Elsevier Logo

English

ThisiscontentfromClinicalKey

Want more answers?

Sign up for your free ClinicalKey trial today!  Your first step in getting the right answers when you need them. ClinicalKey is a clinical knowledge solution designed to help healthcare professionals and students find the right answers by providing in-depth, evidence-based knowledge – all from one resource.

Feb.12.2021

Stable Ischemic Heart Disease

Synopsis

Key Points

  • Stable ischemic heart disease is a clinical syndrome consisting of episodes of reversible mismatch in myocardial oxygen demand and supply related to inadequate blood flow to the myocardium r1
  • Characterized by episodes of angina (ie, retrosternal chest pain or discomfort that may radiate to left arm or jaw) or angina equivalents (eg, dyspnea, faintness, fatigue) r2
  • Usually precipitated by exertion, emotional excitement, or heavy meal, and is often worse in cold weather r3
  • Diagnosis is based on history, physical examination, 12-lead ECG, measurement of serum biochemical markers, and noninvasive testing (eg, exercise ECG testing, exercise or pharmacologic stress testing with functional imaging)
  • Coronary angiography is the gold standard for evaluating the presence of coronary artery disease; it is not routinely indicated to confirm diagnosis in patients with stable angina but may be performed if noninvasive testing suggests high-risk coronary lesions present r3
  • Acute angina symptoms are controlled with sublingual nitroglycerin or short-acting nitrates
  • Manage risk factors for ischemic heart disease using both pharmacologic (eg, aspirin, ACE inhibitors, angiotensin II receptor antagonists, statins) and nonpharmacologic methods, as necessary
  • β-blockers and calcium channel blockers are the first line agents for long-term symptom control. Second line or add-on agents include long-acting nitrates, ranolazine, or ivabradine; none of these agents has been shown to reduce myocardial infarction or ischemic cardiac death
  • Revascularization with either percutaneous coronary intervention or coronary artery bypass graft surgery may be indicated for symptom relief in refractory cases or to improve prognosis in certain patients

Pitfalls

  • Consider acute coronary syndrome in patients presenting with anginal pain lasting more than 15 minutes r4d1
  • Do not administer a nitrate preparation or nitroglycerin in patients who have taken tadalafil in the last 48 hours or vardenafil and sildenafil in the last 24 hours

Terminology

Clinical Clarification

  • Stable ischemic heart disease is a clinical syndrome consisting of episodes of reversible mismatch in myocardial oxygen demand and supply related to inadequate blood supply to the myocardium. Episodes are usually induced by exercise, emotion, or other stress r1
  • Characterized by angina (ie, retrosternal chest pain or discomfort that may radiate to left arm or jaw) or an anginal equivalentr1 (eg, dyspnea, faintness, fatigue); silent ischemia may also occur r2

Classification

  • Classification by mechanism of ischemia, which may occur alone or in combination: r5
    • Fixed or dynamic stenoses of epicardial coronary arteries due to atherosclerotic plaque
    • Focal or diffuse spasm of epicardial coronary arteries in the presence or absence of atherosclerotic plaque
    • Microvascular, or small-vessel, dysfunction
  • Clinical classification of chest pain r5
    • Typical (definite) angina meets all of the following 3 characteristics:
      • Substernal chest discomfort of characteristic quality and duration
      • Provoled by exertion or emotional stress
      • Relieved by rest, nitroglycerin, or both
    • Atypical (probable) angina:
      • Meets 2 of the 3 characteristics of typical angina
    • Noncardiac chest pain
      • Meets 1 or none of the 3 characteristics of typical angina
  • Canadian Cardiovascular Society Angina Classification r5
    • Class I: no limitation of ordinary physical activity; angina with strenuous, rapid, or prolonged exertion only
    • Class II: slight limitation of ordinary physical activity; angina on walking rapidly or uphill, on climbing stairs rapidly, on exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening
    • Class III: marked limitation of ordinary physical activity; angina on walking 1 or 2 level blocks (equivalent to 100-200 m) or 1 flight of stairs at a normal pace under normal conditions
    • Class IV: inability to carry out any physical activity without discomfort; angina at rest

Diagnosis

Clinical Presentation

History

  • Most commonly reported symptom is chest pain that is typically associated with exertion or emotional stress c1c2
    • Characteristically described as a retrosternal chest pain, tightness, heaviness, or pressure c3c4c5c6
      • Pain may radiate to the left arm or shoulder, the lower jaw and teeth, the back between the shoulder blades, or the epigastrium c7c8c9c10c11c12c13
      • May be associated with symptoms such as pain, squeezing or pressure in the arm, neck, or jaw c14c15c16c17
    • Chest pain may be accompanied by shortness of breath or nonspecific symptoms (eg, fatigue, syncope, nausea, vomiting, restlessness, a sense of impending doom) r5c18c19c20c21c22c23c24
      • These nonspecific symptoms in the absence of classic chest pain symptoms may represent anginal equivalents
    • Common precipitants include walking a certain distance (variable), stair climbing, emotional distress, sexual activity, heavy meal, exposure to cold, or waking up in the morning c25
      • Symptoms appear or become more severe with increased levels of exertion r5
      • Angina threshold may vary from day to day and even during the same day
    • Onset is gradual with increasing intensity over several minutes c26
    • Duration of discomfort is brief; less than 10 minutes in most cases r5c27
      • Resolves quickly (usually within 5 minutes) with rest or administration of nitroglycerin
      • May be reduced with further exercise (walk-through angina) or on subsequent exertion (warm-up angina)
  • Note any history of prior episodes of chest pain or risk factors for or known coronary artery disease c28c29c30
  • Any change in pattern of usual chest pain symptoms, level of exertion required to elicit anginal symptoms, or response to medications used may indicate disease progression

Physical examination

  • Physical examination findings may be unremarkable, particularly if patient is asymptomatic at the time c31
  • Signs of associated conditions may be present, such as:
    • Anemia c32
    • Hypertension c33
    • Decreased peripheral pulses c34
    • Carotid, femoral, or renal artery bruits c35c36c37
    • Elevated jugular vein pressure c38
    • Xanthelasma or xanthoma c39
    • Arrhythmia c40
    • Obesity c41
    • Peripheral edema c42
    • Pulmonary rales c43
  • Cardiac examination findings are often normal c44
    • Signs of underlying cardiac disease may be present (eg, cardiac enlargement or murmur) c45c46
    • During or immediately after an episode of myocardial ischemia, a third (S₃) or fourth (S₄) heart sound may be heard. A systolic murmur of mitral insufficiency may be apparent; however, these signs are rare and nonspecific r3c47c48c49
  • Palpation of the chest does not typically reproduce symptoms.r3Reproducible chest wall pain suggests a musculoskeletal causer6c50

Causes and Risk Factors

Causes

Myocardial ischemia is caused by a transient imbalance between blood supply and demand, most commonly as result of obstruction to coronary blood flow due to atherosclerotic coronary artery disease r2c51
  • Less common mechanisms include: r2
    • Focal or diffuse coronary vasospasm r5c52
    • Reduced coronary flow reserve, such as that seen in the setting of microvascular (small-vessel) disease or in endothelial dysfunction c53

Risk factors and/or associations

Age
  • Prevalence of angina increases with age in both sexes
    • Ranges from 5% to 7% in women aged 45 to 64 years to 10% to 12% in women aged 65 to 84 years r3c54c55
    • Ranges from 4% to 7% in men aged 45 to 64 years to 12% to 14% in men aged 65 to 84 years r3c56c57
Sex
  • In older adults, angina is more prevalent in men than women; however, angina is more prevalent in middle-aged women than in men, possibly owing to the higher prevalence of functional disease (eg, microvascular angina) in women r3c58c59c60c61
Genetics
  • Family history of coronary artery disease is associated with increased risk c62
Ethnicity/race
  • Annual rates of new angina episodes are higher in men who are not Black when compared with Black men aged 65 to 85 years; rates are higher in Black men older than 85 years r6c63c64c65c66c67c68c69c70
  • Rates are higher in Black women compared with other women aged 65 years and older, with the greatest magnitude of difference in those older than 85 years r6c71c72c73c74
Other risk factors/associations
  • Risk factors and associations for coronary artery disease r6
    • Hypertension c75
    • Cigarette smoking c76
    • Diabetes mellitus c77
    • Metabolic syndrome c78
    • Dyslipidemia c79
    • Family history of premature coronary artery disease c80
    • Estrogen deficiency c81
    • Overweight and obesity c82c83
    • Physical inactivity c84
    • Renal insufficiency c85
    • Connective tissue diseases, rheumatoid arthritis c86c87
    • Antineoplastic or immunosuppressive therapy c88c89
    • Peripheral artery disease c90
    • Cerebrovascular disease c91
  • Systemic conditions that increase myocardial oxygen demand or decrease oxygen supply r6
    • Fever c92
    • Severe anemia c93
    • Hyperthyroidism c94
    • Tachycardia c95
    • Hypoglycemia c96
    • Pain c97
    • Stimulant use disorder c98
    • Pneumonia c99
    • Asthma c100
    • Chronic obstructive pulmonary disease c101
    • Pulmonary hypertension c102
    • Interstitial pulmonary fibrosis c103
    • Obstructive sleep apnea c104
    • Sickle cell disease c105
    • Pheochromocytoma c106
    • Polycythemia c107
    • Leukemia c108
    • Thrombocytosis c109
    • Hypergammaglobulinemia c110
    • Anxiety c111
    • Arteriovenous fistulae c112
    • Hypertrophic cardiomyopathy c113
    • Aortic stenosis c114
    • Dilated cardiomyopathy c115
    • Significant coronary obstruction c116
    • Microvascular disease c117

Diagnostic Procedures

Primary diagnostic tools

  • Diagnosis is based on history, physical examination, 12-lead ECG, measurement of serum biochemical markers, and noninvasive testing c118
  • Obtain detailed history regarding location, character, and duration of chest pain; its relationship to exertion and other exacerbating or relieving factors; and presence of cardiovascular risk factors r5r6
  • Obtain resting ECG in all patients at presentation r7c119
  • Laboratory tests should be obtained to identify possible causes of ischemia, cardiovascular risk factors, and associated conditions, as well as to determine prognosis r5
    • CBC, fasting blood glucose level, hemoglobin A1C level, fasting lipid profile, and baseline renal function tests c120c121c122
    • Thyroid function tests, if clinically suspicious for thyroid disease c123
    • Cardiac-specific troponin (T or I) levels, if there is concern for unstable angina (eg, prolonged periods of angina, angina at rest, new-onset moderate to severe angina) or if previously stable ischemic heart disease with rapidly increasing or crescendo angina is suspected c124
      • If troponin level is elevated, proceed with management for non–ST segment elevation acute coronary syndrome d1
    • Brain natriuretic peptide/N-terminal pro–B-type natriuretic peptide in patients with suspected heart failure
  • Chest radiography is not routinely indicated in initial work-up as it does not provide specific diagnostic or prognostic information c125
    • Occasionally useful for assessing patients with suspected heart failure or comorbid pulmonary disease, or to exclude another cause of chest pain in atypical presentations
  • Echocardiography is recommended in most patients to exclude alternative causes of angina, identify regional wall motion abnormalities suggestive of coronary artery disease, measure left ventricular ejection fraction for risk stratification purposes, evaluate diastolic function, and assess for valvular disease r5
  • In patients without a known history of ischemic heart disease, proceed with risk stratification to determine whether pretest probability of ischemic heart disease is sufficient to recommend further testing r6
    • Predictive models have been developed for this purpose based on historic and demographic patient features
      • Pretest likelihood of coronary artery disease in symptomatic patients.Table shows a combination of Diamond-Forrester and Coronary Artery Surgery Study (CASS) data. The values represent the percentage of patients with significant coronary artery disease on catheterization.Data from Fihn et al: 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 126(25):e354-471, 2012; Diamond GA et al: Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 300:1350-8, 1979; and Chaitman BR et al: Angiographic prevalence of high-risk coronary artery disease in patient subsets (CASS). Circulation. 64:360-7, 1981.
        Age (y)Nonanginal chest pain: men (%)Nonanginal chest pain: women (%)Atypical angina: men (%)Atypical angina: women (%)Typical angina: men (%)Typical angina: women (%)
        30 to 394234127626
        40 to 4913351228755
        50 to 5920765319373
        60 to 69271472519486
    • Consultation with a cardiologist is recommended to determine pretest risk probability
    • Further testing is most useful in patients for whom the cause of chest pain is truly uncertain; that is, pretest probability of ischemic heart disease is intermediate (variably defined as a probability of ischemic heart disease between 20% and 70% or 15% and 85%r3) r6
    • Other factors may be involved in the decision to refer a patient for further testing, such as degree of uncertainty acceptable to physician and patient, likelihood of alternative diagnosis, cost, potential risks of further testing, and benefits and risks of treatment in the absence of additional testing r6
  • If pretest probability of ischemic heart disease is intermediate or greater, consider noninvasive testing (eg, exercise ECG testing, pharmacologic or exercise imaging stress testing)
    • European guidelines recommend the use of either noninvasive functional imaging or anatomical imaging (cardiac CT angiography) as the initial test for diagnosing coronary artery disease; exercise ECG may be considered if imaging tests are not available r5
  • For patients with a low to intermediate pretest probability (variably defined as less than 10% or less than 20%) of obstructive ischemic heart disease, consider cardiac CT angiography; stress testing is less likely to be indicated
  • Coronary angiography is the gold standard for evaluating the presence of coronary artery disease; however, this invasive procedure is not routinely indicated to establish a diagnosis of ischemic heart disease in patients with stable angina r5
    • Early angiography without previous noninvasive testing may be indicated in patients who have a high pretest probability of ischemic heart disease and: r5
      • Symptoms that are severe, unresponsive to medical therapy, or occur at a low level of exercise, or
      • Clinical evaluation suggesting high risk for a cardiac event
    • May have a role in patients with reduced left ventricular ejection fraction less than 50% and typical angina, in those who cannot undergo stress imaging techniques, or people in certain professions, such as pilots (regulatory requirement)
    • Indicated after risk stratification with noninvasive testing to determine options for revascularization if noninvasive testing suggests presence of high-risk coronary lesions and if a revascularization procedure is reasonable based on patient comorbidities and preferences r6
  • Fractional flow reserve, which may be measured as part of coronary angiography or derived via CT angiography, may be used to determine need for percutaneous coronary intervention by measuring pressure difference across stenosis to assess hemodynamic significance r8

Imaging

  • Echocardiography c126c127
    • A resting transthoracic echocardiogram is recommended in all patients to exclude alternative causes of angina, identify regional wall motion abnormalities suggestive of coronary artery disease, measure left ventricular ejection fraction for risk stratification purposes, evaluate diastolic function, and evaluate presence of significant valvular disease r5
      • Consider in patients with a cardiac murmur on examination, previous myocardial infarction, or symptoms/signs of heart failure
      • May be omitted in very young and healthy patients with a high suspicion of an extracardiac cause of chest pain and in multimorbid patients in whom the result of echocardiography will not influence patient management
  • Noninvasive functional imaging tests
    • Stress test with functional imaging is superior to conventional exercise ECG testing owing to its increased sensitivity in detecting obstructive coronary disease, its ability to quantify and localize areas of ischemia, and its ability to provide diagnostic information in the presence of an abnormal baseline resting electrocardiogram r5
    • Recommended as the initial test in patients with intermediate to high pretest probability of ischemic heart disease and in patients without typical angina symptoms who have a left ventricular ejection fraction less than 50%, if local expertise and availability permit r5r6
      • Also recommended in patients with abnormal baseline ECG findings that prevent accurate interpretation of ECG changes during stress ECG testing
      • Consider in symptomatic patients with previous percutaneous coronary intervention or coronary artery bypass grafting, particularly if evaluating for changes over time in size and location of ischemia
      • Screen patients of childbearing age for possibility of pregnancy or breastfeeding status when considering any testing modality involving possible radiation exposure
    • Exercise stress testing is recommended over pharmacologic testing when possible as it provides a physiologic environment and provides additional physiologic data (ie, exercise time, workload achieved) as well as information about changes in heart rate, blood pressure, and ECG results r3
    • Stress imaging using a pharmacologic stress agent (eg, adenosine, dipyridamole, dobutamine, regadenoson) can be performed in patients who have an inadequate ability to exercise
    • Stress imaging modalities r3
      • Exercise stress echocardiography c128
      • Exercise stress myocardial perfusion imaging (with single photon emission CT) c129
      • Dobutamine stress echocardiography c130c131
      • Dobutamine stress MRI c132c133
      • Vasodilator stress echocardiography c134
      • Vasodilator stress myocardial perfusion imaging (with single photon emission CT) c135
      • Vasodilator stress MRI c136
      • Vasodilator stress myocardial perfusion PET scan c137
  • Cardiac CT angiography and coronary artery calcium scoring c138c139c140
    • Consider CT angiography as an alternative to stress imaging techniques for ruling out ischemic heart disease in patients with low to intermediate pretest probability for ischemic heart disease in whom good image quality can be anticipated r5r6
      • Also consider in patients with an inconclusive exercise ECG or stress imaging test result, those having continued symptoms despite normal exercise ECG findings or stress imaging test results, those with contraindications to stress testing, or those patients who should avoid invasive coronary angiography owing to increased risk r5r6
      • Prescreening is recommended to confirm patients have adequate breath-holding capabilities, have a favorable calcium score and distribution, are not severely obese, and are preferably in sinus rhythm with a heart rate of 65 beats per minute or less (preferably 60 beats per minute or less) r5
      • Cardiac CT angiography techniques and modeling may be used as noninvasive means to derive fractional flow reserve and determine if coronary artery stenosis is hemodynamically significant r9
    • CT also provides measurement of coronary artery calcium score; however, this is not recommended as a standalone test to evaluate ischemia in symptomatic patients
      • Calcium score correlates roughly to total amount of atherosclerosis present in coronary arteries r3
      • Correlation with actual extent of luminal narrowing, or stenosis, is poor
      • A "zero" calcium score does not rule out coronary artery stenosis in symptomatic patients

Functional testing

  • ECG c141
    • A 12-lead ECG is recommended in all patients presenting with symptoms of chest pain concerning for angina or possible anginal equivalent r5
    • Establishes baseline for comparison and has a role in risk stratification
    • Resting ECG findings may be normal, even in patients with a history of severe angina, and do not rule out a diagnosis of ischemia
    • Note findings consistent with ischemic heart disease (eg, prior myocardial infarction, abnormal repolarization pattern)
      • Presence of Q waves, chronic ST segment depression (or other ST-T–wave abnormalities), or poor R-wave progression in the precordial leads may suggest prior myocardial infarction r6
    • Dynamic ST segment changes may be present in the setting of active chest pain due to ischemia
    • Can be diagnostic in patients with coronary vasospasm if characteristic transient ST segment changes are noted at the time of chest pain event and resolve with resolution of pain
    • Associated ECG abnormalities include left ventricular hypertrophy, left or right bundle branch block, preexcitation, arrhythmias, or conduction defects
  • Exercise stress testing c142
    • Exercise ECG is recommended as an alternative to noninvasive imaging tests for establishing a diagnosis in patients with angina symptoms and intermediate pretest probability of coronary artery disease who are able to exercise and have no abnormalities on resting ECG r5
      • Preferred modality; provides additional information about symptoms, heart rate and blood pressure response, presence of arrhythmias, exercise tolerance, and workload achieved, all of which have both diagnostic and prognostic relevance r5
      • Can be used when noninvasive imaging tests are unavailable
      • Less sensitive and specific in female patients r3
      • Performed on treadmill or bicycle using 12-lead ECG monitoring
      • An ECG exercise stress test is considered positive for ischemia when there is greater than or equal to 1 mm (0.1 mV) of horizontal or down-sloping ST segment depression, persisting for at least 0.06 to 0.08 seconds after the J point, in 1 or more ECG leads r3r7r10
      • Inconclusive results can be followed up using alternative stress testing with noninvasive imaging r3
      • Nondiagnostic in patients with resting ECG abnormalities that prevent interpretation of ST segment changes during stress r5
      • Contraindications to exercise stress testing: r11
        • Inability to exercise
        • Ongoing unstable angina
        • Recent (acute) myocardial infarction (less than 48 hours)
        • Decompensated heart failure
        • Acute myocarditis/pericarditis
        • Acute aortic dissection
        • Active endocarditis

Procedures

Cardiac catheterization with coronary angiography c143c144
General explanation
  • A coronary catheter is placed percutaneously in a peripheral blood vessel and advanced into central circulation
    • Femoral or radial arteries are used as access site for coronary angiography
  • Defines coronary artery anatomy and patency
  • Measures intravascular pressure, oxygen saturation in the heart and great vessels, and cardiac contractility and function
  • Coronary pressure-derived fractional flow reserve can be measured for functional assessment of lesion severity in patients with intermediate-grade stenosis without evidence of ischemia in noninvasive testing, or in those with multivessel disease r12
  • Intracoronary imaging (with intravascular ultrasonography or optical coherence tomography) may also be performed in patients being considered for revascularization to establish severity of lesions in the setting of intermediate-grade stenosis or ambiguous findings on angiography r12
  • Usually performed under conscious sedation
Indication r13
  • Myocardial infarction (ST elevation myocardial infarction, non–ST elevation myocardial infarction)
  • Unstable angina
  • Chronic stable angina not controlled by optimal medical therapy
  • Abnormal cardiac stress test result, particularly if findings are high-risk
  • Cardiac arrest
  • New congestive heart failure
  • Before cardiac surgery
Contraindications r14
  • No absolute contraindications
  • Relative contraindications
    • Preexisting renal failure
    • Contrast material allergy (anaphylaxis)
    • Coagulopathy
    • Hemodynamic instability
    • Acute stroke
    • Decompensated congestive heart failure
    • Severe, uncontrolled hypertension
    • Severe anemia
    • Pregnancy
    • Uncooperative patient
    • Active infection, sepsis
Interpretation of results
  • Coronary angiography defines coronary anatomy, including origin, course, length, diameter, and contour of epicardial coronary arteries; presence and severity of coronary artery stenoses; characteristic of obstruction; and presence and extent of any collateral flow
  • Left ventricular ejection fraction, an important prognostic indicator, can be determined
  • Wall motion and contractility can be assessed
  • Valvular function can be assessed and valvular regurgitation quantified, if present

Other diagnostic tools

  • Risk stratification r5c145
    • Identifies patients at high risk for cardiovascular death and myocardial infarction who will benefit from revascularization
    • Conducted in a stepwise fashion based on clinical evaluation, assessment of ventricular function, results of noninvasive testing, and delineation of coronary anatomy
    • Ventricular function
      • Cardiovascular mortality increases as left ventricular ejection fraction declines
        • Left ventricular ejection fraction less than 50% is associated with high risk for cardiovascular death (annual mortality greater than 3%), even without accounting for additional event risk factors r3
    • Exercise stress ECG
      • Duke Treadmill Score combines duration of exercise, severity of ST segment depression or elevation, and development of angina to stratify patients into risk groups r15
        • High risk: cardiovascular mortality greater than 3% per year
        • Intermediate risk: cardiovascular mortality from 1% to 3% per year
        • Low risk: cardiovascular mortality less than 1% per year
    • Cardiovascular imaging findings
      • High risk: r5
        • Area of ischemia greater than 10% on single photon emission CT scan
        • 2 or more segments out of 16 with new perfusion defects or 3 or more dobutamine-induced dysfunctional segments on cardiac MRI
        • 3 or more segments of left ventricle with stress-induced hypokinesia or akinesia on stress echocardiography
      • Intermediate risk: area of ischemia from 1% to 10% or any ischemia less than high risk by cardiovascular magnetic resonance or stress echocardiogram r16
      • Low risk: no ischemia
    • Coronary CT angiography findings r17
      • High risk: significant high-risk lesions (ie, 3-vessel disease with proximal stenosis, left main disease, proximal anterior descending disease)
      • Intermediate risk: significant lesions in large and proximal coronary arteries but not high-risk category
      • Low risk: normal coronary artery or plaques only
    • Invasive coronary angiography findings r10
      • Classified into 1-, 2-, or 3-vessel or left main coronary artery disease on basis of angiography
        • Probability of survival declines progressively with increased number of occluded coronary arteries and presence of severe proximal left anterior descending coronary artery disease r10

Differential Diagnosis

Most common

  • Cardiovascular conditions
    • Acute coronary syndromes d1
      • Include unstable or crescendo angina, non–ST elevation myocardial infarction, and ST elevation myocardial infarction c146c147c148
        • Typically presents as retrosternal chest pain that may radiate to arms, neck, or lower jaw; may be accompanied by dyspnea, diaphoresis, nausea, syncope, or fatigue
      • Diagnosis is based on history, physical examination, ECG findings, and serum cardiac troponin levels
        • Consider acute coronary syndrome in patients presenting with anginal pain lasting more than 15 minutes r4
        • New ST segment elevation at the J point in 2 contiguous leads, persisting for 20 minutes or longer, suggests ST elevation myocardial infarction and is a medical emergency
        • New horizontal or down-sloping ST segment depression and T wave changes suggest non–ST elevation acute coronary syndrome
        • Unstable or crescendo angina lacks the ECG and biochemical evidence for acute myocardial necrosis but has at least 1 of the following features:
          • Occurs at rest or with minimal exertion
          • Lasts at least 20 minutes if not treated with nitroglycerin
          • Severe and new onset (within the past month)
          • Occurs in a crescendo pattern that has progressed and is more severe, prolonged, or frequent than before
    • Pulmonary embolism c149d2
      • Presents with chest pain, dyspnea, tachypnea, and hypoxia. Tachycardia and ST abnormalities on ECG, as well as an elevated cardiac troponin level, 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, which should raise suspicion for deep vein thrombosis
      • Multidetector-row CT angiography is diagnostic for pulmonary embolism; identifies thrombus or thrombi in pulmonary vessels
    • Thoracic aortic dissection c150
      • 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
      • Pain may be characterized as tearing or ripping
      • A murmur of aortic insufficiency may be audible when the dissection extends into the aortic root; brachial or radial pulses may be asymmetrical
      • CT with contrast enhancement is diagnostic for thoracic aortic dissection. Alternate imaging modalities include MRI and transesophageal echocardiogram
    • Pericarditis (acute) c151d3
      • Typically presents as pleuritic precordial or retrosternal pain that may radiate to the back, neck, left shoulder, or arm
      • ECG often shows PR segment depression and diffuse ST segment elevation; troponin levels may be elevated
      • Pain is worse on inspiration, when supine, during swallowing, and during movement; pain is improved when seated and leaning forward
      • A pericardial friction rub is sometimes heard on auscultation
      • Echocardiography is the initial diagnostic study of choice, frequently demonstrating pericardial effusion with or without pericardial thickening
  • Noncardiac conditions
    • Cholecystitis (acute) c152d4
      • 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 the right upper quadrant
      • Right upper quadrant ultrasonography is usually diagnostic, showing an inflamed gallbladder; stones and ductal dilation may be evident
    • Pancreatitis (acute) c153d5
      • Presents with epigastric pain, often with radiation to the back; pain may be severe d6
      • Tenderness to palpation of the upper abdomen, sometimes with rebound tenderness
      • Abdominal CT or ultrasonography shows inflammation of pancreas; lipase and amylase levels are elevated
    • Peptic ulcer disease c154d7
      • Presents with recurrent chest or epigastric pain
      • Pain is rarely related to exertion and may be improved by eating
      • May have tenderness to palpation of the upper abdomen
      • Diagnosis is confirmed on upper gastrointestinal endoscopy
    • Esophageal spasm c155
      • May present with epigastric pain or tightness, which may be relieved by sublingual nitroglycerin
      • May be precipitated by swallowing; associated with dysphagia
      • Pain is rarely related to exertion
      • Sublingual nitroglycerin and certain calcium channel blockers used to treat angina can occasionally alleviate pain due to esophageal reflux or spasm
      • Diagnosis is confirmed by manometry, which reveals premature rapid contractions, or by appearance of "corkscrew" esophagus on barium swallow
    • Costochondritis c156
      • May present with severe pain in the sternal area
      • Characterized by exacerbation with chest motion (eg, respiration, rotation of the torso)
      • Differentiated by characteristic exacerbation with physical maneuvers and absence of ECG abnormalities

Treatment

Goals

  • Eliminate ischemic symptoms
  • Prevent major cardiac events such as myocardial infarction, heart failure, and death

Disposition

Admission criteria

Patients with symptoms suggestive of acute coronary syndrome with or without diagnostic ECG changes or elevated troponin levels

Patients with chest pain associated with hemodynamic instability or congestive heart failure

Criteria for ICU admission
  • Ongoing or refractory ischemic pain, uncontrolled arrhythmias, pulmonary edema, or hemodynamic instability

Recommendations for specialist referral

  • Consult with cardiologist for patients with symptoms suggestive of myocardial ischemia or abnormal functional testing results r4

Treatment Options

Identify and treat conditions that contribute to or complicate ischemic heart disease

Modify risk factors for ischemic heart disease to reduce risk of myocardial infarction and cardiovascular death; use both pharmacologic and nonpharmacologic methods as necessary

  • Daily low-dose aspirin is recommended in all patients with evidence of coronary artery disease r4r6
    • Clopidogrel is indicated as an alternative in case of aspirin intolerance
    • In patients at moderate or high risk of ischemic events and no increased risk of bleeding, addition of a second antiplatelet agent (eg, clopidogrel, prasugrel, ticagrelor) for long-term secondary prevention may be considered r5
    • In patients who have undergone coronary revascularization with stent placement, dual antiplatelet therapy consisting of low-dose aspirin plus antithrombotic agent should be given, typically for at least 1 month (bare metal stent) or at least 6 months (drug-eluting stent); however, a shorter duration of therapy may be considered in those at high risk or life-threatening bleeding risk, given the low risk of stent thrombosis after 1 to 3 months r18
    • Long-term therapy with ticagrelor in addition to aspirin may be beneficial in patients with diabetes who are at high risk for cardiovascular events and low risk for bleeding r19r20
  • Statins are recommended in all patients to reduce risk of myocardial infarction and ischemic stroke, regardless of baseline LDL-C levels r6r21
    • Use high-intensity statin therapy for patients who are aged 75 years or younger
      • For patients who are at very high risk, use maximally tolerated statin therapy plus ezetimibe
        • Very-high-risk patients include those with a history of multiple major atherosclerotic cardiovascular disease events (eg, acute coronary syndrome, myocardial infarction or ischemic stroke, symptomatic peripheral artery disease) or 1 major atherosclerotic cardiovascular disease event and multiple high-risk conditions
      • Consider a PCSK9 inhibitor in patients who are at very high risk and are taking maximally tolerated LDL-C–lowering medication if either of the following exists:
        • LDL-C level is 70 mg/dL or higher, or
        • Non–HDL-C level is 100 mg/dL or higher
    • Use moderate-intensity statin therapy if patient cannot receive high-intensity therapy
    • In patients older than 75 years, initiate either moderate- or high-intensity statin therapy after considering potential reduction in risk, adverse effects and interactions, and overall prognosis
  • Antihypertensive drug therapy, in addition to lifestyle modification, is recommended for patients with blood pressure of 130/80 mm Hg or higher r22
    • Aim for blood pressure target lower than 130/80 mm Hg
    • First line therapy should consist of medications such as ACE inhibitors (or angiotensin II receptor blockers) and β-blockers as required for other indications below
    • Add thiazide diuretics, dihydropyridine calcium channel blockers, or mineralocorticoid receptor antagonists if first line agents fail to control hypertension
  • ACE inhibitors (or angiotensin II receptor blockers) are recommended for patients who also have heart failure, hypertension, chronic kidney disease, or diabetes r10
  • Proton pump inhibitors are recommended for patients on aspirin, dual antiplatelet therapy, or oral anticoagulants who are at risk of gastrointestinal bleeding r5
  • β-blockers are recommended for patients with left ventricular dysfunction or systolic heart failure; consider in patients with previous ST elevation myocardial infarction r5

Control acute angina symptoms with sublingual nitroglycerin or short-acting nitrates

  • These agents dilate epicardial coronary arteries, thereby increasing coronary blood flow r23
  • Most patients with angina are prescribed sublingual nitroglycerin tablets or nitroglycerin spray for home use (unless contraindicated) r4r24
    • Most patients have pain relief within 5 minutes of taking 1 or 2 doses 5 minutes apart; instruct patients to seek emergency medical care if pain is not relieved after 3 doses (maximum dosage) in a 15-minute span or sooner if pain is worsening
    • Both products may be used prophylactically 5 to 10 minutes before planned activity to prevent effort-induced angina; duration of effect is 30 to 40 minutes
  • These rapid-acting formulations of nitroglycerin provide immediate relief of angina symptoms at the onset of an episode or prevent onset in situations in which it is likely to occur r5
  • Isosorbide dinitrate (short-acting) and isosorbide mononitrate (long-acting) are longer-acting nitrate formulations r5
    • Hemodynamic and antianginal effects persist for several hours, conferring longer angina prevention than sublingual nitroglycerin
    • Onset of antianginal action is slower than with sublingual nitroglycerin
  • Short-acting nitrates may cause hypotension and should be taken when patients are sitting or supine; headache is a common adverse effect
  • Do not administer a nitrate preparation or nitroglycerin to patients who have taken tadalafil in the previous 48 hours or vardenafil or sildenafil in the previous 24 hours given risk of severe hypotension

Institute long-term symptom control

  • β-blockers, calcium channel blockers, long-acting nitrates, ranolazine, and ivabradine appear to be equally effective at managing symptoms in patients with stable ischemic heart disease but have not been shown to reduce myocardial infarction or ischemic cardiac death in this population r2
  • Available agents decrease severity, duration, or frequency of angina, usually increasing exercise performance and time to onset of ST segment depression r23
  • β-blockers and calcium channel blockers are considered first line agents r2
    • β-blockers r6
      • Recommended as initial agents to relieve symptoms in most patients r4r6
      • Lower resting heart rate and limit heart rate rises during exercise, keeping myocardial oxygen demand below angina-producing threshold r23
      • Long-term treatment is well tolerated and reduces ischemic burden and threshold in patients with stable ischemic heart disease r6
      • Use of β-blockers in patients post–myocardial infarction and those with heart failure is associated with reduced mortality and reinfarction r2
    • Calcium channel blockers
      • Recommended as alternative first line therapy for symptom relief if adverse effects or contraindications limit use of β-blockers r6
      • All classes of calcium channel blockers are effective coronary vasodilatorsr23 and reduce anginal episodes, increase exercise duration, and reduce use of sublingual nitroglycerin in patients with effort-induced angina r6
        • In addition, nondihydropyridine calcium channel blockers (ie, diltiazem, verapamil) lower myocardial oxygen demand by lowering heart rate and depressing myocardial contractilityr23 and are generally preferred
          • In general, avoid calcium channel blockers in patients with heart failure with reduced ejection fraction owing to the drug's negative inotropic effect
        • Dihydropyridine calcium channel blockers (eg, nifedipine, amlodipine) are more suitable for patients with cardiac conduction defects such as sick sinus syndrome, sinus bradycardia, or significant arteriovenous conduction disturbances r6
    • Combination of nondihydropyridine calcium channel blocker and β-blocker may be used in selected patients with close monitoring for excessive bradycardia or signs of heart failure r5
  • Second line or add-on agents include long-acting nitrates, ranolazine, and ivabradine r2
    • Effective alternatives to first line agents r3
    • Used as monotherapy if first line agents are contraindicated or cause unacceptable adverse effects
    • Long-acting nitrate preparations can be prescribed as an add-on to β-blockers or calcium channel blockers when those medications alone are not effective in preventing angina r6
      • Formulations include nitroglycerin transdermal patch, oral isosorbide dinitrate, and oral isosorbide mononitrate r23
      • It is recommended to maintain a daily nitrate-free interval of 10 to 14 hours to avoid development of nitrate tolerance r6
    • Ranolazine or ivabradine may be used as part of combination therapy with β-blockers or calcium channel blockers when β-blockers or calcium channel blockers alone are not effective r5
    • Trimetazidine and nicorandil are alternative agents that are available in Europe but not the United States r5

Consider revascularization by percutaneous catheter–based techniques or coronary artery bypass graft

  • Decision regarding revascularization is complex and dependent on many patient and anatomic factors, including presence of significant obstructive coronary artery stenosis, amount of related ischemia, and expected benefit in terms of prognosis or symptom relief r3
    • Perform when there is clear evidence of potential to improve patient health status and/or survival
    • Decision to perform surgical or percutaneous revascularization depends on complexity of coronary anatomy according to SYNTAX score, surgical risk based on Society of Thoracic Surgeons risk score, and patient preference r7r25r26
  • Survival advantages for revascularization by coronary artery bypass graft have been well-established in patients with 50% or greater stenosis of the left main coronary artery r3
    • Revascularization provides better symptom reliefr3 but has not been shown to be superior to optimal medical therapy alone in terms of survival in patients with stable angina (excluding those with significant left main coronary artery disease), including those considered high-risk based on stress testing r2
  • European guidelines recommend revascularization to improve survival in patients with left main stenosis greater than 50%, any proximal left anterior descending artery stenosis greater than 50%, 2- to 3-vessel disease with stenosis greater than 50% and impaired left ventricular function or heart failure, last remaining patent vessel with greater than 50% stenosis, or large area of ischemic myocardium demonstrated by functional testing or abnormal fractional flow reserve r3r12
    • Revascularization to improve symptoms is recommended in patients who have hemodynamically significant coronary stenosis in the presence of limiting angina or angina equivalent that is unresponsive to optimal medical therapy r12
  • US guidelines recommend coronary artery bypass graft in preference to percutaneous coronary intervention to improve survival in patients with left main coronary artery stenosis greater than 50%, with 3-vessel coronary artery disease with or without proximal left anterior descending involvement, and with proximal left anterior descending stenosis plus significant stenosis in 1 other vessel r6r27
    • Either coronary artery bypass graft or percutaneous coronary intervention is recommended for symptom improvement in patients with at least 1 significant stenosis (greater than 50% left main or greater than 70% non–left main coronary artery disease) and unacceptable angina despite optimal medical therapy r28

Drug therapy

  • Rapid-acting nitrates r10
    • Nitroglycerin sublingual tablets c157
      • Nitroglycerin Sublingual tablet; Adults: 1 tablet (300 mcg, 400 mcg, or 600 mcg) SL, dissolved under the tongue or in buccal pouch at attack onset; may repeat with 1 tablet every 5 minutes PRN for up to 3 tablets. If chest pain persists after 3 tablets, prompt medical attention should be sought. Guidelines suggest patients with persistent chest pain following 1 dose, should seek prompt medical attention. May use prophylactically 5 to 10 minutes before participating in activities that may precipitate an acute attack.
    • Nitroglycerin spray c158
      • Nitroglycerin Sublingual/Translingual spray; Adults: 400 or 800 mcg (1 or 2 metered spray doses) on or under the tongue at attack onset; may repeat 400 mcg (1 spray) every 5 minutes PRN for up to 1200 mcg (3 sprays). If chest pain persists after 3 sprays, prompt medical attention should be sought. Guidelines suggest patients with persistent chest pain following 1 dose, should seek prompt medical attention. May use prophylactically 5 to 10 minutes before participating in activities that may precipitate an acute attack.
  • Short-acting nitrates
    • Isosorbide dinitrate c159
      • Isosorbide Dinitrate Oral capsule, extended-release; Adults: Initially, 40 mg PO once daily; increase up to 160 mg/day PO. An interdosing interval of more than 14 hours may be necessary to avoid nitrate tolerance.
    • Nitroglycerin topical ointment c160
      • Nitroglycerin Topical ointment; Adults: 15 to 30 mg (2.5 to 5 cm as squeezed from tube, about 1 to 2 inches), applied to the skin every 8 hours while awake and at bedtime; frequency may be increased to every 6 hours if needed. Alternatively, regimen providing 12-hour nitrate-free interval may be used; apply once each morning, then reapply 6 hours later. Max 75: mg/day (12.5 cm).
  • Long-acting nitrates r10
    • Isosorbide mononitrate c161
      • Isosorbide Mononitrate Oral tablet; Adults: 20 mg PO twice daily, with doses given 7 hours apart. However, a starting dose of 5 mg may be appropriate in patients with small stature, which should be increased to at least 10 mg by day 2 to 3 of therapy. Doses greater than 20 mg twice daily have not been adequately studied.
      • Isosorbide Mononitrate Oral tablet; Geriatric: Initiate therapy at the low end of the adult dosage range. Elderly patients may be more sensitive to hypotensive effects of nitrates.
      • Isosorbide Mononitrate Oral tablet, extended-release; Adults: 30 to 60 mg PO in the morning. Rarely, up to 240 mg/day may be needed.
      • Isosorbide Mononitrate Oral tablet, extended-release; Geriatric: Initiate therapy at the low end of the adult dosage range. Geriatric patients may be more sensitive to hypotensive effects of nitrates.
    • Transdermal patch c162
      • Nitroglycerin Transdermal patch - 24 hour; Adults: 1 transdermal patch (0.1 to 0.8 mg/hour), applied topically every 24 hours. To prevent tolerance, leave patch on 12 to 14 hours, then remove for 10 to 12 hours before applying next patch.
  • β-blockers r10
    • Bisoprolol c163
      • Bisoprolol Fumarate Oral tablet; Adults: 5 to 20 mg PO once daily.
    • Carvedilol c164
      • Carvedilol Oral tablet; Adults: 25 to 50 mg PO twice daily has been shown to improve exercise capacity, and increase time to onset of anginal pain or onset of 1-mm ST-segment depression similarly to verapamil, slow-release nifedipine, and isosorbide dinitrate.
    • Metoprolol succinate c165
      • Metoprolol Succinate Oral tablet, extended-release; Adults: Initially, 100 mg PO twice daily. Titrate dosage weekly, if needed, to 400 mg PO once daily. When switching from immediate-release metoprolol, convert to the same total daily dosage of extended-release tablets. To discontinue treatment, reduce dosage gradually over 1 to 2 weeks.
    • Metoprolol tartrate c166
      • Metoprolol Tartrate Oral tablet; Adults: The usual initial dosage is 50 mg PO twice daily (range: 25 to 50 mg PO twice daily). The usual effective dosage range is 100 to 400 mg/day PO given in 2 divided doses.
  • Calcium channel blockers (nondihydropyridines) r10
    • Verapamil c167
      • Verapamil Hydrochloride Oral tablet; Adults: Initially, 80 to 120 mg PO every 8 hours. May increase to 480 mg/day, given in 3 to 4 divided doses.
      • Verapamil Hydrochloride Oral tablet; Geriatric: Use lower initial dose (e.g., 40 mg PO every 8 hours).
    • Diltiazem c168
      • Diltiazem Hydrochloride Oral tablet; Adults: Initially, 30 mg PO 4 times per day before meals and at bedtime; gradually increase dosage. Usual dose: 180 to 360 mg/day. Max: 480 mg/day in 3 or 4 divided doses.
      • Diltiazem Hydrochloride Oral tablet, extended-release; Adults: Initially, 180 mg PO once daily in the morning or evening. Titrate every 1 to 2 weeks. Max: 420 mg/day.
  • Dihydropyridines
    • Nifedipine c169c170
      • Per the FDA and manufacturers, immediate-release nifedipine should not be used to treat hypertension and should only be used to treat patients with chronic stable angina or vasospastic angina. Immediate-release nifedipine has been associated with serious adverse effects when used to treat adult patients with hypertension, hypertensive urgency, hypertensive emergency, or coexisting myocardial infarction.
      • Nifedipine Oral capsule; Adults: Initially, 10 mg PO 3 times daily. Max: 30 mg/dose or 180 mg/day; doses greater than 120 mg/day are rarely needed.
      • Nifedipine Oral capsule; Geriatric: See adult dosage. Initiate at lower end of dosage range.
      • Nifedipine Oral tablet, extended-release; Adults: Initially, 30 to 60 mg PO once daily. Max: 90 mg/day.
      • Nifedipine Oral tablet, extended-release; Geriatric: See adult dosage. Initiate at lower end of dosage range.
    • Amlodipine c171c172
      • Amlodipine Besylate Oral tablet; Adults: 5 to 10 mg PO once daily. Usual dosage: 10 mg PO once daily.
  • Other antianginal agents
    • Ranolazine c173
      • Ranolazine Oral tablet, extended-release; Adults: 500 mg PO twice daily in combination with other antianginal agents (e.g., amlodipine, beta-blockers, nitrates); increase to Max 1,000 mg PO twice daily if needed to control symptoms. One trial increased initial dose after 1 week. Closely monitor response. Obtain baseline and follow-up ECGs to evaluate QT interval. Do not use with potent CYP3A4 inhibitors.
      • Ranolazine Oral tablet, extended-release; Adult patients taking diltiazem, verapamil, aprepitant, erythromycin, or fluconazole: Limit to 500 mg PO twice daily.
    • Ivabradine c174
      • Ivabradine Oral tablet; Adults: 5 mg PO twice daily initially. Start at 2.5 mg PO twice daily in patients with conduction defects or in those whom bradycardia could lead to hemodynamic compromise. After 2 weeks, adjust dose to achieve resting heart rate of 50 to 60 bpm. For resting heart rate more than 60 bpm, increase dose by 2.5 mg PO twice daily. For resting heart rate of 50 to 60 bpm, maintain current dose. For a resting heart rate less than 50 bpm or symptomatic bradycardia, decrease dose by 2.5 mg PO twice daily; if current dose is 2.5 mg PO twice daily, discontinue therapy. After that, adjust dose as needed based on resting heart rate and tolerability. Max: 7.5 mg PO twice daily.
  • Antiplatelet drugs r5
    • Aspirin c175
      • Aspirin Oral tablet; Adults: 75 mg to 162 mg PO daily indefinitely. Use lower dose of 100 mg/day or less if history of aspirin-induced bleeding or risk factors for bleeding. If high-risk for MI, add clopidogrel.
    • Clopidogrel c176
      • Clopidogrel Bisulfate Oral tablet; Adults: 75 mg PO once daily.
    • Prasugrel c177
      • Prasugrel Oral tablet; Adults and Geriatric Adults less than 75 years of age and weighing less than 60 kg: 60 mg PO as a loading dose, then consider a lower maintenance dose of 5 mg PO once daily. Optimal duration of therapy is not known. Also give aspirin 75 mg/day to 325 mg/day PO.
      • Prasugrel Oral tablet; Adults and Geriatric Adults less than 75 years of age and weighing 60 kg or more: 60 mg PO as a loading dose, then 10 mg PO once daily. The optimal duration of therapy is not known. Also give aspirin 75 mg/day to 325 mg/day PO.
      • Prasugrel Oral tablet; Geriatric 75 years or older: Use in this population is generally not recommended, except in high-risk patients with a past history of myocardial infarction or diabetes, where studies have demonstrated benefit is greater than risk. In such patients, if weight is 60 kg or more: 60 mg PO as a loading dose, then 10 mg PO once daily. If weight is less than 60 kg: 60 mg PO as a loading dose, then consider a lower maintenance dose of 5 mg PO once daily. The optimal duration of therapy is not known. All patients should also take aspirin 75 mg/day to 325 mg/day PO.
    • Ticagrelor c178
      • Ticagrelor Oral tablet; Adults: 180 mg PO loading dose plus aspirin (usually 325 mg PO) then, beginning 12 hours after loading dose, 90 mg PO twice daily plus aspirin 75 to 100 mg (i.e., 81 mg) PO once daily for 1 year. After 1 year, 60 mg PO twice daily and continue aspirin maintenance dose. Avoid maintenance doses of aspirin above 100 mg/day.
  • ACE inhibitors
    • Lisinopril c179c180c181c182
      • Lisinopril Oral tablet; Adults: Initially, 10 mg PO once daily. The usual dosage range is 20 to 40 mg PO once daily; lower doses may be necessary in patients with impaired renal function, the elderly, and in those receiving diuretics. Max: 80 mg/day.
    • Ramipril c183c184c185c186
      • Ramipril Oral tablet; Adults: Initially, 2.5 mg PO once daily. In combination with a diuretic, reduce the initial dose to 1.25 mg PO once daily. The usual dosage is 2.5 to 20 mg PO per day, given in 1 to 2 divided doses. Adjust dosage based on clinical response. In a titration study, dividing the dose twice daily was superior to once daily dosing, suggesting antihypertensive efficacy with once daily dosing may not be adequately maintained in some patients.
  • Angiotensin II receptor antagonists
    • Irbesartan c187c188c189c190
      • Irbesartan Oral tablet; Adults: Initially, 150 mg PO once daily unless the patient is volume-depleted. For volume-depleted patient, begin with 75 mg PO once daily. If needed, titrate up to 300 mg PO once daily. Alternatively, a small dose of a diuretic may be added.
    • Losartan c191c192c193c194
      • Losartan Potassium Oral tablet; Adults and Adolescents: Initially, 50 mg PO once daily, unless patient is volume depleted. Maintenance dosage range: 25 to 100 mg/day PO, given in 1 to 2 divided doses. Adding a diuretic has greater blood pressure reduction vs. increasing losartan dosage above 50 mg/day. When volume depletion suspected (e.g., diuretics), start at 25 mg PO once daily.
    • Telmisartan c195c196c197c198
      • Telmisartan Oral tablet; Adults, including the geriatric: Initially, 40 mg PO once daily, unless volume-depleted. Begin therapy with 20 mg PO once daily in volume-depleted patients (e.g., patients taking diuretics). The dosage range is 20 to 80 mg PO once daily.
  • Statins
    • Atorvastatin c199
      • Atorvastatin Calcium Oral tablet; Adults: 10 to 20 mg PO once daily. May start at 40 mg once daily for greater than 45% LDL-reduction. Range: 10 to 80 mg once daily.
    • Pitavastatin c200
      • Pitavastatin Calcium Oral tablet; Adults: 2 mg PO once daily. Analyze lipid concentrations 4 weeks after initiation or dosage titration. Max: 4 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Pravastatin
      • Pravastatin Sodium Oral tablet; Adults: Initially, 40 mg PO once daily. If needed, the dose may be increased to 80 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Rosuvastatin c201
      • Rosuvastatin Calcium Oral tablet; Adults: 10 mg PO once daily; 5 mg once daily may be used for less aggressive LDL-reduction, patients with CrCl less than 30 mL/minute, higher risk for myopathy, or for Asian patients. Dose range: 5 to 40 mg once daily. Consider 20 mg once daily for marked hypercholesterolemia (LDL more than 190 mg/dL). Reserve 40 mg/day for insufficient response; 40 mg/day has been associated with higher risk of myopathy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Simvastatin c202
      • Simvastatin Oral tablet; Adults: Initially, 10 to 20 mg PO at bedtime. In patients with CHD, risk factors for CHD, or familial homozygous hypercholesterolemia, starting dose is 40 mg PO once daily in the evening. Usual dosage range: 5 to 40 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Only use 80 mg in patients who have been taking 80 mg chronically without myopathy.
  • Nonstatin lipid-lowering agents
    • Ezetimibe r21c203
      • Ezetimibe Oral tablet; Adults: 10 mg PO once daily.
    • Proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease inhibitors
      • Evolocumab r29c204
        • Evolocumab Solution for injection; Adults: 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously once monthly.
      • Alirocumab r30c205
        • Alirocumab Solution for injection; Adults: 75 mg subcutaneously once every 2 weeks. If LDL-C response is inadequate, increase to 150 mg subcutaneously once every 2 weeks. Measure LDL-C concentrations 4 to 8 weeks after initiation or titration. 300 mg subcutaneously once every 4 weeks may also be used. Measure LDL-C just prior to the next scheduled dose. If LDL-C reduction is inadequate, adjust the dose to 150 mg every 2 weeks with the new dose on the next scheduled dosing date and reassess LDL-C within 4 to 8 weeks.

Nondrug and supportive care

Smoking cessation r31c206d4

Nutrition c207

  • Modify nutrition counseling based on individual patient factors (eg, lipid profile, blood pressure, required caloric intake, alcohol intake)
  • Emphasize intake of vegetables, fruits, nuts, whole grains, lean vegetable or animal protein, and fish r32
  • Minimize intake of trans fats, red meat and processed red meats, refined carbohydrates, and sweetened beverages r32

Weight management r31c208

  • BMI goal is 18.5 to 24.9 kg/m²; waist circumference goal is less than 89 cm for females and less than 102 cm for males
  • If weight loss is required, initial weight loss goal should be 5% to 10% below baseline

Physical activity c209

  • Before discharge from acute care setting, provide patient with instructions on specific activity recommendations (eg, lifting, stair climbing, housework, yard work, sexual activity)
  • Goal is 30 to 60 minutes of moderate intensity aerobic activity for 5 to 7 days per week; supplement with 2 days of resistance training r31
  • Counsel patients to report exercise-associated symptoms

Prevention of infectious diseases r33

  • Pneumococcal vaccine is recommended for high-risk patients who have cardiovascular disease and are older than 65 years c210
  • Yearly influenza vaccine is recommended for patients with cardiovascular disease r7c211
Procedures
Percutaneous coronary intervention c212
General explanation
  • Invasive therapeutic technique in which a catheter is guided via the radial artery (preferred) or femoral artery to the stenosed or occluded coronary artery (or arteries) for the purpose of alleviating lesion(s) and revascularizing myocardial tissue
  • Techniques include:
    • Percutaneous transluminal coronary angioplasty (balloon dilation) r34c213
    • Intracoronary stenting r34
      • Bare metal stent c214
      • Drug-eluting stent c215
        • Thought to reduce restenosis and improve clinical outcomes; typically first line approach r35
    • Atheroablative technologies (eg, atherectomy) r34c216
  • Currently, 80% to 85% of percutaneous coronary interventions involve balloon dilation and coronary stenting r36
Indication
  • Decision regarding revascularization in stable ischemic heart disease is complex and dependent on many patient and anatomic factors, including presence of significant obstructive coronary artery stenosis, amount of related ischemia, and expected benefit in terms of prognosis and/or symptom relief
  • Revascularization may be indicated in patients with flow-limiting coronary stenoses and symptoms that persist despite optimal medical therapy and/or potential for improvement of prognosis
  • A multidisciplinary (heart team) approach to revascularization decisions is recommended when optimal revascularization strategy is not straightforward
    • Both an interventional cardiologist and a cardiac surgeon should review patient's medical condition and coronary anatomy, determine whether percutaneous coronary intervention and/or coronary artery bypass graft are technically feasible and reasonable, and discuss revascularization options with the patient before selecting a treatment strategy
  • Refer to published guidelines, including those from the American College of Cardiology (2017) or the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (2018), for detailed indications r12r13
Contraindications
  • Percutaneous coronary intervention to improve survival should not be performed in stable patients with significant (greater than 50% diameter stenosis) unprotected left main coronary artery disease who have anatomy unfavorable to this intervention and who are good candidates for coronary artery bypass graft (preferred approach) r28
  • May not be appropriate for patients with certain comorbidities (eg, chronic kidney disease, diabetes) in whom coronary artery bypass graft surgery is associated with better outcomes among patients with an acceptable surgical risk
  • Percutaneous coronary intervention with coronary stenting (ie, bare metal or drug-eluting stents) should not be performed if the patient is not likely to be able to tolerate and comply with dual antiplatelet therapy for the duration of treatment appropriate to the type of stent implanted r28
Complications
  • Myocardial infarction
  • Arrhythmia
  • Stroke
  • Reaction to contrast material
  • Vascular perforation or dissection
  • Emergent coronary artery bypass graft
  • Death
Coronary artery bypass graft surgery c217c218c219
General explanation
  • Open surgical procedure in which an artery (ie, internal mammary artery) or a vein (ie, saphenous vein) is grafted around the occluded portion of the coronary artery or arteries for the purpose of revascularizing the affected myocardial tissue r37
Indication
  • Decision regarding revascularization in stable ischemic heart disease is complex and dependent on many patient and anatomic factors, including presence of significant obstructive coronary artery stenosis, amount of related ischemia, and expected benefit in terms of prognosis and/or symptom relief
  • Revascularization may be indicated in patients with flow-limiting coronary stenoses and symptoms that persist despite medical treatment
  • Coronary artery bypass graft is indicated to improve survival in patients with significant (greater than 50% diameter stenosis) left main coronary artery stenosis, 3-vessel coronary artery disease with or without proximal left anterior descending coronary artery involvement, and proximal left anterior descending coronary artery stenosis plus significant stenosis in 1 other vessel r27
  • Coronary artery bypass graft surgery may be preferred over percutaneous coronary intervention in patients with certain comorbidities (eg, chronic kidney disease, diabetes)
  • A multidisciplinary (heart team) approach to revascularization decisions is recommended when the optimal revascularization strategy is not straightforward
    • Both an interventional cardiologist and a cardiac surgeon review patient's medical condition and coronary anatomy, determine whether percutaneous coronary intervention and/or coronary artery bypass graft are technically feasible and reasonable, and discuss revascularization options with the patient before selecting a treatment strategy
  • Refer to published guidelines, including those from the American College of Cardiology (2017) or the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (2018), for detailed indications r12r13
Complications
  • Myocardial infarction
  • Arrhythmia
  • Neurologic abnormalities
  • Stroke
  • Renal dysfunction
  • Sternal infection
  • Death

Comorbidities

  • Diabetes c220
    • Use β-blockers with caution
      • Vasodilating β-blockers (carvedilol, labetalol, nebivolol) may be preferable as these have fewer metabolic effects in patients with type 2 diabetes r38
    • Sodium-glucose cotransporter 2 inhibitors and glucagonlike peptide 1 receptor agonists are the recommended oral antihyperglycemic agents in patients with type 2 diabetes, as these have been shown to reduce major adverse cardiac events and hospitalization from heart failure r5r38
    • Ranolazine has glucose-lowering effect, particularly in patients with poorly controlled type 2 diabetes r38
  • Heart failure c221
    • β-blockers may simultaneously confer a symptomatic benefit for patients with angina and a mortality benefit for patients with heart failure
      • Use with caution and only in patients in a compensated state owing to the negative inotropic effect
      • Metoprolol succinate, carvedilol, and bisoprolol are FDA approved for patients with congestive heart failure
    • In general, avoid calcium channel blockers in patients with heart failure with reduced ejection fraction owing to the drug's negative inotropic effect
  • Hypertension r22c222
    • Antihypertensive drug therapy, in addition to lifestyle modification, is recommended for patients with blood pressure of 130/80 mm Hg or higher
    • Aim for blood pressure target lower than 130/80 mm Hg
    • First line therapy should consist of medications such as ACE inhibitors (or angiotensin II receptor blockers) and β-blockers as required for other indications
    • Add thiazide diuretics, dihydropyridine calcium channel blockers, or mineralocorticoid receptor antagonists if first line agents fail to control hypertension
  • Atrial fibrillation c223
    • Use of aspirin in combination with oral anticoagulant therapy for atrial fibrillation increases risk for major bleeding compared to either agent alone with no additional reduction in risk of stroke or cardiovascular events in patients with stable ischemic heart disease r39r40
    • Monotherapy with either warfarin (INR target of 2-3) or a novel oral anticoagulant is recommended r40r41
  • Peripheral vascular disease c224
    • Mild peripheral vascular disease: there is no contraindication for use of β-blockers or calcium channel blockers
    • Severe peripheral vascular disease and pain during rest: calcium channel blockers are preferred; avoid β-blockers
  • Bradyarrhythmias r6c225
    • Use β-blockers with caution in patients with significant bradyarrhythmias
    • Use diltiazem and verapamil (ie, nondihydropyridine calcium channel blockers) with caution in patients with significant bradyarrhythmias
    • When used alone, short-acting dihydropyridine calcium channel blockers may induce reflex tachycardia and thereby increase risk of sudden cardiac death; concomitant use of β-blockers may reduce this risk
    • Exercise caution when using concomitant β-blockers and heart rate–limiting calcium channel blockers (ie, diltiazem, verapamil) owing to their combined effects impairing conduction across the atrioventricular node; this is a frequent cause of hospitalization in older adult patients
  • Ischemic dilated cardiomyopathy c226
    • Calcium channel blockers may relieve angina, although they have not been found to confer a mortality benefit in this population
    • In general, avoid calcium channel blockers in patients with heart failure with reduced ejection fraction owing to the drug's negative inotropic effect
  • Asthma c227
    • Avoid β-blockers owing to their potential exacerbation of bronchospasm in patients prone to wheezing and bronchoconstriction
  • Migraine c228
    • β-blockers and calcium channel blockers may be beneficial
    • Nitrates may worsen headaches
  • Use of amphetamines and/or cocaine c229c230d8
    • β-blockers may allow unopposed α-adrenergic effects of these drugs, which may lead to significant vasospasm
    • Consider using calcium channel blockers

Special populations

  • Patients with vasospastic (Prinzmetal) angina r5
    • Calcium channel blockers and long-acting nitrates are first line agents for preventive treatment
    • All patients should also achieve optimal coronary risk factor control, in particular through smoking cessation and aspirin
  • Patients with refractory angina
    • Defined as symptoms caused by established reversible ischemia that last for at least 3 months and are not controlled by escalating medical therapy, bypass grafting, or percutaneous coronary intervention
    • Certain patients may be candidates for novel treatments such as: r5
      • Enhanced external counterpulsation r10
      • Coronary sinus constriction
      • Spinal cord stimulation

Monitoring

  • During the first year of medical therapy, follow-up evaluations every 4 to 6 months are recommended. After the first year of therapy, evaluations every 6 to 12 months are recommended if the patient is stable r6c231c232
    • Follow-up evaluation r42
      • Assessment of symptoms and clinical function
      • Monitoring of cardiac risk factors
      • Assessment of the adequacy of and adherence to recommended lifestyle changes and medical therapy
      • Surveillance for complications of stable ischemic heart disease, including heart failure and arrhythmias
    • Resting 12-lead ECG is indicated at least annually in patients with stable ischemic heart disease, as well as at the time of any clinical change c233
    • In patients not known to have diabetes mellitus, measure fasting blood glucose every 3 years to detect new-onset diabetes mellitus c234
    • In patients with established diabetes mellitus, measure glycosylated hemoglobin at least annually to assess glycemic control
    • Obtain a lipid profile annually c235
    • Obtain measurements of hemoglobin, thyroid function, serum electrolytes, and renal function annually or as prompted by clinical findings c236c237c238c239
    • Standard exercise ECG, imaging stress tests, or coronary CT angiography are not routinely indicated as part of follow-up assessment in patients with stable ischemic heart disease with no change in clinical status or with worsening of symptoms r42c240c241c242
    • Assessment of left ventricular ejection fraction and segmental wall motion by echocardiography or radionuclide imaging is recommended for patients with new or worsening heart failure or evidence of interval myocardial infarction by history or ECG r42c243c244c245c246c247c248
    • Echocardiography to assess left ventricular function, valvular status, and cardiac dimensions, and noninvasive stress imaging to assess for silent ischemia may be considered for asymptomatic patients every 3 to 5 years r5
  • Patients who have undergone revascularization with either percutaneous coronary intervention or coronary artery bypass graft within 6 months should be monitored according to the percutaneous coronary intervention and coronary artery bypass graft guidelines r27r28
  • Patients with stable ischemic heart disease who have accelerating symptoms or decreasing functional capacity require prompt reassessment

Complications and Prognosis

Complications

  • Myocardial infarction c249
  • Left ventricular dysfunction and failure c250c251
  • Arrhythmias c252
  • Death c253

Prognosis

  • Prognosis is worse in patients with microvascular disease, severe proximal left anterior descending artery disease, 2-vessel disease, left main coronary artery disease, and 3-vessel disease who have reduced left ventricular function and/or diabetes r4r43
  • Patients with poor exercise capacity and those with evidence of severe ischemia at low workload are at higher risk of mortality r4r43
  • Prognosis is also influenced by age and coexisting medical conditions such as heart failure, cerebrovascular disease, diabetes mellitus, and chronic kidney disease r6
    • Smoking, hypertension, dyslipidemia, family history of premature coronary artery disease, obesity, and sedentary lifestyle confer a greater risk of complications
    • Depression, stress, and poor social support also have been demonstrated to be strongly and independently associated with increased mortality

Screening and Prevention

Screening

At-risk populations

  • Patients with severe hypercholesterolemia (LDL-C levels of 190 mg/dL or higher), adults with diabetes, and adults aged 40 to 75 years r21

Screening tests

  • Screen to identify candidates who may benefit from lifestyle or pharmacologic interventions (lipid-lowering therapy) aimed at reducing cardiovascular risk r21
    • Evaluate adults without preexisting atherosclerotic cardiovascular disease every 4 to 6 years with tests that measure traditional cardiovascular risk factors
      • Fasting blood glucose (or other assessment of diabetes) c254
      • Total and HDL-C c255c256
      • Blood pressure c257
      • Question regarding tobacco use c258
    • Based on these, estimate 10-year cardiovascular risk using the ASCVD Risk Predictor Plus r21r44r45

Prevention

  • Control modifiable risk factors for coronary artery disease such as:
  • Specific prevention recommendations are available in a clinical practice guideline from the American College of Cardiology/American Heart Association r46
Patel AV et al: Challenges with evidence-based management of stable ischemic heart disease. Curr Cardiol Rep. 19(2):11, 201728185167Thadani U: Management of stable angina--current guidelines: a critical appraisal. Cardiovasc Drugs Ther. 30(4):419-26, 201627638354Task Force Members et al: 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the Management of Stable Coronary Artery Disease of the European Society of Cardiology. Eur Heart J. 34(38):2949-3003, 201323996286Scottish Intercollegiate Guidelines Network: Management of Stable Angina: A National Clinical Guideline. SIGN guideline 151. SIGN website. Published April 2018. Accessed January 20, 2021. https://www.sign.ac.uk/sign-151-stable-anginahttps://www.sign.ac.uk/sign-151-stable-anginaKnuuti J et al: 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 41(3):407-77, 202031504439Fihn SD et al: 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 126(25):e354-471, 201223166211Katz D et al: Stable ischemic heart disease. Ann Intern Med. 171(3):ITC17-32, 201931382288Cami E et al: Assessment of lesion-specific ischemia using fractional flow reserve (FFR) profiles derived from coronary computed tomography angiography (FFRCT) and invasive pressure measurements (FFRINV): importance of the site of measurement and implications for patient referral for invasive coronary angiography and percutaneous coronary intervention. J Cardiovasc Comput Tomogr. 12(6):480-92, 201830274795Kueh SH et al: Fractional flow reserve computed tomography in the evaluation of coronary artery disease. Cardiovasc Diagn Ther. 7(5):463-74, 201729255690Fihn SD et al: 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 130(19):1749-67, 201425070666Wolk MJ et al: ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol. 63(4):380-406, 201424355759Neumann FJ et al: 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 40(2):87-165, 201930165437Patel MR et al: ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 appropriate use criteria for coronary revascularization in patients with stable ischemic heart disease: a report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons. J Am Coll Cardiol. 69(17):2212-41, 201728291663Guidelines for coronary angiography. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of diagnostic and therapeutic cardiovascular procedures (subcommittee on coronary angiography). J Am Coll Cardiol. 10(4):935-50, 19873655158Miller TD et al: Noninvasive stress testing for coronary artery disease. Cardiol Clin. 32(3):387-404, 201425091965Shaw LJ et al: Comparative definitions for moderate-severe ischemia in stress nuclear, echocardiography, and magnetic resonance imaging. JACC Cardiovasc Imaging. 7(6):593-604, 201424925328Yang Y et al: A clinical model to identify patients with high-risk coronary artery disease. JACC Cardiovasc Imaging. 8(4):427-34, 201525797120Levine GN et al: 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Thorac Cardiovasc Surg. 152(5):1243-75, 201627751237Bhatt DL et al: Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial. Lancet. 394(10204):1169-80, 201931484629Steg PG et al: Ticagrelor in patients with stable coronary disease and diabetes. N Engl J Med. 381(14):1309-20, 201931475798Grundy SM et al: 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 73(24):3168-209, 201930423391Whelton PK et al: 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 71(6):e13-e115, 201829133356Kones R et al: Stable ischemic heart disease. Cardiol Clin. 32(3):333-51, 201425091962Boden WE et al: Role of short-acting nitroglycerin in the management of ischemic heart disease. Drug Des Devel Ther. 9:4793-805, 201526316714Society of Thoracic Surgeons: STS Short-Term Risk Calculator. STS website. Updated November 15, 2018. Accessed January 20, 2021. https://www.sts.org/resources/risk-calculatorhttps://www.sts.org/resources/risk-calculatorSerruys PW et al: Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 360(10):961-72, 200919228612Hillis LD et al: 2011 ACCF/AHA guideline for coronary artery bypass graft surgery: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 124(23):2610-42, 201122064600Levine GN et al: ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 124:e574-651, 201122064601Sabatine MS et al: Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 372(16):1500-9, 201525773607Robinson JG et al: Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 372(16):1489-99, 201525773378Smith SC Jr et al: AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. J Am Coll Cardiol. 58(23):2432-46, 201122055990Arnett DK et al: 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 74(10):e177-e232, 201930894318Amsterdam EA et al: 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 130(25):e344-426, 201425249585Kumar A et al: Acute coronary syndromes: diagnosis and management, part II. Mayo Clin Proc. 84(11):1021-36, 200919880693Feinberg J et al: Drug-eluting stents versus bare-metal stents for acute coronary syndrome. Cochrane Database Syst Rev. 8:CD012481, 201728832903Kumar A et al: Acute coronary syndromes: diagnosis and management, part I. Mayo Clin Proc. 84(10):917-38, 200919797781Ashley EA et al: Coronary artery disease. In: Cardiology Explained. Remedica; 2004. http://www.ncbi.nlm.nih.gov/books/NBK2216/https://www.ncbi.nlm.nih.gov/books/NBK2216/Arnold SV et al: Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association. Circulation. 141(19):e779-e806, 202032279539Lee SR et al: Meta-analysis of oral anticoagulant monotherapy as an antithrombotic strategy in patients with stable coronary artery disease and nonvalvular atrial fibrillation. Am J Cardiol. 124(6):879-85, 201931311662Ullah W et al: Safety and efficacy of anticoagulant monotherapy in atrial fibrillation and stable coronary artery disease: a systematic review and meta-analysis. Eur J Intern Med. 81:54-9, 202032709546 Lip GYH et al: Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest. 154(5):1121-201, 201830144419Qaseem A et al: Management of stable ischemic heart disease: summary of a clinical practice guideline from the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons. Ann Intern Med. 157(10):735-43, 201223165665National Institute for Health and Care Excellence: Stable Angina: Management. Clinical guideline CG126. NICE website. Published July 2011. Last updated August 2016. Accessed January 20, 2021. https://www.nice.org.uk/guidance/cg126https://www.nice.org.uk/guidance/cg126American College of Cardiology: ASCVD Risk Predictor Plus. ACC website. Accessed January 20, 2021. http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/Goff DC et al: 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 129:S49-73, 201424222018Arnett DK et al: 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 140(11):e596-e646, 201930879355
;