Acute Coronary Syndromes

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 minutes^r3 and may last for hours, especially in ST-elevation myocardial infarction^r8
  • 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, possibly cardiac, and noncardiac as descriptors to indicate suspected cause of chest pain ^r6r9
  • 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 hours^r7c33
    • 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 ^c39
  • Palpitations ^c40
  • Diaphoresis ^c41
  • Lightheadedness ^c42
  • Presyncope or syncope ^c43
  • Upper abdominal pain ^c44
  • Heartburn unrelated to meals ^c45
  • Nausea or vomiting ^c46

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 ^c47
• Appearance may be pale or diaphoretic; patient may be anxious ^c48c49c50
• Heart rate may be within reference range, low, or rapid ^c51c52c53
• Blood pressure may be within reference range, elevated (owing to pain), or low (owing to cardiogenic shock) ^c54c55c56
• 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 ^c57c58c59c60
• Jugular venous distention may indicate heart failure or right ventricular infarction ^c61
• 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 ^c62c63c64
• New or worse systolic murmur may indicate papillary muscle ischemia or rupture ^c65
• Fine rales may be heard in patients with heart failure or cardiogenic shock ^c66

Causes

• Coronary thrombosis, precipitated by disruption of atheromatous plaque (most common) ^c67
• Other ischemic causes
  • Nonthrombotic causes of partial or complete obstruction to coronary blood flow (eg, embolus, spasm) ^c68c69c70
  • Other conditions in which myocardial oxygen supply cannot meet demand (eg, arrhythmia, thyrotoxicosis, hypotension, anemia, respiratory failure, overexertion) ^{c71c72c73c74c75c76c77}
  • 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 ^r1c78c79
  • Spontaneous coronary artery dissection ^r10c80
    • Epicardial coronary artery dissection not associated with atherosclerosis or trauma; not iatrogenic ^c81
    • May be the cause of 1% to 4% of acute coronary syndromes cases overall; most common cause of pregnancy-associated myocardial infarction ^r10
  • 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 (myocardial infarction with nonobstructive coronary arteries); prevalence estimated to be approximately 6% among patients diagnosed with myocardial infarction who undergo angiography ^r4r5
    • MINOCA may be due to: ^r9
      • Coronary causes (eg, embolism, microvascular dysfunction, spasm, thrombosis, dissection)
      • Non-coronary cardiac causes (eg, trauma, cardiomyopathy, cardiotoxins, myocarditis, strenuous exercise)
      • Non-cardiac causes (eg, inflammation, pulmonary embolism, sepsis, stroke)

Risk factors and/or associations

Primary diagnostic tools

• Primary means of diagnosis are history, physical examination, ECG, and serum biomarkers ^{r6r13c123c124c125}
  • The mnemonic ACS can be used to organize important components of the initial evaluation of suspected acute coronary syndrome: ^r9
    • A = abnormal ECG; perform ECG to assess for evidence of ischemia
    • C = clinical context; consider clinical presentation and available data and laboratory results
    • S = stable patient; assess clinical stability of patient
  • Features of history and physical examination that correlate with high likelihood of acute coronary syndromes include: ^r14
    • 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
  • Always consider potential cardiac causes 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, consider acute coronary syndrome when accompanying symptoms such as shortness of breath, syncope, or acute delirium are present or when an unexplained fall occurs ^r6
• Perform a 12-lead ECG on all patients with symptoms suggestive of acute coronary syndromes within 10 minutes of presentation ^r1r6r9
  • 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 ^c126c127
• Obtain chest radiograph for all patients ^c128
• 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 ^r15(Thrombolysis in Myocardial Infarction) score and GRACE ^r16(Global Registry of Acute Coronary Events) score
  • 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
    • Emergent coronary angiography is indicated within 120 minutes of initial presentation for patients with ST-elevation myocardial infarction if capability is available ^r2
    • Emergent coronary angiography (ie, as soon as feasible) is indicated for patients presenting with non–ST-elevation myocardial infarction/unstable angina and any of the following very-high-risk features: ^r1r9
      • Hemodynamic instability
      • Refractory/recurrent chest pain despite medical management
      • Acute heart failure presumed secondary to ongoing ischemia
      • Life-threatening arrhythmia or cardiac arrest after presentation
      • Mechanical complications
      • Recurrent ECG changes suggestive of ischemia
    • Early coronary angiography (ie, within 24 hours) is recommended in patients with non–ST-elevation myocardial infarction/unstable angina who do not have an emergent indication for intervention, but are assessed to be at high clinical risk on the basis of: ^r1
      • Elevated cardiac markers
      • Elevated TIMI (Thrombolysis in Myocardial Infarction) score
      • GRACE (Global Registry of Acute Coronary Events) score of greater than 140
      • Dynamic changes in ECG results
      • Other clinical risk factors conferring high clinical risk
    • For patients who have an urgent or emergent indication for coronary angiography who present to a facility without percutaneous coronary intervention capability, make transfer arrangements immediately to facilitate timely intervention ^r9
    • For patients with non–ST-elevation myocardial infarction who are stable, coronary angiography may be delayed or deferred unless a new ischemic event occurs or additional testing demonstrates obstructive coronary disease ^r1r9
  • 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 ^r1c129c130

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 assays^r9c131c132
  • 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 ^r9r17
    • European guidelines recommend use of the 0 h / 1h or 0 h / 2 h algorithms for risk stratification
    • Algorithms can be used to stratify patients into the following groups:
      • Rule-out; patients may be appropriate for early discharge and outpatient management
      • Rule-in; further evaluation likely needed to establish accurate diagnosis
      • Observe; patients do not qualify for rule-out or rule-in management, but should be assessed on an individual basis to determine next steps
  • 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 normal, 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
  • Obtain further levels 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 ^r6c133
• 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 ^r3c134
  • 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 ^r1r2c135

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 ^r6r18c136
• Echocardiography is recommended to evaluate regional and global left ventricular function, assess for complications, and evaluate differential diagnoses ^r9r19c137
  • 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 ^r19
• Radionuclide imaging can be used to assess wall motion, but it also reliably detects loss of myocardial tissue viability ^r9c138
  • 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 ^r1r9r20c139
• Cardiac MRI can be used in assessment of ventricular function, myocardial perfusion, scarring, and viability, and in conjunction with pharmacologic stress testing ^r19r21
  • Helps differentiate acute versus chronic myocardial infarction and is also used in evaluation of certain other causes of acute chest pain
  • Has particular value in establishing diagnosis of MINOCA (Myocardial infarction with nonobstructive coronary arteries) after angiography ^r9

Functional testing

• ECG ^r5r9c140
  • 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 at least 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

Other diagnostic tools

• Risk assessment stratification
  • TIMI (Thrombolysis in Myocardial Infarction) score ^r15r22c143
    • 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 ^r15
      • 3 or more risk factors for coronary artery disease ^r15
      • Prior coronary stenosis of 50% or more ^r15
      • ST deviation
      • 2 or more anginal events in prior 24 hours ^r15
      • Use of aspirin in prior 7 days ^r15
      • 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% ^r15
      • Score of 2: 8.3% ^r15
      • Score of 3: 13.2% ^r15
      • Score of 4: 19.9% ^r15
      • Score of 5: 26.2% ^r15
      • Score of 6 or 7: 40.9% ^r15
  • GRACE (Global Registry of Acute Coronary Events) score ^r16r23c144
    • 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 nomogram^r23
    • Can be used for risk stratification of patients with either ST-elevation myocardial infarction or non–ST-elevation myocardial infarction/unstable angina

Most common

• Life-threatening cardiopulmonary conditions should be considered immediately
  • Pulmonary embolism ^c145d1
    • Sudden obstruction of a portion of the pulmonary arterial vasculature, usually by embolization of a lower extremity or pelvic thrombus
    • 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 ^c146d2
    • 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 ^c147d4
    • Inflammation of the pericardium with or without pericardial effusion
    • 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 ^c148d5
    • Abnormal systolic bulging or billowing of 1 or both leaflets of the mitral valve toward the left atrium during systole
    • 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 ^c149
    • 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
    • Diagnosis is confirmed by coronary angiogram showing normal coronary artery anatomy and left ventricular apical ballooning
• Noncardiac conditions
  • Cholecystitis ^c150d6
    • Acute inflammation of the gallbladder, most commonly resulting from obstruction of cystic duct by an impacted gallstone
    • 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 ^c151d7
    • Sudden onset of pancreatic parenchymal inflammation with a disease course that can range from mild to severe
    • 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 ^c152d8
    • 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 ^c153
    • 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 ^c154
    • 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) ^c155d9
    • 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

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

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

Drug therapy

• Analgesia
  • Nitrates
    • Nitroglycerin ^r1r2c163
      • 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 ^r1r2c164
    • 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 ^r1r2r9c165
    • 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 ^{r51r52r53c166}
    • Oral therapy
      • Ticagrelor ^c167
        • 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 ^c168c169
        • 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 ^c170
        • 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 ^c171
        • 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 ^c172
    • Eptifibatide ^c173
      • 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 ^r1c174
      • 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 ^c175
  • Unfractionated heparin ^c176
    • 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 ^c177
    • 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 ^c178
    • 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 ^c179
    • 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 ^c180
    • 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 ^c181
    • Reteplase (Recombinant) Solution for injection; Adults: 10 units IV every 30 minutes for 2 doses.
  • Tenecteplase ^c182
    • 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 ^c183
    • 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 ^c184
    • 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 ^c185
    • 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 ^c186
    • 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 ^c187
    • 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 ^c188
    • 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 ^c189
    • 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 ^c190
    • 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 ^c191
    • 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 ^c192
    • 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 ^c193
    • 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 ^c194
    • 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 ^c195
    • 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 ^c196
    • 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 ^c197
    • Rosuvastatin Calcium Oral tablet; Adults: 20 or 40 mg PO once daily.
• Colchicine
  • Colchicine Oral tablet; Adults: 0.5 mg PO once daily.

Nondrug and supportive care

Initial supportive care includes: ^r1r2c198

• Oxygen therapy ^c199
  • 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 ^r9r39

• Cardiac rehabilitation ^c200
  • 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 ^r40c201d10
  • 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 ^c202
  • Modify nutrition counseling on the basis of 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 ^r54r55r56
    • Mediterranean diet is often recommended; however, a 2019 Cochrane review found a paucity of evidence for secondary prevention ^r57
    • DASH diet (Dietary Approaches to Stop Hypertension) is also recommended to reduce cardiovascular risk ^c203
  • Minimize intake of processed meats, refined carbohydrates, and sweetened beverages ^{r56c204c205c206}
  • Decrease intake of sodium and alcohol, and substitute healthy fats for saturated and trans fats ^{r40c207c208c209c210c211}
• Weight management ^c212
  • 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 ^r40
  • If weight loss is required, initial weight loss goal should be 5% to 10% below baseline ^r40c213
• Physical activity
  • Before discharge from acute care setting, provide patient with instructions on specific activity recommendations (eg, lifting, stair climbing, housework, yardwork, sexual activity) ^c214
  • Perform risk assessment, including physical activity history and exercise test, before recommending exercise plan ^c215c216
  • Goal is 150 minutes of moderate-intensity aerobic activity or 75 minutes of higher-intensity aerobic activity per week (split up over multiple days); supplement with resistance training at least twice per week ^r40r55
  • 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 aged older than 65 years ^c217
  • Annual influenza vaccine is recommended for patients with cardiovascular disease ^c218
  • Administer other vaccines, including COVID-19, in accordance with age-specific CDC recommendations ^r58

Comorbidities ^r1r39

• Hypertension ^c226c227d11
  • 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% ^r64r65
  • In adults who have had myocardial infarction or acute coronary syndrome, it is reasonable to continue β-blockers as long-term therapy for hypertension ^r64
• Dyslipidemia ^c228c229d12
  • Targeting specific lipid levels is controversial; use of intensive statin therapy, without specific goal direction, is recommended in all patients who can tolerate it ^r37
  • Reduce LDL-C by at least 50% with high-intensity statin therapy or maximally tolerated statin therapy ^r37
    • 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
    • European guidelines recommend even lower goal LDL-C levels of lower than 55 mg/dL in general and lower than 40 mg/dL in patients with recurrent atherothrombotic events ^r9
• Diabetes ^c230
  • Aggressively control blood glucose levels and maintain at 180 mg/dL or less while avoiding hypoglycemia ^r1
  • Treat most patients with type 2 diabetes and coronary artery disease 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) ^r66
  • Strongest evidence for cardiovascular benefit has been demonstrated with liraglutide, dulaglutide, semaglutide, empagliflozin, dapagliflozin, and canagliflozin ^r66
  • May be started during admission, at discharge, or during outpatient follow-up
• Heart failure ^c231d13
  • 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 ^c232
  • 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 ^r1r21
• Obesity
  • Regular assessment of BMI is recommended with clinical follow-up
  • Counsel patients with overweight or obesity on diet, lifestyle, and goals for weight loss
  • Glucagonlike peptide 1 receptor agonist therapy can be beneficial for weight loss, in addition to diet and exercise
  • Bariatric surgery referral is reasonable for patients with severe obesity despite lifestyle modification and pharmacologic therapy

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 ^r67
• 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
  • Many medications used for acute and chronic coronary disease management (eg atenolol, ACE inhibitors, angiotensin receptor blockers, direct renin inhibitors, angiotensin receptor-neprilysin inhibitors and aldosterone antagonists) are contraindicated in patients who are pregnant or contemplating pregnancy, owing to risk of fetal toxicity ^r39
  • 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 [Thrombolysis in Myocardial Infarction] 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
• Patients with cancer ^r9
  • Management strategy should account for life expectancy and bleeding risks
    • Invasive strategy recommended in patients with high-risk acute coronary syndrome and expected survival of 6 months or greater
    • Consider conservative management in patients with expected survival less than 6 months and/or very high bleeding risk
  • Aspirin not recommended in patients with cancer and platelet count below 10,000 platelets/microliter
  • Clopidogrel not recommended in patients with cancer and platelet count below 30,000 platelets/microliter
  • Prasugrel and ticagrelor not recommended in patients with cancer and platelet count below 50,000 platelets/microliter
• Patients with MINOCA (myocardial infarction with nonobstructive coronary arteries) ^r9
  • MINOCA encompasses a heterogeneous group of cardiac and non-cardiac causes
  • If underlying etiology remains indeterminate after coronary angiography, non-invasive imaging studies (eg, echocardiography, cardiac MRI, CT) are recommended to determine underlying cause
  • Cardiac MRI can help determine underlying etiology in a significant majority of patients with presumptive MINOCA diagnosis and should be performed as soon as feasible, preferably during the index admission
  • Management of MINOCA is tailored to the underlying etiology
  • Consider secondary prevention therapies for those who do have some evidence of coronary atherosclerotic disease and for management of any identified comorbidities

At-risk populations

• Populations at risk for coronary artery disease (and acute coronary syndromes) ^r1r2
  • Advanced age (a65 years or older) ^{c271c272c273c274c275c276c277c278c279}
  • Male sex ^{c280c281c282c283c284c285c286c287c288}
  • Family history of coronary artery disease (or acute coronary syndromes) ^{c289c290c291c292c293c294c295c296c297}
  • Type 2 diabetes ^{c298c299c300c301c302c303c304c305c306}
  • Hypertension ^{c307c308c309c310c311c312c313c314c315}
  • Renal insufficiency ^{c316c317c318c319c320c321c322c323c324}
  • Prior myocardial infarction ^{c325c326c327c328c329c330c331c332c333}
  • Prior coronary revascularization ^{c334c335c336c337c338c339c340c341c342}
  • Use of antineoplastic and immunosuppressive therapies ^{c343c344c345c346c347c348c349c350c351c352c353c354}
  • Smoking history ^{c355c356c357c358c359c360c361c362c363c364}

Screening tests

• Global risk tools are used to estimate risk of experiencing a coronary heart disease event over a specific period (often 10 years) ^r56
  • 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 ^r56
    • American Heart Association/American College of Cardiology web-based calculator^r71c365
    • Framingham Risk Score ^r56c366
    • Systematic Coronary Risk Evaluation ^r56r72c367
  • 10-year atherosclerotic cardiovascular disease risk categories as assessed with these tools include: ^r56
    • Low (less than 5%)
    • Borderline (5% to less than 7.5%)
    • Intermediate (7.5% or higher to less than 20%)
    • High (20% or higher)
  • Atherosclerotic cardiovascular disease risk as assessed with these tools includes: ^r56
    • 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 ^c368