2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes
2014; Lippincott Williams & Wilkins; Volume: 130; Issue: 25 Linguagem: Inglês
10.1161/cir.0000000000000134
ISSN1524-4539
AutoresEzra A. Amsterdam, Nanette K. Wenger, Ralph G. Brindis, Donald E. Casey, Théodore G. Ganiats, David R. Holmes, Allan S. Jaffe, Hani Jneid, Rosemary F. Kelly, Michael C. Kontos, Glenn N. Levine, Philip R. Liebson, Debabrata Mukherjee, Eric D. Peterson, Marc S. Sabatine, Richard W. Smalling, Susan J. Zieman,
Tópico(s)Antiplatelet Therapy and Cardiovascular Diseases
ResumoHomeCirculationVol. 130, No. 252014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUB2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary SyndromesA Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Ezra A. Amsterdam, MD, FACC, Nanette K. Wenger, MD, MACC, FAHA, Ralph G. Brindis, MD, MPH, MACC, FSCAI, Donald E. CaseyJr, MD, MPH, MBA, FACP, FAHA, Theodore G. Ganiats, MD, David R. HolmesJr, MD, MACC, Allan S. Jaffe, MD, FACC, FAHA, Hani Jneid, MD, FACC, FAHA, FSCAI, Rosemary F. Kelly, MD, Michael C. Kontos, MD, FACC, FAHA, Glenn N. Levine, MD, FACC, FAHA, Philip R. Liebson, MD, FACC, FAHA, Debabrata Mukherjee, MD, FACC, Eric D. Peterson, MD, MPH, FACC, FAHA, Marc S. Sabatine, MD, MPH, FACC, FAHA, Richard W. Smalling, MD, PhD, FACC, FSCAI and Susan J. Zieman, MD, PhD, FACC Ezra A. AmsterdamEzra A. Amsterdam †ACC/AHA Representative. Search for more papers by this author , Nanette K. WengerNanette K. Wenger Search for more papers by this author , Ralph G. BrindisRalph G. Brindis ‡ACC/AHA Task Force on Practice Guidelines Liaison. Search for more papers by this author , Donald E. CaseyJrDonald E. CaseyJr §American College of Physicians Representative. Search for more papers by this author , Theodore G. GaniatsTheodore G. Ganiats ‖American Academy of Family Physicians Representative. Search for more papers by this author , David R. HolmesJrDavid R. HolmesJr †ACC/AHA Representative. Search for more papers by this author , Allan S. JaffeAllan S. Jaffe Search for more papers by this author , Hani JneidHani Jneid †ACC/AHA Representative. Search for more papers by this author , Rosemary F. KellyRosemary F. Kelly ¶Society of Thoracic Surgeons Representative. Search for more papers by this author , Michael C. KontosMichael C. Kontos Search for more papers by this author , Glenn N. LevineGlenn N. Levine †ACC/AHA Representative. Search for more papers by this author , Philip R. LiebsonPhilip R. Liebson †ACC/AHA Representative. Search for more papers by this author , Debabrata MukherjeeDebabrata Mukherjee †ACC/AHA Representative. Search for more papers by this author , Eric D. PetersonEric D. Peterson Search for more papers by this author , Marc S. SabatineMarc S. Sabatine Search for more papers by this author , Richard W. SmallingRichard W. Smalling Search for more papers by this author and Susan J. ZiemanSusan J. Zieman †ACC/AHA Representative. Search for more papers by this author Originally published23 Sep 2014https://doi.org/10.1161/CIR.0000000000000134Circulation. 2014;130:e344–e426is corrected byCorrectionOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2014: Previous Version 1 Table of ContentsPreamble e346Introduction e3471.1. Methodology and Evidence Review e3471.2. Organization of the GWC e3481.3. Document Review and Approval e3491.4. Scope of the CPG e349Overview of Acs e3492.1. Definition of Terms e3492.2. Epidemiology and Pathogenesis e3492.2.1. Epidemiology e3492.2.2. Pathogenesis e350Initial Evaluation and Management e3503.1. Clinical Assessment and Initial Evaluation: Recommendation e3503.1.1. ED or Outpatient Facility Presentation: Recommendations e3523.2. Diagnosis of NSTE-ACS e3523.2.1. History e3523.2.2. Physical Examination e3523.2.3. Electrocardiogram e3533.2.4. Biomarkers of Myocardial Necrosis e3533.2.5. Imaging e3533.3. Prognosis–Early Risk Stratification: Recommendations e3533.3.1. Rationale for Risk Stratification and Spectrum of Risk: High, Intermediate, and Low e3543.3.2. Estimation of Level of Risk e3543.3.2.1. History: Angina Symptoms and Angina Equivalents e3543.3.2.2. Demographics and History in Diagnosis and Risk Stratification e3543.3.2.3. Early Estimation of Risk e3553.3.2.4. Electrocardiogram e3553.3.2.5. Physical Examination e3573.4. Cardiac Biomarkers and the Universal Definition of MI: Recommendations e3573.4.1. Biomarkers: Diagnosis e3573.4.2. Biomarkers: Prognosis e3573.4.3. Cardiac Troponins e3573.4.3.1. Prognosis e3583.4.4. CK-MB and Myoglobin Compared With Troponin e3593.5. Immediate Management e3593.5.1. Discharge From the ED or Chest Pain Unit: Recommendations e359Early Hospital Care e3594.1. Standard Medical Therapies e3604.1.1. Oxygen: Recommendation e3604.1.2. Anti-Ischemic and Analgesic Medications e3604.1.2.1. Nitrates: Recommendations e3604.1.2.2. Analgesic Therapy: Recommendations e3614.1.2.3. Beta-Adrenergic Blockers: Recommendations e3624.1.2.4. Calcium Channel Blockers: Recommendations e3624.1.2.5. Other Anti-Ischemic Interventions e3634.1.2.6. Cholesterol Management e3634.2. Inhibitors of the Renin-Angiotensin-Aldosterone System: Recommendations e3634.3. Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or Likely NSTE-ACS e3644.3.1. Initial Oral and Intravenous Antiplatelet Therapy in Patients With Definite or Likely NSTE-ACS Treated With an Initial Invasive or Ischemia-Guided Strategy: Recommendations e3644.3.1.1. Aspirin e3654.3.1.2. P2Y12 Receptor Inhibitors e3654.3.2. Initial Parenteral Anticoagulant Therapy in Patients With Definite NSTE-ACS: Recommendations e3674.3.2.1. Low-Molecular-Weight Heparin e3674.3.2.2. Bivalirudin e3674.3.2.3. Fondaparinux e3674.3.2.4. Unfractionated Heparin e3674.3.2.5. Argatroban e3684.3.3. Fibrinolytic Therapy in Patients With Definite NSTE-ACS: Recommendation e3684.4. Ischemia-Guided Strategy Versus Early Invasive Strategies e3684.4.1. General Principles e3684.4.2. Rationale and Timing for Early Invasive Strategy e3684.4.2.1. Routine Invasive Strategy Timing e3684.4.3. Rationale for Ischemia-Guided Strategy e3684.4.4. Early Invasive and Ischemia-Guided Strategies: Recommendations e3684.4.4.1. Comparison of Early Versus Delayed Angiography e3704.4.5. Subgroups: Early Invasive Strategy Versus Ischemia-Guided Strategy e3714.4.6. Care Objectives e3714.5. Risk Stratification Before Discharge for Patients With an Ischemia-Guided Strategy of NSTE-ACS: Recommendations e3714.5.1. Noninvasive Test Selection e3714.5.2. Selection for Coronary Angiography e372Myocardial Revascularization e3725.1. Percutaneous Coronary Intervention e3725.1.1. PCI–General Considerations: Recommendation e3725.1.2. PCI–Antiplatelet and Anticoagulant Therapy e3725.1.2.1. Oral and Intravenous Antiplatelet Agents: Recommendations e3725.1.2.2. GP IIb/IIIa Inhibitors: Recommendations e3735.1.2.3. Anticoagulant Therapy in Patients Undergoing PCI: Recommendations e3745.2. Timing of Urgent CABG in Patients With NSTE-ACS in Relation to Use of Antiplatelet Agents: Recommendations e375Late Hospital Care, Hospital Discharge, and Posthospital Discharge Care e3766.1. General Principles (Cardioprotective Therapy and Symptom Management) e3766.2. Medical Regimen and Use of Medications at Discharge: Recommendations e3766.2.1. Late Hospital and Posthospital Oral Antiplatelet Therapy: Recommendations e3766.2.2. Combined Oral Anticoagulant Therapy and Antiplatelet Therapy in Patients With NSTE-ACS e3786.2.3. Platelet Function and Genetic Phenotype Testing e3796.3. Risk Reduction Strategies for Secondary Prevention e3796.3.1. Cardiac Rehabilitation and Physical Activity: Recommendation e3796.3.2. Patient Education: Recommendations e3806.3.3. Pneumococcal Pneumonia: Recommendation e3806.3.4. NSAIDs: Recommendations e3806.3.5. Hormone Therapy: Recommendation e3806.3.6. Antioxidant Vitamins and Folic Acid: Recommendations e3816.4. Plan of Care for Patients With NSTE-ACS: Recommendations e3816.4.1. Systems to Promote Care Coordination e382Special Patient Groups e3827.1. NSTE-ACS in Older Patients: Recommendations e3827.2. HF: Recommendations e3837.2.1. Arrhythmias e3837.2.2. Cardiogenic Shock: Recommendation e3867.3. Diabetes Mellitus: Recommendation e3867.3.1. Adjunctive Therapy e3877.4. Post–CABG: Recommendation e3877.5. Perioperative NSTE-ACS Related to Noncardiac Surgery: Recommendations e3877.6. CKD: Recommendations e3887.6.1. Antiplatelet Therapy e3887.7. Women: Recommendations e3897.8. Anemia, Bleeding, and Transfusion: Recommendations e3897.9. Thrombocytopenia e3907.10. Cocaine and Methamphetamine Users: Recommendations e3907.11. Vasospastic (Prinzmetal) Angina: Recommendations e3917.12. ACS With Angiographically Normal Coronary Arteries: Recommendation e3927.13. Stress (Takotsubo) Cardiomyopathy: Recommendations e3927.14. Obesity e3937.15. Patients Taking Antineoplastic/Immunosuppressive Therapy e393Quality of Care and Outcomes for ACS–Use of Performance Measures and Registries e3938.1. Use of Performance Measures and Registries: Recommendation e393Summary and Evidence Gaps e393References e394Appendix 1.Author Relationships With Industry and Other Entities (Relevant) e414Appendix 2.Reviewer Relationships With Industry and Other Entities (Relevant) e417Appendix 3.Abbreviations e422Appendix 4.Additional Tables e423PreambleThe American College of Cardiology (ACC) and the American Heart Association (AHA) are committed to the prevention and management of cardiovascular diseases through professional education and research for clinicians, providers, and patients. Since 1980, the ACC and AHA have shared a responsibility to translate scientific evidence into clinical practice guidelines (CPGs) with recommendations to standardize and improve cardiovascular health. These CPGs, based on systematic methods to evaluate and classify evidence, provide a cornerstone of quality cardiovascular care.In response to published reports from the Institute of Medicine1,2 and the ACC/AHA’s mandate to evaluate new knowledge and maintain relevance at the point of care, the ACC/AHA Task Force on Practice Guidelines (Task Force) began modifying its methodology. This modernization effort is published in the 2012 Methodology Summit Report3 and 2014 perspective article.4 The latter recounts the history of the collaboration, changes over time, current policies, and planned initiatives to meet the needs of an evolving healthcare environment. Recommendations on value in proportion to resource utilization will be incorporated as high-quality comparative-effectiveness data become available.5 The relationships between CPGs and data standards, appropriate use criteria, and performance measures are addressed elsewhere.4Intended Use–CPGs provide recommendations applicable to patients with or at risk of developing cardiovascular disease. The focus is on medical practice in the United States, but CPGs developed in collaboration with other organizations may have a broader target. Although CPGs may be used to inform regulatory or payer decisions, the intent is to improve the quality of care and be aligned with the patient’s best interest.Evidence Review–Guideline writing committee (GWC) members are charged with reviewing the literature; weighing the strength and quality of evidence for or against particular tests, treatments, or procedures; and estimating expected health outcomes when data exist. In analyzing the data and developing CPGs, the GWC uses evidence-based methodologies developed by the Task Force.6 A key component of the ACC/AHA CPG methodology is the development of recommendations on the basis of all available evidence. Literature searches focus on randomized controlled trials (RCTs) but also include registries, nonrandomized comparative and descriptive studies, case series, cohort studies, systematic reviews, and expert opinion. Only selected references are cited in the CPG. To ensure that CPGs remain current, new data are reviewed biannually by the GWCs and the Task Force to determine if recommendations should be updated or modified. In general, a target cycle of 5 years is planned for full revisions.1Guideline-Directed Medical Therapy–Recognizing advances in medical therapy across the spectrum of cardiovascular diseases, the Task Force designated the term “guideline-directed medical therapy” (GDMT) to represent recommended medical therapy as defined mainly by Class I measures, generally a combination of lifestyle modification and drug- and device-based therapeutics. As medical science advances, GDMT evolves, and hence GDMT is preferred to “optimal medical therapy.” For GDMT and all other recommended drug treatment regimens, the reader should confirm the dosage with product insert material and carefully evaluate for contraindications and possible drug interactions. Recommendations are limited to treatments, drugs, and devices approved for clinical use in the United States.Class of Recommendation and Level of Evidence–Once recommendations are written, the Class of Recommendation (COR; ie, the strength the GWC assigns to the recommendation, which encompasses the anticipated magnitude and judged certainty of benefit in proportion to risk) is assigned by the GWC. Concurrently, the Level of Evidence (LOE) rates the scientific evidence supporting the effect of the intervention on the basis on the type, quality, quantity, and consistency of data from clinical trials and other reports (Table 1).4 Unless otherwise stated, recommendations are presented in order by the COR and then the LOE. Where comparative data exist, preferred strategies take precedence. When more than 1 drug, strategy, or therapy exists within the same COR and LOE and there are no comparative data, options are listed alphabetically.Table 1. Applying Classification of Recommendations and Level of EvidenceTable 1. Applying Classification of Recommendations and Level of EvidenceRelationships With Industry and Other Entities–The ACC and AHA exclusively sponsor the work of GWCs without commercial support, and members volunteer their time for this activity. The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that might arise through relationships with industry or other entities (RWI). All GWC members and reviewers are required to fully disclose current industry relationships or personal interests from 12 months before initiation of the writing effort. Management of RWI involves selecting a balanced GWC and requires that both the chair and a majority of GWC members have no relevant RWI (see Appendix 1 for the definition of relevance). GWC members are restricted with regard to writing or voting on sections to which their RWI apply. In addition, for transparency, GWC members’ comprehensive disclosure information is available as an online supplement. Comprehensive disclosure information for the Task Force is available as an additional supplement. The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds representing different geographic regions, sexes, ethnicities, races, intellectual perspectives/biases, and scopes of clinical practice. Selected organizations and professional societies with related interests and expertise are invited to participate as partners or collaborators.Individualizing Care in Patients With Associated Conditions and Comorbidities–The ACC and AHA recognize the complexity of managing patients with multiple conditions, compared with managing patients with a single disease, and the challenge is compounded when CPGs for evaluation or treatment of several coexisting illnesses are discordant or interacting.7 CPGs attempt to define practices that meet the needs of patients in most, but not all, circumstances and do not replace clinical judgment.Clinical Implementation–Management in accordance with CPG recommendations is effective only when followed; therefore, to enhance their commitment to treatment and compliance with lifestyle adjustment, clinicians should engage the patient to participate in selecting interventions on the basis of the patient’s individual values and preferences, taking associated conditions and comorbidities into consideration (eg, shared decision making). Consequently, there are circumstances in which deviations from these guidelines are appropriate.The recommendations in this CPG are the official policy of the ACC and AHA until they are superseded by a published addendum, focused update, or revised full-text CPG.Jeffrey L. Anderson, MD, FACC, FAHAChair, ACC/AHA Task Force on Practice Guidelines1. Introduction1.1. Methodology and Evidence ReviewThe recommendations listed in this CPG are, whenever possible, evidence based. An extensive evidence review was conducted through October 2012, and other selected references published through April 2014 were reviewed by the GWC. Literature included was derived from research involving human subjects, published in English, and indexed in MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality Reports, and other selected databases relevant to this CPG. The relevant data are included in evidence tables in the Online Data Supplement. Key search words included but were not limited to the following: acute coronary syndrome, anticoagulant therapy, antihypertensives, anti-ischemic therapy, antiplatelet therapy, antithrombotic therapy, beta blockers, biomarkers, calcium channel blockers, cardiac rehabilitation, conservative management, diabetes mellitus, glycoprotein IIb/IIIa inhibitors, heart failure, invasive strategy, lifestyle modification, myocardial infarction, nitrates, non-ST-elevation, P2Y12receptor inhibitor, percutaneous coronary intervention, renin-angiotensin-aldosterone inhibitors, secondary prevention, smoking cessation, statins, stent, thienopyridines, troponins, unstable angina, and weight management. Additionally, the GWC reviewed documents related to non-ST-elevation acute coronary syndrome (NSTE-ACS) previously published by the ACC and AHA. References selected and published in this document are representative and not all-inclusive.1.2. Organization of the GWCThe GWC was composed of clinicians, cardiologists, internists, interventionists, surgeons, emergency medicine specialists, family practitioners, and geriatricians. The GWC included representatives from the ACC and AHA, American Academy of Family Physicians, American College of Emergency Physicians, American College of Physicians, Society for Cardiovascular Angiography and Interventions (SCAI), and Society of Thoracic Surgeons (STS).1.3. Document Review and ApprovalThis document was reviewed by 2 official reviewers each nominated by the ACC and AHA; 1 reviewer each from the American Academy of Family Physicians, American College of Emergency Physicians, SCAI, and STS; and 37 individual content reviewers (including members of the American Association of Clinical Chemistry, ACC Heart Failure and Transplant Section Leadership Council, ACC Cardiovascular Imaging Section Leadership Council, ACC Interventional Section Leadership Council, ACC Prevention of Cardiovascular Disease Committee, ACC Surgeons’ Council, Association of International Governors, and Department of Health and Human Services). Reviewers’ RWI information was distributed to the GWC and is published in this document (Appendix 2).This document was approved for publication by the governing bodies of the ACC and the AHA and endorsed by the American Association for Clinical Chemistry, SCAI, and the STS.1.4. Scope of the CPGThe 2014 NSTE-ACS CPG is a full revision of the 2007 ACCF/AHA CPG for the management of patients with unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI) and the 2012 focused update.8 The new title, “Non-ST-Elevation Acute Coronary Syndromes,” emphasizes the continuum between UA and NSTEMI. At presentation, patients with UA and NSTEMI can be indistinguishable and are therefore considered together in this CPG.In the United States, NSTE-ACS affects >625 000 patients annually,* or almost three fourths of all patients with acute coronary syndrome (ACS).9 In selecting the initial approach to care, the term “ischemia-guided strategy” has replaced the previous descriptor, “initial conservative management,” to more clearly convey the physiological rationale of this approach.The task of the 2014 GWC was to establish a contemporary CPG for the optimal management of patients with NSTE-ACS. It incorporates both established and new evidence from published clinical trials, as well as information from basic science and comprehensive review articles. These recommendations were developed toguide the clinician in improving outcomes for patients with NSTE-ACS. Table 2 lists documents deemed pertinent to this effort and is intended for use as a resource, thus obviating the need to repeat extant CPG recommendations.Table 2. Associated CPGs and StatementsTitleOrganizationPublication Year/ReferenceCPGsStable ischemic heart diseaseACC/AHA/AATS/PCNA/SCAI/STS201410* 201211Atrial fibrillationAHA/ACC/HRS201412Assessment of cardiovascular riskACC/AHA201313Heart failureACC/AHA201314Lifestyle management to reduce cardiovascular riskAHA/ACC201315Management of overweight and obesity in adultsAHA/ACC/TOS201316ST-elevation myocardial infarctionACC/AHA201317Treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adultsACC/AHA201318Acute myocardial infarction in patients presenting with ST-segment elevationESC201219Device-based therapyACC/AHA/HRS201320Third universal definition of myocardial infarctionESC/ACC/AHA/WHF201221Acute coronary syndromes in patients presenting without persistent ST-segment elevationESC201122Coronary artery bypass graft surgeryACC/AHA201123Hypertrophic cardiomyopathyACC/AHA201124Effectiveness-based guidelines for the prevention of cardiovascular disease in womenAHA/ACC201125Percutaneous coronary interventionACC/AHA/SCAI201126Secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular diseaseAHA/ACC201127Assessment of cardiovascular risk in asymptomatic adultsACC/AHA201028Myocardial revascularizationESC201029Unstable angina and non–ST-elevation myocardial infarctionNICE201030†Guidelines for cardiopulmonary resuscitation and emergency cardiovascular care–part 9: postcardiac arrest careAHA201031Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressureNHLBI200332StatementsKey data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes and coronary artery diseaseACC/AHA201333Practical clinical considerations in the interpretation of troponin elevationsACC201234Testing of low-risk patients presenting to the emergency department with chest painAHA201035Primary prevention of cardiovascular diseases in people with diabetes mellitusAHA/ADA200736Prevention and control of influenzaCDC200537*The full-text SIHD CPG is from 2012.11 A focused update was published in 2014.10†Minor modifications were made in 2013. For a full explanation of the changes, see http://publications.nice.org.uk/unstable-angina-and-nstemi-cg94/changes-after-publication.AATS indicates American Association for Thoracic Surgery; ACC, American College of Cardiology; ADA, American Diabetes Association; AHA, American Heart Association; CDC, Centers for Disease Control and Prevention; CPG, clinical practice guideline; ESC, European Society of Cardiology; HRS, Heart Rhythm Society; NHLBI, National Heart, Lung, and Blood Institute; NICE, National Institute for Health and Clinical Excellence; PCNA, Preventive Cardiovascular Nurses Association; SCAI, Society for Cardiovascular Angiography and Interventions; SIHD, stable ischemic heart disease; STS, Society of Thoracic Surgeons; TOS, The Obesity Society; and WHF, World Heart Federation.The GWC abbreviated the discussion sections to include an explanation of salient information related to the recommendations. In contrast to textbook declaratory presentations, explanations were supplemented with evidence tables. The GWC also provided a brief summary of the relevant recommendations and references related to secondary prevention rather than detailed reiteration. Throughout, the goal was to provide the clinician with concise, evidence-based contemporary recommendations and the supporting documentation to encourage their application.2. Overview Of ACS2.1. Definition of TermsACS has evolved as a useful operational term that refers to a spectrum of conditions compatible with acute myocardial ischemia and/or infarction that are usually due to an abrupt reduction in coronary blood flow (Figure 1). A key branch point is ST-segment elevation (ST-elevation) or new left bundle-branch block on the electrocardiogram (ECG), which is an indication for immediate coronary angiography to determine if there is an indication for reperfusion therapy to open a likely completely occluded coronary artery. Separate CPGs have been developed for ST-elevation myocardial infarction (STEMI).17Download figureDownload PowerPointFigure 1. Acute Coronary Syndromes. The top half of the figure illustrates the progression of plaque formation and onset and complications of NSTE-ACS, with management at each stage. The numbered section of an artery depicts the process of atherogenesis from 1) normal artery to 2) extracellular lipid in the subintima to 3) fibrofatty stage to 4) procoagulant expression and weakening of the fibrous cap. ACS develops with 5) disruption of the fibrous cap, which is the stimulus for thrombogenesis. 6) Thrombus resorption may be followed by collagen accumulation and smooth muscle cell growth. Thrombus formation and possible coronary vasospasm reduce blood flow in the affected coronary artery and cause ischemic chest pain. The bottom half of the figure illustrates the clinical, pathological, electrocardiographic, and biomarker correlates in ACS and the general approach to management. Flow reduction may be related to a completely occlusive thrombus (bottom half, right side) or subtotally occlusive thrombus (bottom half, left side). Most patients with ST-elevation (thick white arrow in bottom panel) develop QwMI, and a few (thin white arrow) develop NQMI. Those without ST-elevation have either UA or NSTEMI (thick red arrows), a distinction based on cardiac biomarkers. Most patients presenting with NSTEMI develop NQMI; a few may develop QwMI. The spectrum of clinical presentations including UA, NSTEMI, and STEMI is referred to as ACS. This NSTE-ACS CPG includes sections on initial management before NSTE-ACS, at the onset of NSTE-ACS, and during the hospital phase. Secondary prevention and plans for long-term management begin early during the hospital phase. Patients with noncardiac etiologies make up the largest group presenting to the ED with chest pain (dashed arrow). *Elevated cardiac biomarker (eg, troponin), Section 3.4. ACS indicates acute coronary syndrome; CPG, clinical practice guideline; Dx, diagnosis; ECG, electrocardiogram; ED, emergency department; Ml, myocardial infarction; NQMI, non-Q-wave myocardial infarction; NSTE-ACS, non-ST-elevation acute coronary syndromes; NSTEMI, non-ST-elevation myocardial infarction; QwMI, Q-wave myocardial infarction; STEMI, ST-elevation myocardial infarction; and UA, unstable angina. Modified with permission from Libby et al.38The absence of persistent ST-elevation is suggestive of NSTE-ACS (except in patients with true posterior myocardial infarction [MI], Sections 3.3.2.4, 4.3.2, and 7.2.2). NSTE-ACS can be further subdivided on the basis of cardiac biomarkers of necrosis (eg, cardiac troponin, Sections 3.2.4 and 3.4). If cardiac biomarkers are elevated and the clinical context is appropriate, the patient is considered to have NSTEMI34; otherwise, the patient is deemed to have UA. ST depression, transient ST-elevation, and/or prominent T-wave inversions may be present but are not required for a diagnosis of NSTEMI. Abnormalities on the ECG and elevated troponins in isolation are insufficient to make the diagnosis of ACS but must be interpreted in the appropriate clinical context. Thus, UA and NSTEMI are closely related conditions whose pathogenesis and clinical presentations are similar but vary in severity. The conditions differ primarily by whether the ischemia is severe enough to cause myocardial damage leading to detectable quantities of myocardial injury biomarkers. The term “possible ACS” is often assigned during initial evaluation if the ECG is unrevealing and troponin data are not yet available. UA can present without any objective data of myocardial ischemic injury (normal ECG and normal troponin), in which case the initial diagnosis depends solely on the patient’s clinical history and the clinician’s interpretation and judgment. However, with the increasing sensitivity of troponin assays, biomarker-negative ACS (ie, UA) is becoming rarer.39 The pathogenesis of ACS is considered in the “Third Universal Definition of Myocardial Infarction.”21 This statement defines MI caused by a primary coronary artery process such as spontaneous plaque rupture as MI type 1 and one related to reduced myocardial oxygen supply and/or increased myocardial oxygen demand (in the absence of a direct coronary artery process) as a MI type 2 (Appendix 4, Table A and Section 3.4 for an additional discussion on the diagnosis of MI).2.2. Epidemiology and Pathogenesis2.2.1. EpidemiologyIn the United States, the median age at ACS presentation is 68 years (interquartile range 56 to 79), and the male-to-female ratio is approximately 3:2.40 Some patients have a history of stable angina, whereas in others, ACS is the initial presentation of coronary artery disease (CAD). It is estimated that in the United States, each year, >780 000 persons will experience an ACS. Approximately 70% of these will have NSTE-ACS.9 Patients with NSTE-ACS typically have more comorbidities, both cardiac and no
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