Acute coronary syndromes

Resident Survival Guide

Acute Coronary Syndrome Chapters
Heart Attack Patient Information
Unstable Angina Patient Information
Overview
Classification Unstable Angina Non-ST Elevation Myocardial Infarction ST Elevation Myocardial Infarction
Causes
Differential Diagnosis
Treatment
AHA/ACC Guidelines for Acute Coronary Syndrome
Guideline for Risk Stratification in ACS
Guideline for Pre-Hospital Evaluation and Care
Guidelines for Initial Management of ACS
Guidelines for Long-term management and secondary prevention
Guidelines for Patients with Atrial Fibrillation Complicating ACS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mitra Chitsazan, M.D.[2] Yamuna Kondapally, M.B.B.S[3]; Tarek Nafee, M.D. [4]; Sabawoon Mirwais, M.B.B.S, M.D.[5]; James Nasr[6]

Synonyms and keywords: acute coronary syndrome, acute coronary syndromes, ST-elevation myocardial infarction, non-ST-segment elevation acute coronary syndrome, unstable angina, STEMI, NSTEMI, NSTE-ACS, myocardial infarction, chest pain, coronary thrombosis, high-sensitivity troponin, plaque rupture, plaque erosion, spontaneous coronary artery dissection, MINOCA

Overview

Acute coronary syndrome (ACS) refers to a spectrum of clinical conditions caused by a sudden reduction in blood supply to the myocardium, most commonly resulting from disruption of an unstable coronary artery atherosclerotic plaque with associated partial or complete coronary thrombosis. Plaque disruption may occur through plaque rupture, plaque erosion, or, less commonly, a calcified nodule with superimposed thrombus.

ACS encompasses three related clinical entities that exist along a continuum of severity: unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). Unstable angina is differentiated from NSTEMI by the absence of elevated cardiac troponin and therefore by the absence of detectable myocardial necrosis. The widespread use of high-sensitivity cardiac troponin assays has reduced the frequency of true unstable angina diagnoses because many patients previously classified as having unstable angina are now found to have small degrees of myocardial injury.

The most common presenting symptom of ACS is chest pain or chest discomfort, classically described as pressure, heaviness, tightness, or squeezing. Pain may radiate to the left arm, both arms, neck, jaw, back, or epigastrium and may be associated with dyspnea, nausea, vomiting, diaphoresis, syncope, or fatigue. ACS must be distinguished from stable angina, which is usually predictable, occurs with exertion or emotional stress, and improves with rest or nitroglycerin.

Each year, more than 7 million people worldwide are diagnosed with ACS, including more than 1 million hospitalized patients in the United States. Approximately 5% of patients hospitalized with ACS die before hospital discharge. Approximately 14% of patients experiencing ACS in the United States do not survive the event.

Historical Perspective

The clinical understanding of ACS evolved from the recognition that angina pectoris, unstable angina, and myocardial infarction represent related manifestations of acute myocardial ischemia. Earlier classifications separated unstable angina, NSTEMI, and STEMI primarily by symptoms, ECG findings, and cardiac enzyme patterns. The development of cardiac-specific biomarkers, particularly troponin, allowed more accurate detection of myocardial injury and reduced reliance on older biomarkers such as CK-MB.

The introduction of high-sensitivity cardiac troponin assays further refined the distinction between unstable angina and NSTEMI. Many patients previously diagnosed with unstable angina are now recognized to have small degrees of myocardial injury and are therefore classified as NSTEMI. Contemporary ACS management has also shifted toward early ECG interpretation, rapid reperfusion for STEMI, invasive risk-stratified management for NSTE-ACS, potent antiplatelet therapy, high-intensity lipid-lowering therapy, and structured secondary prevention.

Classification

ACS is classified based on clinical history, electrocardiogram (ECG) findings, and cardiac troponin levels.

Unstable Angina

Unstable angina is characterized by myocardial ischemia without detectable myocardial necrosis.

• ECG findings: Normal ECG, nonspecific ST-T changes, transient ST-segment depression, or T-wave inversion.
• Cardiac troponin: Normal, without a rise and/or fall pattern above the assay-specific diagnostic threshold.
• Coronary pathology: Partial or transient coronary obstruction causing myocardial ischemia without significant myonecrosis.

Non-ST-Segment Elevation Myocardial Infarction

Non-ST-segment elevation myocardial infarction (NSTEMI) is characterized by myocardial ischemia with myocardial necrosis but without persistent diagnostic ST-segment elevation.

• ECG findings: ST-segment depression ≥0.5 mm, T-wave inversion >1 mm, transient ST-segment elevation, or nonspecific changes; no persistent diagnostic ST-segment elevation.
• Cardiac troponin: Elevated, with a rise and/or fall pattern consistent with acute myocardial injury.
• Coronary pathology: Usually partial or subtotal coronary obstruction causing subendocardial ischemia and myonecrosis.

ST-Segment Elevation Myocardial Infarction

ST-segment elevation myocardial infarction (STEMI) is characterized by acute myocardial ischemia with persistent diagnostic ST-segment elevation and myocardial necrosis.

• ECG findings: New ST-segment elevation in ≥2 contiguous leads: ≥1 mm in most leads, with V2-V3 thresholds of ≥2 mm in men ≥40 years, ≥2.5 mm in men <40 years, or ≥1.5 mm in women.
• Cardiac troponin: Usually elevated, with a rise and/or fall pattern.
• Coronary pathology: Usually acute complete coronary occlusion causing transmural ischemia and infarction.

STEMI accounts for approximately 30% of ACS, whereas non-ST-segment elevation acute coronary syndrome (NSTE-ACS) accounts for approximately 70%. The pathophysiology of ACS is dynamic, and patients may progress from one ACS phenotype to another during the same presentation.

Under the Fourth Universal Definition of Myocardial Infarction, myocardial infarction caused by atherosclerotic plaque rupture, erosion, fissuring, or dissection with intraluminal thrombus is classified as type 1 myocardial infarction.

Defining Lesion Severity. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization. (Please do not edit).

Angiography to Define Anatomy and Assess Lesion Severity

The standard procedure for defining coronary anatomy and assessing the degree of coronary artery stenosis is still coronary angiography.

• Severe Stenosis: diameter stenosis severity of 70% for non-left main disease and 50% for left main illness .
• A diameter stenosis severity of 40% to 69% is referred to as an angiographically intermediate coronary stenosis, and it usually necessitates further examination to determine its physiological significance .
• Longer lesions may cause more ischemia than a single severe lesion .

Causes

The most common cause of ACS is disruption of an atherosclerotic plaque with superimposed thrombus formation. Important causes and mechanisms include:

• Plaque rupture with exposure of thrombogenic necrotic core material and acute coronary thrombosis.
• Plaque erosion, in which thrombus forms over an eroded endothelial surface without frank fibrous cap rupture. Plaque erosion may be more common in women than men in autopsy studies.
• Calcified nodule, in which protruding nodular calcification disrupts the luminal surface and promotes thrombus formation.
• Coronary artery spasm, including vasospastic or Prinzmetal angina.
• Spontaneous coronary artery dissection (SCAD).
• Coronary embolism.
• Coronary arteritis.
• Myocardial infarction with nonobstructive coronary arteries (MINOCA), which is a working diagnosis requiring evaluation for ischemic and nonischemic mechanisms. MINOCA occurs in approximately 5% to 6% of patients with myocardial infarction.

Other conditions may produce myocardial oxygen supply-demand mismatch and acute myocardial injury that can mimic or accompany ACS. These include:

• Hypotension
• Severe anemia
• Severe hypertension
• Tachycardia
• Bradycardia
• Severe aortic stenosis
• Hypertrophic cardiomyopathy
• Sepsis
• Severe heart failure
• Pulmonary embolism
• Myocarditis
• Cardiac contusion
• Cardiotoxic drugs
• Stress cardiomyopathy or Takotsubo cardiomyopathy

Risk Factors

Traditional risk factors for atherosclerosis and ACS include:

• Dyslipidemia
• Hypertension
• Smoking
• Diabetes mellitus
• Obesity
• Family history of premature coronary artery disease
• Advanced age
• Male sex
• Chronic kidney disease
• Prior coronary artery disease

Emerging and nontraditional risk factors include hypertensive disorders of pregnancy, air pollution, psychosocial stress, disturbed sleep, chronic inflammatory disease, and alterations in the microbiome.

Differentiating Acute Coronary Syndrome from Other Diseases

The differential diagnosis of ACS is broad and includes life-threatening and non-life-threatening conditions. A systematic approach is required to identify alternative diagnoses while avoiding delay in treatment of true ACS.

Cardiovascular Causes Other Than ACS

Important cardiovascular causes that may mimic ACS include aortic dissection, pericarditis, myocarditis, aortic stenosis, hypertrophic cardiomyopathy, and Takotsubo cardiomyopathy.

• Aortic dissection may cause abrupt tearing chest or back pain, pulse deficit, neurologic symptoms, syncope, or widened mediastinum.
• Pericarditis may cause pleuritic chest pain improved by leaning forward, a pericardial friction rub, and diffuse ST-segment elevation without territorial reciprocal changes.
• Myocarditis may follow a viral illness and may cause troponin elevation without obstructive coronary disease.
• Takotsubo cardiomyopathy may present with chest pain, ECG changes, troponin elevation, and transient left ventricular wall-motion abnormalities, often after emotional or physical stress.

Pulmonary Causes

Important pulmonary causes include pulmonary embolism, pneumothorax, pneumonia, and pleuritis.

• Pulmonary embolism may cause acute dyspnea, tachycardia, pleuritic chest pain, hypoxemia, and elevated D-dimer.
• Pneumothorax may cause unilateral pleuritic chest pain and decreased breath sounds.
• Pneumonia and pleuritis may cause pleuritic pain, cough, fever, hypoxemia, or abnormal chest imaging.

Gastrointestinal Causes

Important gastrointestinal causes include gastroesophageal reflux disease, esophageal spasm, peptic ulcer disease, pancreatitis, cholecystitis, and esophageal rupture.

• Gastrointestinal causes may be suggested by epigastric tenderness, meal-related pain, vomiting, dysphagia, odynophagia, Murphy sign, elevated lipase, or subcutaneous emphysema.

Musculoskeletal Causes

Important musculoskeletal causes include costochondritis, chest wall trauma, rib fracture, and cervical radiculopathy.

• Musculoskeletal causes may be suggested by reproducible tenderness on palpation, focal chest wall pain, trauma history, or pain with movement.

Psychiatric Causes

Panic disorder and anxiety may cause chest tightness, hyperventilation, paresthesias, palpitations, sweating, trembling, and fear of dying.

• Psychiatric causes should be considered only after clinically important cardiopulmonary causes, including ACS, have been evaluated when clinically plausible.

Other Causes

Other causes include herpes zoster and sickle cell crisis.

• Herpes zoster may be suggested by dermatomal pain or rash.
• Sickle cell crisis may cause chest pain due to vaso-occlusion or acute chest syndrome.

Acute aortic dissection is a critical diagnosis that can mimic ACS. A normal ECG and normal troponin values do not exclude aortic dissection. An elevated D-dimer may support further evaluation in the appropriate clinical setting, but imaging is required when clinical suspicion for acute aortic syndrome is significant.

SYNTAX Score to Calculate the Complexity of Coronary Artery Lesions. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization. (Please do not edit.)

Class IIb

" 1. In patients with multivessel CAD, an assessment of CAD complexity, such as the SYNTAX score, may be useful to guide revascularization (Level of Evidence B-R)".

Differential Diagnoses of Acute Coronary Syndromes in the Setting of Chest Pain

Cardiac	Pulmonary	Vascular	Gastrointestinal	Orthopedic	Other
Myopericarditis Cardiomyopathiesa	Pulmonary embolism	Aortic dissection	Esophagitis Esophageal spasm	Musculoskeletal disorders	Anxiety disorders
Tachyarrhythmias	(Tension)-Pneumothorax	Symptomatic aortic aneurysm	Peptic ulcer, gastritis	Chest trauma	Herpes zoster
Acute heart failure	Bronchitis, pneumonia	Stroke	Pancreatitis	Muscle injury/inflammation	Anemia
Hypertensive emergencies	Pleuritis		Cholecystitis	Costochondritis
Aortic valve stenosis				Cervical spine pathologies
Tako-Tsubo cardiomyopathy
Coronary spasm
Cardiac trauma
Bold = Common and/or important differential diagnoses aDilated, hypertrophic and restrictive cardiomyopathies may cause angina or chest discomfort

Treatment

• To view the detailed treatment of Unstable angina/NSTEMI click here.
• To view the detailed treatment of STEMI click here.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization. Recommendations to prefer PCI or CABG (Please do not edit)

Patients With Complex Disease

Class I

"1. In patients who require revascularization for significant left main CAD with high complexity CAD, it is recommended to choose CABG over PCI to improve survival (Level of Evidence: A) "

Class IIa

" 2. In patients who require revascularization for multivessel CAD with complex or diffuse CAD (eg, SYNTAX score >33), it is reasonable to choose CABG over PCI to confer a survival advantage (Level of Evidence B-R)".

Patients with Diabetes

Class I

"1. In patients with diabetes and multivessel CAD with the involvement of the LAD, who are appropriate candidates for CABG, CABG (with a LIMA to the LAD) is recommended in preference to PCI to reduce mortality and repeat revascularizations(Level of Evidence: A) "

Class IIa

" 2. In patients with diabetes who have multivessel CAD amenable to PCI and an indication for revascularization and are poor candidates for surgery, PCI can be useful to reduce long-term ischemic outcomes (Level of Evidence B-NR)".

Class IIb

" 3. In patients with diabetes who have left main stenosis and low- or intermediate-complexity CAD in the rest of the coronary anatomy, PCI may be considered an alternative to CABG to reduce major adverse cardiovascular out-comes. (Level of Evidence B-R)".

Patients With Previous CABG

Class IIa

" 1. In patients with previous CABG with a patent LIMA to the LAD who need repeat revascularization, if PCI is feasible, it is reasonable to choose PCI over CABG (Level of Evidence B-NR)".

'' 2. In patients with previous CABG and refractory angina on GDMT that is attributable to LAD disease, it is reasonable to choose CABG over PCI when an internal mammary artery (IMA) can be used as a conduit to the LAD (Level of Evidence C-LD)

Class IIb

" 3. In patients with previous CABG and complex CAD, it may be reasonable to choose CABG over PCI when an IMA can be used as a conduit to the LAD (Level of Evidence B-NR)".

Dual antiplatelet therapy (DAPT)

Class IIa

" 1. In patients with multivessel CAD amenable to treatment with either PCI or CABG who are unable to access, tolerate, or adhere to DAPT for the appropriate duration of treatment, CABG is reasonable in preference to PCI(Level of evidence B-NR)".

Revascularization in Pregnant Patients

Class IIa

" 1. In pregnant patients with STEMI not caused by spontaneous coronary artery dissection (SCAD), it is reasonable to perform primary PCI as the preferred revascularization strategy. (Level of Evidence C-LD)".

'' 2. In pregnant patients with NSTE-ACS, an invasive strategy is reasonable if medical therapy is ineffective for the management of life-threatening complications (Level of Evidence C-LD)

Revascularization in Older Patients

Class I

"1. In older adults, as in all patients, the treatment strategy for CAD should be based on an individual patient’s preferences, cognitive function, and life expectancy(Level of Evidence: B-NR) "

Revascularization in Patients With Chronic Kidney Disease

Class I

"1. In patients with CKD undergoing contrast media injection for coronary angiography, measures should be taken to minimize the risk of contrast-induced acute kidney injury(Level of Evidence: C-LD) "

''2. In patients with STEMI and CKD, coronary angiography and revascularization are recommended, with adequate measures to reduce the risk of AKI.(Level of evidence C-EO )''

Class IIa

" 3. In high-risk patients with NSTE-ACS and CKD, it is reasonable to perform coronary angiography and revascularization, with adequate measures to reduce the risk of AKI (Level of Evidence B-NR)".

" 4. In low-risk patients with NSTE-ACS and CKD, it is reasonable to weigh the risk of coronary angiography and revascularization against the potential benefit(Level of Evidence C-EO)''

Class III (No Benefit)

"5. In asymptomatic patients with stable CAD and CKD, routine angiography and revascularization are not recommended if there is no compelling indication. (Level of Evidence:B-R) "

Revascularization in Patients Before Noncardiac Surgery

Class III (No Benefit)

"1. In patients with non–left main or noncomplex CAD who is undergoing noncardiac surgery, routine coronary revascularization is not recommended solely to reduce perioperative cardiovascular events. (Level of Evidence:B-R) "

Revascularization in Patients to Reduce Ventricular Arrhythmias

Class I

"1. In patients with ventricular fibrillation, polymorphic ventricular tachycardia (VT), or cardiac arrest, revascularization of significant CAD is recommended to improve survival. (Level of Evidence: B-NR) "

Class III (No Benefit)

"2. In patients with CAD and suspected scar-mediated sustained monomorphic VT, revascularization is not recommended for the sole purpose of preventing recurrent VT. (Level of Evidence:C-LD) "

Revascularization in Patients With Spontaneous coronary artery dissection (SCAD)

Class IIb

" 1. In patients with SCAD who have hemody-namic instability or ongoing ischemia despite conservative therapy, revascularization may be considered if feasible (Level of Evidence C-LD)".

Class III (Harm)

"2. Routine revascularization for SCAD should not be performed (Level of Evidence:C-LD) "

Revascularization in Patients With Cardiac Allografts

Class IIa

" 1. In patients with cardiac allograft vasculopathy and severe, proximal, discrete coronary lesions, revascularization with PCI is reasonable (Level of Evidence C-LD)".

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization (Please do not edit). RECOMMENDATIONS FOR ADDRESSING PSYCHOSOCIAL FACTORS AND LIFESTYLE CHANGES AFTER REVASCULARIZATION

Cardiac Rehabilitation and Education

Class I

"1. In patients who have undergone revascularization, a comprehensive cardiac rehabilitation program (home-based or center-based) should be prescribed either before hospital discharge or during the first outpatient visit to reduce deaths and hospital readmissions and improve quality of life (Level of Evidence: A) "

''2. Patients who have undergone revascularization should be educated about CVD risk factors and their modification to reduce cardiovascular events. (Level of evidence C-LD)''

Smoking Cessation in Patients After Revascularization

Class I

"1. In patients who use tobacco and have undergone coronary revascularization, a combination of behavioral interventions plus pharmacotherapy is recommended to maximize cessation and reduce adverse cardiac events (Level of Evidence: A) "

''2. In patients who use tobacco and have under-gone coronary revascularization, smoking cessation interventions are recommended during hospitalization and should include supportive follow-up for at least 1 month after discharge to facilitate tobacco cessation and reduce morbidity and mortality (Level of evidence A)''

Psychological Interventions in Patients After Revascularization

Class I

"1. In patients who have undergone coronary revascularization who have symptoms of depression, anxiety, or stress, treatment with cognitive behavioral therapy, psychological counseling, and/or pharmacological interventions is beneficial to improve quality of life and cardiac outcomes (Level of Evidence: B-R) "

Class IIb

" 2. In patients who have undergone coronary revascularization, it may be reasonable to screen for depression and refer or treat when it is indicated to improve quality of life and recovery. (Level of Evidence C-LD)".

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization (Please do not edit). Revascularization Outcomes

Assessment of Outcomes in Patients After Revascularization

Class I

"1. With the goal of improving patient outcomes, it is recommended that cardiac surgery and PCI programs participate in state, regional, or national clinical data registries and receive periodic reports of their risk-adjusted out-comes as a quality assessment and improvement strategy (Level of Evidence: B-NR) "

Class IIa

" 1. With the goal of improving patient outcomes, it is reasonable for cardiac surgery and PCI programs to have a quality improvement program that routinely 1) reviews institutional quality programs and outcomes 2) reviews individual operator outcomes 3) provides peer review of difficult or complicated cases 4) performs random case reviews (Level of Evidence C-LD)".

Class IIb

" 3. Smaller volume cardiac surgery and PCI programs may consider affiliating with a high-volume center to improve patient care. (Level of Evidence C-EO)".

Pathophysiology

The pathophysiology of ACS centers on acute coronary plaque disruption, activation of the coagulation cascade, platelet activation, and thrombosis.

Plaque Rupture and Thrombosis

Progressive lipid accumulation and inflammation within an atherosclerotic plaque lead to plaque instability. Vulnerable plaques often have thin fibrous caps, large lipid cores, inflammatory cell infiltration, and increased local proteolytic activity. Plaque rupture exposes thrombogenic material to circulating blood and promotes platelet adhesion, activation, and aggregation.

Activated platelets release adenosine diphosphate (ADP) and thromboxane A2, which amplify platelet recruitment. ADP activates the platelet P2Y12 receptor, leading to activation of the glycoprotein IIb/IIIa receptor and platelet aggregation. Tissue factor exposure and thrombin generation activate the coagulation cascade, resulting in fibrin-rich thrombus formation.

When thrombosis completely occludes the vessel, STEMI typically occurs with transmural myocardial ischemia and infarction. When the thrombus is nonocclusive or transiently occlusive, NSTE-ACS typically occurs with subendocardial ischemia, NSTEMI, or unstable angina. Complete vessel occlusion does not always produce classic ST-segment elevation; occlusion of vessels supplying the lateral or posterior wall may present with less typical ECG findings, including ST-segment depression or posterior infarction patterns.

Post-ACS Inflammatory Milieu

Patients remain at increased risk for recurrent cardiovascular events for months to years after an ACS event. This increased risk is partly related to residual coronary atherosclerotic burden, thrombogenicity, endothelial dysfunction, and the inflammatory milieu after ACS.

Diagnosis

Clinical Presentation

Chest discomfort at rest is the most common presenting symptom of ACS, affecting approximately 79% of men and 74% of women with ACS. Approximately 40% of men and 48% of women may present with nonspecific symptoms such as dyspnea, either alone or in combination with chest pain.

Other symptoms may include:

• Pain between the shoulder blades, neck, jaw, shoulder, or arm
• Nausea or vomiting
• Diaphoresis
• Fatigue
• Syncope or dizziness
• Epigastric pain
• Palpitations
• Acute heart failure symptoms

Older adults, women, and patients with diabetes mellitus or chronic kidney disease may be more likely to present with dyspnea, fatigue, weakness, syncope, or other symptoms rather than classic chest pain.

Electrocardiography

A 12-lead electrocardiogram should be obtained and interpreted within 10 minutes of first medical contact in patients with suspected ACS.

Key ECG findings include:

• STEMI: New ST-segment elevation in ≥2 contiguous leads: ≥1 mm in most leads, with V2-V3 thresholds of ≥2 mm in men ≥40 years, ≥2.5 mm in men <40 years, or ≥1.5 mm in women, measured at the J-point.
• NSTE-ACS: ST-segment depression, T-wave inversion, transient ST-segment elevation, or nonspecific ST-T changes.
• Possible STEMI equivalents or occlusion MI patterns: Posterior myocardial infarction, de Winter T waves, Wellens pattern, ST-segment elevation in aVR with diffuse ST-segment depression, and new or presumed new left bundle branch block in the appropriate clinical setting. These findings should prompt urgent evaluation for occlusive coronary disease and possible emergent coronary angiography.

Serial ECGs at 15- to 30-minute intervals are recommended for patients with persistent or recurrent symptoms or an initial nondiagnostic ECG when clinical suspicion remains high.

Cardiac Biomarkers

High-sensitivity cardiac troponin is the preferred biomarker for diagnosing myocardial infarction. Troponin is organ-specific but not disease-specific; therefore, interpretation must incorporate the clinical presentation, ECG findings, and the presence or absence of a rise and/or fall pattern.

A diagnosis of acute myocardial infarction requires acute myocardial injury, defined by a rise and/or fall in cardiac troponin with at least one value above the 99th percentile upper reference limit, plus evidence of acute myocardial ischemia.

In patients with chronic kidney disease, troponin may be chronically elevated. Diagnosis depends on clinical context and dynamic change over time rather than a single isolated value.

Risk Stratification

Validated risk scores can support disposition and treatment decisions, but they do not replace clinical judgment.

GRACE Risk Score

The GRACE risk score is used in patients with suspected or confirmed ACS to estimate in-hospital and postdischarge risk of death or death/myocardial infarction.

Key variables include:

• Age
• Heart rate
• Systolic blood pressure
• Serum creatinine
• Killip class
• Cardiac arrest at presentation
• ST-segment deviation
• Elevated cardiac biomarkers

The GRACE Risk Score is useful for predicting death or MI in patients with ACS and may be superior to subjective physician assessment in patients with STEMI or intermediate-risk NSTE-ACS.

TIMI Risk Score for UA/NSTEMI

The TIMI Risk Score for UA/NSTEMI is used in patients with unstable angina or NSTEMI to estimate 14-day risk of all-cause mortality, myocardial infarction, or urgent revascularization.

Key variables include:

• Age ≥65 years
• ≥3 CAD risk factors
• Known coronary stenosis ≥50%
• ST-segment deviation
• ≥2 anginal episodes in the prior 24 hours
• Aspirin use in the prior 7 days
• Elevated cardiac biomarkers

HEART Score

The HEART Score is commonly used in patients with undifferentiated emergency department chest pain to estimate 6-week risk of major adverse cardiac events.

Key variables include:

• History
• ECG
• Age
• Risk factors
• Troponin

The HEART and TIMI scores are commonly used for emergency department chest pain risk stratification.

Treatment

Initial Management

Patients with suspected ACS should receive rapid evaluation, risk assessment, and transfer to an emergency department or PCI-capable facility when appropriate. Initial management includes:

• Aspirin: A loading dose of 162 to 325 mg should be administered promptly unless contraindicated.
• 12-lead ECG: Obtain and interpret within 10 minutes of first medical contact.
• Cardiac monitoring: Continuous rhythm monitoring should be used in patients with suspected ACS.
• Oxygen: Supplemental oxygen is recommended for oxygen saturation <90%, respiratory distress, or other features of hypoxemia. Routine oxygen is not recommended for normoxemic patients.
• Nitroglycerin: Sublingual nitroglycerin 0.4 mg may be given every 5 minutes for ongoing ischemic chest discomfort, up to 3 doses, if not contraindicated.
• Avoid nitroglycerin in patients with hypotension, suspected right ventricular infarction, severe aortic stenosis, recent phosphodiesterase-5 inhibitor use, or other nitrate contraindications.
• Analgesia: Persistent severe pain should prompt reassessment for ongoing ischemia, hemodynamic instability, or an alternative diagnosis.

Medical Therapy

Antiplatelet Therapy

Dual antiplatelet therapy (DAPT) with aspirin and an oral P2Y12 receptor inhibitor is recommended for most patients with ACS, unless contraindicated. The agent and duration should be individualized according to ischemic risk, bleeding risk, revascularization strategy, and the need for oral anticoagulation.

• Aspirin: Loading dose followed by low-dose aspirin, usually 81 mg daily.
• Ticagrelor or prasugrel: Recommended in preference to clopidogrel in patients with ACS undergoing PCI when not contraindicated.
• Prasugrel: Contraindicated in patients with prior stroke or transient ischemic attack. It should be used cautiously in patients ≥75 years or weighing <60 kg because of increased bleeding risk.
• Upstream P2Y12 therapy in NSTE-ACS: In patients with NSTE-ACS scheduled for an invasive strategy with angiography delayed beyond 24 hours, upstream treatment with clopidogrel or ticagrelor may be considered.

Anticoagulation

Parenteral anticoagulation is recommended in the initial management of ACS, whether the treatment strategy is invasive or conservative, unless contraindicated. Options include:

• Unfractionated heparin
• Low-molecular-weight heparin, such as enoxaparin
• Direct thrombin inhibitors, such as bivalirudin
• Factor Xa inhibitors, such as fondaparinux

The choice of anticoagulant depends on the ACS subtype, renal function, bleeding risk, timing of angiography, and planned reperfusion or revascularization strategy.

Beta-Blockers

Oral beta-blocker therapy is generally favored early after ACS in the absence of contraindications, particularly in patients with hypertension, tachycardia, ongoing ischemia, reduced left ventricular systolic function, or ventricular arrhythmias. Intravenous beta-blockers should be avoided in patients with hypotension, acute heart failure, bradycardia, heart block, or risk factors for cardiogenic shock.

Renin-Angiotensin-Aldosterone System Inhibitors

Per the 2025 ACC/AHA ACS guideline:

• ACE inhibitor or ARB: Indicated in high-risk patients with ACS, including patients with left ventricular ejection fraction ≤40%, hypertension, diabetes mellitus, chronic kidney disease, or anterior STEMI, to reduce death and major adverse cardiovascular events.
• ACE inhibitor or ARB: Reasonable in patients with ACS who are not considered high risk.
• Mineralocorticoid receptor antagonist: Indicated in patients with ACS and LVEF ≤40% with heart failure symptoms and/or diabetes mellitus, if renal function and potassium level permit.

Concomitant use of both an ACE inhibitor and an ARB should be avoided because it increases adverse events without additional clinical benefit.

Lipid-Lowering Therapy

High-intensity statin therapy is recommended for all patients with ACS unless contraindicated. It should be initiated or continued as early as possible, regardless of baseline LDL-C level.

In patients already receiving maximally tolerated statin therapy who have LDL-C ≥70 mg/dL, addition of nonstatin lipid-lowering therapy is recommended. Options include ezetimibe, evolocumab, alirocumab, inclisiran, or bempedoic acid, selected according to LDL-C level, required LDL-C reduction, cost, availability, patient preference, and comorbidities.

PCSK9 inhibitor therapy has been shown to reduce major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease, with greater absolute benefit in patients at higher baseline risk.

Procedural / Surgical Therapy

STEMI Reperfusion

Early reperfusion is the central treatment for eligible patients with STEMI.

• Primary PCI: In patients with STEMI presenting within 12 hours after symptom onset, primary PCI is recommended with a goal of first medical contact to device activation of ≤90 minutes at PCI-capable hospitals or ≤120 minutes when transfer is required.
• Primary PCI from 12 to 24 hours: In patients presenting 12 to 24 hours after symptom onset, primary PCI is reasonable when there is clinical or ECG evidence of ongoing ischemia.
• Fibrinolytic therapy: In patients with STEMI presenting within 12 hours of symptom onset, fibrinolytic therapy should be administered if no contraindication exists and primary PCI cannot be performed within 120 minutes from first medical contact.
• Pharmaco-invasive strategy: After fibrinolytic therapy, coronary angiography with intent to perform PCI is generally performed within 3 to 24 hours, or urgently if there is failed reperfusion or clinical instability.
• Late occluded infarct artery: In stable patients with a totally occluded infarct artery >24 hours after symptom onset without ongoing ischemia, acute severe heart failure, or life-threatening arrhythmia, routine PCI should not be performed.
• Cardiogenic shock: Emergency revascularization of the culprit vessel by PCI or coronary artery bypass grafting (CABG) is indicated, irrespective of time from symptom onset.

Fibrinolytic options include alteplase, reteplase, and tenecteplase. Dosing must account for agent, age, body weight, contraindications, and bleeding risk. Dose reduction is particularly relevant for tenecteplase in patients ≥75 years.

NSTE-ACS Invasive Strategy

Patients with NSTE-ACS should be stratified by ischemic and bleeding risk. Very high-risk features warrant immediate or emergent invasive evaluation. High-risk features generally support an early invasive strategy, often within 24 hours. Lower-risk patients may undergo delayed invasive evaluation or selective ischemia-guided management.

Very high-risk features include:

• Hemodynamic instability
• Cardiogenic shock
• Refractory or recurrent chest pain despite medical therapy
• Life-threatening ventricular arrhythmia or cardiac arrest
• Mechanical complications of myocardial infarction
• Acute heart failure clearly related to ACS
• Dynamic ST-segment or T-wave changes, particularly with recurrent symptoms

Among patients with NSTEMI who undergo coronary angiography, approximately 60% receive PCI, 10% undergo CABG, and 30% are initially managed medically.

Vascular Access

Radial arterial access is preferred for PCI when feasible because it reduces access-site bleeding and vascular complications compared with femoral access.

Long-Term Management

Dual Antiplatelet Therapy Duration

Per the 2025 ACC/AHA ACS guideline:

• Default strategy: DAPT with aspirin and an oral P2Y12 inhibitor is recommended for at least 12 months in patients with ACS who are not at high bleeding risk.
• Shortened DAPT or de-escalation: Shorter DAPT duration, P2Y12 inhibitor monotherapy, or de-escalation from ticagrelor or prasugrel to clopidogrel may be considered in selected patients to reduce bleeding risk.
• Patients requiring oral anticoagulation: Aspirin is usually discontinued 1 to 4 weeks after PCI, with continuation of oral anticoagulation plus a P2Y12 inhibitor, preferably clopidogrel.
• Proton pump inhibitor: A proton pump inhibitor is recommended in patients receiving DAPT who are at high risk for gastrointestinal bleeding.

Extended DAPT beyond 12 months may reduce recurrent MI and ischemic stroke but increases major bleeding. A meta-analysis of 24 randomized clinical trials with 79,073 patients found that DAPT >12 months was associated with 3.8 fewer cases of MI per 1000 person-years and 4.9 more cases of major bleeding per 1000 person-years.

Lipid Management

Lifelong lipid-lowering therapy is indicated after ACS. For patients with ACS, the LDL-C treatment threshold in the 2025 ACC/AHA ACS guideline is ≥70 mg/dL despite maximally tolerated statin therapy. In very-high-risk patients, lower LDL-C goals may be considered according to contemporary dyslipidemia guidance.

Cardiac Rehabilitation

All eligible patients with ACS should be referred to an outpatient cardiac rehabilitation program before hospital discharge. Cardiac rehabilitation reduces death, MI, hospital readmissions, and improves functional status and quality of life.

Home-based cardiac rehabilitation is a reasonable alternative to center-based rehabilitation in selected patients when center-based participation is not feasible.

Lifestyle Modification

Lifestyle modification after ACS includes:

• Smoking cessation
• Heart-healthy dietary pattern
• Regular physical activity
• Weight management
• Blood pressure control
• Diabetes management
• Medication adherence
• Participation in cardiac rehabilitation

Smoking cessation substantially reduces the risk of recurrent cardiovascular events and mortality. In the YOUNG-MI registry, patients who continued smoking had an all-cause mortality rate of 13.2%, compared with 4.1% in patients who quit.

Special Populations

Management should be individualized in patients with high bleeding risk, older adults, chronic kidney disease, pregnancy-associated ACS, SCAD, and patients requiring long-term oral anticoagulation. Evidence-based ACS therapy should not be withheld solely because of age or sex, but dosing and procedural decisions should incorporate renal function, frailty, bleeding risk, hemodynamic status, coronary anatomy, and patient preferences.

Prevention

Primary Prevention

Primary prevention of ACS focuses on modification of atherosclerotic risk factors:

• Blood pressure control
• Lipid management with statin therapy when indicated
• Smoking cessation
• Glycemic control in patients with diabetes mellitus
• Weight management
• Regular physical activity
• Heart-healthy dietary pattern
• Treatment of chronic inflammatory and cardiometabolic risk factors when present

Aspirin is no longer routinely recommended for primary prevention in most adults and should be individualized according to cardiovascular risk and bleeding risk.

Secondary Prevention

Secondary prevention after ACS includes lifelong pharmacotherapy, risk factor modification, and structured follow-up.

Core components include:

• Aspirin indefinitely unless contraindicated
• P2Y12 inhibitor therapy for at least 12 months in most patients, with duration individualized by ischemic and bleeding risk
• High-intensity statin therapy
• Additional nonstatin lipid-lowering therapy if LDL-C remains above threshold despite maximally tolerated statin therapy
• ACE inhibitor or ARB, particularly in patients with LVEF ≤40%, hypertension, diabetes, chronic kidney disease, or anterior STEMI
• Beta-blocker therapy when indicated
• Mineralocorticoid receptor antagonist in patients with LVEF ≤40% and heart failure symptoms and/or diabetes mellitus, when renal function and potassium permit
• Cardiac rehabilitation
• Smoking cessation
• Annual influenza vaccination

Special Populations

Women

Women with ACS should receive the same evidence-based diagnostic evaluation, pharmacologic therapy, and revascularization strategy as men, unless contraindicated. Attention should be given to weight-based and renal-dose adjustment of antiplatelet and anticoagulant therapy to reduce bleeding risk.

Women are more likely than men to present with symptoms other than classic chest pain, including dyspnea, nausea, fatigue, or epigastric discomfort. However, chest discomfort remains the most common presenting symptom in both women and men.

SCAD is an important cause of ACS in younger women and in pregnancy or the postpartum period. Management should be individualized according to anatomy, ongoing ischemia, hemodynamic stability, and clinical risk.

Older Adults

Older adults with ACS should receive guideline-directed medical therapy and invasive evaluation when clinically appropriate. Treatment decisions should incorporate ischemic risk, bleeding risk, frailty, cognitive function, comorbidities, functional status, life expectancy, and patient preferences.

Chronic Kidney Disease

Patients with chronic kidney disease have higher ischemic and bleeding risk after ACS. Troponin may be chronically elevated; therefore, diagnosis should rely on clinical context, ECG findings, and serial troponin change rather than a single value.

When coronary angiography or PCI is performed, measures should be used to reduce the risk of contrast-associated acute kidney injury, including appropriate hydration, minimizing contrast volume, and avoiding nephrotoxins when possible.

Pregnancy

ACS during pregnancy is uncommon but high risk. SCAD is an important cause of pregnancy-associated ACS. In pregnant patients with STEMI not caused by SCAD, primary PCI is generally the preferred reperfusion strategy when feasible. In pregnant patients with NSTE-ACS, an invasive strategy is reasonable when medical therapy is ineffective or when life-threatening complications occur.

Prognosis

Prognosis after ACS depends on age, infarct size, left ventricular function, renal function, diabetes, hemodynamic status, coronary anatomy, success of reperfusion or revascularization, bleeding risk, and adherence to secondary prevention therapy.

Patients remain at increased risk for recurrent MI, stroke, heart failure, arrhythmias, and cardiovascular death after ACS. Early revascularization when indicated, DAPT, high-intensity lipid-lowering therapy, RAAS inhibition in appropriate patients, smoking cessation, blood pressure control, diabetes management, and cardiac rehabilitation reduce recurrent cardiovascular events.

Complications that may worsen prognosis include:

• Arrhythmia
• Cardiogenic shock
• Acute heart failure
• Mitral regurgitation due to papillary muscle dysfunction or rupture
• Ventricular septal rupture
• Left ventricular free wall rupture
• Left ventricular aneurysm
• Pericarditis
• Recurrent myocardial infarction
• Stroke
• Major bleeding related to antithrombotic therapy
• Sudden cardiac death

Indications for Referral

Patients with suspected ACS require urgent emergency evaluation. Immediate referral to an emergency department or activation of emergency medical services is indicated for patients with:

• Chest pain or pressure suspicious for ACS
• New ischemic ECG changes
• Elevated or dynamically changing cardiac troponin
• Hemodynamic instability
• Syncope with suspected cardiac cause
• Acute heart failure symptoms
• Life-threatening arrhythmia
• Suspected STEMI or STEMI equivalent
• Persistent or recurrent ischemic symptoms despite initial therapy

Patients recovering from ACS should be referred for:

• Cardiology follow-up
• Cardiac rehabilitation
• Lipid management and preventive cardiology when LDL-C remains above target despite therapy
• Smoking cessation support when applicable
• Diabetes, hypertension, and chronic kidney disease management when applicable