/AHA Task Force on Practice Guidelines liaison. ACCF/ AHA Task Force on Performance Measures liaison. ACEP representative. #SCAI representative. **Former Task Force member during this writing effort. This document was approved by the American College of Cardiology Foundation Board of Trustees and the American Heart Association Science and Advisory Coordinating Committee in June 2012. The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIR.0b013e3182742cf6/- / DC1. The online-only Comprehensive Relationships Table is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/ CIR.0b013e3182742cf6/-/DC2. The American Heart Association requests that this document be cited as follows: O Gara PT, Kushner FG, Ascheim DD, Casey Jr DE, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, WooYJ, Zhao DX. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362 e425. This article has been copublished in the Journal of the American College of Cardiology. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.cardiosource.org) and the American Heart Association (my.americanheart.org). A copy of the document is available at http://my.americanheart.org/statements by selecting either the By Topic link or the By Publication Date link. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com. Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development, visit http://my.americanheart.org/statements and select the Policies and Development link. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/Copyright-Permission- Guidelines_UCM_300404_Article.jsp. A link to the Copyright Permissions Request Form appears on the right side of the page. 2012 by the American College of Cardiology Foundation and the American Heart Association, Inc. O Gara et al 2013 ACCF/AHA STEMI Guideline e363 Table of Contents Preamble e364 1. Introduction e366 1.1. Methodology and Evidence Review e366 1.2. Organization of the Writing Committee e367 1.3. Document Review and Approval e367 2. Background e367 2.1. Definition and Diagnosis e367 2.2. Epidemiology e367 2.3. Early Risk Assessment e369 3. Onset of MI e369 3.1. Patient-Related Delays and Initial Treatment e369 3.2. Mode of Transport to the Hospital e369 3.3. Patient Education e369 Community Preparedness and System Goals for Reperfusion Therapy e370 Regional Systems of STEMI Care, Reperfusion Therapy, and Time-to- Treatment Goals: Recommendations e370 Regional Systems of STEMI Care and Goals for Reperfusion Therapy e371 Strategies for Shortening Door-to-Device Times e372 3.5. Prehospital Fibrinolytic Therapy e373 The Relationship Between Sudden Cardiac Death and STEMI e373 Evaluation and Management of Patients With STEMI and Out-of- Hospital Cardiac Arrest: Recommendations e373 4. Reperfusion at a PCI-Capable Hospital e374 4.1. Primary PCI e374 Primary PCI in STEMI: Recommendations e374 4.2. Aspiration Thrombectomy: Recommendation e375 4.3. Use of Stents in Primary PCI e375 Use of Stents in Patients With STEMI: Recommendations e375 4.4. Adjunctive Antithrombotic Therapy for Primary PCI e375 Antiplatelet Therapy to Support Primary PCI for STEMI: Recommendations e375 Anticoagulant Therapy to Support Primary PCI: Recommendations e378 5. Reperfusion at a Non PCI-Capable Hospital e379 Fibrinolytic Therapy When There Is an Anticipated Delay to Performing Primary PCI Within 120 Minutes of FMC: Recommendations e379 Timing of Fibrinolytic Therapy e379 Choice of Fibrinolytic Agent e379 Contraindications and Complications With Fibrinolytic Therapy e380 5.1.4. Adjunctive Antithrombotic Therapy With Fibrinolysis e380 Adjunctive Antiplatelet Therapy With Fibrinolysis: Recommendations e380 Adjunctive Anticoagulant Therapy With Fibrinolysis: Recommendations e380 Assessment of Reperfusion After Fibrinolysis e381 Transfer to a PCI-Capable Hospital After Fibrinolytic Therapy e381 Transfer of Patients With STEMI to a PCI-Capable Hospital for Coronary Angiography After Fibrinolytic Therapy: Recommendations e381 Transfer for Cardiogenic Shock e382 Transfer for Failure of Fibrinolytic Therapy e382 Transfer for Routine Early Coronary Angiography After Fibrinolytic Therapy e382 6. Delayed Invasive Management e384 Coronary Angiography in Patients Who Initially Were Managed With Fibrinolytic Therapy or Who Did Not Receive Reperfusion: Recommendations e384 PCI of an Infarct Artery in Patients Initially Managed With Fibrinolysis or Who Did Not Receive Reperfusion Therapy: Recommendations e384 PCI of a Noninfarct Artery Before Hospital Discharge: Recommendations e385 Adjunctive Antithrombotic Therapy to Support Delayed PCI After Fibrinolytic Therapy e386 Antiplatelet Therapy to Support PCI After Fibrinolytic Therapy: Recommendations e386 Anticoagulant Therapy to Support PCI After Fibrinolytic Therapy: Recommendations e387 7. Coronary Artery Bypass Graft Surgery e387 CABG in Patients With STEMI: Recommendations e387 Timing of Urgent CABG in Patients With STEMI in Relation to Use of Antiplatelet Agents: Recommendations e388 8. Routine Medical Therapies e388 Beta Blockers: Recommendations e388 8.2. Renin-Angiotensin-Aldosterone System Inhibitors: Recommendations e390 Recommendations for Lipid Management e390 8.4. Nitrates e391 Calcium Channel Blockers e391 8.6. Oxygen e391 Analgesics: Morphine, Nonsteroidal Anti-inflamma- tory Drugs, and Cyclooxygenase II Inhibitors e391 9. Complications After STEMI e391 9.1. Cardiogenic Shock e391 Treatment of Cardiogenic Shock: Recommendations e391 9.2. Severe HF e392 9.3. RV Infarction e392 9.4. Mechanical Complications e392 9.4.1. Diagnosis e392 9.4.2. Mitral Regurgitation e392 Ventricular Septal Rupture e392 LV Free-Wall Rupture e393 9.4.5. LV Aneurysm e393 Electrical Complications During the Hospital Phase of STEMI e393 9.5.1. Ventricular Arrhythmias e393 9.5.2. Implantable Cardioverter-Defibrillator Therapy Before Discharge e393 AF and Other Supraventricular Tachyarrhythmias e393 Bradycardia, AV Block, and Intraventricular Conduction Defects e394 Pacing in STEMI: Recommendation e394 9.6. Pericarditis e394 Management of Pericarditis After STEMI: Recommendations e394 9.7. Thromboembolic and Bleeding Complications . e395 9.7.1. Thromboembolic Complications e395 Anticoagulation: Recommendations e395 Heparin-Induced Thrombocytopenia e395 9.7.2. Bleeding Complications e395 Treatment of ICH e396 Vascular Access Site Bleeding . e396 Acute Kidney Injury e397 Hyperglycemia e397 10. Risk Assessment After STEMI e397 Use of Noninvasive Testing for Ischemia Before Discharge: Recommendations e397 Assessment of LV Function: Recommendation . e398 Assessment of Risk for SCD: Recommendation e398 Posthospitalization Plan of Care e399 Posthospitalization Plan of Care: Recommendations e399 The Plan of Care for Patients With STEMI e399 Smoking Cessation e399 Cardiac Rehabilitation e399 Systems of Care to Promote Care Coordination e399 Unresolved Issues and Future Research Directions e401 12.1. Patient Awareness e401 Regional Systems of Care e401 Transfer and Management of Non High-Risk Patients After Administration of Fibrinolytic Therapy e401 12.4. Antithrombotic Therapy e401 12.5. Reperfusion Injury e401 Approach to Noninfarct Artery Disease e401 Prevention of SCD e402 Prevention of HF e402 References e402 Appendix 1. Author Relationships With Industry and Other Entities (Relevant) e419 Appendix 2. Reviewer Relationships With Industry and Other Entities (Relevant) e422 Appendix 3. Abbreviation List e425 Preamble The medical profession should play a central role in evaluating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When prop- erly applied, expert analysis of available data on the benefits and risks of these therapies and procedures can improve the quality of care, optimize patient outcomes, and favorably affect costs by focusing resources on the most effective strategies. An orga- nized and directed approach to a thorough review of evidence has resulted in the production of clinical practice guidelines that assist physicians in selecting the best management strategy for an individual patient. Moreover, clinical practice guidelines can provide a foundation for other applications, such as performance measures, appropriate use criteria, and both quality improve- ment and clinical decision support tools. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly pro- duced guidelines in the area of cardiovascular disease since 1980. The ACCF/AHA Task Force on Practice Guidelines (Task Force), charged with developing, updating, and revis- ing practice guidelines for cardiovascular diseases and proce- dures, directs and oversees this effort. Writing committees are charged with regularly reviewing and evaluating all available evidence to develop balanced, patient-centric recommenda- tions for clinical practice. Experts in the subject under consideration are selected by the ACCF and AHA to examine subject-specific data and write guidelines in partnership with representatives from other medical organizations and specialty groups. Writing commit- tees are asked to perform a formal literature review; weigh the strength of evidence for or against particular tests, treatments, or procedures; and include estimates of expected outcomes where such data exist. Patient-specific modifiers, comorbidi- ties, and issues of patient preference that may influence the choice of tests or therapies are considered. When available, information from studies on cost is considered, but data on efficacy and outcomes constitute the primary basis for the rec- ommendations contained herein. In analyzing the data and developing recommendations and supporting text, the writing committee uses evidence-based methodologies developed by the Task Force.1 The Class of Recommendation (COR) is an estimate of the size of the treatment effect considering risks versus benefits in addi- tion to evidence and/or agreement that a given treatment or procedure is or is not useful/effective or in some situations may cause harm. The Level of Evidence (LOE) is an esti- mate of the certainty or precision of the treatment effect. The writing committee reviews and ranks evidence supporting O Gara et al 2013 ACCF/AHA STEMI Guideline e365 each recommendation with the weight of evidence ranked as LOE A, B, or C according to specific definitions that are included in Table 1. Studies are identified as observational, retrospective, prospective, or randomized where appro- priate. For certain conditions for which inadequate data are available, recommendations are based on expert con- sensus and clinical experience and are ranked as LOE C. When recommendations at LOE C are supported by histori- cal clinical data, appropriate references (including clinical reviews) are cited if available. For issues for which sparse data are available, a survey of current practice among the members of the writing committee is the basis for LOE C recommendations and no references are cited. The schema for COR and LOE is summarized in Table 1, which also provides suggested phrases for writing recommendations within each COR. A new addition to this methodology is separation of the Class III recommendations to delineate whether the recom- mendation is determined to be of no benefit or is associ- ated with harm to the patient. In addition, in view of the increasing number of comparative effectiveness studies, comparator verbs and suggested phrases for writing recom- mendations for the comparative effectiveness of one treat- ment or strategy versus another are included for COR I and IIa, LOE A or B only. In view of the advances in medical therapy across the spectrum of cardiovascular diseases, the Task Force has designated the term guideline-directed medical therapy Table 1. Classification of Recommendation and Level of Evidence A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. For comparative effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated. (GDMT) to represent optimal medical therapy as defined by ACCF/AHA guideline-recommended therapies (primarily Class I). This new term, GDMT, will be used throughout sub- sequent guidelines. Because the ACCF/AHA practice guidelines address patient populations (and healthcare providers) residing in North America, drugs that are not currently available in North America are discussed in the text without a specific COR. For studies performed in large numbers of subjects outside North America, each writing committee reviews the potential influ- ence of different practice patterns and patient populations on the treatment effect and relevance to the ACCF/AHA target population to determine whether the findings should inform a specific recommendation. The ACCF/AHA practice guidelines are intended to assist healthcare providers in clinical decision making by describ- ing a range of generally acceptable approaches to the diag- nosis, management, and prevention of specific diseases or conditions. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and patient in light of all the circumstances presented by that patient. As a result, situ- ations may arise for which deviations from these guidelines may be appropriate. Clinical decision making should involve consideration of the quality and availability of expertise in the area where care is provided. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care. The Task Force recognizes that situations arise in which additional data are needed to inform patient care more effectively; these areas are identified within each respective guideline when appropriate. Prescribed courses of treatment in accordance with these recommendations are effective only if followed. Because lack of patient understanding and adherence may adversely affect outcomes, physicians and other healthcare providers should make every effort to engage the patient s active participation in prescribed medical regimens and lifestyles. In addition, patients should be informed of the risks, benefits, and alterna- tives to a particular treatment and should be involved in shared decision making whenever feasible, particularly for COR IIa and IIb, for which the benefit-to-risk ratio may be lower. The Task Force makes every effort to avoid actual, poten- tial, or perceived conflicts of interest that may arise as a result of relationships with industry and other entities (RWI) among the members of the writing committee. All writing committee members and peer reviewers of the guideline are required to disclose all current healthcare-related relation- ships, including those existing 1 year before initiation of the writing effort. In December 2009, the ACCF and AHA implemented a new RWI policy that requires the writing committee chair plus a minimum of 50% of the writing com- mittee to have no relevant RWI. (Appendix 1 includes the ACCF/AHA definition of relevance.) These statements are reviewed by the Task Force and all members during each conference call and/or meeting of the writing committee, and members provide updates as changes occur. All guideline recommendations require a confidential vote by the writing committee and must be approved by a consensus of the vot- ing members. Members may not draft or vote on any text or recommendations pertaining to their RWI. Members who recused themselves from voting are indicated in the list of writing committee members, and specific section recusals are noted in Appendix 1. Authors and peer reviewers RWI pertinent to this guideline are disclosed in Appendixes 1 and 2, respectively. In addition, to ensure complete transparency, writing committee members comprehensive disclosure information including RWI not pertinent to this docu- ment is available as an online supplement. Comprehensive disclosure information for the Task Force is also available online at http://www.cardiosource.org/ACC/About-ACC/ Who-We-Are/Leadership/Guidelines-and-Documents-Task- Forces.aspx. The work of writing committees is supported exclusively by the ACCF and AHA without commercial sup- port. Writing committee members volunteered their time for this activity. In an effort to maintain relevance at the point of care for practicing physicians, the Task Force continues to oversee an ongoing process improvement initiative. As a result, in response to pilot projects, several changes to these guidelines will be apparent, including limited narrative text, a focus on summary and evidence tables (with references linked to abstracts in PubMed), and more liberal use of summary rec- ommendation tables (with references that support LOE) to serve as a quick reference. In April 2011, the Institute of Medicine released 2 reports: Finding What Works in Health Care: Standards for Systematic Reviews and Clinical Practice Guidelines We Can It is noteworthy that the IOM cited ACCF/AHA prac- tice guidelines as being compliant with many of the proposed standards. A thorough review of these reports and of our cur- rent methodology is under way, with further enhancements anticipated. The recommendations in this guideline are considered cur- rent until they are superseded by a focused update or the full- text guideline is revised. Guidelines are official policy of both the ACCF and AHA. Jeffrey L. Anderson, MD, FACC, FAHA Chair, ACCF/AHA Task Force on Practice Guidelines 1.1. Methodology and Evidence Review The recommendations listed in this document are, whenever possible, evidence based. The current document constitutes a full revision and includes an extensive evidence review, which was conducted through November 2010, with additional selected references added through August 2012. Searches were limited to studies conducted in human subjects and reviews and other evidence pertaining to human subjects; all were published in English. Key search words included but were not limited to: acute coronary syndromes, percutaneous coronary intervention, coronary artery bypass graft, myocar- dial infarction, ST-elevation myocardial infarction, coronary stent, revascularization, anticoagulant therapy, antiplatelet O Gara et al 2013 ACCF/AHA STEMI Guideline e367 therapy, antithrombotic therapy, glycoprotein IIb/IIIa inhibitor therapy, pharmacotherapy, proton-pump inhibitor, implantable cardioverter-defibrillator therapy, cardiogenic shock, fibrinolytic therapy, thrombolytic therapy, nitrates, mechanical complications, arrhythmia, angina, chronic sta- ble angina, diabetes, chronic kidney disease, mortality, mor- bidity, elderly, ethics, and contrast nephropathy. Additional searches cross-referenced these topics with the following subtopics: percutaneous coronary intervention, coronary artery bypass graft, cardiac rehabilitation, and secondary prevention. Additionally, the committee reviewed documents related to the subject matter previously published by the ACCF and AHA. References selected and published in this document are representative and not all-inclusive. To provide clinicians with a comprehensive set of data, whenever deemed appropriate or when published, the abso- lute risk difference and number needed to treat or harm are provided in the guideline, along with confidence intervals (CI) and data related to the relative treatment effects such as odds ratio (OR), relative risk (RR), hazard ratio (HR), or incidence rate ratio. The focus of this guideline is the management of patients with ST-elevation myocardial infarction (STEMI). Updates to the 2004 STEMI guideline were published in 2007 and Particular emphasis is placed on advances in reper fusion therapy, organization of regional systems of care, transfer algorithms, evidence-based antithrombotic and medi- cal therapies, and secondary prevention strategies to opti mize patient-centered care. By design, the document is narrower in scope than the 2004 STEMI Guideline, in an attempt to pro- vide a more focused tool for practitioners. References related to management guidelines are provided whenever appropriate, including those pertaining to percutaneous coronary interven- tion (PCI), coronary artery bypass graft (CABG), heart failure (HF), cardiac devices, and secondary prevention. 1.2. Organization of the Writing Committee The writing committee was composed of experts representing cardiovascular medicine, interventional cardiology, electro- physiology, HF, cardiac surgery, emergency medicine, inter- nal medicine, cardiac rehabilitation, nursing, and pharmacy. The American College of Physicians, American College of Emergency Physicians, and Society for Cardiovascular Angi- ography and Interventions assigned official representatives. 1.3. Document Review and Approval This document was reviewed by 2 outside reviewers each nominated by the ACCF and the AHA, as well as 2 review- ers each from the American College of Emergency Physicians and Society for Cardiovascular Angiography and Interven- tions and 22 individual content reviewers (including members from the ACCF Interventional Scientific Council and ACCF Surgeons Scientific Council). All reviewer RWI information was distributed to the writing committee and is published in this document (Appendix 2). This document was approved for publication by the gov- erning bodies of the ACCF and the AHA and was endorsed by the American College of Emergency Physicians and Society for Cardiovascular Angiography and Interventions. 2.1. Definition and Diagnosis STEMI is a clinical syndrome defined by characteristic symp- toms of myocardial ischemia in association with persistent electrocardiographic (ECG) ST elevation and subsequent release of biomarkers of myocardial necrosis. Diagnostic ST elevation in the absence of left ventricular (LV) hypertrophy or left bundle-branch block (LBBB) is defined by the Euro- pean Society of Cardiology/ACCF/AHA/World Heart Fed- eration Task Force for the Universal Definition of Myocardial Infarction as new ST elevation at the J point in at least 2 con- tiguous leads of 2 mm (0.2 mV) in men or 1.5 mm (0.15 mV) in women in leads V2 V3 and/or of 1 mm (0.1 mV) in other contiguous chest leads or the limb leads.7 The major- ity of patients will evolve ECG evidence of Q-wave infarc- tion. New or presumably new LBBB has been considered a STEMI equivalent. Most cases of LBBB at time of presen- tation, however, are not known to be old because of prior electrocardiogram (ECG) is not available for comparison. New or presumably new LBBB at presentation occurs infre- quently, may interfere with ST-elevation analysis, and should not be considered diagnostic of acute myocardial infarction (MI) in isolation.8 Criteria for ECG diagnosis of acute STEMI in the setting of LBBB have been proposed (see Online Data Supplement 1). Baseline ECG abnormalities other than LBBB (eg, paced rhythm, LV hypertrophy, Brugada syndrome) may obscure interpretation. In addition, ST depression in 2 precor- dial leads (V1 V4) may indicate transmural posterior injury; multilead ST depression with coexistent ST elevation in lead aVR has been described in patients with left main or proximal left anterior descending artery occlusion.9 Rarely, hyperacute T-wave changes may be observed in the very early phase of STEMI, before the development of ST elevation. Transtho- racic echocardiography may provide evidence of focal wall motion abnormalities and facilitate triage in patients with ECG findings that are difficult to interpret. If doubt persists, immediate referral for invasive angiography may be necessary to guide therapy in the appropriate clinical context.10,11 Car- diac troponin is the preferred biomarker for diagnosis of MI. In 2009, approximately 683000 patients were discharged from US hospitals with a diagnosis of acute coronary syndrome (ACS). Community incidence rates for STEMI have declined over the past decade, whereas those for non ST-elevation ACS have increased (Figure 1). At present, STEMI comprises approximately 25% to 40% of MI presen- (approximately 7% to 18%) mortality rates from STEMI also have decreased significantly in association with a substantial increase in the frequency of care that includes GDMT and interventions ( defect-free care).13,15 18 In the United States, important regional differences exist in 30-day acute MI hospital mortality and readmission rates for Medicare ben- eficiaries 65 years of age.19 Understanding the reasons for such differences may provide opportunities for performance Approximately 30% of patients with STEMI are women. Female sex was a strong independent predictor of failure to receive reperfusion therapy among patients who had no contraindications in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Compared with men, women included in the NCDR (National Cardiovascular Data Registry) ACTION Registry GWTG (Get With The Guidelines) pre- sented later after symptom onset, had longer door-to-fibrino- lysis and door-to-balloon (or device) (D2B) times, and less often received aspirin or beta blockers within 24 hours of presentation. Women further were characterized by a higher risk for bleeding with antithrombotic therapy, which persisted after consideration of age, weight, blood pressure (BP) at presentation, renal function, baseline hematocrit, and other Nonwhites represented 13.3% of patients with STEMI at hospitals participating in the ACTION Registry GWTG Importantly, disparities in the treatment of racial and ethnic minorities appear to be improv- ing over time.23 In an assessment of the effects of a statewide program for treatment of STEMI, institution of a coordinated regional approach to triage and management was associated with significant improvements in treatment times that were similar for whites and blacks and for women and men.23 The writing committee endorses the desirability of collecting and using accurate data on patient race and ethnicity to detect dis- parities, guide quality improvement initiatives, and strengthen ties to the community.24 Approximately 23% of patients with STEMI in the United States have diabetes mellitus,17 and three quarters of all deaths among patients with diabetes mellitus are related to coronary artery disease.25,26 Diabetes mellitus is associated with higher short- and long-term mortality after STEMI,27,28 and in patients with diabetes mellitus, both hyperglycemia and hypoglycemia are associated with worse outcomes.29 Hyperglycemia at presentation in patients who do not have diabetes mellitus by history has been associated with worse Myocardial tissue perfusion after restoration of epicardial coronary flow was more impaired among patients with diabetes mellitus ( no-reflow ).28,35,36 Management of patients with diabetes mellitus and STEMI should be the same as for patients without diabetes mellitus, with attention to moderate glycemic control. The elderly comprise a growing segment of the population and present special challenges for diagnosis and management that may lead to disparities in care and delays in treatment. Additional issues to consider include the risks of antithrom- botic and interventional therapies and the appropriate bound- aries of care within the context of individual comorbidities, frailty, and advanced-care directives. Clinical trials frequently have limited enrollment of older populations.37 Treatments that are effective in younger populations usually are indicated in the elderly, with the caveat that the elderly more often have absolute or relative contraindications to their use. Impaired renal function associated with aging requires careful attention to drug dosing.38,39 In an analysis of 8578 patients with STEMI from 226 US hospitals participating in the CRUSADE quality improvement initiative from September 2004 to December 2006, 7% of eli- gible patients did not receive reperfusion therapy.21 The factor most strongly associated with not providing reperfusion ther- apy in eligible patients was increasing age. Evidence suggests that even the very elderly have reasonable post-MI outcomes when treated aggressively with reperfusion therapy,40 though individual circumstances vary. Both the GWTG Quality Improvement Program and the North Carolina Reperfusion of Acute Myocardial Infarction in Carolina Emergency Department s initiative demonstrated that focused quality improvement efforts and programs designed to systematize care across integrated regional cen- ters can lessen disparities and improve the care of elderly patients with STEMI.23,41 Numerous studies have highlighted the fact that patients with chronic kidney disease of all stages less frequently receive guideline-recommended interventions than do patients with nor- mal renal function, despite evidence of benefit from most acute In a project that linked the US Renal Data System database with the NRMI (National Registry of Myocardial Infarction) 3, patients on dialysis had longer prehospital delays, werelessoftenrecognizedashavinganacuteMI,andlessoftenhad STelevationorLBBBoninitialECGthanpatientsnotondialysis. apy, and only 70% received aspirin on admission. The in-hospital Figure 1. Age- and sex-adjusted incidence rates of acute MI, 1999 to 2008. I bars represent 95% con- fidence intervals. MI indicates myocardial infarction; STEMI, ST-elevation myocardial infarction. Reprinted with permission from Yeh et al.14 O Gara et al 2013 ACCF/AHA STEMI Guideline e369 mortality rate was 21.3% among patients on dialysis, compared with 11.7% for patients with end-stage renal failure not on dialy- sis. At discharge, only 67% of patients on dialysis were pre- scribed aspirin, and only 57% were prescribed beta blockers. In the GRACE (Global Registry of Acute Coronary Events) regis- try, the in-hospital mortality rate was approximately 30% among patients with STEMI or LBBB MI with stage 4 or 5 chronic kidney disease. Both fibrinolysis and primary PCI were associ- ated with higher bleeding rates in patients with severely reduced Progressive renal dysfunction is a strong pre- dictor of bleeding with antithrombotic therapy, a risk that may reflect intrinsic renal dysfunction and/or failure to adjust or avoid antithrombotic medications that are dependent on renal 2.3. Early Risk Assessment Global risk assessment provides an opportunity to integrate various patient characteristics into a semiquantitative score that can convey an overall estimate of a patient s prognosis; can dictate the acuity, intensity, and location of care; and can provide the patient and family with a more informed sense of potential outcome. Higher risk scores generally imply that higher-intensity treatments may be appropriate within the context of the patient s health status. Some of the independent predictors of early death from STEMI include age, Killip class, time to reperfusion, cardiac arrest, tachycardia, hypotension, anterior infarct location, prior infarction, diabetes mellitus, smoking status, renal func- tion, and biomarker findings.48,49 Whereas the Thrombolysis In Myocardial Infarction (TIMI) risk score was developed specifically in patients with STEMI (http://www.mdcalc.com/ timi-risk-score-for-stemi), the GRACE model (http://www. outcomes-umassmed.org/grace/acs_risk/acs_risk_content. html) predicts in-hospital and 6-month mortality rate across the spectrum of patients presenting with ACS, including those with ST elevation or ST depression. Risk assessment is a con- tinuous process that should be repeated throughout hospital- ization and at time of discharge. 3. Onset of MI 3.1. Patient-Related Delays and Initial Treatment Patients with STEMI do not seek medical care for approxi- mately 1.5 to 2 hours after symptom onset, and little change in this interval has occurred over the past 10 years.50,51 Patient delay times are often longer in women, blacks, the elderly, and Medicaid-onlyrecipientsandareshorterforMedicarerecipients (compared with privately insured patients) and patients who are taken directly to the hospital by emergency medical services Patients may delay seeking care because their symptoms differ from their preexisting bias that a heart attack should present dramatically with severe, crushing chest Approximately one third of patients with MI experience symptoms other than chest pain.7 Other reasons for delay in seeking treatment include 1) inappropriate reasoning that symp- toms will be self-limited or are not serious55 57 ; 2) attribution of symptoms to other preexisting conditions; 3) fear of embarrass- ment should symptoms turn out to be a false alarm ; 4) reluc- stereotypes of who is at risk for a heart attack, an especially common trait among women59 ; 6) lack of knowledge of the importance of rapid action, the benefits of calling EMS or 9-1-1, and the availability of reperfusion therapies54 ; and 7) attempted self-treatment with prescription and/or nonprescrip- To avoid such delays, healthcare providers should assist patients when possible in making anticipatory plans for timely recognition and response to an acute event. Family members, close friends, or advocates also should be enlisted as reinforcement for rapid action when the patient experiences symptoms of possible STEMI.60,61 Discussions should include a review of instructions for taking aspirin62 and nitroglycerin in response to chest pain. Emergency medi- cal dispatchers are trained to instruct patients with possible STEMI symptoms to chew non enteric-coated aspirin (162 to 325 mg), unless contraindicated, while personnel are en route. If nitroglycerin is prescribed, the patient should be advised to take 1 nitroglycerin dose promptly. If symptoms are unim- proved or worsening 5 minutes after 1 dose, the patient should be instructed to call 9-1-1 immediately. 3.2. Mode of Transport to the Hospital Even though >98% of the US population is covered by 9-1-1 patients with STEMI often do not call EMS or 9-1-1 and are not transported to the hospital by ambulance. In a 2011 observational study from the ACTION Registry GWTG that used data reported from a limited number of predomi- nantly PCI-capable US hospitals, EMS transport was used for Older US surveys reported EMS activation rates of 23% to 53%, with substantial Patients with possible ischemic symptoms should be trans- ported to the hospital by ambulance rather than by friends or relatives because 1) 1 in every 300 patients with chest pain transported to the emergency department (ED) by private vehicle suffers cardiac arrest en route67 ; and 2) there is a sig- nificant association between arrival at the ED by ambulance and earlier delivery of reperfusion therapy.64 66,68 In addition, the performance of prehospital ECGs by trained personnel is associated with shorter reperfusion times69 and lower mortal- ity rates from STEMI. The use of prehospital ECGs, particu- larly when coupled with communication of STEMI diagnosis and preferential transport to a PCI-capable hospital, has been shown to result in rapid reperfusion times and excellent clini- 3.3. Patient Education The AHA and National Institutes of Health Act in Time to Heart Attack Signs campaign73 stresses that patients can increase their chance of surviving STEMI by learning the warning symptoms, filling out a survival plan, and discuss- ing risk reduction with their physician. These materials are available on the National Institutes of Health Heart Attack Web page (http://health.nih.gov/topic/HeartAttack/).74 Health- care providers should target their educational interventions to patients at increased risk for ACS.75 3.4. Community Preparedness and System Goals for Reperfusion Therapy 3.4.1. Regional Systems of STEMI Care, Reperfusion Therapy, and Time-to-Treatment Goals: Recommendations See Figure 2. Class I 1. All communities should create and maintain a re- gional system of STEMI care that includes assess- ment and continuous quality improvement of EMS and hospital-based activities. Performance can be facilitated by participating in programs such as Mission: Lifeline and the D2B Alliance.71,76 78 (Level of Evidence: B) 2. Performance of a 12-lead ECG by EMS personnel at the site of first medical contact (FMC) is recom- mended in patients with symptoms consistent with (Level of Evidence: B) 3. Reperfusion therapy should be administered to all eligible patients with STEMI with symptom onset within the prior 12 hours.81,82 (Level of Evidence: A) 4. Primary PCI is the recommended method of reperfu- sion when it can be performed in a timely fashion by (Level of Evidence: A) 5. EMS transport directly to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI, with an ideal FMC-to-device time system goal of 90 minutes or less.*70 72 (Level of Evidence: B) 6. Immediate transfer to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI who initially arrive at or are transported to a non PCI-capable hospital, with an FMC-to-device time system goal of 120 minutes or (Level of Evidence: B) 7. In the absence of contraindications, fibrinolytic therapy should be administered to patients with STEMI at non PCI-capable hospitals when the an- ticipated FMC-to-device time at a PCI-capable hos- pital exceeds 120 minutes because of unavoidable (Level of Evidence: B) 8. When fibrinolytic therapy is indicated or chosen as the primary reperfusion strategy, it should be ad- ministered within 30 minutes of hospital arrival.*89 93 (Level of Evidence: B) Class IIa 1. Reperfusion therapy is reasonable for patients with STEMI and symptom onset within the prior 12 to 24 hours who have clinical and/or ECG evidence of on- going ischemia. Primary PCI is the preferred strat- egy in this population.81,94,95 (Level of Evidence: B) *The proposed time windows are system goals. For any individual patient, every effort should be made to provide reperfusion therapy as rapidly as possible. Figure 2. Reperfusion therapy for patients with STEMI. The bold arrows and boxes are the preferred strategies. Performance of PCI is dictated by an anatomically appropriate culprit stenosis. *Patients with cardiogenic shock or severe heart failure initially seen at a non PCI-capable hospital should be transferred for cardiac catheterization and revascularization as soon as possible, irrespective of time delay from MI onset (Class I, LOE: B). Angiography and revascularization should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy. CABG indicates coronary artery bypass graft; DIDO, door-in door- out, FMC, first medical contact; LOE, Level of Evidence; MI, myocardial infarction; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction. O Gara et al 2013 ACCF/AHA STEMI Guideline e371 3.4.1.1. Regional Systems of STEMI Care and Goals for Reperfusion Therapy Any regional medical system must seek to enable rapid rec- ognition and timely reperfusion of patients with STEMI. System delays to reperfusion are correlated with higher rates of mortality and morbidity.96 100 Although attention to certain performance metrics, such as D2B, door-to-needle, and door-in door-out times, have catalyzed important insti- tutional quality improvement efforts, broader initiatives at a systems level are required to reduce total ischemic time, the principal determinant of outcome.101,102 Questions have been raised about the overreliance on primary PCI for reper- fusion, especially in the United States, and the unintended consequences that have evolved as familiarity with fibrino- lysis has waned.101 The writing committee reiterates the prin- ciple highlighted in the 2004 ACC/AHA STEMI guideline, namely that the appropriate and timely use of some form of reperfusion therapy is likely more important than the choice of therapy. 4 Greatest emphasis is to be placed on the delivery of reperfusion therapy to the individual patient as rapidly as possible. Only a minority of US hospitals are capable of performing and any delay in time to reperfusion (D2B) after hospital arrival is associated with a higher adjusted risk of in-hospital mortality in a continuous, nonlinear fashion.96 Strict time goals for reperfusion may not always be relevant or possible for patients who have an appropriate reason for delay, including initial uncertainty about diagnosis, the need for evaluation and treatment of other life-threatening condi- tions (eg, acute respiratory failure, cardiac arrest), delays involving informed consent, and long transport times due to geographic distance or adverse weather. To reduce hospital treatment delays, the ACC initiated the D2B Alliance in 2006 to improve door-to-device times in patients with STEMI.104 The D2B Alliance goal was for participating PCI-capable hospitals to achieve a D2B time of 90 minutes for at least 75% of nontransferred patients with STEMI. The Alliance met this goal by 2008.105 A longitudinal study of hospitals par- ticipating in the NCDR CathPCI Registry demonstrated that patients treated in hospitals that had been enrolled in the D2B Alliance for 3 months were significantly more likely to have D2B times of 90 minutes than patients treated in nonenrolled In a similar manner, the AHA launched Mission: Lifeline in 2007 to improve health system readiness and response to with a focus on the continuum of care from EMS activation to primary PCI. Patients may present directly by private transport to a PCI-capable hospital, in which case all medical care occurs in a single center responsible for opti- mizing door-to-device times. For patients who call 9-1-1, direct care begins with FMC, defined as the time at which the EMS provider arrives at the patient s side. EMS person- nel should be accountable for obtaining a prehospital ECG, making the diagnosis, activating the system, and deciding whether to transport the patient to a PCI-capable or non PCI- capable hospital. Consideration should be given to the devel- opment of local protocols that allow preregistration and direct transport to the catheterization laboratory of a PCI-capable hospital (bypassing the ED) for patients who do not require emergent stabilization upon arrival. Although false posi- tives are a concern when EMS personnel and/or emergency physicians are allowed to activate the cardiac catheteriza- tion laboratory, the rate of false activations is relatively low (approximately 15%) and is more than balanced by earlier treatment times for the majority of patients for whom noti- fication is appropriate.108 114 The concept of what constitutes false activation is evolving.115,116 For patients who arrive at or are transported by EMS to a non PCI-capable hospital, a decision about whether to transfer immediately to a PCI- capable hospital or to administer fibrinolytic therapy must be made. Each of these scenarios involves coordination of dif- ferent elements of the system. On the basis of model systems of STEMI care in the United States and Europe,77,78,117 121 Mission: Lifeline recommends a multifaceted community- wide approach that involves patient education, improve- ments in EMS and ED care, establishment of networks of STEMI-referral (non PCI-capable) and STEMI-receiving (PCI-capable) hospitals, and coordinated advocacy efforts to work with payers and policy makers to implement healthcare system redesign. Detailed information about this program can be found on the AHA website.122 Several factors should be considered in selecting the type of reperfusion therapy (Figure 2). For patients with STEMI presenting to a PCI-capable hospital, primary PCI should be accomplished within 90 minutes. For patients presenting to a non PCI-capable hospital, rapid assessment of 1) the time from onset of symptoms, 2) the risk of complications related to STEMI, 3) the risk of bleeding with fibrinolysis, 4) the presence of shock or severe HF, and 5) the time required for transfer to a PCI-capable hospital must be made and a deci- sion about administration of fibrinolytic therapy reached. Even when interhospital transfer times are short, there may be relative advantages to a strategy of immediate fibrinolytic therapy versus any delay to primary PCI for eligible patients who present within the first 1 to 2 hours after symptom Several trials have suggested a benefit of transferring patients with STEMI from a non PCI-capable hospital to a PCI-capable hospital for primary PCI,83,125 but in many instances, transfer times are prolonged and delays may be unavoidable. In the NCDR,126,127 only 10% of transferred patients were treated within 90 minutes of initial presenta- tion, with a median first door-to-device time of 149 minutes. In many communities, a significant percentage of patients with STEMI who present initially to a non PCI-capable hos- pital cannot physically be transferred to a PCI-capable hos- pital and achieve an FMC-to-device time treatment goal of 90 minutes. DANAMI-2 (Danish Multicenter Randomized Study on Thrombolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction) showed that a reperfusion strategy involving the transfer of patients with STEMI from a non PCI-capable hospital to a PCI-capable hospital for primary PCI was superior to the use of fibrino- lysis at the referring hospital, driven primarily by a reduc- tion in the rate of reinfarction in the primary PCI treated In this study, the average first door-to-device time delay was approximately 110 minutes.85 Shorter system delays were associated with a reduced mortality rate for both fibrinolysis- and primary PCI treated patients. In an analysis of approximately 19000 propensity score matched patients with STEMI from NRMI-2, -3, -4, and -5, when delays related to transfer for primary PCI exceeded 120 minutes from FMC, the survival advantage of primary PCI over fibrinolysis was negated. Delays beyond 120 minutes occurred in nearly half the patients in the analysis.100 Thus, interhospital transfer to a PCI-capable hospital is the recommended triage strategy if primary PCI consistently can be performed within 120 min- utes of FMC. Fibrinolytic therapy, in the absence of contrain- dications to its use, should be administered within 30 minutes of first door arrival when this 120-minute time goal cannot be met. Transfer delays can occur at multiple levels and for Efforts are needed to reduce the time delay between arrival to and transfer from a non PCI-capable hos- pital (ie, door-in door-out). Among a subset of 14821 patients in the NCDR ACTION GWTG registry, the median door-in door-out time was 68 minutes (interquartile range, 43 to 120 minutes). A door-in door-out time 30 minutes, achieved in only 11% of patients, was associated with shorter delays to reperfusion and a lower in-hospital mortality rate.129 Because estimation of treatment times for patients can be inaccurate, the decision to transfer for primary PCI should be based on actual, historical times achieved within the regional system, with quality assurance programs to ensure that such goals are consistently met. A reasonable goal would be that 90% of patients should meet the 120-minute time-to-treatment stan- dard to achieve performance standards. Several triage and transfer strategies have been tested and are discussed further in Section 5.3. The term facilitated PCI was used previously to describe a strategy of full- or half-dose fibrinolysis, with or without administration of a glycoprotein (GP) IIb/IIIa receptor antagonist, with immediate transfer for planned PCI within 90 to 120 minutes. Two large stud- ies failed to show a net clinical benefit with this strategy.130,131 The term rescue PCI refers to the transfer for PCI of patients who demonstrate findings of failed reperfusion with fibrino- The term pharmacoinvasive strategy refers to the administration of fibrinolytic therapy either in the prehospital setting or at a non PCI-capable hospital, followed by immedi- ate transfer to a PCI-capable hospital for early coronary angi- ography and PCI when appropriate. Patients with STEMI who are best suited for immediate interhospital transfer for primary PCI without fibrinolysis are those patients who present with shock or other high-risk features, those with high bleeding risk with fibrinolytic therapy, and those who present >3 to 4 hours after symptom onset and who have short transfer times. Patients best suited for initial fibrinolytic therapy are those with low bleeding risk who present very early after symptom onset (<2 to 3 hours) to a non PCI-capable hospital and who have longer delay to PCI. Because patients with STEMI may first present with cardiac arrest, regional systems also should emphasize early access to care (recognition of the problem and bystander activation of EMS), rapid dispatch, bystander cardiopulmonary resuscita- tion(CPR),defibrillationwhenindicated,advancedcardiaclife support,andanorganizedapproachtopostresuscitationcare.In addition, family members of patients who have had STEMI or other manifestations of coronary artery disease should be referred to CPR training programs that have a social support component and can familiarize them with the use of auto- mated external defibrillators. 3.4.1.2. Strategies for Shortening Door-to-Device Times The D2B time interval includes 3 key components: door-to-ECG time, ECG to catheterization laboratory time, and laboratory arrival to device time.132 All 3 inter- vals are dependent on system factors that may vary across Public reporting and national initiatives have focused much and the many reasons for sys- Studies have shown marked differences in the timeliness of primary PCI across hospitals. Focusing on the processes of care at the top-performing institutions, research has revealed characteristics of institutions associated with Top hospitals have specific cultural attributes that include 1) a commitment to an explicit goal of improving D2B times that is motivated by internal and external pressures, including senior management support; 2) innova- tive protocols; 3) flexibility in refining standardized protocols; 4) uncompromising individual clinical leaders; 5) collab- orative teams; 6) data feedback to monitor progress, identify problems, and successes; and 7) an organizational culture that fosters resilience to challenges or setbacks to improvement In addition, several key processes are associated strongly with more timely treatment (Checklist). Other studies have indicated that PCI-capable hospitals receiving patients in transfer can reduce their D2B times by coordinating with the referring hospitals and activating their systems while patients are being transported.78 Currently, it is estimated that almost 90% of patients presenting to a hospital with PCI capability and without a clinical reason for delay have a D2B time 90 minutes.136 Some innovative programs are achieving much faster In addition, with improvements in timeliness of care across the country, racial disparities in reperfusion times have been reduced significantly.140 In an analysis of patients with STEMI reported by hospitals to the Centers for Medicare & Medicaid Services, median D2B times fell from 96 minutes in the year ending December 31, 2005, to 64 minutes in the 3 quarters ending September 30, 2010. This decline was accompanied by an increase in the percent- age of patients with D2B times <90 minutes, from 44.2% to Nevertheless, despite substantial improvements in D2B times, evidence that these efforts have translated into reduced mortality rates is lacking. The absence of demon- strated benefit may relate to reduced power to show change in Checklist. Improving Door-to-Device Times Prehospital ECG to diagnose STEMI is used to activate the PCI team while the patient is en route to the hospital. 2. Emergency physicians activate the PCI team. A single call to a central page operator activates the PCI team. Goal is set for the PCI team to arrive in the catheterization laboratory with in 20 minutes after being paged. Timely data feedback and analysis are provided to members of the STEMI care team. O Gara et al 2013 ACCF/AHA STEMI Guideline e373 survival in a population with a relatively low mortality rate, improved early survival of higher-risk patients, and chang- ing STEMI demographics. These findings support the goal of comprehensive efforts to improve all aspects of acute MI care to improve survival rates. 3.5. Prehospital Fibrinolytic Therapy The time delay from symptom onset to treatment can be short- ened by administration of prehospital fibrinolytic therapy by a trained EMS unit either with a physician on board142 147 or with a hospital-based physician148 152 in direct contact, especially in rural areas. Multiple randomized controlled trials (RCTs) have demonstrated the safety and feasibility of prehospital fibrino- lytic therapy, with decreased treatment times ranging from 30 A meta-analysis of 6 higher- quality RCTs revealed an approximately 60-minute reduction in time from symptom onset to delivery of fibrinolytic therapy with prehospital versus hospital-based administration, with a corresponding 17% reduction in risk of all-cause hospital Analysis of a subgroup of patients enrolled in the CAPTIM (Comparaison de l Angioplastie Primaire et de la Thrombolyse) trial within 2 hours of symptom onset showed a significantly lower 5-year mortality rate for patients treated with prehospital fibrinolysis than for patients managed with primary PCI (P=0.04).123,142 These salutary results for early presenters were confirmed in a subsequent analysis of com- bined data from the CAPTIM and WEST (Which Early ST- Elevation Myocardial Infarction Therapy) trials.155 Data from the USIC (Unit de Soins Intensifs Coronaires) Registry and the Swedish Registry of Cardiac Intensive Care also suggest that prehospital fibrinolytic therapy may lower STEMI mor- At the present time, however, prehospital fibrinolytic ther- apy is not used in most communities in the United States. EMS in rural areas, where prehospital fibrinolysis would poten- tially be of benefit, often have neither the resources to train paramedics nor the funding for necessary equipment. Use of prehospital fibrinolysis is more widespread in some regions of Europe and the United Kingdom. The writing committee endorses the need for further research into the implementation of prehospital strategies to reduce total ischemic time. 3.6. The Relationship Between Sudden Cardiac Death and STEMI 3.6.1. Evaluation and Management of Patients With STEMI and Out-of-Hospital Cardiac Arrest: Recommendations Class I 1. Therapeutic hypothermia should be started as soon as possible in comatose patients with STEMI and out-of-hospital cardiac arrest caused by ventricular fibrillation (VF) or pulseless ventricular tachycar- dia (VT), including patients who undergo primary (Level of Evidence: B) 2. Immediate angiography and PCI when indicated should be performed in resuscitated out-of-hospital cardiac arrest patients whose initial ECG shows (Level of Evidence: B) See Online Data Supplement 2 for additional data on PCI for cardiac arrest. Almost 70% of the coronary heart disease deaths annually in the United States occur out of hospital, usually presenting as sudden death due to cardiac arrest.175 Resuscitation is attempted by EMS personnel in approximately 60% of these out-of-hospital cardiac arrest cases; the remaining patients are deceased on arrival of the EMS team.175 177 Although only 23% of out-of-hospital cardiac arrest cases have a shockable initial rhythm (primarily VF), the majority of neurologically intact survivors come from this subgroup.175,176 The median rate of survival to hospital discharge with any first recorded rhythm is only 7.9%175 ; the rate of survival in patients who are in VF initially is much higher (median 22%, range 8% to 40%), as documented in 10 US and Canadian regions participating in the National Institutes of Health sponsored Resuscitation Survival from out-of-hospital cardiac arrest is optimal when both CPR and defibrillation are initiated early.178 Survival from VF specifically is inversely related to the time interval between its onset and termination, with the odds of survival decreasing 7% to 10% for each minute of delay from onset to The percentage of patients who are found in VF and the likelihood of survival are higher if the patient s collapse is witnessed, if bystander CPR is performed, and if a monitor/defibrillator can be applied quickly.181 Community strategies that improve the delivery of early defibrillation to out-of-hospital cardiac arrest victims include training and equipping first responders (fire and law enforce- ment), EMS personnel, and paramedics to defibrillate, as well as placing automated external defibrillators in highly popu- lated locations such as airports, commercial aircraft, and gam- bling casinos ( public access defibrillation ).182 193 The latter strategy has been shown to approximately double the number of neurologically intact out-of-hospital cardiac arrest sur- vivors when laypersons are trained and equipped to provide early CPR and defibrillation with automated external defibril- lators, compared with providing CPR alone while awaiting arrival of EMS personnel.183 Two RCTs have reported improved rates of neurologi- cally intact survival to hospital discharge when comatose patients with out-of-hospital VF or nonperfusing VT car- diac arrest were cooled to 32 C to 34 C for 12 or 24 hours beginning minutes to hours after the return of spontaneous Additional studies with historical control groups also have shown improved neurological outcomes after therapeutic hypothermia for comatose survivors of VF Accordingly, therapeutic hypothermia should be initiated in patients with STEMI and out-of-hospital cardiac arrest. Cooling should begin before or at the time of cardiac catheterization. Approximately 5% of patients with STEMI who survive to reach the hospital will experience a cardiac arrest during Reports from high-volume PCI centers indicate that 4% to 11% of patients with STEMI who are treated with PCI are brought to cardiac catheterization after being resuscitated from out-of-hospital cardiac arrest.77,197,198 However, the percentage of out-of-hospital cardiac arrest vic- tims whose event is triggered by an acute coronary occlusion is less clear. The majority of out-of-hospital cardiac arrest patients who cannot be resuscitated have significant coronary Coronary atherosclerosis is also present in the majority of cardiac arrest victims who survive and undergo Because of the high prevalence of acute coronary artery occlusions in out-of-hospital cardiac arrest patients who are resuscitated successfully, especially those whose initial rhythm is VF in the setting of STEMI, the AHA 2010 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care201 recommend emer- gency coronary angiography with prompt opening of the infarct artery. Out-of-hospital cardiac arrest victims with ini- tial VF who survive to hospital admission have a rate of sur- vival to hospital discharge of 60% after early PCI. The AHA issued a policy statement calling for communi- ties to establish regional systems of care for out-of-hospital The statement defines 2 different levels of cardiac resuscitation centers and lists the essential elements of such a system. PCI-capable hospitals become ideal can- didates to serve as Level I cardiac resuscitation centers that can offer a wide range of services, including timely PCI when indicated, a goal-directed care bundle,202,203 therapeutic frequent or continuous electroencephalo- graphic monitoring, a multidisciplinary team approach, and neuropsychiatric evaluation for survivors. All other partici- pating hospitals should be trained and equipped as Level II cardiac resuscitation centers, which are capable of initiating therapeutic hypothermia and transferring patients for primary postresuscitation care. Ideally, out-of-hospital cardiac arrest outcomes should be measured and compared within a dedi- cated registry. Lastly, it is important for organizations that collect and publicly report STEMI and PCI data to consider resuscitated out-of-hospital cardiac arrest patients separately from their hospital and individual operator quality score- cards because such patients, even with optimal care, have a much higher mortality rate than that of patients with STEMI who have not had a cardiac arrest.204 206 Public reporting in this instance might have the unintended consequence of reducing appropriate care.207 4. Reperfusion at a PCI-Capable Hospital 4.1. Primary PCI 4.1.1. Primary PCI in STEMI: Recommendations See Table 2 for a summary of recommendations from this section. Class I 1. Primary PCI should be performed in patients with STEMI and ischemic symptoms of less than 12 hours (Level of Evidence: A) 2. Primary PCI should be performed in patients with STEMI and ischemic symptoms of less than 12 hours duration who have contraindications to fi- brinolytic therapy, irrespective of the time delay (Level of Evidence: B) 3. Primary PCI should be performed in patients with STEMI and cardiogenic shock or acute severe HF, irrespective of time delay from MI onset (Section (Level of Evidence: B) Class IIa 1. Primary PCI is reasonable in patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia between 12 and 24 hours after symptom on- (Level of Evidence: B) Class III: Harm 1. PCI should not be performed in a noninfarct artery at the time of primary PCI in patients with STEMI who are hemodynamically stable.216 218 (Level of Evidence: B) Primary PCI of the infarct artery is preferred to fibrinolytic therapy when time-to-treatment delays are short and the patient presents to a high-volume, well-equipped center with experienced interventional cardiologists and skilled support staff. Compared with fibrinolytic therapy, primary PCI pro- duces higher rates of infarct artery patency, TIMI 3 flow, and access site bleeding and lower rates of recurrent ischemia, reinfarction, emergency repeat revascularization procedures, intracranial hemorrhage (ICH), and death.82 Early, successful PCI also greatly decreases the complications of STEMI that result from longer ischemic times or unsuccessful fibrinolytic therapy, allowing earlier hospital discharge and resumption of daily activities. Primary PCI has its greatest survival benefit in high-risk patients. PCI outcomes have been shown to be worse with delays to treatment and with low-volume hospitals and operators. Quality metrics for both laboratory and operator performance and considerations with regard to primary PCI at hospitals without on-site cardiac surgery are reviewed in the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coro- nary Intervention, Section 7.219 Table 2. Primary PCI in STEMI COR LOE References Ischemic symptoms <12 h and contraindications to fibrinolytic therapy irrespective of time delay from FMC Cardiogenic shock or acute severe HF irrespective of time delay from MI onset I B 212 215 Evidence of ongoing ischemia 12 to 24 h after symptom onset PCI of a noninfarct artery at the time of primary PCI in patients without hemodynamic compromise III: Harm B 216 218 COR indicates Class of Recommendation; FMC, first medical contact; HF, heart failure; LOE, Level of Evidence; MI, myocardial infarction; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction. O Gara et al 2013 ACCF/AHA STEMI Guideline e375 Potential complications of primary PCI include problems with the arterial access site; adverse reactions to volume loading, contrast medium, and antithrombotic medications; technical complications; and reperfusion events. The no- reflow phenomenon refers to suboptimal myocardial perfu- sion despite restoration of epicardial flow in the infarct artery and has been attributed to the combined effects of inflam- mation, endothelial injury, edema, atheroembolization, vasospasm, and myocyte reperfusion injury.220 No-reflow is associated with a reduced survival rate. Treatment and prevention strategies have included use of the GP IIb/IIIa antagonist abciximab, vasodilators (nitroprusside, vera- pamil, adenosine), and inhibitors of various metabolic path- ways (nicorandil, pexelizumab), albeit without consistent effect. 