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Jan.23.2023

Acute Coronary Syndromes

Synopsis

Key Points

  • Acute coronary syndromes are several potentially life-threatening conditions associated with acute myocardial ischemia and/or infarction that most commonly result from a sudden decrease in coronary blood flow precipitated by acute thrombosis secondary to a rupture or eroded atherosclerotic coronary plaque
    • Syndromes include ST-elevation myocardial infarction, non–ST-elevation myocardial infarction, and unstable angina
  • Syndromes typically present as retrosternal chest pain that may radiate to the arms, neck, and/or lower jaw; may be accompanied by dyspnea, diaphoresis, nausea, syncope, and fatigue
  • Diagnosis is based on history, physical examination, ECG, and cardiac troponin levels
  • Treatment consists of the following:
    • Initial care includes administration of supplemental oxygen, aspirin, nitrates, IV morphine, a β-blocker (or calcium channel blocker), an ACE inhibitor (or angiotensin receptor blocker), and a statin
    • Antithrombotic therapy is a cornerstone of treatment and is composed of long-term antiplatelet therapy and short-term anticoagulation therapy
    • Therapeutic reperfusion is the treatment of choice in most patients with ST-elevation myocardial infarction
      • Preferred option is percutaneous coronary intervention; alternative treatments include fibrinolytic therapy or coronary artery bypass graft
    • Patients with non–ST-elevation myocardial infarction/unstable angina may be treated using early invasive strategy (angiography and percutaneous coronary intervention) or ischemia-guided strategy
      • Early invasive strategy is recommended for patients with uncontrolled pain, arrhythmia, or hypotension, or patients with other risk factors suggesting a high likelihood of further cardiac events
      • Ischemia-guided strategy may be considered for patients assessed at low or intermediate clinical risk and entails routine medical care followed by noninvasive ischemic evaluation (using coronary CT angiography or stress testing), with invasive management triggered by recurrent ischemia or demonstrated obstructive coronary artery disease r1
        • May also be more appropriate for patients in whom other clinical conditions (eg, severe comorbidities) or personal considerations apply
        • Invasive strategy with intent to perform revascularization before hospital discharge is reasonable to consider even in patients initially assigned to conservative management with an ischemia-guided strategy
  • Comorbidities that may affect treatment include diabetes, heart failure, and chronic kidney disease
  • Complications include cardiogenic shock, severe heart failure, right ventricular infarction, mechanical complications, electrical complications, pericarditis, thromboemboli, bleeding, and acute kidney injury
  • Prognosis varies based on ST-elevation status; overall, 6-month mortality is 12% to 13%; secondary prevention is key to prognosis r1

Urgent Action

  • Timeliness is essential for treatment of acute coronary syndromes; time from symptom onset to presentation dictates management strategy, particularly in patients with ST-elevation myocardial infarction in whom reperfusion by percutaneous coronary intervention should be achieved within 120 minutes from first medical contact or fibrinolytic therapy should be started within 30 minutes r2

Pitfalls

  • Failure to institute therapeutic intervention within appropriate time frame
  • Failure to identify and treat life-threatening complications (eg, cardiogenic shock, rupture of cardiac structures, life-threatening ventricular arrhythmias)
  • Failure to consider a cardiac cause of chest pain when gastrointestinal medications relieve pain

Terminology

Clinical Clarification

  • Acute coronary syndrome encompasses several potentially life-threatening conditions associated with acute myocardial ischemia and/or infarction that result from a sudden decrease in coronary blood flow or an increase in myocardial demand that exceeds perfusion r3

Classification

  • Acute coronary syndromes represent a spectrum of disease, including ST-elevation myocardial infarction, non–ST-elevation myocardial infarction, and unstable angina r3
    • Atherosclerotic coronary artery obstruction is often, but not always, present
    • MINOCA (myocardial infarction in the absence of obstructive coronary artery disease) is found in 5% to 6% of all patients undergoing coronary angiography r4
    • Acute myocardial infarction
      • Acute myocardial injury with clinical evidence of acute myocardial ischemia and detection of rise and/or fall of cardiac troponin values with at least 1 value above the 99th percentile upper reference limit, plus at least 1 of the following:
        • Symptoms of myocardial ischemia
        • New ischemic ECG changes
        • Development of pathologic Q waves
        • Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in pattern consistent with ischemic cause
        • For some types of myocardial infarction, identification of a coronary thrombus by angiography or autopsy
      • 2 categories: r5
        • Acute ST-elevation myocardial infarction
          • Transmural ischemia and myocardial necrosis (infarction) associated with release of chemical biomarkers and characterized by ECG changes that include ST-segment elevation or new left bundle branch block, followed by development of pathologic Q waves
        • Acute non–ST-elevation myocardial infarction
          • Myocardial ischemia and necrosis (infarction) associated with the release of chemical biomarkers, but without ECG changes associated with ST-elevation myocardial infarction
    • Unstable angina r3
      • New onset of symptomatic myocardial ischemia or change in pattern of myocardial ischemia (eg, occurring with increasing frequency, duration, or intensity; with less exertion; or at rest)
        • ECG and chemical evidence of acute myocardial necrosis are absent
  • Myocardial infarction (ST-elevation myocardial infarction or non–ST-elevation myocardial infarction) is further classified by cause as follows: r5
    • Type 1: spontaneous myocardial infarction
      • Caused by atherothrombotic coronary artery disease and usually precipitated by atherosclerotic plaque disruption (rupture or erosion)
    • Type 2: secondary to ischemic imbalance
      • Condition other than coronary artery disease (eg, coronary artery spasm, coronary embolus, arrhythmia, anemia, hypotension, respiratory failure) that creates an imbalance between myocardial oxygen supply and demand
    • Type 3: results in death; biomarkers are unavailable
      • Death in the context of symptoms consistent with myocardial ischemia, but without documented release of chemical biomarkers
    • Type 4a: related to percutaneous coronary intervention
      • Elevated cardiac biomarker levels associated with at least 1 of the following:
        • New ischemic ECG changes
        • New pathologic Q waves
        • Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality
        • Angiographic findings demonstrating flow-limiting complication
    • Type 4b: related to stent thrombosis
      • Detected by angiography or autopsy in the context of myocardial ischemia and release of cardiac biomarkers
    • Type 4c: in-stent restenosis, or restenosis after balloon angioplasty in the infarct territory
      • May be the only angiographic explanation when no other culprit lesion or thrombus can be identified
    • Type 5: related to coronary artery bypass grafting
      • Elevation of cardiac biomarker levels associated with new pathologic Q waves or left bundle branch block, angiographically demonstrated coronary artery occlusion, or other imaging showing new loss of myocardium or regional wall motion abnormality

Diagnosis

Clinical Presentation

History

  • Obtain a focused but thorough history of presenting symptoms as well as previous similar episodes, associated features, and known cardiovascular risk factors r6
  • Pain c1
    • Usually characterized as substernal pressure or tightness;r7 varies in intensity, but may increase in crescendo-like pattern to become very severe, especially in ST-elevation myocardial infarction c2
    • May be bilateral or unilateral, but occurs more commonly on left side
    • May radiate to left or right arm, both arms, neck, or lower jaw r7c3c4c5
    • May be associated with diaphoresis, dyspnea, nausea, vomiting, fatigue, or syncope r7c6c7c8c9c10c11
    • May be precipitated by exertion but may also occur at rest c12c13
    • Disagreement exists over the diagnostic significance of relief with nitroglycerin; typical pattern involves prompt relief within several minutes of taking sublingual nitroglycerin c14
    • Duration usually exceeds 10 minutesr3 and may last for hours, especially in ST-elevation myocardial infarctionr8
    • May be absent or may be nonclassic in nature or distribution
      • Nonclassic presentations are more common in patients aged 75 years or older, in female patients, and in patients with diabetes, chronic kidney disease, or dementia r1r6
        • Examples include pain or discomfort in the shoulders, arms, neck, back, throat, upper abdomen, or jaw as well as shortness of breath and fatigue; these are considered anginal equivalents c15c16c17c18c19c20c21c22c23c24c25c26
      • Although the terms typical and atypical have traditionally been used to categorize chest pain, recent guidelines discourage this practice, instead recommending the use of cardiac, possible cardiac, and noncardiac as descriptors to indicate suspected cause of chest pain r6
    • Characteristics that suggest noncardiac pain include: r1
      • Pleuritic in nature c27
      • Predominantly located in mid or lower abdomen c28c29
      • Localized by fingertip c30
      • Reproducible by palpation or movement c31c32
      • Brief duration (eg, seconds) or continuous for more than 24 hoursr7c33
      • Most severe at onset c34
      • Radiation to legs c35c36
      • Sharp or stabbing quality r7c37c38
      • Positional in nature r6
  • Symptoms commonly associated with myocardial ischemia include: r6
    • Dyspnea
    • Palpitations
    • Diaphoresis
    • Lightheadedness
    • Presyncope or syncope
    • Upper abdominal pain
    • Heartburn unrelated to meals
    • Nausea or vomiting

Physical examination

  • In patients presenting with chest pain, perform a focused cardiovascular examination initially to facilitate diagnosis of acute coronary syndrome or other potentially serious causes of chest pain and to identify complications r6
  • Findings may be unremarkable, especially with non–ST-elevation myocardial infarction and unstable angina c39
  • Appearance may be pale or diaphoretic; patient may be anxious c40c41c42
  • Heart rate may be within reference range, low, or rapid c43c44c45
  • Blood pressure may be within reference range, elevated (owing to pain), or low (owing to cardiogenic shock) c46c47c48
  • Respiratory rate is usually within reference range, but it may be elevated in patients with extensive infarction and heart failure; Cheyne-Stokes respiration may occur in heart failure or cardiogenic shock c49c50c51
  • Jugular venous distention may indicate heart failure or right ventricular infarction c52
  • Heart tones are often muffled. S₄ is common; S₃ may be audible in patients with heart failure, either preexisting or resulting from acute left ventricular dysfunction due to ischemia or infarction c53c54c55
  • New or worse systolic murmur may indicate papillary muscle ischemia or rupture c56
  • Fine rales may be heard in patients with heart failure or cardiogenic shock c57

Causes and Risk Factors

Causes

  • Coronary thrombosis, precipitated by disruption of atheromatous plaque (most common) c58
  • Other ischemic causes
    • Nonthrombotic causes of partial or complete obstruction to coronary blood flow (eg, embolus, spasm) c59c60c61
    • Other conditions in which myocardial oxygen supply cannot meet demand (eg, arrhythmia, thyrotoxicosis, hypotension, anemia, respiratory failure, overexertion) c62c63c64c65c66c67c68
    • Cocaine and methamphetamine cause acute coronary syndromes through superimposed myocardial demand; cocaine also induces coronary thrombosis, arterial dissection, coronary artery spasm, and direct myocardial toxicity r1c69c70
    • Spontaneous coronary artery dissection r9c71
      • Epicardial coronary artery dissection not associated with atherosclerosis or trauma; not iatrogenic
      • May be the cause of 1% to 4% of acute coronary syndromes cases overall; most common cause of pregnancy-associated myocardial infarction r9
    • Patients with ischemic myocardial infarction but no angiographic obstructive coronary artery disease (at least 50% diameter stenosis in a major epicardial vessel) are described as having MINOCA; prevalence estimated to be about 6% among patients diagnosed with myocardial infarction r4r5

Risk factors and/or associations

Age
  • Uncommon before age 40 years in males and 50 years in females; risk then rises progressively r3c72c73c74c75c76c77c78
  • Average age of first myocardial infarction is 65.6 years in males and 72 years in females r10c79c80
  • Average age of females with spontaneous coronary artery dissection ranges from 45 to 53 years r9c81
Sex
  • More common in males than in females r11c82c83
  • Myocardial infarction with nonobstructive coronary arteries is more common in females r5
  • Spontaneous coronary artery dissection occurs overwhelmingly in females r9c84c85
Genetics
  • Positive family history is associated with increased risk c86c87
Ethnicity/race
  • Recent prevalence data for myocardial infarction in the United States r10
    • Non-Hispanic White population: 4% for males, 2.2% for females c88c89
    • Non-Hispanic Black population: 4% for males, 2.2% for females c90c91
    • Hispanic population: 3.4% for males, 2% for females c92c93
Other risk factors/associations
  • Previous myocardial infarction, angina, or revascularization c94c95c96
  • Use of NSAIDs (except aspirin) or cyclooxygenase-2 inhibitors c97c98
  • Use of antineoplastic or immunosuppressive therapy c99c100
  • Peripheral artery disease c101
  • Cerebrovascular disease c102
  • Other risk factors and associations generally reflect those of coronary artery disease

Diagnostic Procedures

Primary diagnostic tools

  • Primary means of diagnosis are history, physical examination, ECG, and serum biomarkers c113c114
    • Features of history and physical examination that correlate with high likelihood of acute coronary syndromes include: r12
      • Chest or left arm pain or discomfort that reproduces symptomatic character of previously documented angina
      • Known history of coronary artery disease
      • New mitral regurgitation murmur
      • Hypotension
      • Diaphoresis
      • Rales or pulmonary edema
    • Always consider cardiac cause of chest pain even if gastrointestinal medications relieve pain
    • Potential cardiac causes should always be considered in female patients who present with chest pain, with emphasis on accompanying symptoms that are more common in female patients with acute coronary syndrome r6
    • In patients aged 75 years or older presenting with chest pain, acute coronary syndrome should be considered when accompanying symptoms such as shortness of breath, syncope, or acute delirium are present or when an unexplained fall occurs r6
  • All patients with symptoms suggestive of acute coronary syndromes should have a 12-lead ECG performed within 10 minutes of presentation r1r6
    • If initial ECG result is not diagnostic and patient continues to experience symptoms, repeat ECG at 15- to 30-minute intervals within first hour r1
    • Serial ECG tests are also helpful in following evolution of ischemic process
    • Apply supplemental leads if posterior or inferior infarction is suspected and if 12-lead ECG is not diagnostic
    • Normal ECG results do not preclude diagnosis of acute coronary syndromes; normal tracing results are seen in 1% to 6% of cases r1
  • Draw blood from all patients at presentation with symptoms suggestive of acute coronary syndromes to measure cardiac biomarkers r1
    • Cardiac-specific troponin levels (T or I) are highly sensitive and specific; they are the preferred diagnostic biomarker for initial testing c115c116
  • Obtain chest radiograph for all patients c117
  • Choice of other studies is guided by whether ECG changes suggest ST-elevation myocardial infarction or non–ST-elevation myocardial infarction/unstable angina; in the latter case, choice is also guided by validated risk assessment tools such as TIMI score (Thrombolysis in Myocardial Infarction)r13 and GRACE score (Global Registry of Acute Coronary Events)r14
    • Coronary angiography is recommended for most patients with ST-elevation myocardial infarction or high-risk non–ST-elevation myocardial infarction/unstable angina r1r2
      • Coronary angiography is essential for visualizing coronary anatomy and distribution and for locating and quantifying intraluminal blockages; in many cases, it can be coupled with therapeutic intervention (reperfusion) r1
      • Immediate coronary angiography (ie, within 90-120 minutes) is recommended when percutaneous intervention is available, such as in: r1
        • ST-elevation myocardial infarction r2
        • Unstable non–ST-elevation myocardial infarction/unstable angina with: r1
          • Refractory ischemic pain
          • Heart failure
          • New or worsening mitral regurgitation
          • Hemodynamic instability
          • Sustained ventricular arrhythmias
      • Early coronary angiography (ie, within 24 hours) is recommended in patients with non–ST-elevation myocardial infarction/unstable angina who are at high risk, including those with: r1
        • GRACE scorer14 of more than 140
        • Elevated troponin levels demonstrating rise or fall
        • New ST depression
      • For patients with non–ST-elevation myocardial infarction who are stable, coronary angiography may be delayed or deferred unless a new ischemic event occurs r1
    • Other early imaging studies such as echocardiography, radionuclide testing, and cardiac MRI may be helpful in localizing area of ischemia or injury, assessing extent and acuity of injury, and evaluating possible alternative diagnoses r5
    • Coronary CT angiography or stress testing can be used to further evaluate patients in whom an acute coronary syndrome was initially suspected but whose ECG results and troponin levels are not diagnostic r1c118c119

Laboratory

  • Obtain troponin I or T levels at presentation and at 3 to 6 hours after onset of symptoms if using sensitive assays;r1time intervals can be shortened with use of highly sensitive cardiac troponin assaysr15c120c121
    • High-sensitivity cardiac troponin assays facilitate rapid detection or exclusion of myocardial injury with greater diagnostic accuracy and are preferred if available r6
    • Algorithms to include or exclude acute myocardial infarction have been developed for screening of patients presenting with chest pain based on consecutive high-sensitivity troponin levels measured at 0 and either 1, 2, or 3 hours r15r16
    • Both peak level and degree of change are diagnostically important
    • Criteria for laboratory diagnosis of myocardial necrosis include: r5
      • Troponin I or T levels above 99th percentile of upper norm, plus a serial increase or decrease of at least 20% of an elevated level
      • For troponin I or T levels that do not exceed 99th percentile, a change of 3 standard deviations or more from initial value is diagnostic
    • Further levels should be obtained if interim symptoms or ECG changes suggest ongoing ischemia
  • Serum creatine kinase–MB (myocardial band) isoenzyme and myoglobin, which were previously used in diagnosis of acute myocardial infarction, are demonstrably inferior to cardiac troponin assays and no longer considered useful for diagnosis of acute myocardial injury r6c122
  • B-type natriuretic hormone measured at presentation or shortly thereafter provides a baseline against which subsequent levels can be compared to gain prognostic information and to help guide therapy r3c123
    • Rise in level of B-type natriuretic hormone is associated with worse prognosis
  • Fasting lipid profile is recommended, preferably within 24 hours of admission, to assess for dyslipidemia r1r2c124

Imaging

  • Obtain chest radiograph as a baseline for subsequent comparison and to assess for pulmonary vascular congestion; also useful to evaluate for other potential cardiac, pulmonary, and thoracic causes of symptoms r6r17c125
  • Echocardiography is recommended to evaluate regional and global left ventricular function, assess for complications, and evaluate differential diagnoses r15r18c126
    • Regional wall motion abnormalities seen on echocardiogram may provide indirect evidence and localization of ischemia or necrosis (eg, in patients with nondiagnostic ECG or in whom cardiac biomarkers were not measured) r2
    • Additionally, echocardiography is often used early during post–myocardial infarction period to assess left ventricular function, an important prognostic indicator
    • May reveal presence of mechanical complications or pericardial effusion or tamponade r18
  • Radionuclide imaging can be used to assess wall motion, but it also reliably detects loss of myocardial tissue viability r15c127
    • Useful means of diagnosing myocardial necrosis when biomarkers have not been measured
    • Can also be used to exclude diagnosis of myocardial infarction when normal function and viability are demonstrated
  • Coronary CT angiography is recommended as a reasonable means of excluding acute coronary syndrome in patients with low to intermediate likelihood of coronary artery disease and whose ECG and troponin levels are not diagnostic r1r15c128
  • Cardiac MRI can be used in assessment of ventricular function, myocardial perfusion, scarring, and viability, and in conjunction with pharmacologic stress testing r18r19
    • Helps differentiate acute versus chronic myocardial infarction and is also used in evaluation of certain other causes of acute chest pain

Functional testing

  • ECG r5c129
    • Always compare ECG with a previous tracing if available
    • If inferior myocardial infarction is suspected, apply right-sided leads V4R, V5R, and V6R and posterior leads V7 to V9, in addition to traditional leads
    • ECG patterns
      • New ST-segment elevation at J point of 2 contiguous leads persisting for 20 minutes or longer suggests ST-elevation myocardial infarction r5
        • Cut point of 1 mm or greater in all leads except V2 and V3, where the following cut points apply: r5
          • 2 mm or greater in male patients aged 40 years or older
          • 2.5 mm or greater in male patients younger than 40 years
          • 1.5 mm or greater in female patients regardless of age
        • May be preceded by hyperacute T waves
        • Reciprocal ST-segment depression may be observed
      • New horizontal or down-sloping ST-segment depression and T-wave changes suggest non–ST-elevation acute coronary syndrome r5
        • Criteria are as follows:
          • 0.5 mm or greater ST-segment depression in 2 contiguous leads and/or T-wave inversion 0.1 mV or higher in 2 contiguous leads with prominent R wave or R/S ratio greater than 1 r5
    • Other findings that commonly accompany myocardial ischemia include conduction delays, arrhythmias, and decrease in amplitude of precordial R waves (compared with previous tracings)
    • Left bundle branch blocks may obscure typical findings of infarction
    • An acute coronary syndrome is not excluded by a normal ECG result or a result in which the criteria are not fully met
    • Pseudonormalization may occur during the evolution of an acute coronary syndrome as ST-segment depression transitions to ST-segment elevation

Procedures

Cardiac catheterization with angiography r12r17c130c131
General explanation
  • Catheters are placed percutaneously in peripheral blood vessels and advanced into central circulation
  • Measures intravascular pressure, oxygen saturation in heart and great vessels, and cardiac contractility and function
  • Angiography delineates anatomic structures and coronary artery patency
  • Usually performed under light sedation
Indication
  • Myocardial infarction
  • Unstable angina
  • Chest pain thought to have cardiac origin
  • Abnormal cardiac stress test results
Contraindications
  • No absolute contraindications
  • Relative contraindications
    • Contrast material allergy
    • Hemodynamic instability
    • Severe, uncontrolled hypertension
    • Severe anemia
    • Decompensated congestive heart failure
Interpretation of results
  • Angiography shows anatomy of coronary vessels and presence and degree of coronary artery obstruction
    • Patients with myocardial infarction but no angiographically obstructive coronary artery disease (50% or larger diameter stenosis in a major epicardial vessel) meet diagnostic criteria for MINOCA r5
  • Left ventricular ejection fraction, an important prognostic indicator, can be calculated
  • Wall motion and contractility can be assessed
  • Valvular function can be assessed and valvular regurgitation quantified, if present

Other diagnostic tools

  • Risk assessment stratification
    • TIMI score r13r20c132
      • Used to stratify risk in patients with non–ST-elevation myocardial infarction/unstable angina to determine disposition (ICU versus other settings) and to identify high-risk patients who will benefit from aggressive antithrombotic and early invasive management (versus ischemia-guided or noninvasive medical management)
      • 1 point is tabulated for each of the following criteria:
        • Age 65 years or older r13
        • 3 or more risk factors for coronary artery disease r13
        • Prior coronary stenosis of 50% or more r13
        • ST deviation
        • 2 or more anginal events in prior 24 hours r13
        • Use of aspirin in prior 7 days r13
        • Elevated cardiac biomarker levels
      • Scores correlate with risk of all-cause mortality, new or recurrent myocardial infarction, or requirement for urgent revascularization
        • Score of 0 or 1: 4.7% r13
        • Score of 2: 8.3% r13
        • Score of 3: 13.2% r13
        • Score of 4: 19.9% r13
        • Score of 5: 26.2% r13
        • Score of 6 or 7: 40.9% r13
    • GRACE score r14r21c133
      • More complex instrument that likewise predicts mortality based on points assigned for Killip class, systolic blood pressure, heart rate, serum creatinine level, cardiac arrest at admission, ST-segment deviation, and cardiac enzyme levels; point total can be matched to mortality risk on a published nomogramr21
      • Can be used for risk stratification of patients with either ST-elevation myocardial infarction or non–ST-elevation myocardial infarction/unstable angina

Differential Diagnosis

Most common

  • Life-threatening cardiopulmonary conditions should be considered immediately
    • Pulmonary embolism c134d1
      • Presents with chest pain, dyspnea, tachypnea, and hypoxia; tachycardia, ST abnormalities on ECG, and elevated cardiac troponin levels may be present
      • Chest pain is usually pleuritic; dyspnea is usually prominent and may be overwhelming; edema, tenderness, or a palpable "cord" may be present in 1 or both lower extremities
      • Multidetector-row CT angiography is diagnostic for pulmonary embolism; shows thrombus or thrombi in pulmonary vessels
    • Dissecting aortic aneurysm c135d2
      • Presents with sudden, severe chest pain that may radiate to the back; may be associated with hypotension or diaphoresis; nonspecific ECG changes and elevated cardiac troponin levels may be present d3
      • Pain is characterized as tearing or ripping
      • Murmur of aortic insufficiency may be audible; pulses may be asymmetrical
      • CT with contrast enhancement is diagnostic for dissecting aortic aneurysm; transesophageal echocardiogram or cardiac MRI can be performed if CT is contraindicated or unavailable r6
  • Other cardiac conditions
    • Pericarditis c136d4
      • Presents as pleuritic precordial or retrosternal pain that may radiate to the back, neck, and left shoulder/arm; ECG often shows PR-segment depression and ST-segment elevation; troponin levels may be elevated
      • Pain is worse on inspiration, in supine position, during swallowing, and during movement; pain is improved when patient is seated and leaning forward. A pericardial friction rub is sometimes heard on auscultation
      • Echocardiography is diagnostic study of choice, usually demonstrating effusion with or without thickening of pericardium
      • Cardiac MRI with gadolinium enhancement can show changes consistent with acute myopericarditis and demonstrate presence of other cardiac pathologies r6
    • Mitral valve prolapse c137d5
      • May present with palpitations, fatigue, syncope, and orthostatic hypotension
      • Midsystolic click and systolic murmur may be audible
      • Echocardiography is diagnostic, showing prolapsing valve with or without valve thickening
    • Takotsubo cardiomyopathy c138
      • Transient cardiac syndrome involving left ventricular apical akinesis
      • Produces chest pain, ST elevation, and sometimes elevated cardiac enzyme levels
      • Usually brought on by intense emotional (eg, bereavement) or physical stress; exact cause is unknown
      • Most patients are postmenopausal patients
      • Diagnosis is confirmed by coronary angiogram showing normal coronary artery anatomy and left ventricular apical ballooning
  • Noncardiac conditions
    • Cholecystitis c139d6
      • Presents with epigastric pain that may be poorly localized at first, mimicking anginal pain
      • Nausea and vomiting are often prominent, and there is tenderness to palpation in right upper quadrant; troponin levels are not elevated
      • Right upper quadrant ultrasonography is usually diagnostic, showing inflamed gallbladder; stones and ductal dilatation may be evident
    • Pancreatitis c140d7
      • Presents with epigastric pain, often with radiation to the back; pain may be severe
      • Tenderness to palpation of upper abdomen, sometimes with rebound tenderness
      • Abdominal CT or ultrasonography shows inflammation of pancreas; lipase and amylase levels are elevated
    • Perforated peptic ulcer c141d8
      • Presents with sudden severe epigastric pain; may involve associated hypotension or shock
      • Tenderness to palpation of upper abdomen, with peritoneal signs
      • Upright chest radiograph finds free air under diaphragm; abdominal CT scan may localize ulcer and perforation
    • Esophageal spasm c142
      • May present with epigastric pain or tightness, which may be relieved by sublingual nitroglycerin
      • May be precipitated by swallowing; associated with dysphagia
      • Diagnosis is confirmed by manometry, which finds premature rapid contractions, or by appearance of corkscrew esophagus on barium swallow
    • Costochondritis c143
      • May present with severe pain in sternal area
      • Characterized by exacerbation with chest motion (eg, respiration, rotation of torso)
      • Differentiated from acute coronary syndromes by characteristic exacerbation with physical maneuvers and absence of ECG abnormalities
    • Prodromal or early herpes zoster (varicella-zoster infection) c144d9
      • Infection in midthoracic dermatomes can present as excruciating pain that mimics acute coronary syndromes
      • Not associated with dyspnea, ECG changes, or troponin release
      • Diagnosis may not become apparent until lesions appear; distribution and characteristic features (clustered vesicles) of lesions are usually diagnostic, but polymerase chain reaction test can be used for confirmation

Treatment

Goals

  • Relief of ischemia
  • Prevention of myocardial infarction (or limitation of infarct size)
  • Preservation of left ventricular function
  • Prevention of death

Disposition

Admission criteria

All patients with confirmed acute coronary syndrome require admission to hospital telemetry unit r1r2

  • Patients with symptoms suggesting acute coronary syndrome but without diagnostic ECG changes or elevated troponin levels may be observed in telemetry unit, chest pain unit, or emergency department while undergoing serial ECGs, troponin measurements, and other testing r1
  • Patients who have obvious noncardiac cause of acute chest pain or possible acute coronary syndrome but are low risk per clinical risk stratification accounting for history, physical examination, ECG results, and troponin level may be reasonably discharged home. Routine admission for further diagnostic testing is not indicated r6

For patients with ST-elevation myocardial infarction who present to a facility without the capability to perform percutaneous coronary intervention, transfer to a hospital with appropriate facilities if transfer can be achieved within first-medical-contact-to-balloon-time window of 90 minutes or less r2

Criteria for ICU admission r1
  • Ongoing ischemic pain
  • Large infarction
  • Uncontrolled arrhythmias
  • Pulmonary edema
  • Hemodynamic instability

Recommendations for specialist referral

  • Consult cardiologist for all patients with confirmed acute coronary syndrome
  • Refer patients with symptoms suggestive of myocardial ischemia but without evidence of acute coronary syndrome to cardiologist

Treatment Options

Initial treatment in all patients

  • Assess and stabilize airway, breathing, and circulation; resuscitate if needed r22
  • Administer supplemental oxygen if needed to maintain oxygen saturation greater than 90% r1
  • Treat any associated life-threatening arrhythmia according to advanced cardiovascular life support protocols r23r24r25
  • Analgesia r15
    • Treat chest pain with nitroglycerin
      • Initial route is sublingual; IV administration is indicated if ischemic pain persists after 3 sublingual doses
      • Avoid use of nitrates with recent history of phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil, vardenafil) r1r2
    • Severe discomfort may require IV morphine r1r2
  • Antiplatelet therapy r1r2
    • Cornerstone of management; includes aspirin, P2Y₁₂ inhibitors, and/or glycoprotein IIb/IIIa inhibitors
      • Give aspirin as soon as possible to all patients without contraindications r19r26
        • Provides analgesia and reduces platelet aggregation to inhibit thrombus formation
        • Loading dose followed by daily dosing is recommended
        • Avoid other NSAIDs
      • Use of a P2Y₁₂ inhibitor (eg, ticagrelor, prasugrel, clopidogrel) is recommended in addition to aspirin r15
        • Reduces platelet aggregation by blocking the P2Y₁₂ adenosine diphosphate receptor on platelets, which reduces thrombus formation, increases bleeding time, and reduces blood viscosity
        • For patients undergoing percutaneous coronary intervention, a loading dose (either before or at time of procedure) followed by daily dosing is recommended
        • For patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention, European guidelines recommend prasugrel or ticagrelor preferentially over clopidogrel; cangrelor may be an option for patients who are unable to take an oral P2Y₁₂ inhibitor r27
        • Oral therapy
          • Ticagrelor
            • Recommended in the absence of contraindications for all patients at moderate to high risk of ischemic events (eg, elevated cardiac troponin levels) regardless of initial treatment strategy and including those pretreated with clopidogrel (which should be discontinued when ticagrelor is started) r15
            • Compared with clopidogrel
              • Greater antiplatelet effect with significant reduction in risk of thrombotic events r28
              • Greater risk of bleeding r29
              • Positive mortality benefit has been observed in non–ST-elevation myocardial infarction/unstable angina patients r1
            • Compared with prasugrel
              • Less myonecrosis was observed after percutaneous coronary intervention r30
            • Discontinue 5 days before elective coronary artery bypass graft surgery and 24 hours before urgent coronary artery bypass graft surgery
          • Prasugrel
            • FDA-approved for patients with acute coronary syndromes undergoing percutaneous coronary intervention; not FDA-approved for medical management of acute coronary syndromes
            • Greater antiplatelet effect with significant reduction in risk of thrombotic events compared with clopidogrel or ticagrelor; greater risk of bleeding compared with clopidogrel or ticagrelor r31
            • Recommended in patients who are proceeding to percutaneous coronary intervention if there are no contraindications r15
            • Preferred over ticagrelor in European Society of Cardiology guidelines for patients with non–ST-elevation myocardial infarction who undergo percutaneous coronary intervention r15
            • Discontinue 7 days before elective coronary artery bypass graft surgery r1
            • Due to increased risk of bleeding and uncertain efficacy, use in patients aged 75 years or older is not recommended except in high-risk situations (eg, diabetes, history of myocardial infarction) where use may be considered
            • In older or low-weight patients, a reduced dose of prasugrel compared with standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting against excess risk for bleeding r32
          • Clopidogrel
            • Standard therapy for acute coronary syndromes before introduction of newer agents; relatively high rate of atherothrombotic events compared with newer agents, which conversely increase bleeding risk r28
            • Recommended for patients who cannot receive ticagrelor or prasugrel or who require oral anticoagulation r15
            • 2020 trial suggested that, in patients aged 70 years or older presenting with non–ST-elevation acute coronary syndrome, clopidogrel is a favorable alternative, causing fewer bleeding events without an increase in the combined end point of all-cause death, myocardial infarction, stroke, and bleeding r33
            • Discontinue 5 days before elective coronary artery bypass graft surgery or 24 hours before urgent coronary artery bypass graft surgery r1
        • Cangrelor
          • Oral P2Y12 platelet inhibitor (eg, ticagrelor, prasugrel, clopidogrel) should also be administered to maintain platelet inhibition
            • Ticagrelor 180 mg PO may be administered at any time during or immediately after discontinuation of cangrelor infusion
            • Prasugrel 60 mg PO or clopidogrel 600 mg PO may be administered after discontinuation of the cangrelor infusion. Do not administer prasugrel or clopidogrel prior to discontinuation of cangrelor
          • Reduced intraprocedural stent thrombosis compared with clopidogrel r34
      • Glycoprotein IIb/IIIa inhibitors (eg, eptifibatide, tirofiban) may be used as bailout therapy when there is angiographic evidence of a large thrombus, slow or absent reperfusion, or other thrombotic complication r15r27
        • Reduce platelet aggregation through interruption of the final common pathway of fibrinogen-mediated cross-linkage of platelets
        • Discontinue eptifibatide or tirofiban 2 to 4 hours before coronary artery bypass graft surgery r1
  • Anticoagulants r1r2r15
    • Parenteral agents are used during initial management of acute coronary syndromes in combination with antiplatelet drugs
    • Recommended at time of diagnosis and during percutaneous coronary interventions
    • Choice of anticoagulant depends on timing of percutaneous intervention and individual thrombosis and bleeding risk
      • Unfractionated heparin is recommended for patients undergoing percutaneous coronary intervention
        • Indirect thrombin inhibitor
      • Bivalirudin may be considered as an alternative for patients with contraindications to unfractionated heparin (eg, heparin-induced thrombocytopenia) who need anticoagulation r1
        • Direct thrombin inhibitor
        • Used only for patients undergoing percutaneous coronary intervention
        • Compared to heparin: r35
          • No significant difference in composite end point of death from any cause, myocardial infarction, or major bleeding at 180 days
          • No significant difference in the secondary end point of stent thrombosis
      • Enoxaparin and fondaparinux may also used in some circumstances
        • Enoxaparin
          • Indirect thrombin inhibitor
          • More effective anticoagulant than unfractionated heparin but carries a higher risk of bleeding r12r17
        • Fondaparinux
          • Factor Xa inhibitor c145
          • May only be used in combination with another anticoagulant in the setting of percutaneous coronary intervention owing to increased risk of catheter thrombosis r1
  • ACE inhibitors r26
    • Initiate ACE inhibitors as soon as patient is hemodynamically stable, ideally within 24 hours of presentation, and continue indefinitely, especially in patients with the following: r1r2
      • Pulmonary congestion c146
      • Heart failure c147
      • Anterior ST-elevation myocardial infarction c148
      • Left ventricular ejection fraction of 40% or less c149
      • Diabetes c150
      • Stable chronic kidney disease c151
    • Angiotensin receptor blockers may be an alternative in patients for whom ACE inhibitors are contraindicated or not tolerated r1r2
  • β-Blockers r1r2
    • Oral β-blocker should be initiated within 24 hours of presentation, unless contraindication exists, and continued indefinitely r1r2
      • Preferred oral agents for patients with stabilized heart failure and reduced systolic function include bisoprolol, carvedilol, and metoprolol succinate r1
      • Due to mortality benefit of β-blocker therapy, patients not initially started on it should be evaluated often for initiation of therapy
    • IV β-blockers may be administered initially in patients with ST-elevation myocardial infarction who are hypertensive or who have ongoing ischemia; do not administer in patients at risk for shock r2
  • Calcium channel blockers
    • Alternative to β-blockers for patients in whom β-blockers are contraindicated or not tolerated; used as an adjunct to β-blockers if patient has continuing or recurring ischemic symptoms r1r2
    • Immediate release nifedipine is contraindicated in patients with ST-elevation myocardial infarction and should not be used in patients with non–ST-elevation myocardial infarction without concomitant β-blocker therapy r1r2
    • Diltiazem and verapamil are preferred nondihydropyridine calcium channel blockers r1r2
  • HMG CoA reductase inhibitors (statins) r36
    • Initiate unless contraindication exists
    • Start high-intensity statin therapy at highest tolerated dose as early as possible and continue it as long-term maintenance r15
      • Atorvastatin and rosuvastatin are the only agents with high-intensity dosing

For ST-elevation myocardial infarction r2r27r37

  • Percutaneous coronary intervention is preferred reperfusion strategy in patients whose symptom onset is within previous 12 hours r26
    • Reasonable approach in patients with symptom onset within 12 to 24 hours and evidence of ongoing ischemia r2
    • Should be done regardless of time from symptom onset in patients with any of the following:
      • Contraindication to fibrinolysis
      • Cardiogenic shock
      • Electrical instability
      • Severe acute heart failure
  • Fibrinolytic therapy is recommended in patients with symptom onset within previous 12 hours if percutaneous coronary intervention cannot be achieved within 120 minutes of first medical contact; administer fibrinolytic therapy within 30 minutes of hospital arrival r2r26
    • Reasonable approach in patients with symptom onset within 12 to 24 hours who have evidence of ongoing ischemia, large area of myocardium at risk, or hemodynamic compromise r2
  • Urgent coronary artery bypass grafting is recommended for patients whose coronary artery anatomy precludes effective percutaneous coronary intervention and who have ongoing ischemia, severe heart failure, or cardiogenic shock
    • May be considered for patients without cardiogenic shock in whom neither percutaneous coronary intervention nor fibrinolytic therapy is appropriate and whose symptom onset was within previous 6 hours r2

For non–ST-elevation myocardial infarction or unstable angina

  • 2 treatment approaches may be taken, depending on clinical circumstances and risk assessment
    • Early invasive strategy includes prompt cardiac catheterization and reperfusion r1
      • Immediate intervention is recommended for patients with ongoing ischemic pain, hemodynamic compromise, or electrical instability r15
        • Urgent coronary artery bypass grafting is recommended for such patients whose coronary artery anatomy precludes effective percutaneous coronary intervention r15
      • Early invasive approach within 24 hours of admission is recommended for patients assessed to be at high clinical risk on the basis of: r15
        • Elevated cardiac markers
        • Elevated TIMI risk score
        • GRACE score of more than 140
        • Dynamic changes in ECG results
        • Other clinical risk factors
      • Reasonable to postpone catheterization for 24 to 72 hours (delayed invasive approach) for stable patients who are not at high risk or in whom other personal or clinical considerations favor delay
    • Conservative management without early coronary angiography r26
      • Ischemia-guided strategy includes routine medical care followed by noninvasive ischemic evaluation (using coronary CT angiography or stress testing), with invasive management triggered by recurrent ischemia or demonstrated obstructive coronary artery disease r1
      • Appropriate for stable patients assessed at low or intermediate clinical risk
      • Appropriate for patients in whom other clinical conditions (eg, severe comorbidities) or personal considerations apply
      • Invasive strategy with intent to perform revascularization before hospital discharge is reasonable to consider even in patients initially assigned to conservative management r19

Secondary prevention r26

  • Start patients who are treated for myocardial infarction on the following drugs and continue indefinitely (in absence of any contraindications): r38
    • ACE inhibitor
    • Dual antiplatelet therapy (aspirin plus a second antiplatelet) unless an indication for anticoagulation is present r39
      • Continue dual antiplatelet therapy irrespective of the stent type for at least 12 months in most patients after myocardial infarction;r15r39 continue aspirin alone indefinitely
      • Optimal duration of dual antiplatelet therapy is not definitively known and remains an area of active investigation
        • Several large studies demonstrated significantly reduced rates of stent thrombosis and major adverse cardiovascular events with extension of dual antiplatelet therapy beyond 12 months in patients who had undergone coronary stenting, albeit with increased bleeding risk r40r41
        • Conversely, several meta-analyses have found comparable rates of major adverse cardiovascular events and significantly lower bleeding rates with shorter durations (3 months or less or 6 months) of dual antiplatelet therapy compared to longer durations (12 months or more than 12 months) in patients with acute coronary syndrome treated with percutaneous coronary intervention r42r43
      • American College of Cardiology/American Heart Association guidelines state: r1r39
        • Shorter duration (less than 12 months) is reasonable if bleeding risks outweigh potential benefits
        • Longer duration (more than 12 months) may be considered on individual basis, balancing risks and benefits
      • European guidelines state that duration of dual antiplatelet therapy can be shortened (less than 12 months), extended (more than 12 months), or modified on an individual basis, with consideration for ischemic and bleeding risk, adverse events, comorbidities, other medications, and drug availability r15
    • β-blocker
      • Continue indefinitely in patients with reduced left ventricular ejection fraction
      • Consider continuing for 12 months after myocardial infarction for patients without reduced left ventricular ejection fraction
        • There is limited contemporary data to support continuing β-blockers beyond 12 months after myocardial infarction for patients without reduced left ventricular ejection fraction
          • A single cohort study found continuing β-blocker therapy for 1 year or more after myocardial infarction was associated with reduced mortality compared to less than 1 year
          • Other data suggests β-blockers may be discontinued as soon as 3 months postmyocardial infarction
    • High-intensity statin therapy r36
  • These secondary prevention measures are largely directed at atherothrombotic coronary artery disease and may not be appropriate as routine treatment for all patients with MINOCA; treatment should be individualized in these patients depending on underlying mechanism and patient characteristics r4
  • Patients with reduced left ventricular ejection fraction following myocardial infarction should be considered for an implantable cardioverter defibrillator r26
  • Aldosterone antagonists may be considered for patients with reduced ejection fraction following myocardial infarction
    • Indicated as an adjunct for patients already on β-blocker and ACE inhibitor (or angiotensin receptor blocker) who have left ventricular ejection fraction of 40% or less, diabetes, or heart failure r1
    • Spironolactone is a nonspecific aldosterone receptor antagonist and is associated with progestogenic and androgenic effects (eg, gynecomastia, erectile dysfunction, menstrual irregularities, hirsutism, mastalgia); eplerenone has lower affinity for androgen, progesterone, and glucocorticoid receptors and thus a lower incidence of these adverse effects

Drug therapy

  • Analgesia
    • Nitrates
      • Nitroglycerin r1r2c152
        • Sublingual
          • Nitroglycerin Sublingual tablet; Adults: 300 to 400 mcg SL every 5 minutes for up to 3 doses.
        • IV
          • Nitroglycerin Solution for injection; Adults: 5 mcg/minute continuous IV infusion, initially. Titrate by 5 mcg/minute every 3 to 5 minutes to clinical response, or a dose of 20 mcg/minute. May further titrate by 10 mcg/minute, and if the desired effect is still not achieved, by 20 mcg/minute. Max titration: 20 mcg/minute every 3 to 5 minutes. Usual dose range: 5 to 100 mcg/minute. Max: 200 mcg/minute.
    • Morphine r1r2c153
      • Morphine Sulfate Solution for injection; Adults: 4 to 8 mg IV once, then 1 to 8 mg IV every 5 to 30 minutes as needed.
  • Antiplatelet drugs
    • Aspirin r1r2r15r27c154
      • ST-elevation myocardial infarction dosing
        • Aspirin Chewable tablet; Adults: 300 to 325 mg PO (non-enteric coated, chewable) once as soon as possible, then 75 to 100 mg PO once daily indefinitely (preferred); however, lower loading doses (162 mg) and higher maintenance doses (up to 325 mg/day) may be used.
      • Non–ST-elevation myocardial infarction or unstable angina dosing
        • Aspirin Chewable tablet; Adults: 150 to 325 mg PO (non-enteric coated, chewable) once as soon as possible, then 75 to 162 mg PO once daily indefinitely. Maintenance doses up to 325 mg/day have been used in special circumstances.
    • P2Y₁₂ inhibitors r44r45r46c155
      • Oral therapy
        • Ticagrelor c156
          • Ticagrelor Oral tablet; Adults: 180 mg PO loading dose, then 90 mg PO twice daily in combination with low-dose aspirin. Reduce dose to 60 mg PO twice daily in combination with low-dose aspirin after 1 year.
        • Prasugrel c157c158
          • Prasugrel Oral tablet; Adults weighing less than 60 kg: 60 mg PO loading dose, then 5 mg PO once daily in combination with aspirin.
          • Prasugrel Oral tablet; Adults weighing 60 kg or more: 60 mg PO loading dose, then 10 mg PO once daily in combination with aspirin.
        • Clopidogrel c159
          • For medical management of ST-elevation myocardial infarction
            • Clopidogrel Bisulfate Oral tablet; Adults 18 to 75 years: 300 mg PO loading dose, followed by 75 mg PO once daily for 14 days to 12 months.
            • Clopidogrel Bisulfate Oral tablet; Adults older than 75 years: 75 mg PO once daily for 14 days to 12 months.
          • For medical management of non–ST-elevation myocardial infarction or unstable angina
            • Clopidogrel Bisulfate Oral tablet; Adults: 300 mg PO loading dose, followed by 75 mg PO once daily for up to 12 months.
          • For percutaneous coronary intervention
            • Clopidogrel Bisulfate Oral tablet; Adults: 300 or 600 mg PO loading dose, within 24 hours and if more than 24 hours since fibrinolytic, respectively, followed by 75 mg PO once daily for at least 12 months.
      • IV therapy
        • Cangrelor c160
          • Cangrelor Solution for injection; Adults: 30 mcg/kg IV bolus before PCI, followed 4 mcg/kg/minute continuous IV infusion for at least 2 hours or the duration of PCI, whichever is longer. Transition to an oral P2Y12 platelet inhibitor after cangrelor discontinuation.
    • Glycoprotein IIb/IIIa inhibitors c161
      • Eptifibatide c162
        • ST-elevation myocardial infarction
          • Eptifibatide Solution for injection; Adults: 180 mcg/kg (Max: 22.6 mg) IV bolus, followed by 2 mcg/kg/minute (Max: 15 mg/hour) continuous IV infusion until hospital discharge or 18 to 24 hours after PCI, whichever is earlier. Administer an additional 180 mcg/kg IV bolus 10 minutes after the first bolus. Minimum duration: 12 hours.
        • Non–ST-elevation myocardial infarction or unstable angina
          • Eptifibatide Solution for injection; Adults: 180 mcg/kg (Max: 22.6 mg) IV bolus, followed by 2 mcg/kg/minute (Max: 15 mg/hour) continuous IV infusion until hospital discharge or initiation of CABG surgery up to 72 hours or until hospital discharge or 18 to 24 hours after PCI, whichever is earlier, allowing for up to 96 hours of therapy. Administer an additional 180 mcg/kg IV bolus 10 minutes after the first bolus in persons undergoing PCI.
      • Tirofiban r1c163
        • ST-elevation myocardial infarction
          • Tirofiban Hydrochloride Solution for injection; Adults: 25 mcg/kg IV bolus, followed by 0.15 mcg/kg/minute for up to 18 to 24 hours.
        • Non–ST elevation myocardial infarction or unstable angina
          • Tirofiban Hydrochloride Solution for injection; Adults: 25 mcg/kg IV bolus, followed by 0.15 mcg/kg/minute for up to 18 hours.
  • Anticoagulants c164
    • Unfractionated heparin c165
      • ST-elevation myocardial infarction r2
        • Concomitant glycoprotein IIb/IIIa antagonist therapy planned
          • Heparin Sodium (Porcine) Solution for injection; Adults: 50 to 70 units/kg IV bolus as needed to achieve therapeutic ACT.
        • No concomitant glycoprotein IIb/IIIa antagonist therapy planned
          • Heparin Sodium (Porcine) Solution for injection; Adults: 70 to 100 units/kg IV bolus as needed to achieve therapeutic ACT.
      • Non–ST-elevation myocardial infarction/unstable angina r1
        • Heparin Sodium (Porcine) Solution for injection; Adults: 60 units/kg (Max: 4,000 units) IV bolus, then 12 units/kg/hour (Max: 1,000 units/hour) continuous IV infusion, initially. Adjust dose to maintain target anti-factor Xa concentration or aPTT. Continue infusion for 48 hours or until PCI.
    • Bivalirudin c166
      • ST-elevation myocardial infarction r2
        • Bivalirudin Solution for injection; Adults: 0.75 mg/kg IV bolus, followed by 1.75 mg/kg/hour continuous IV infusion for the duration of the procedure. Monitor ACT 5 minutes after the bolus dose and administer an additional 0.3 mg/kg IV bolus if needed. Consider extending the duration of the infusion for up to 4 hours post-procedure.
      • Non–ST-elevation myocardial infarction/unstable angina
        • Bivalirudin Solution for injection; Adults: 0.1 mg/kg IV bolus, followed by 0.25 mg/kg/hour continuous IV infusion until diagnostic angiography or PCI. Administer an additional 0.5 mg/kg IV bolus and increase the infusion to 1.75 mg/kg/hour during PCI.
    • Enoxaparin c167
      • ST-elevation myocardial infarction
        • Enoxaparin Sodium (Porcine) Solution for injection; Adults 18 to 74 years: 30 mg IV bolus plus 1 mg/kg subcutaneously, followed by 1 mg/kg subcutaneously every 12 hours (Max: 100 mg for the first 2 doses only) until hospital discharge, for up to 8 days or revascularization. Administer an additional 0.3 mg/kg IV bolus at the time of PCI if subcutaneous enoxaparin given more than 8 hours earlier.
        • Enoxaparin Sodium (Porcine) Solution for injection; Adults 75 years and older: 0.75 mg/kg subcutaneously every 12 hours (Max: 75 mg for the first 2 doses only) until hospital discharge, for up to 8 days or revascularization.
      • Non–ST-elevation myocardial infarction/unstable angina
        • Enoxaparin Sodium (Porcine) Solution for injection; Adults: 1 mg/kg subcutaneously every 12 hours until discharge or revascularization. An initial 30 mg IV bolus has been used in select patients.
    • Fondaparinux c168
      • ST-elevation myocardial infarction
        • Fondaparinux Sodium Solution for injection; Adults: 2.5 mg IV as a single dose, followed by 2.5 mg subcutaneously once daily until hospital discharge, for up to 8 days or revascularization.
      • Non–ST-elevation myocardial infarction/unstable angina
        • Fondaparinux Sodium Solution for injection; Adults: 2.5 mg subcutaneously once daily until discharge or revascularization.
  • Fibrinolytics
    • Alteplase c169
      • Alteplase Solution for injection; Adults weighing 67 kg or less: 15 mg IV bolus, followed by 0.75 mg/kg IV over next 30 minutes, and then 0.5 mg/kg IV over the next 60 minutes.
      • Alteplase Solution for injection; Adults weighing more than 67 kg: 15 mg IV bolus, followed by 50 mg IV over next 30 minutes, and then 35 mg IV over the next 60 minutes.
    • Reteplase c170
      • Reteplase (Recombinant) Solution for injection; Adults: 10 units IV every 30 minutes for 2 doses.
    • Tenecteplase c171
      • Tenecteplase Solution for injection; Adults weighing less than 60 kg: 30 mg IV as a single dose.
      • Tenecteplase Solution for injection; Adults weighing 60 to 69 kg: 35 mg IV as a single dose.
      • Tenecteplase Solution for injection; Adults weighing 70 to 79 kg: 40 mg IV as a single dose
      • Tenecteplase Solution for injection; Adults weighing 80 to 89 kg: 45 mg IV as a single dose.
      • Tenecteplase Solution for injection; Adults weighing 90 kg or more: 50 mg IV as a single dose.
  • β-Blockers
    • Bisoprolol c172
      • Bisoprolol Fumarate Oral tablet; Adults: 1.25 mg PO once daily, initially. Increase the dose every 2 weeks as tolerated. Max: 10 mg/day.
    • Carvedilol c173
      • Carvedilol Oral tablet; Adults: 6.25 mg PO twice daily, initially. If tolerated, increase the dose to 12.5 mg PO twice daily after 3 to 10 days and then 25 mg PO twice daily after another 3 to 10 days. A lower starting dose of 3.125 mg PO twice daily may be used and/or titration slowed if needed.
    • Metoprolol c174
      • Immediate-release
        • Metoprolol Tartrate Oral tablet; Adults: 25 to 50 mg PO every 6 to 12 hours, initially. Increase the dose over 2 to 3 days as tolerated to the target dose of 100 mg PO twice daily.
      • Extended-release
        • Metoprolol Succinate Oral tablet, extended-release; Adults: 12.5 or 25 mg PO once daily for 2 weeks. Double the dose every 2 weeks as tolerated, up to the target dosage of 200 mg PO once daily.
  • Calcium channel blockers
    • Diltiazem c175
      • Immediate-release
        • Diltiazem Hydrochloride Oral tablet; Adults: 30 to 80 mg PO 4 times daily.
      • Extended-release
        • Diltiazem Hydrochloride Oral capsule, extended release 24 hour; Adults: 120 to 360 mg PO once daily.
    • Verapamil c176
      • Immediate-release
        • Verapamil Hydrochloride Oral tablet; Adults: 80 to 160 mg PO 3 times daily.
      • Extended-release
        • Verapamil Hydrochloride Oral capsule, extended-release; Adults: 240 to 480 mg PO once daily.
  • ACE inhibitors
    • Captopril c177
      • Captopril Oral tablet; Adults: 6.25 to 12.5 mg PO 3 times daily, initially. Increase the dose to 25 mg PO 3 times daily over the next several days and then 50 mg PO 3 times daily over the next several weeks.
    • Lisinopril c178
      • Lisinopril Oral tablet; Adults who are hemodynamically stable: 5 mg PO every 24 hours for 2 doses, then after 48 hours, 10 mg PO once daily.
      • Lisinopril Oral tablet; Adults who have low systolic blood pressure (100 to 120 mmHg): 2.5 mg PO once daily for 3 days, then 2.5 or 5 mg PO once daily.
    • Ramipril c179
      • Ramipril Oral tablet; Adults: 2.5 mg PO twice daily, initially. May reduce dose to 1.25 mg PO twice daily if hypotension occurs. Increase the dose as tolerated after 3 weeks up to 5 mg PO twice daily.
    • Trandolapril c180
      • Trandolapril Oral tablet; Adults: 0.5 to 1 mg PO once daily, initially. Increase the dose every 2 weeks as tolerated up to 4 mg PO once daily.
  • Angiotensin receptor blockers
    • Losartan c181
      • Losartan Potassium Oral tablet; Adults: 25 to 50 mg PO once daily, initially. Increase the dose every 2 weeks as tolerated up to 50 to 150 mg/day. Max: 150 mg/day.
    • Valsartan c182
      • Valsartan Oral tablet; Adults: 20 mg PO twice daily, initially. Increase the dose to 40 mg PO twice daily within 7 days and then up to 160 mg PO twice daily as tolerated.
  • Aldosterone antagonists
    • Eplerenone c183
      • Eplerenone Oral tablet; Adults: 25 mg PO once daily, initially. Increase the dose within 4 weeks as tolerated to 50 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Spironolactone c184
      • Spironolactone Oral tablet; Adults: 12.5 to 25 mg PO once daily, initially. May increase the dose to 50 mg PO once daily, if tolerated and clinically indicated.
  • High-intensity HMG CoA reductase inhibitors (statins)
    • Atorvastatin c185
      • Atorvastatin Calcium Oral tablet; Adults: 80 mg PO once daily; reduce dose to 40 mg PO once daily if unable to tolerate higher dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Rosuvastatin c186
      • Rosuvastatin Calcium Oral tablet; Adults: 20 or 40 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Nondrug and supportive care

Initial supportive care includes: r1r2c187

  • Oxygen therapy c188
    • Provide supplemental oxygen to patients who have arterial oxygen saturation of less than 90%, respiratory distress, or other evidence of hypoxemia r1

Risk reduction strategies for secondary prevention

  • Cardiac rehabilitation c189
    • Refer all patients with acute coronary syndromes to a comprehensive outpatient cardiovascular rehabilitation program, either upon hospital discharge or at first follow-up office visit r1
    • Alternatively, a home-based cardiac rehabilitation program may be sufficient for low-risk patients
    • Aerobic exercise can begin 1 to 2 weeks after discharge for patients who have undergone percutaneous coronary intervention or coronary artery bypass graft surgery r1
    • Resistance exercise can begin 2 to 4 weeks after starting aerobic exercise r1
  • Smoking cessation r38c190d10
    • Advise all patients to avoid exposure to tobacco smoke, including secondhand smoke; those who use tobacco should be advised to quit at each contact
      • Provide assistance in quitting through referral to smoking cessation program and/or prescribing pharmacotherapy (eg, bupropion, varenicline)
  • Nutrition c191
    • Modify nutrition counseling based on individual patient factors (eg, lipid profile, blood pressure, required caloric intake, alcohol intake)
    • Diets should emphasize nonstarchy vegetables, minimize added sugars and refined grains, and avoid highly processed foods; these diets are inherently relatively low in cholesterol r47r48r49
      • Mediterranean diet is often recommended; however, a 2019 Cochrane review found a paucity of evidence for secondary prevention r50
      • DASH diet (Dietary Approaches to Stop Hypertension) is also recommended to reduce cardiovascular risk c192
    • Minimize intake of processed meats, refined carbohydrates, and sweetened beverages r49
    • Decrease intake of sodium and alcohol, and substitute healthy fats for saturated and trans fats r38c193c194c195c196c197
  • Weight management c198
    • BMI goal is 18.5 to 24.9 kg/m²; waist circumference goal is less than 89 cm for female patients, less than 102 cm for male patients r38
    • If weight loss is required, initial weight loss goal should be 5% to 10% below baseline r38c199
  • Physical activity
    • Before discharge from acute care setting, provide patient with instructions on specific activity recommendations (eg, lifting, stair climbing, housework, yardwork, sexual activity) c200
    • Perform risk assessment, including physical activity history and exercise test, before recommending exercise plan c201c202
    • Goal is 150 minutes of moderate-intensity aerobic activity per week (eg, 30-60 minutes on 5 days); supplement with resistance training at least twice per week r38r47
    • Counsel patients to report exercise-associated symptoms
  • Prevention of infectious diseases r1
    • Pneumococcal vaccine is recommended for high-risk patients with cardiovascular disease who are older than 65 years c203
    • Annual influenza vaccine is recommended for patients with cardiovascular disease c204
    • Administer other vaccines, including COVID-19, in accordance with age-specific CDC recommendations r51
Procedures
Percutaneous coronary intervention c205
General explanation
  • Invasive therapeutic technique in which catheter is guided via radial artery (preferred) or femoral artery to stenosed/occluded coronary artery (or arteries) to alleviate lesion(s) and revascularize myocardial tissue
    • Radial approach is preferredr15r52 over femoral, because it is associated with a consistent reduction in mortality and major bleeding complications for ST-elevation myocardial infarctionr53 and non–ST-elevation myocardial infarction/unstable anginar29
  • May be done on culprit lesion only or in multivessel form
    • Complete revascularization with percutaneous coronary intervention during index hospital admission is recommended for patients with acute ST-elevation myocardial infarction and multivessel coronary artery disease who are hemodynamically stable r26
      • Multivessel intervention has been shown to be safe; reduces rate of subsequent major cardiac events r54
    • Culprit lesion only is favored approach in patients with multivessel disease who have cardiogenic shock; subsequent intervention in noninfarct arteries may be performed as planned, staged procedure r2r26
  • Techniques include:
    • Percutaneous transluminal coronary angioplasty (balloon dilation) r12c206
    • Intracoronary stenting r12c207
      • Bare metal stent c208
        • Risk of restenosis due to smooth muscle hyperplasia
        • May be used for patients who may not be able to tolerate 1 year of dual antiplatelet therapy with aspirin and a P2Y₁₂ inhibitor r55
      • Drug-eluting stent r12c209
        • Coated with sirolimus, everolimus, or paclitaxel to reduce risk of restenosis due to smooth muscle hyperplasia
        • Sirolimus and paclitaxel have been compared and found to be equally effective in reducing stent thrombosis r55
        • Requires at least 1 year of antiplatelet therapy with a P2Y₁₂ inhibitor r55
    • Atheroablative technologies, such as atherectomy r12c210
  • Currently, 80% to 85% of percutaneous coronary interventions involve balloon dilation and coronary stenting r17
Indication
  • ST-elevation myocardial infarction r2r26
    • Ischemic symptoms less than 12 hours in duration
    • Minimal time-to-treatment delays
      • Percutaneous coronary intervention can be delivered within 120 minutes of the time when fibrinolysis could have been given
    • More than 12 hours after onset of symptoms with evidence of continuing myocardial ischemia or cardiogenic shock
  • Non–ST-elevation myocardial infarction r1r26
    • Intermediate or higher risk of adverse cardiovascular events (predicted 6-month mortality above 3%) and no contraindications to angiography (such as active bleeding or comorbidity)
    • Low risk of adverse cardiovascular events (predicted 6-month mortality 3% or less) with recurring ischemia demonstrated by ischemia testing or symptoms
    • Benefit of early invasive strategy with coronary angiography is less certain
Contraindications
  • May not be appropriate for patients with certain comorbidities (eg, diabetes), in whom coronary artery bypass graft surgery is associated with better outcomes (among those with acceptable surgical risk) r19
Coronary artery bypass graft surgery c211
General explanation
  • Open surgical procedure in which a piece of artery (eg, internal mammary artery) or vein (eg, saphenous) is grafted around occluded portion of coronary artery or arteries to revascularize affected myocardial tissue r56
Indication
  • ST-elevation myocardial infarction r2
    • Urgent coronary artery bypass graft surgery is indicated in patients with coronary anatomy not amenable to percutaneous coronary intervention who have cardiogenic shock, severe heart failure, ongoing or recurrent ischemia, or other high-risk characteristics
    • Emergency coronary artery bypass graft surgery within 6 hours of symptom onset in patients who did not have cardiogenic shock and who are not candidates for alternative reperfusion strategies (percutaneous coronary intervention or fibrinolysis)
  • Non–ST-elevation myocardial infarction r1
    • Emergency coronary artery bypass graft surgery is reasonable for those who have failed percutaneous coronary intervention, with continuing ischemia, hemodynamic compromise, or threatened arterial occlusion with significant myocardium at risk, and who are appropriate candidates for surgery r19
Contraindications
  • Potential for excess mortality when performed early after ST-elevation myocardial infarction r1

Comorbidities r1

  • Hypertension c212c213
    • In patients with increased cardiovascular risk (including stable ischemic heart disease), reduction of systolic blood pressure to less than 130/80 mm Hg has been shown to reduce cardiovascular disease complications by 25% and all-cause mortality by 27% r57r58
    • In adults who have had myocardial infarction or acute coronary syndrome, it is reasonable to continue β-blockers as long-term therapy for hypertension r58
  • Dyslipidemia c214c215
    • Targeting specific lipid levels is controversial; use of intensive statin therapy, without specific goal direction, is recommended in all patients who can tolerate it r36
    • Reduce LDL-C by at least 50% with high-intensity statin therapy or maximally tolerated statin therapy r36
      • In very-high-risk ASCVD (atherosclerotic cardiovascular disease), use LDL-C threshold of 70 mg/dL to consider addition of nonstatins to statin therapy
      • Very high risk includes:
        • History of at least multiple major atherosclerotic cardiovascular events or history of 1 major atherosclerotic cardiovascular event and multiple high-risk conditions
      • Reasonable to add ezetimibe to maximally tolerated statin therapy when LDL-C level remains at 70 mg/dL or higher
      • For patients at very high risk whose LDL-C level remains at 70 mg/dL or higher on maximally tolerated statin and ezetimibe therapy, adding a PCSK9 inhibitor is reasonable, although long-term safety (longer than 3 years) is uncertain
  • Diabetes c216
    • Aggressively control blood glucose levels and maintain at 180 mg/dL or less while avoiding hypoglycemia r1
    • Most patients with type 2 diabetes and coronary artery disease should be treated with oral glucose-lowering agent proven to reduce major cardiovascular events and/or cardiovascular mortality (either sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide 1 receptor agonist) r59
    • Strongest evidence for cardiovascular benefit has been demonstrated with liraglutide, dulaglutide, semaglutide, empagliflozin, dapagliflozin, and canagliflozin r59
    • May be started during admission, at discharge, or outpatient follow-up
  • Heart failure c217
    • May complicate diagnosis, because troponin levels may be elevated owing to acute heart failure
    • Base revascularization strategy on: r1
      • Extent of coronary artery disease
      • Cardiac lesions
      • Left ventricular dysfunction
      • Prior revascularization
    • In the presence of a large area of ischemia or significant heart failure, a percutaneous ventricular assist device or an intra-aortic balloon pump may be needed during surgical intervention r1
  • Chronic kidney disease c218
    • Adjust pharmacotherapy dosages according to creatinine clearance in patients with chronic kidney disease
    • Provide adequate hydration to patients undergoing angiography; minimize volume of contrast media used r1r19

Special populations

  • Older patients (aged 75 years or older) r1
    • Adjust pharmacotherapy dosages according to weight and/or creatinine clearance in older patients
    • Tailor care to consider patient preferences and goals, functional and cognitive status, comorbidities, drug interactions, and life expectancy
    • Survival advantage associated with early invasive strategy in patients with non–ST-elevation myocardial infarction is also seen in patients aged 80 years and older r60
  • Female patients r1
    • Consider adjusting antiplatelet and anticoagulant dosages according to weight and/or creatinine clearance to reduce risk of bleeding
    • Pregnant patients may undergo myocardial revascularization if ischemia-guided therapy is ineffective
    • Do not use early invasive strategy to manage female patients with non–ST-elevation myocardial infarction/unstable angina and low-risk assessment (eg, low TIMI score, troponin levels within reference range) because risk of harm outweighs likely benefit r1
  • Patients acutely intoxicated with cocaine or methamphetamine r1
    • β-Blockers are contraindicated owing to risk of coronary spasm
    • Benzodiazepines may be used alone or with nitroglycerin to manage hypertension and tachycardia associated with cocaine or methamphetamine intoxication

Monitoring

  • Perform noninvasive testing for ischemia before discharge in patients with ST-elevation myocardial infarction who have not had coronary angiography,r2 and consider it in other patients to evaluate exercise tolerance (eg, in patients with uncorrected noninfarct stenoses)r1c219c220
  • Measure left ventricular function before discharge in all patients with acute coronary syndromes, if measurement was not obtained earlier in hospital stay r1r2c221
  • Postdischarge management includes monitoring for recurrent symptoms and adjustment of medications based on clinical and laboratory parameters
    • During the first year, outpatient follow-up is recommended every 4 to 6 months; thereafter, 6- to 12-month intervals are reasonable for stable disease r61c222c223
  • At each follow-up visit, ask patients about interval symptoms of ischemia, heart failure, and arrhythmias and perform a focused cardiovascular examination c224
  • Monitor patients for adherence to an optimal medical regimen c225
  • Testing
    • Obtain serial LDL-C measurements 4 to 12 weeks from start of treatment; results should show 50% reduction r36c226c227
      • Monitor every 3 to 12 months thereafter if expected response is achieved
    • In patients who are not known to have diabetes, obtain hemoglobin A1C measurement every 3 years r61c228
    • Measure hemoglobin level, thyroid function, renal function, and serum electrolyte levels yearly r61c229c230c231c232
    • ECG may be considered in asymptomatic patients on a yearly basis; done as needed in patients experiencing new or worsening cardiac symptoms r61c233
    • Stress testing at intervals of 1 to 2 years may be appropriate in patients with prior evidence of silent ischemia or in patients who are felt to be at high risk for recurrent ischemia; the need for routine testing in other patients is not established r61
      • Stress testing
        • ECG evaluation during stress (pharmacologically or exercise-induced) used to detect ischemia and estimate prognosis
          • Treadmill stress test is preferred method c234
            • Used in patients who can exercise and whose ECG is free of ST changes at rest, which might affect interpretation
            • Imaging modality (eg, single-photon emission CT with radioactive tracer, echocardiography) may be added for patients whose ECG results have ST changes at rest that might affect interpretation
          • Pharmacologic stress test with imaging (ie, single-photon emission CT with radioactive tracer, echocardiography, cardiac MRI) is performed in patients whose physical limitations preclude exercise; pharmacologic agents may include adenosine, dipyridamole, or dobutamine c235
        • Can be used to evaluate patients with nondiagnostic ECG and biomarker levels within reference range, in the absence of ongoing pain or signs of heart failure
        • Indicated to evaluate exercise tolerance in low- and intermediate-risk patients with non–ST-elevation acute coronary syndromes who have been symptom free while at rest for 12 to 24 hours r1
          • Performed before hospital discharge or within 72 hours after discharge on outpatient basis
        • Indicated to identify residual risk for ischemia before discharge of patients with ST-elevation myocardial infarction who have not had coronary angiography and who might be candidates for revascularization r2
        • Contraindicated in patients with evidence of active ischemia, uncontrolled heart failure, or significant arrhythmias r6
    • Echocardiography is often used early during post–myocardial infarction period to assess left ventricular function (ejection fraction), an important prognostic indicator c236
      • Patients whose left ventricular ejection fraction is 40% or less initially should undergo serial testing at least 40 days later to assess risk of arrhythmia and potential indications for implantable defibrillator r2
  • Drug therapy monitoring
    • Analgesia
      • Place patients receiving continuous infusion nitroglycerin on telemetry with continuous blood pressure monitoring; avoid use if patient's systolic blood pressure is less than 90 mm Hg or greater than 30 mm Hg below baseline r2
      • Monitor blood pressure and respiratory rate in patients receiving morphine
    • Antiplatelet therapy (eg, P2Y₁₂ inhibitors, aspirin)
      • Monitor for clinical signs and symptoms of bleeding including routine CBC with careful attention to platelet count
    • Glycoprotein IIb/IIIa inhibitors (eg, eptifibatide, tirofiban)
      • Patients receiving glycoprotein IIb/IIIa inhibitor therapy should have routine monitoring of activated clotting time, activated partial thromboplastin time, and CBC as well as routine monitoring for other clinical signs/symptoms of bleeding
      • Monitor renal function to assess for dosage adjustments
    • Systemic anticoagulants (eg, unfractionated heparin, bivalirudin, low-molecular-weight heparin, fondaparinux)
      • Unfractionated heparin infusions are titrated to goal activated clotting time or activated partial thromboplastin time; monitor patient for clinical signs and symptoms of bleeding or heparin-induced thrombocytopenia with routine CBC
      • Bivalirudin infusion is titrated to goal activated clotting time; monitor patient for clinical signs and symptoms of bleeding with routine CBC
      • Low-molecular-weight heparin (eg, enoxaparin) does not require routine monitoring for clinical efficacy; monitor patient for clinical signs and symptoms of bleeding with routine CBC as well as renal function for necessary dose adjustments
      • Fondaparinux does not require routine monitoring for clinical efficacy; monitor patient for clinical signs and symptoms of bleeding with routine CBC as well as renal function tests for necessary dose adjustments
    • ACE inhibitors and angiotensin receptor blockers
      • Patients receiving ACE inhibitors or angiotensin receptor blockers should have routine monitoring of blood pressure and serum creatinine and potassium levels
    • β-Blockers
      • Patients initiated on β-blockers should have routine monitoring of blood pressure and heart rate; may hold therapy for bradycardia; however, due to mortality benefit, patient should be evaluated often for reinitiation of therapy r1r2
    • Statins
      • Patients on high-intensity statin therapy should have routine drug-drug interaction evaluation
      • Monitor lipid panel, with focus on LDL reduction, and creatine phosphokinase, liver function tests, and serum creatinine for clinical signs and symptoms of rhabdomyolysis

Complications and Prognosis

Complications

  • Electrical complications c237
    • Ventricular arrhythmias c238
      • Ventricular tachycardia c239
      • Ventricular fibrillation c240d11
    • Supraventricular arrhythmias c241
      • Atrial fibrillation c242d12
      • Atrial flutter c243
      • Other supraventricular tachyarrhythmias c244
    • Bradyarrhythmias c245
      • Atrioventricular block c246
      • Bundle branch block c247
  • Complications of left ventricular function c248
  • Other mechanical complications
    • Mitral regurgitation c251d14
    • Ventricular septal rupture c252
    • Left ventricular free-wall rupture c253
    • Left ventricular aneurysm c254
  • Pericarditis c255
  • Thromboembolic complications, including stroke c256c257d15
  • Acute kidney injury c258d16
  • Complications due to medications
    • Bleeding, including gastrointestinal and cerebral (eg, anticoagulants, antiplatelet agents, fibrinolytics)
    • Refractory hypotension (calcium channel blockers)

Prognosis

  • Overall 6-month mortality for acute coronary syndromes is 12% to 13% r11
    • In-hospital mortality rate for ST-elevation myocardial infarction is approximately 5% to 6% r2
    • 1-year mortality rate for ST-elevation myocardial infarction is approximately 7% to 18% r2
  • Number of leads showing ST depression and magnitude of ST depression are indicative of the extent of ischemia and correlate with prognosis r15
  • Secondary prevention represents an essential aspect of reducing risk for further ischemic events and improving long-term outcomes r11

Screening and Prevention

Screening

At-risk populations

Screening tests

  • Global risk tools are used to estimate risk of experiencing a coronary heart disease event over a specific period (often 10 years) r49
    • For adults aged 40 to 75 years, assess traditional cardiovascular risk factors routinely; for adults aged 20 to 39 years, it is reasonable to assess traditional risk factors at least every 4 to 6 years r49
      • American Heart Association/American College of Cardiology web-based calculatorr62c353
      • Framingham Risk Score r49c354
      • Systematic Coronary Risk Evaluation r49r63c355
    • 10-year ASCVD risk categories as assessed with these tools include: r49
      • Low (less than 5%)
      • Borderline (5% to less than 7.5%)
      • Intermediate (7.5% or higher to less than 20%)
      • High (20% or higher)
    • ASCVD risk as assessed with these tools includes: r49
      • Risk of myocardial infarction
      • Stable or unstable angina
      • Stroke
      • Transient ischemic attack
      • Peripheral arterial disease of atherosclerotic origins
    • Decisions about specific interventions (eg, statin treatment and its intensity) are based on these risk categories
    • For patients with intermediate predicted risk or for select adults with borderline predicted risk, coronary artery calcium measurement can be a useful tool in refining risk assessment for statin therapy c356

Prevention

  • Prevention of acute coronary syndromes hinges on control of modifiable factors affecting cardiovascular risk (accounts for 80% of risk), such as: r49r64
    • Smoking c357d10
    • Hypertension c358
    • Hyperlipidemia c359
    • Diabetes c360
    • Overweight and obesity c361
    • Nutrition and diet r49
    • Exercise and physical activity r49
  • Aspirin
    • Recommendations for aspirin for primary prevention of cardiovascular disease should be made based on an individual assessment of potential cardiovascular benefits and bleeding risks; net benefit even in at-risk patients is small r65
    • American College of Cardiology/American Heart Association guidelines state: r49
      • Low-dose aspirin may be considered for select adults aged 40 to 70 years who are at higher ASCVD risk but not at increased bleeding risk
      • Aspirin should not be used routinely for primary prevention in adults older than age 70 years
        • Determination of ASCVD risk in this context should consider the totality of evidence, including risk estimator scores as well as factors not included in risk score calculations, such as:
          • Strong family history of premature myocardial infarction
          • Inability to achieve lipid, blood pressure, or glucose targets
          • Significant elevation in coronary artery calcium score
    • US Preventive Services Task Force recommendations state: r65
      • Decision to initiate low-dose aspirin for primary prevention of cardiovascular disease in adults aged 40 to 59 years who have 10% or greater 10-year cardiovascular risk (as assessed per American College of Cardiology/American Heart Association ASCVD risk estimator) should be individualized
      • Aspirin should not be initiated for primary prevention in adults older than age 60 years
  • Colchicine
    • Antiinflammatory medications for secondary prevention of cardiovascular events may be reasonably considered as adjunct therapy for patients at high risk
    • Although formal guideline recommendations for colchicine have not been established, several large randomized controlled trials and meta-analyses have demonstrated substantial clinical benefit of colchicine in coronary artery disease r66
      • In a large randomized controlled trial involving patients with chronic coronary disease, risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo; most patients were already receiving established secondary prevention therapies r67
      • In a large randomized controlled trial involving patients who had experienced recent myocardial infarction, use of colchicine 0.5 mg daily, as compared to placebo, led to fewer ischemic cardiovascular events (hazard ratio, 0.77; 95% confidence interval, 0.61 to 0.96; P = .02) r68
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