Nanette K. Wenger, MD 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; Mark A. Creager, MD, FACC, FAHA; David DeMets, PhD; Steven M. Ettinger, MD, FACC; Robert A. Guyton, MD, FACC; Judith S. Hochman, MD, FACC, FAHA; Frederick G. Kushner, MD, FACC, FAHA; E. Magnus Ohman, MD, FACC; William Stevenson, MD, FACC, FAHA; Clyde W. Yancy, MD, FACC, FAHA Table of Contents Developed in Collaboration With the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine Preamble (UPDATED)...e182 Introduction (UPDATED)...e184 Organization of Committee and Evidence Review (UPDATED)...e184 Document Review and Approval (UPDATED)...e185 Purpose of These Guidelines...e185 Overview of the Acute Coronary Syndromes...e186 Definition of Terms...e186 Pathogenesis of UA/NSTEMI...e186 Presentations of UA and NSTEMI...e189 Management Before UA/NSTEMI and Onset of UA/NSTEMI...e189 Identification of Patients at Risk of UA/NSTEMI...e189 Interventions to Reduce Risk of UA/NSTEMI...e190 Onset of UA/NSTEMI...e191 Recognition of Symptoms by Patient...e191 Silent and Unrecognized Events...e191 Initial Evaluation and Management...e191 Clinical Assessment...e191 Emergency Department or Outpatient Facility Presentation...e195 Questions to Be Addressed at the Initial Evaluation...e196 Early Risk Stratification...e196 Estimation of the Level of Risk...e198 Rationale for Risk Stratification...e198 History...e198 Anginal Symptoms and Anginal Equivalents...e198 Demographics and History in Diagnosis and Risk Stratification...e199 Estimation of Early Risk at Presentation...e200 Electrocardiogram...e202 Physical Examination...e203 Noncardiac Causes of Symptoms and Secondary Causes of Myocardial Ischemia...e204 Cardiac Biomarkers of Necrosis and the Redefinition of AMI...e204 Creatine Kinase-MB...e205 Cardiac Troponins...e205 Clinical Use...e205 Clinical Use of Marker Change Scores...e207 Bedside Testing for Cardiac Markers...e208 Myoglobin and CK-MB Subforms Compared With Troponins...e208 Summary Comparison of Biomarkers of Necrosis: Singly and in Combination...e208 Other Markers and Multimarker Approaches...e208 Ischemia...e208 Coagulation ...e209 Platelets...e209 Inflammation...e209 B-Type Natriuretic Peptides...e210 Immediate Management...e210 Chest Pain Units...e211 Discharge From ED or Chest Pain Unit...e212 Early Hospital Care...e213 Anti-Ischemic and Analgesic Therapy...e214 General Care...e215 Use of Anti-Ischemic Therapies...e215 Nitrates...e215 Morphine Sulfate...e217 Beta-Adrenergic Blockers...e217 Calcium Channel Blockers...e219 Inhibitors of the Renin-Angiotensin-Aldosterone System...e220 Other Anti-Ischemic Therapies...e221 Intra-Aortic Balloon Pump Counterpulsation...e221 Analgesic Therapy...e221 Recommendations for Antiplatelet/Anticoagulant Therapy in Patients for Whom Diagnosis of UA/NSTEMI Is Likely or Definite (UPDATED)...e221 Antiplatelet Therapy: Recommendations (UPDATED)...e221 Anticoagulant Therapy: Recommendations...e223 Additional Management Considerations for Antiplatelet and Anticoagulant Therapy: Recommendations (UPDATED)...e223 Antiplatelet/Anticoagulant Therapy in Patients for Whom Diagnosis of UA/NSTEMI Is Likely or Definite (NEW SECTION)...e224 Newer P2Y12 Receptor Inhibitors...e224 Choice of P2Y12 Receptor Inhibitors for PCI in UA/NSTEMI...e227 Timing of Discontinuation of P2Y12 Receptor Inhibitor Therapy for Surgical Procedures...e227 Interindividual Variability in Responsiveness to Clopidogrel...e228 Optimal Loading and Maintenance Dosages of Clopidogrel...e228 Proton Pump Inhibitors and Dual Antiplatelet Therapy for ACS...e229 Glycoprotein IIb/IIIa Receptor Antagonists (Updated to Incorporate Newer Trials and Evidence)...e230 Older Antiplatelet Agents and Trials (Aspirin, Ticlopidine, Clopidogrel)...e231 Aspirin...e231 Adenosine Diphosphate Receptor Antagonists and Other Antiplatelet Agents...e233 Anticoagulant Agents and Trials...e236 Unfractionated Heparin...e237 Low-Molecular-Weight Heparin...e238 LMWH Versus UFH...e238 Extended Therapy with LMWHs...e241 Direct Thrombin Inhibitors...e241 Factor Xa Inhibitors...e244 Long-Term Anticoagulation...e245 Platelet GP IIb/IIIa Receptor Antagonists...e246 Fibrinolysis...e251 Initial Conservative Versus Initial Invasive Strategies (UPDATED)...e251 General Principles...e252 Rationale for the Initial Conservative Strategy...e252 Rationale for the Invasive Strategy...e253 Timing of Invasive Therapy (NEW SECTION)...e253 Immediate Angiography...e254 Deferred Angiography...e254 Comparison of Early Invasive and Initial Conservative Strategies...e254 Subgroups...e257 Care Objectives...e258 Risk Stratification Before Discharge...e260 Care Objectives...e260 Noninvasive Test Selection...e262 Selection for Coronary Angiography...e263 Patient Counseling...e263 Coronary Revascularization...e263 Recommendations for Revascularization With PCI and CABG in Patients With UA/NSTEMI (UPDATED)...e263 Late Hospital Care, Hospital Discharge, and Post-Hospital Discharge Care...e263 Medical Regimen and Use of Medications...e263 Long-Term Medical Therapy and Secondary Prevention...e265 Convalescent and Long-Term Antiplatelet Therapy (UPDATED)...e266 Beta Blockers...e266 Inhibition of the Renin-Angiotensin-Aldosterone System...e267 Nitroglycerin...e267 Calcium Channel Blockers...e267 Warfarin Therapy (UPDATED)...e267 Lipid Management...e268 Blood Pressure Control...e270 Diabetes Mellitus...e270 Smoking Cessation...e270 Weight Management...e271 Physical Activity...e271 Patient Education...e272 Influenza...e272 Depression...e272 Nonsteroidal Anti-Inflammatory Drugs...e272 Hormone Therapy...e272 Antioxidant Vitamins and Folic Acid...e273 Postdischarge Follow-Up...e273 Cardiac Rehabilitation...e274 Return to Work and Disability...e275 Other Activities...e276 Patient Records and Other Information Systems...e277 Special Groups...e277 Women...e277 Profile of UA/NSTEMI in Women...e278 Management...e278 Pharmacological Therapy...e278 Coronary Artery Revascularization...e278 Initial Invasive Versus Initial Conservative Strategy...e279 Stress Testing...e281 Conclusions...e281 Diabetes Mellitus (UPDATED)...e281 Profile and Initial Management of Diabetic and Hyperglycemic Patients With UA/NSTEMI...e281 Intensive Glucose Control (NEW SECTION)...e282 Coronary Revascularization...e283 Conclusions...e284 Post-CABG Patients...e284 Pathological Findings...e285 Clinical Findings and Approach...e285 Conclusions...e285 Older Adults...e285 Pharmacological Management...e286 Functional Studies...e286 Percutaneous Coronary Intervention in Older Patients...e287 Contemporary Revascularization Strategies in Older Patients...e287 Conclusions...e287 Chronic Kidney Disease (UPDATED) ...e288 Angiography in Patients With CKD (NEW SECTION)...e288 Cocaine and Methamphetamine Users...e290 Coronary Artery Spasm With Cocaine Use...e290 Treatment...e291 Methamphetamine Use and UA/NSTEMI...e292 Variant (Prinzmetal's) Angina...e292 Clinical Picture...e292 Pathogenesis...e292 Diagnosis...e293 Treatment...e293 Prognosis...e293 Cardiovascular "Syndrome X"...e294 Definition and Clinical Picture...e294 Treatment...e295 Takotsubo Cardiomyopathy...e295 Conclusions and Future Directions...e295 Recommendations for Quality of Care and Outcomes for UA/NSTEMI (NEW SECTION)...e297 Quality Care and Outcomes (NEW SECTION)...e297 References...e297 Appendix 1.