Acute Coronary Syndrome PDF

A c u t e C o ro n a r y S y n d ro m e Raman Nohria, MD*, Brian Antono, MD, MPH KEYWORDS  Cardiovascular disease  Coronary artery disease  Ischemia  Troponin  STEMI KEY POINTS  Acute chest pain warrants a 12-lead electrocardiogram within 10 minutes of presentation bec...

A c u t e C o ro n a r y S y n d ro m e Raman Nohria, MD*, Brian Antono, MD, MPH KEYWORDS  Cardiovascular disease  Coronary artery disease  Ischemia  Troponin  STEMI KEY POINTS  Acute chest pain warrants a 12-lead electrocardiogram within 10 minutes of presentation because early detection of ST-elevation myocardial infarction improves clinical outcomes. If this evaluation cannot occur within 10 minutes, the patient should be immediately trans- ferred to an emergency department.  Stable or noncardiac chest pain should undergo a systematic evaluation in the outpatient setting.  Dual antiplatelet therapy, high intensity statin therapy, and beta-blocker therapy are the hallmarks of pharmacotherapy for myocardial infarction. EPIDEMIOLOGY Approximately 1.2 million people in the United States are hospitalized each year due to acute coronary syndrome (ACS), with estimated direct costs of $117 billion annually.1 In 2020, ACS resulted in approximately 112,000 deaths in the United States.2 Most ACS hospitalizations and deaths are attributable to myocardial infarction (MI).1,2 The most common symptom of ACS and MI is chest pain. One percent of primary care visits are due to chest pain.3 PATHOPHYSIOLOGY ACS represents a sudden reduction in blood flow through the coronary arteries to the ventricular myocardium. This reduced flow to the myocardium means that the myocar- dial oxygen demand cannot be met, leading to MI and injury.4–6 The most common etiology for sudden blood flow reduction through the coronary arteries is disruption of a coronary plaque that leads to thrombus formation.4 6 The differential diagnosis for myocardial injury also includes coronary artery spasm, coronary artery dissection, pulmonary embolism, myocarditis, and noncardiac conditions such as severe anemia.6–8 Department of Family Medicine and Community Health, Duke University School of Medicine, 2100 Erwin Road, Durham, NC 27705, USA * Corresponding author. E-mail address: [email protected] Prim Care Clin Office Pract 51 (2024) 53–64 https://doi.org/10.1016/j.pop.2023.07.003 primarycare.theclinics.com 0095-4543/24/ª 2023 Elsevier Inc. All rights reserved. Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en agosto 05, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados. 54 Nohria & Antono DEFINITIONS AND TAXONOMY ACS is suspected in patients who present with chest pain due to a sudden decrease in coronary blood flow. ACS can be subdivided into two categories: ST-elevation myocardial infarction (STEMI) and non-ST-elevation ACS (NSTE-ACS). STEMI repre- sents ST-elevation seen on electrocardiogram (ECG) with biomarker evidence of car- diac injury. NSTE-ACS includes both non-ST elevated myocardial infarction (NSTEMI) and unstable angina. ECG changes will be present in NSTE-ACS, but these changes will not show ST-elevation. An elevated troponin will also be present in NSTEMI. APPROACH TO CHEST PAIN Symptoms Chest pain or chest discomfort is the most common complaint among patients who are later diagnosed with MI. Patients experiencing ischemic chest pain frequently report pressure, heaviness, tightness, squeezing, gripping, or burning. In addition to the anterior chest, patients may report pain in other locations including the jaw, neck, shoulder, arm, back, and upper abdomen. Table 1 depicts the likelihood ratios of patient factors in predicting ACS. Traditionally, chest pain or discomfort consistent with possible myocardial ischemia has been described as typical versus atypical; however, the term “atypical” is now discouraged from use given its frequent misinterpretation as benign.7 To reduce confusion, suspected causes of chest pain should be stratified as cardiac, possible cardiac, or noncardiac.7 Evaluation Acute chest pain includes new-onset symptoms or pain with a change in intensity, dura- tion, or pattern. Such cases warrant a 12-lead ECG within 10 minutes of presentation because early detection of STEMI improves clinical outcomes.7 If focused history, physical examination, and ECG are most consistent with an acute cardiac or possible cardiac etiology, or if an ECG assessment and interpretation cannot occur within 10 mi- nutes, the patient should be immediately transferred to the emergency department (ED). Alternatively, stable chest pain represents chronic symptom burden that is associated with predictable triggers such as physical exertion or emotional stress. Patients with stable chest pain or noncardiac chest pain can be evaluated in the outpatient setting. DIAGNOSTIC TESTING Electrocardiogram Patients who present to the primary care office with chest pain should receive an ECG as part of their chest pain evaluation. This ECG should be compared with the patient’s Table 1 Patient factors in predicting acute coronary syndrome Characteristic Likelihood Ratio 95% Confidence Interval Crushing, substernal chest pain 1.9 0.9–2.9 Pain that radiates to the arms 2.6 1.8–3.7 History of prior abnormal stress test 3.1 2.0–4.7 Pain that varies with breathing or position 0.5 0.4–0.6 Pain that is reproduced on palpation 0.3 0.14–0.5 Original table; information obtained from Refs.6,9 Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en agosto 05, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados.  Acute Coronary Syndrome 55 baseline ECG, if available. The evidence of ischemia may be harder to appreciate in patients with underlying ECG abnormalities, such as the presence of a left-bundle branch block, ventricular-paced rhythm, and/or delta wave pattern.7 Common ECG findings that are more likely to raise suspicion for ACS include T-wave inversions, q-wave, ST-depression, and ST-elevation.6,9 High-Sensitivity Troponin High-sensitivity cardiac troponin (cTn) is the preferred biomarker test for workup of chest pain in the inpatient or ED setting. The cTn level is considered significant if it is elevated above the 99% percentile of the upper reference limit. It is important to follow serial cTn levels because cTn may not increase until several hours after the in- dex ACS event.10 The presence of elevated cTn levels in a patient presenting with chest pain concerning for ACS should prompt consideration for coronary revascular- ization. It should be noted that cTn elevation is not disease-specific. Other conditions that can lead to cTn elevation include chronic kidney disease, heart failure, pulmonary embolism, myocarditis, and arrhythmia. Chest Pain Clinical Prediction Tools For patients who rule out for ACS, risk stratification can help identify patients at-risk for symptomatic coronary artery disease (CAD) (Fig. 1). For the outpatient evaluation of chest pain, there is no validated screening tool for evaluating patients who present with symptoms concerning for ACS.11 For patients who present to the outpatient setting with stable chest pain, the Marburg Heart Score can be used to determine the likelihood that a patient’s chest pain is caused by CAD.12 The score uses patient’s age, sex, risk factors, and clinical history to determine the likelihood that a patient’s Pa ent reports acute Obtain history and No chest pain in EKG. High suspicion for Determine Marburg Score. outpa ent office visit ACS (see Table 1)? Yes High Risk Low Risk (Marburg score 3–5) (Marburg score 0-2) Refer pa ent to ED Chest pain unlikely to Yes be caused by CAD. Rule STEMI? Manage according to out other causes of ACC/AHA guidelines chest pain. No Obtain high-sensi vity cardiac Diagnose NSTE-ACS; Posi ve troponin at presenta on and admit and manage at 1–2 h according to ACC/AHA Nega ve guidelines Determine risk of major adverse cardiovascular event or inpa ent HEART score Asymptoma c Low Risk Intermediate Risk High Risk (HEART score 0–3) (HEART score 4–6) (HEART score 7–10) No addi onal tes ng No addi onal inpa ent Further workup Invasive Coronary recommended tes ng recommended recommended; Angiography consider calcium consider stress tes ng artery score in or CCTA outpa ent se ng Fig. 1. Evaluation for acute coronary syndrome. (Information from Refs.6,8,10–12) Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en agosto 05, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados. 56 Nohria & Antono chest pain is caused by CAD.13 It should be noted than an ECG evaluation is not required to calculate the Marburg Heart Score. Among outpatient risk scores, the Mar- burg Heart Score provides higher sensitivity and specificity when compared with clin- ical judgment for identifying if a patient’s chest pain is due to CAD.11 A low score (0–2) correlates to a 3% likelihood that CAD is causing a patient’s chest pain, and therefore, patients with this score are unlikely to benefit from further testing.11,12 A high-risk score (3–5) correlates to a 23% likelihood that CAD is causing a patient’s chest pain.11,12 Patients with this score should be transferred to the ED for consideration of an urgent workup to rule out unstable CAD. The HEART score is a clinical prediction tool designed to risk stratify patients with chest pain in the inpatient or ED setting who rule out for ACS.9,14–16 The score uses the clinical history, ECG, age, patient risk factors, and troponin level to determine the risk of major adverse cardiac events (MACE) in the next 30 days. This tool is not validated in the primary care setting.17 A low score (0–3) correlates to a 1.7% risk of MACE, and therefore, patients with this score are unlikely to benefit from further workup in the inpatient setting. A patient with an intermediate score (4–6) warrants further workup with stress testing, as this score correlates to a 17% risk of MACE. A high-risk score of 7 to 10 correlates to 50% MACE, and patients with this score are typically considered for coronary angiography. For patients diagnosed with NSTE-ACS, the thrombosis in myocardial infarction risk score determines the pooled risk of subsequent ischemic events/deaths.9 Further Testing Based on Risk Stratification The 2021 American College of Cardiology (ACC)/American Heart Association (AHA) chest pain guideline recommends against further testing in patients with acute, low- risk chest pain (HEART score 0–3) or stable intermittent low-risk chest pain (Marburg 0–2).7 Risk stratification testing is recommended for patients with acute chest pain rated as intermediate risk (HEART score 4–6). Options for stress testing include exer- cise testing coupled with ECG, echocardiography, or nuclear imaging and pharmaco- logic stress testing coupled with echocardiography, MRI, or nuclear imaging such as single-photon emission computed tomography (SPECT) and PET. Choosing the appropriate stress test depends on a variety of factors and consider- ations.18 Exercise ECG testing is the most cost-effective test; however, it is less sen- sitive in identifying obstructive disease than other imaging modalities.7 To qualify for an exercise ECG test, patients must be able to perform activities of daily living or achieve greater than four metabolic equivalents of exercise. Patients must also have a baseline ECG that does not demonstrate evidence of ST depression, paced rhythm, digitalis use, left-bundle branch block, or delta wave pattern.7 A stress myocardial perfusion study (SPECT or PET) and stress echocardiography diagnose ischemia by comparing resting images to post-stress images18 and have a higher sensitivity and specificity than exercise ECG testing.7 Assuming that the patient was adequately stressed, a normal stress test can be considered valid for 1-year.7 This means that if a patient has recurrent symptoms that are unchanged relative to the index event that lead to the stress test, no further stress testing is recommended for up to 1-year. Coronary Angiography Coronary computed tomography angiography (CCTA) can also be considered for intermediate-risk patients as an alternative to stress testing or if a patient has contra- indications to stress testing. CCTA can help to establish a diagnosis of obstructive and nonobstructive CAD as well as the severity of CAD.7 Invasive coronary angiography Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en agosto 05, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados.  Acute Coronary Syndrome 57 (ICA), by contrast, is typically reserved for patients with acute chest pain that is deemed high risk (HEART score >6). Patients who are taken for ICA are clinically sus- pected to have a high-grade obstructive lesion and ICA can help establish which revi- sualization approach, percutaneous or surgical, would be the most appropriate intervention.7 A normal CCTA or ICA can be considered valid for up to 2 years in pa- tients who present with recurrent, but unchanged, symptoms relative to the index event that lead to testing with coronary angiography.7 MANAGEMENT Table 2 summarizes the inpatient management for STEMI and NSTE-ACS. Myocardial Infarction Coronary angiography, followed by percutaneous coronary intervention (PCI), should be performed within 120 minutes of patients presenting to the ED with STEMI.4,8 In health systems that do not have PCI capability, fibrinolytics should be administered to patients without contraindications.8,19 Once patients receive fibrinolytics, they should be transferred to health systems capable of performing PCI.19 Table 2 Summary of management of acute coronary syndrome23,24 STEMI NSTE-ACS Early hospital care Preferred strategy: Preferred strategy: Coronary Coronary angiography (timing angiography 1 primary PCI will depend on patient (goal PCI  120 min from first stability and risk of future contact) clinical events) Alternative: Anticoagulation (initiated at Fibrinolytics (if PCI not time of diagnosis) available) Aspirin (loading dose on Anticoagulation (bolus pre- or admission) intra-PCI to achieve target P2Y12 inhibitor (loading dose ACT) pre- or intra-PCI) Aspirin (loading dose pre-PCI) P2Y12 inhibitor (loading dose pre- or intra-PCI) Late hospital and Pharmacologic management postdischarge care High-intensity statin Aspirin P2Y12 inhibitor Beta-blocker (start within 24 h) Consider SGLT2i (if diabetic or HF) Non-pharmacologic management Referral to cardiac rehab Smoking cessation counseling Flu vaccination ACE inhibitor (start within ACE inhibitor (consider 24 h; consider ARB if ACE starting if LVEF < 40%; intolerance) consider ARB if ACE intolerance) Abbreviations: ACE, angiotensin-converting enzyme; ACT, activated clotting time; ARB, angio- tensin receptor blockers; HF, heart failure; LVEF, left ventricular ejection fraction; NSTE-ACS, non- ST-elevation acute coronary syndrome; PCI, percutaneous coronary intervention; SGLT2i, sodium–glucose cotransporter-2 inhibitors; STEMI, ST-elevation myocardial infarction. Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en agosto 05, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados. 58 Nohria & Antono Non-ST-Elevation-Acute Coronary Syndrome Coronary angiography should be performed in all patients with NSTE-ACS. For pa- tients who receive coronary angiography, approximately 60% will receive PCI, whereas the remainder will receive either bypass surgery or medical therapy alone.20 In the hospital, patients with NSTE-ACS should be initiated on parenteral anticoagu- lation, and dual-antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitor. On discharge from the hospital, patients should be transitioned to DAPT.21,22 POST-DISCHARGE MANAGEMENT Antiplatelet Agents DAPT lowers risk of stent thrombosis and recurrent MI.25,26 Patients on DAPT should be monitored for bleeding, and in particular gastrointestinal bleeding, as a common side effect of therapy. DAPT should be continued for at least 1 year, however, shorter duration can be considered in patients that are at high risk of bleeding. The determi- nation of shorter course should be made in concert with the patient’s cardiologist.22 All patients with ACS should continue low-dose aspirin indefinitely to reduce subse- quent major cardiovascular events such as MI.27 P2Y12 inhibitors include clopidogrel, prasugrel, or ticagrelor. DAPT with clopidogrel reduces cardiovascular deaths and MI compared with aspirin alone.28 Certain genetic variants may cause clopidogrel resis- tance, and observational data suggest an increased risk of cardiovascular events among such individuals,29,30 but current evidence does not show improved outcomes with pretreatment genetic screening.31 Ticagrelor and prasugrel confer better cardio- vascular outcomes than clopidogrel,32,33 with ticagrelor demonstrating reduction in all-cause mortality. In addition, ticagrelor has no significant difference in bleeding compared with clopidogrel, but 10% to 20% of patients taking ticagrelor report non-exertional dyspnea that often improves within 1 week of treatment.32 Prasugrel has been shown to be nonbeneficial or even harmful to patients 75 years, less than 60 kg, or with history of cerebrovascular events.33 One trial showed prasugrel improved cardiovascular outcomes without difference in bleeding when compared with ticagrelor, though asymmetric rates of treatment discontinuation between the two study groups may have overestimated the benefit of prasugrel.34 Statins Multiple large randomized trials have shown reductions in cardiovascular events and mortality with intensive statin therapy for secondary prevention.35 As such, the ACC/ AHA cholesterol guideline recommends starting high-intensity statin therapy for all pa- tients 75 years with ACS regardless of their lipid profile.36 The decision to initiate sta- tins for older adults greater than 75 years with ACS should weigh potential benefit versus competing adverse effects and comorbidities. Beta-Blockers A 2019 Cochrane review demonstrated significant reduction in all-cause and cardio- vascular mortality with initiation of beta-blockers in patients with ACS.37 Beta blockers also reduced short-term risk of MI but did not alter the risk of angina. Patients should be started on oral beta-blockers within 24 hours of ACS event unless contraindicated (allergy to beta-blockers, acute decompensated heart failure, increased risk of cardio- genic shock, atrioventricular block, asthma, or chronic obstructive lung disease).23,24 Beta-blocker use may be discontinued after 2 to 3 years if no other indications are pre- sent for beta-blocker therapy or side effects (symptomatic bradycardia, broncho- spasm, fatigue, hypoglycemia) are present.38 Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en agosto 05, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados.  Acute Coronary Syndrome 59 Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers ACE inhibitors reduce mortality among patients with recent MI, particularly those with left ventricular dysfunction.39 Patients with STEMI should be started on ACE inhibitors within 24 hours and continue indefinitely. Starting an ACE inhibitor should also be considered if a patient with NSTE-ACS has left ventricular ejection fraction less than 40%, hypertension, diabetes, or chronic kidney disease.23 Angiotensin receptor blockers provide a similar mortality benefit to ACE inhibitors and should be considered for patients with ACS who are intolerant of ACE inhibitors.23,24 Antidiabetic Drugs Glucagon-like Peptide-1 (GLP-1) receptor agonists (GLP-1 RA) are injectable medica- tions that control appetite, slow food transit through the stomach, and regulate insulin and glucagon secretion. SGLT-2 inhibitors (SGLT2i) are oral medications that upregu- late excretion of glucose and sodium in the urine, thereby lowering blood glucose level. Large randomized controlled trials of multiple GLP-1 RA (dulaglutide, liraglutide, semaglutide) and SGLT2i (empagliflozin, canagliflozin) have demonstrated reduction in atherosclerotic cardiovascular disease (ASCVD) events in diabetic patients.40–42 Thus, both drug classes should be preferentially considered for patients with diabetes who experience an MI.40–42 SGLT2i therapy should also be initiated in any patients presenting with concomitant heart failure, regardless of left ventricular function.43,44 Non-pharmacologic Management Patients who experience an MI can further reduce their mortality by abstaining from smoking and receiving influenza vaccination. A retrospective cohort study demonstrated that smokers aged 50 years or less who quit smoking within 1 year after MI experienced a lower all-cause and cardiac mortality.45 Counseling for smoking cessation should begin during the patient’s hospitalization for ACS.8 An randomized control trial (RCT) and meta- analysis demonstrated that patients who receive a flu vaccine as early as 72 hours of PCI or revascularization had a reduction in cardiac and all-cause mortality at 1-year.46,47 Patients with ACS should also receive a referral for cardiac rehabilitation. A 2016 systematic review and meta-analysis demonstrated the mortality benefit for patients who participate in cardiac rehabilitation.48 Home-based cardiac rehabilitation may be an alternative for patients who are unable to participate in outpatient cardiac reha- bilitation. One systematic review demonstrated that patients adhere to home-based cardiac rehabilitation at a higher rate.49 Ultimately, home-based and outpatient car- diac rehabilitation demonstrate similar improvements in functional capacity, quality of life, and risk factor modification after 12 months of participation.49 The optimal diet for secondary prevention remains an active area of investigation. A 2022 RCT (CORDIOPREV) comparing a low-fat diet and Mediterranean diet for sec- ondary prevention demonstrated that the Mediterranean diet was associated with lower risk of MACE.50,51 Depression may be present in as many as 20% of patients who have recently expe- rienced ACS, and its presence may inhibit efforts in lifestyle changes.52 Treatment with medications or psychotherapy may improve depression symptoms and reduce car- diac events and mortality.53,54 Although depression is common, the benefits of routinely screening ACS patients for depression remain unclear.55 SUMMARY ACS represents a sudden reduction in blood flow through the coronary arteries to the ventricular myocardium. ACS can manifest as STEMI and NSTE-ACS, which includes Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en agosto 05, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados. 60 Nohria & Antono both NSTEMI and unstable angina. Common risk factors include both nonmodifiable (age, sex) and modifiable (tobacco use, hyperlipidemia, diabetes mellitus, and hyper- tension) characteristics. There is no validated outpatient screening tool for evaluating patients who present with symptoms concerning for ACS. Coronary angiography with percutaneous or surgical revascularization should be performed in all patients with STEMI or NSTE-ACS. Patients with an MI should receive DAPT, high-intensity statin therapy, and beta-blocker therapy. SGLT2i therapy may also be beneficial in patients with MI. Post-MI lifestyle changes should emphasize smoking cessation, flu vaccina- tion within 72 hours of revascularization, and cardiac rehabilitation. For patients with a recent MI, the Mediterranean diet may further lower a patient’s risk for major adverse cardiac events. CLINICS CARE POINTS  Further testing is not recommended in low-risk individuals (Marburg Score