Angina pectoris is a clinical symptom of precordial discomfort or pressure due to transient myocardial ischemia without infarction. Stable angina is angina that is typically precipitated by exertion or psychologic stress and relieved by rest or sublingual nitroglycerin. Diagnosis is by symptoms, electrocardiography, and myocardial imaging. Treatment may include antiplatelet medications, nitrates, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, statins, and coronary angioplasty or coronary artery bypass graft surgery.
Etiology of Stable Angina
Angina pectoris occurs when:
Myocardial oxygen demand exceeds the ability of coronary arteries to supply an adequate amount of oxygenated blood
Such imbalance between supply and demand can occur when the arteries are narrowed. Narrowing usually results from:
Coronary artery atherosclerosis
Narrowing of the coronary arteries can also result from:
Coronary artery embolism (rare)
Acute coronary thrombosis can cause angina if obstruction is partial or transient, but it usually causes acute myocardial infarction (MI).
Because myocardial oxygen demand is determined mainly by heart rate, systolic wall tension, and contractility, narrowing of a coronary artery typically results in angina that occurs during exertion and is relieved by rest.
In addition to exertion, cardiac workload can be increased by disorders such as hypertension, aortic stenosis, aortic regurgitation, or hypertrophic cardiomyopathy. In such cases, angina can occur whether atherosclerosis is present or not. These disorders can also decrease relative myocardial perfusion because increased myocardial mass and stiffness can reduce diastolic flow through the coronary arteries.
A decreased oxygen supply, as in severe anemia or hypoxia, can also precipitate or aggravate angina.
Pathophysiology of Stable Angina
Angina may be:
Stable
Unstable
In stable angina, the relationship between workload or demand and ischemia is usually relatively predictable.
Unstable angina is clinically worsening angina (eg, angina at rest or with increasing frequency and/or intensity of episodes) and is considered an acute coronary syndrome.
Atherosclerotic arterial narrowing is not entirely fixed; it varies with the normal fluctuations in arterial tone that occur in all people. Thus, more people have angina in the morning, when arterial tone is relatively high (1, 2). Also, abnormal endothelial function may contribute to variations in arterial tone; for example, in endothelium damaged by atheromas, stress of a catecholamine surge causes vasoconstriction rather than the normal vasodilatory response (3).
As the myocardium becomes ischemic, coronary sinus blood pH falls, cellular potassium is lost, lactate accumulates, ECG abnormalities appear, and ventricular function (both systolic and diastolic) deteriorates. Left ventricular (LV) diastolic pressure usually increases during angina, sometimes inducing pulmonary congestion and dyspnea. The full mechanism by which ischemia causes discomfort is unclear but may involve afferent nerve fiber stimulation by hypoxic metabolites (4).
Pathophysiology references
1. Willich SN. European survey on circadian variation of angina pectoris (ESCVA): design and preliminary results. J Cardiovasc Pharmacol. 1999;34 Suppl 2:S9-S31. doi:10.1097/00005344-199908002-00003
2. Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57(19):e215-e367. doi:10.1016/j.jacc.2011.02.011
3. Vita JA, Treasure CB, Yeung AC, et al. Patients with evidence of coronary endothelial dysfunction as assessed by acetylcholine infusion demonstrate marked increase in sensitivity to constrictor effects of catecholamines. Circulation. 1992;85(4):1390-1397. doi:10.1161/01.cir.85.4.1390
4. Foreman RD, Garrett KM, Blair RW. Mechanisms of cardiac pain. Compr Physiol. 2015;5(2):929-960. doi:10.1002/cphy.c140032
Symptoms and Signs of Stable Angina
Angina may be a vague, barely troublesome ache or may rapidly become a severe, intense precordial crushing sensation. It is rarely described as "pain." Discomfort is most commonly felt beneath the sternum, although location varies. Discomfort may radiate to the left shoulder and down the inside of the left arm, even to the fingers; straight through to the back; into the throat, jaws, and teeth; and, occasionally, down the inside of the right arm. It may also be felt in the upper abdomen.
Typical angina classically has the following characteristics (1):
Substernal location
Exacerbated by exercise or emotional stress
Relieved by nitroglycerin
"Atypical" symptoms, including bloating, gas, abdominal distress, or burning or tenderness in the back, shoulders, arms, or jaw, may occur in some patients. Patients often ascribe these symptoms to indigestion; belching may even relieve the symptoms. Other patients have dyspnea due to the sharp, reversible increase in LV filling pressure that often accompanies ischemia. Frequently, the patient’s description is imprecise, and whether the problem is angina, dyspnea, or both may be difficult to determine.
Although patients who present with atypical symptoms are generally thought to have a lower likelihood of cardiac ischemia than those with typical symptoms, females with cardiac ischemia do commonly have atypical symptoms such as epigastric symptoms, palpitations, and discomfort in locations other than substernal (1). Furthermore, females with angina are at a higher risk than males for underdiagnosis of cardiac causes. For these reasons, a high index of suspicion for cardiac ischemia should be maintained when females present with atypical symptoms.
Older patients with cardiac ischemia may present with dyspnea, syncope, unexplained falls, or delirium (1).
Because ischemic symptoms require a minute or more to resolve, briefer, fleeting sensations rarely represent angina.
Between and even during attacks of angina, physical findings may be normal. However, during the attack, heart rate may increase modestly, blood pressure (BP) is often elevated, heart sounds become more distant, and the apical impulse is more diffuse. The second heart sound (S2) may become paradoxical because LV ejection is more prolonged during an ischemic attack. A fourth heart sound (S4) is common, and a third heart sound (S3) may develop. A mid or late systolic apical murmur, shrill or blowing—but not especially loud—may occur if ischemia causes localized papillary muscle dysfunction, causing mitral regurgitation.
Stable angina is typically triggered by exertion or strong emotion, usually persists no more than a few minutes, and subsides with rest. Response to exertion is usually predictable, but in some patients, exercise that is tolerated one day may precipitate angina the next because of variations in arterial tone. Symptoms are exaggerated when exertion follows a meal or occurs in cold weather; walking into the wind or first contact with cold air after leaving a warm room may precipitate an attack. Symptom severity is often classified by the degree of exertion resulting in angina (see table ).
Canadian Cardiovascular Society Classification System for Angina Pectoris
Class | Activities Triggering Chest Pain |
|---|---|
1 | Strenuous, rapid, or prolonged exertion |
Not usual physical activities (eg, walking, climbing stairs) | |
2 | Walking rapidly |
Walking uphill | |
Climbing stairs rapidly | |
Walking or climbing stairs after meals | |
Cold | |
Wind | |
Emotional stress | |
3 | Walking, even 1 or 2 blocks at usual pace and on level ground |
Climbing stairs, even 1 flight | |
4 | Any physical activity |
Sometimes occurring at rest | |
Campeau L. The Canadian Cardiovascular Society grading of angina pectoris revisited 30 years later. Can J Cardiol. 2002;18(4):371-379; Ferraro R, Latina JM, Alfaddagh A, et al. Evaluation and Management of Patients With Stable Angina: Beyond the Ischemia Paradigm: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;76(19):2252-2266. doi:10.1016/j.jacc.2020.08.078 | |
Attacks may vary from several a day to symptom-free intervals of weeks, months, or years. Attacks may increase in frequency (called crescendo angina), leading to MI or death. Conversely, attacks may gradually decrease or disappear if adequate collateral coronary circulation develops, the ischemic area infarcts, or heart failure or intermittent claudication supervenes and limits activity.
Nocturnal angina occurs with changes in respiration, pulse rate, and BP sufficient to cause myocardial oxygen supply-demand mismatch. Contributing factors may include normal autonomic changes during sleep (particularly increased sympathetic tone and altered coronary blood flow in rapid eye movement [REM] sleep) and sleep disordered breathing in patients with pre-existing coronary stenosis (2). Nocturnal angina may also be a sign of recurrent LV failure, an equivalent of nocturnal dyspnea. The recumbent position increases venous return, stretching the myocardium and increasing wall stress, which increases oxygen demand.
Angina decubitus is angina that occurs spontaneously when a person is lying down but not necessarily at night. It is usually accompanied by a modestly increased heart rate and a sometimes markedly higher BP, which increase oxygen demand. These increases may be the cause of rest angina or the result of ischemia induced by plaque rupture and thrombus formation. If angina is not relieved, unmet myocardial oxygen demand increases further, making MI more likely. Pericarditis is also in the differential diagnosis for chest pain that worsens in the supine position, particularly if sharp.
Unstable angina
Because angina characteristics are usually predictable for a given patient, any changes (ie, angina at rest, new-onset angina, increasing angina, new nocturnal angina, or new angina decubitus) should be considered serious, especially when the angina is severe (ie, Canadian Cardiovascular Society class 3 or 4). Such changes are termed unstable angina and require prompt evaluation and treatment.
Symptoms and signs references
1. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;144(22):e368-e454. doi:10.1161/CIR.0000000000001029
2. Bonsignore MR, Smirne S, Marrone O, Insalaco G, Salvaggio A, Bonsignore G. Myocardial ischemia during sleep. Sleep Med Rev. 1999;3(3):241-255. doi:10.1016/s1087-0792(99)90005-9
Diagnosis of Stable Angina
History and physical examination
Electrocardiography (ECG)
Stress testing with ECG or imaging (using echocardiography, radionuclide imaging, positron emission tomography [PET], or MRI)
CT angiography or CT fractional flow reserve (CT FFR)
Coronary angiography for significant symptoms, positive stress test, or significant lesions noted on CT FFR
Diagnosis of angina is suspected if chest discomfort is typical, including being precipitated by exertion and relieved by rest, or if symptoms are atypical. Presence in the history of significant risk factors for coronary artery disease (CAD) adds weight to reported symptoms, even if atypical. A high index of suspicion for CAD is maintained when females report atypical (or typical) symptoms.
Patients whose chest discomfort lasts > 20 minutes or occurs during rest or who have syncope or heart failure are evaluated for an acute coronary syndrome.
Chest discomfort may also be caused by gastrointestinal disorders (eg, gastroesophageal reflux, esophageal spasm, indigestion, cholelithiasis), costochondritis, anxiety, panic attacks, hyperventilation, and other cardiac disorders (eg, aortic dissection, pericarditis, mitral valve prolapse, supraventricular tachycardia, atrial fibrillation), even when coronary blood flow is not compromised.
ECG is always performed. More specific tests include stress testing with ECG or with myocardial imaging (eg, echocardiography, radionuclide imaging, PET, MRI), coronary CT angiography, and coronary angiography. Noninvasive tests are considered first.
ECG
If angina is present, especially during exertion, ECG is indicated. Because angina resolves quickly with rest, ECG rarely can be performed during an attack except during stress testing.
ECG is critical in the evaluation of angina to rapidly determine whether patients are experiencing a ST-segment elevation myocardial infarction (STEMI) or a non-STEMI acute coronary syndrome (including unstable angina). ECG can also screen for prior myocardial infarction, arrhythmias, and left ventricular hypertrophy (1).
If performed during an episode of angina, ECG is likely to show reversible ischemic changes:
T wave discordant to the QRS vector
ST-segment depression (typically)
ST-segment elevation
Decreased R-wave height
Intraventricular or bundle branch conduction disturbances
Arrhythmia (usually ventricular extrasystoles)
Between episodes of angina, the ECG may be normal, may show evidence of prior infarction, or may show evidence of ischemia.
A normal ECG does not exclude coronary ischemia as a cause for angina (2).
Stress testing
Stress testing is used to:
Confirm the diagnosis
Evaluate disease severity
Determine appropriate exercise levels for the patient
Help predict prognosis
Exercise stress testing with ECG is performed if a patient has a normal resting ECG and can exercise. Most often it is used in conjunction with additional myocardial imaging. Exercise ECG alone has a sensitivity of approximately 46 to 68% and a specificity of approximately 54 to 77% for obstructive coronary artery disease (1, 3). However, exercise ECG alone can miss severe CAD (even left main or 3-vessel disease). False-positive test results occur, but some of these may represent true ischemic changes caused by microvascular disease (4).
Stress testing with myocardial imaging is usually performed when the resting ECG is abnormal because false-positive ST-segment shifts are common on the stress ECG. Exercise or pharmacologic stress (eg, with dobutamine or dipyridamole infusion) may be used depending on the patient's ability to exercise. Imaging options include stress echocardiography (sensitivity for obstructive CAD of 80 to 89% and specificity of 72 to 89%), myocardial perfusion imaging with single-photon emission CT (SPECT) (sensitivity of 83 to 90% and specificity of 63 to 76%), or PET, and stress MRI (1).
The choice of imaging technique depends on institutional availability and expertise. Exercise ECG remains widely available and inexpensive. Stress imaging can help assess LV function and response to stress; identify areas of ischemia, infarction, and viable tissue; and determine the site and extent of myocardium at risk. Stress echocardiography can also detect ischemia-induced mitral regurgitation.
If the clinical or working diagnosis is unstable angina, early stress testing is contraindicated, except in certain low-risk patients (5, 6).
Noninvasive imaging of the coronary arteries
Coronary CT angiography (CCTA) can accurately identify coronary stenosis and has a number of advantages (1). CCTA is noninvasive, and in patients presenting with stable angina, it can exclude coronary stenosis with high accuracy (sensitivity of 93 to 99% and specificity of 67 to 86%) (1). Noninvasive estimation of the fractional flow reserve (FFR, the ratio of maximal flow through the stenotic area to normal maximal flow) across significant lesions and estimation of lesion-specific ischemia are also possible (2, 7). In addition, CCTA can establish existing stent or bypass graft patency, can show cardiac and coronary venous anatomy, and can assess calcified and noncalcified plaque burden. However, radiation exposure is greater than with other modalities, and CT angiography must be used judiciously in patients with a heart rate of > 65 beats/minute, those with irregular heart beats, those with impaired kidney function, and pregnant patients. Patients must also be able to hold their breath for 15 to 20 seconds, 3 to 4 times during the study.
CCTA is suggested by some as an initial diagnostic test of choice, along with echocardiography, for patients with stable angina, in particular patients younger than 65 years of age with a intermediate or high probability of obstructive CAD (8, 9). It can help categorize patients into those with obstructive and those with nonobstructive disease for further diagnosis and treatment.
Other indications for CCTA include:
Patients who are asymptomatic but at high risk (10)
Patients with atypical or typical angina who have inconclusive exercise stress test results, cannot undergo exercise stress testing, or need to undergo major noncardiac surgery
Patients in whom invasive coronary angiography was unable to locate a major coronary artery or graft
Coronary calcium scoring, obtained via a noncontrast CT scan, can detect the amount of calcium present in coronary artery plaque. The calcium score is roughly proportional to the risk of subsequent coronary events. Coronary calcium scoring is primarily used in screening asymptomatic patients (11), in conjunction with existing risk estimation tools such as PREVENT.
Cardiac magnetic resonance imaging (MRI) is valuable in evaluating many cardiac and great vessel abnormalities. It may be used to evaluate CAD by several techniques, which enable direct visualization of coronary stenosis, assessment of flow in the coronary arteries, evaluation of myocardial perfusion and metabolism, evaluation of wall motion abnormalities during stress, and assessment of infarcted myocardium vs viable myocardium.
Indications for cardiac MRI include evaluation of cardiac structure and function and assessment of myocardial viability. Cardiac MRI, specifically stress perfusion MRI and quantitative myocardial blood flow analysis, may also be indicated for diagnosis and risk assessment in patients with either known CAD or an intermediate to high likelihood of having CAD (10). Stress perfusion MRI has a reported sensitivity of approximately 89% and specificity of approximately 84% for flow-limiting coronary stenosis.
Coronary angiography
Coronary angiography is the gold standard for diagnosing coronary artery disease but is not always necessary to confirm the diagnosis. It is indicated primarily to locate and assess severity of coronary artery lesions when revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) is being considered. Angiography may also be indicated when knowledge of coronary anatomy is necessary to advise about work or lifestyle needs (eg, discontinuing job or sports activities). Although angiographic findings do not directly show hemodynamic significance of coronary lesions, guidewires with pressure or flow sensors can be used to estimate blood flow across stenoses. Blood flow is expressed as fractional flow reserve (FFR, the ratio of maximal flow through the stenotic area to normal maximal flow). If FFR or similar measurements are not available, obstruction is assumed to be physiologically significant when the luminal diameter is reduced > 70%. Angina does not usually develop when the diameter reduction is < 70% unless spasm or thrombosis is present (12).
Intravascular ultrasound (IVUS) provides images of coronary artery structure. An ultrasound probe on the tip of a catheter is inserted in the coronary arteries during angiography. Optical coherence tomography (OCT) is another imaging modality that can be used during coronary angiography that uses near-infrared light to provide high-resolution cross-sectional images of the coronary arteries, which are higher in resolution than with IVUS. Both IVUS and OCT are used to guide stent placement during percutaneous coronary intervention; IVUS is also used to evaluate the extent and significance of some left coronary artery stenoses (6).
Diagnosis references
1. Joshi PH, de Lemos JA. Diagnosis and Management of Stable Angina: A Review. JAMA. 2021;325(17):1765-1778. doi:10.1001/jama.2021.1527
2. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;144(22):e368-e454. doi:10.1161/CIR.0000000000001029
3. Fletcher GF, Ades PA, Kligfield P, et al. Exercise standards for testing and training: a scientific statement from the American Heart Association. Circulation. 2013;128(8):873-934. doi:10.1161/CIR.0b013e31829b5b44
4. Sinha A, Dutta U, Demir OM, et al. Rethinking False Positive Exercise Electrocardiographic Stress Tests by Assessing Coronary Microvascular Function. J Am Coll Cardiol. 2024;83(2):291-299. doi:10.1016/j.jacc.2023.10.034
5. Bhatt DL, Lopes RD, Harrington RA. Diagnosis and Treatment of Acute Coronary Syndromes: A Review. JAMA. 2022;327(7):662-675. doi:10.1001/jama.2022.0358
6. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
7. Slipczuk L, Blankstein R, Bucciarelli-Ducci C, et al. State of the Art: Evaluation and Medical Management of Nonobstructive Coronary Artery Disease in Patients With Chest Pain: A Scientific Statement From the American Heart Association. Circulation. 2025;152(23):e443-e466. doi:10.1161/CIR.0000000000001394
8. Montone RA, Rinaldi R, Niccoli G, et al. Optimizing Management of Stable Angina: A Patient-Centered Approach Integrating Revascularization, Medical Therapy, and Lifestyle Interventions. J Am Coll Cardiol. 2024;84(8):744-760. doi:10.1016/j.jacc.2024.06.015
9. van der Bijl P, Gulati M, Saraste A, et al. Contemporary, non-invasive imaging diagnosis of chronic coronary artery disease. Lancet. 2025;406(10519):2577-2587. doi:10.1016/S0140-6736(25)01586-7
10. Expert Panel on Cardiac Imaging, Litmanovich D, Hurwitz Koweek LM, et al. ACR Appropriateness Criteria® Chronic Chest Pain-High Probability of Coronary Artery Disease: 2021 Update. J Am Coll Radiol. 2022;19(5S):S1-S18. doi:10.1016/j.jacr.2022.02.021
11. Greenland P, Lloyd-Jones DM. Role of Coronary Artery Calcium Testing for Risk Assessment in Primary Prevention of Atherosclerotic Cardiovascular Disease: A Review. JAMA Cardiol. 2022;7(2):219-224. doi:10.1001/jamacardio.2021.3948
12. Patel MR, Calhoon JH, Dehmer GJ, 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. 2017;69(17):2212-2241. doi:10.1016/j.jacc.2017.02.001
Treatment of Stable Angina
Acute symptom management with nitroglycerin
Modification of risk factors
Lipid management and antiplatelet therapy (aspirin and sometimes clopidogrel, prasugrel, or ticagrelor)
Beta-blockers
Sometimes long-acting nitroglycerin and calcium channel blockers for symptom control
Often angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs)
Lipid-lowering agents
Revascularization if symptoms persist despite medical therapy
This discussion of treatment focuses on patients with stable angina due to chronic obstructive coronary disease. Patients with ischemia and nonobstructed coronary arteries (INOCA), including patients with microvascular angina and vasospastic angina, are discussed elsewhere (1).
Acute symptom management
To relieve symptoms during an acute attack, sublingual nitroglycerin is the most effective medication (2, 3). Nitroglycerin is a potent smooth-muscle relaxant and vasodilator. Its main sites of action are in the peripheral vascular tree, especially in the venous or capacitance system, and in coronary blood vessels. Even severely atherosclerotic vessels may dilate in areas without atheroma. Nitroglycerin lowers systolic BP and dilates systemic veins, thus reducing myocardial wall tension, a major determinant of myocardial oxygen need. Sublingual nitroglycerin is given for an acute attack or for prevention before exertion. Dramatic relief usually occurs within 1.5 to 3 minutes, is complete by about 5 minutes, and lasts up to 30 minutes. The dose may be repeated every 4 to 5 minutes up to 3 times if relief is incomplete. Patients should always carry nitroglycerin tablets or aerosol spray to use promptly at the onset of an angina attack. Patients should store tablets in a tightly sealed, light-resistant glass container, so that potency is not lost. Because the medication deteriorates quickly, small amounts should be obtained frequently.
Risk modification
Reversible risk factors are modified as much as possible. People who smoke tobacco should stop smoking; smoking cessation provides important short- and long-term benefits, including a 36% reduction in all-cause mortality after at least 2 years (3, 4). Weight loss alone often reduces the severity of angina. Guideline-based nutrition and physical activity recommendations should be followed. An exercise program emphasizing walking often improves the sense of well-being, reduces the risk of acute ischemic events, and improves exercise tolerance. Mental health care should be sought when appropriate, particularly for depression and anxiety.
Hypertension (BP > 130/80 for patients with CAD) and elevated blood pressure (systolic BP 120 to 129) are treated diligently because even mild hypertension increases cardiac workload (3). Aggressive reduction of total cholesterol and low-density lipoprotein (LDL) cholesterol (via diet plus statins) slows the progression of CAD, may cause some lesions to regress, and improves endothelial function and thus arterial response to stress. High-intensity statin therapy, when tolerated, is recommended, with ezetimibe, a PSCK9 inhibitor, or other agents as useful adjuncts or alternatives (2, 3). Patients with heart failure and stable angina should be treated per guidelines (5), including receiving a sodium-glucose-cotransporter-2 (SGLT2) inhibitor; patients with type 2 diabetes should receive an SGLT2 inhibitor or a glucagon-like-peptide-1 (GLP-1) receptor agonist.
Antiplatelet agents inhibit platelet aggregation. Aspirin binds irreversibly to platelets and inhibits cyclooxygenase and platelet aggregation. Low-dose aspirin is recommended for all patients with stable angina and chronic coronary artery disease (2, 3). Dual-antiplatelet therapy is used after percutaneous coronary intervention (for stable disease, or after acute coronary syndrome in previously stable disease), with aspirin and a P2Y12 inhibitor (eg, clopidogrel, prasugrel, ticagrelor) usually for 12 months. Patients unable to tolerate one agent should receive the other alone.
Influenza, COVID-19, and pneumococcal vaccination are recommended in patients with chronic coronary artery disease (3).
Colchicine may also be used for secondary prevention in patients with chronic coronary artery disease (3).
Medications for stable angina
In addition to reducing the risk of future events, the main goals of angina treatment are to:
Relieve symptoms
Prevent or reduce ischemia
(See also table .)
To prevent ischemia, several classes of medications are used:
Beta-blockers: Most patients, unless contraindicated or not tolerated
Long-acting nitrates: If needed
Calcium channel blockers: If needed
Beta-blockers are a first-line therapy for patients with stable angina and left ventricular ejection fraction (LVEF) ≤ 50% or previous myocardial infarction; they reduce the risk of death or major adverse cardiovascular event (3). Beta-blockers block sympathetic stimulation of the heart and reduce systolic BP, heart rate, contractility, and cardiac output, thus decreasing myocardial oxygen demand and increasing exercise tolerance. Beta-blockers also increase the threshold for ventricular fibrillation. Most patients tolerate these agents well. Many beta-blockers are available and effective. Dose is titrated upward as needed until limited by bradycardia or adverse effects. Beta-blockers, other than labetalol and carvedilol (6), which also have alpha blocking activity, should not be used in patients with vasospastic angina because they may cause coronary vasospasm from unopposed alpha-receptor activity (1).
Patients who are at risk of beta-blocker intolerance (eg, those with asthma) may be tried on a cardioselective beta-blocker (eg, bisoprolol) perhaps with pulmonary function testing before and after medication administration to detect drug-induced bronchospasm. Patients who cannot tolerate beta-blockers are given a non-dihydropyridine calcium channel blocker (eg, diltiazem, verapamil), which has negative chronotropic effects and reduces myocardial oxygen demand (3). Non-dihydropyridine calcium channel blockers can be used alone in patients with beta-blocker intolerance or asthma and normal left ventricular systolic function but may increase cardiovascular mortality in patients with left ventricular systolic dysfunction.
Long-acting nitrates (oral or transdermal) are used if symptoms persist after the beta-blocker dose is maximized, or as a therapy for symptomatic stable angina if a beta-blocker is not indicated or tolerated (3). If angina occurs at predictable times, a nitrate is given to cover those times. Oral nitrates include isosorbide dinitrate and isosorbide mononitrate (the active metabolite of the dinitrate). They are effective within 1 to 2 hours; their effect lasts 4 to 6 hours. Sustained-release formulations of isosorbide mononitrate appear to be effective throughout the day. For transdermal use, cutaneous nitroglycerin patches have largely replaced nitroglycerin ointments, primarily because ointments are inconvenient and messy. Patches slowly release the medication for a prolonged effect; exercise capacity improves 4 hours after patch application and wanes in 18 to 24 hours. Nitrate tolerance may occur, especially when plasma concentrations are kept constant. Because risk of myocardial infarction is highest in early morning, an afternoon or early evening respite period from nitrates is reasonable unless a patient commonly has angina at that time. For nitroglycerin, an 8- to 10-hour respite period seems sufficient. Isosorbide dinitrate requires a 12-hour respite period to minimize the risk of tolerance. If given once a day, sustained-release isosorbide mononitrate does not appear to elicit tolerance.
Dihydropyridine calcium channel blockers may be used if symptoms persist despite use of nitrates or if nitrates are not tolerated (2, 3). Calcium channel blockers are particularly useful if hypertension or coronary spasm is also present. Different types of calcium channel blockers have different effects. Dihydropyridine calcium channel blockers (eg, nifedipine, amlodipine, felodipine) have no chronotropic effects and vary substantially in their negative inotropic effects. Shorter-acting dihydropyridines, particularly nifedipine (7), may cause acute hypotension and reflex tachycardia and are associated with increased mortality in patients with CAD; they should not be used alone to treat stable angina. Longer-acting formulations of dihydropyridines have fewer tachycardic effects; they are most commonly used with a beta-blocker. Among longer-acting dihydropyridines, amlodipine has the weakest negative inotropic effects; it may be used in patients with left ventricular systolic dysfunction (8).
Ranolazine is a sodium channel blocker that can be used to treat chronic angina in patients whose symptoms persist despite beta-blockers, long-acting nitrates, or calcium channel blockers (3). Because ranolazine may cause QT interval prolongation, it is usually reserved for patients in whom symptoms persist despite optimal treatment with other antianginal agents. Dizziness, headache, constipation, and nausea may occur (2).
Ivabradine is a sinus node inhibitor that inhibits inward sodium/potassium current in a certain gated channel (funny or "f" channel) in sinus node cells, thus slowing heart rate without decreasing contractility. It can be used for symptomatic treatment of chronic stable angina in patients with normal sinus rhythm at 70 beats per minute or greater who cannot take beta-blockers (1) or other anti-anginal therapy. However, it may be harmful in combination with standard therapy (3).
ACE inhibitors, ARBs, or an angiotensin receptor/neprilysin inhibitor are given as indicated for patients with concomitant heart failure, chronic kidney disease, hypertension, or diabetes.
Lipid-lowering agents (statins and others) are generally recommended for all patient with chronic coronary disease (3).
Revascularization
Revascularization, either with PCI (eg, angioplasty and stent placement) or CABG, should be considered if angina persists despite pharmacologic therapy and worsens quality of life or if anatomic lesions (noted during angiography) put a patient at high risk of mortality (3). The choice between PCI and CABG depends on the extent and location of anatomic lesions, the experience of the operator and medical center, and, to some extent, patient preference (9).
PCI is usually preferred for 1- or 2-vessel disease with suitable anatomic lesions and is sometimes used for 3-vessel disease with suitable anatomy. As stent technology improves, PCI is being used for more complicated lesions (eg, lesions that are long or near bifurcation points). PCI can also be used for left main coronary artery disease (LMCA) in the appropriate clinical setting (10, 11, 12, 13). FFR is used to clarify the hemodynamic significance of coronary stenoses when they are equivocal, or in patients who have not had prior evaluation for ischemia, including stress testing (3).
CABG is very effective in selected patients with angina. CABG is superior to PCI in patients with diabetes and multivessel disease, and in some other patients with diffuse, complex multivessel disease that is amenable to grafting (3, 14, 15, 16, 17, 18).
CABG improves survival for patients with left main disease, those with 3-vessel disease and poor left ventricular function, and some patients with 2-vessel disease (18). However, for patients with mild or moderate angina () or 3-vessel disease and good ventricular function, CABG appears to only marginally improve survival. Several studies show better long-term outcomes following CABG than with PCI for patients with diabetes and proximal left anterior descending disease (18). For patients with 1-vessel disease, outcomes with pharmacologic therapy, PCI, and CABG are similar; exceptions are left main disease and proximal left anterior descending disease, for which revascularization (either by PCI or CABG) appears advantageous.
Treatment references
1. Montone RA, Rinaldi R, Niccoli G, et al. Optimizing Management of Stable Angina: A Patient-Centered Approach Integrating Revascularization, Medical Therapy, and Lifestyle Interventions. J Am Coll Cardiol. 2024;84(8):744-760. doi:10.1016/j.jacc.2024.06.015
2. Joshi PH, de Lemos JA. Diagnosis and Management of Stable Angina: A Review. JAMA. 2021;325(17):1765-1778. doi:10.1001/jama.2021.1527
3. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023;148(9):e9-e119. doi:10.1161/CIR.0000000000001168
4. Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: a systematic review. JAMA. 2003;290(1):86-97. doi:10.1001/jama.290.1.86
5. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063
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9. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the ACC/AHA Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(2):e21–e129. doi: 10.1016/j.jacc.2021.09.006
10. Nerlekar N, Ha FJ, Verma KP, et al. Percutaneous Coronary Intervention Using Drug-Eluting Stents Versus Coronary Artery Bypass Grafting for Unprotected Left Main Coronary Artery Stenosis: A Meta-Analysis of Randomized Trials. Circ Cardiovasc Interv. 2016;9(12):e004729. doi:10.1161/CIRCINTERVENTIONS.116.004729
11. Stone GW, Sabik JF, Serruys PW, et al. Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease [published correction appears in N Engl J Med. 2019 Oct 31;381(18):1789]. N Engl J Med. 2016;375(23):2223-2235. doi:10.1056/NEJMoa1610227
12. Stone GW, Kappetein AP, Sabik JF, et al. Five-Year Outcomes after PCI or CABG for Left Main Coronary Disease [published correction appears in N Engl J Med. 2020 Mar 12;382(11):1078]. N Engl J Med. 2019;381(19):1820-1830. doi:10.1056/NEJMoa1909406
13. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367(25):2375–2384. doi:10.1056/NEJMoa1211585
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15. BARI 2D Study Group, Frye RL, August P, et al. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009;360(24):2503-2515. doi:10.1056/NEJMoa0805796
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Prognosis for Stable Angina
The main adverse outcomes of stable angina pectoris are the development of unstable angina, myocardial infarction, or sudden death due to arrhythmias. The annual risk of death or myocardial infarction is approximately 3 to 4% in patients with stable angina receiving medical therapy, no history of MI, a normal resting ECG, and normal BP (1). Factors associated with an increased mortality risk include poor exercise capacity, more severe angina, impaired glucose tolerance or diabetes, decreased glomerular filtration rate, and in males, sexual problems (1, 2).
Prognosis also worsens with increasing age, increasingly severe anginal symptoms, presence of anatomic lesions, and poor ventricular function (3). Lesions in the left main coronary artery or proximal left anterior descending artery indicate particularly high risk. Although prognosis correlates with number and severity of coronary arteries affected, prognosis is surprisingly good for patients with stable angina, even those with 3-vessel disease, if ventricular function is normal.
Prognosis references
1. Joshi PH, de Lemos JA. Diagnosis and Management of Stable Angina: A Review. JAMA. 2021;325(17):1765-1778. doi:10.1001/jama.2021.1527
2. Kahan T, Forslund L, Held C, et al. Risk prediction in stable angina pectoris. Eur J Clin Invest. 2013;43(2):141-151. doi:10.1111/eci.12025
3. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2023 Sep 26;148(13):e148] [published correction appears in Circulation. 2023 Dec 5;148(23):e186]. Circulation. 2023;148(9):e9-e119. doi:10.1161/CIR.0000000000001168
Key Points
Angina pectoris occurs when cardiac workload exceeds the ability of coronary arteries to supply an adequate amount of oxygenated blood.
Symptoms of stable angina pectoris range from a vague, barely troublesome ache to a severe, intense precordial crushing sensation; they are typically precipitated by exertion, last no more than a few minutes, and subside with rest.
Testing for diagnosis and risk stratification includes electrocardiography, coronary CT angiography, and stress testing.
Give nitroglycerin for immediate relief of angina.
Maintain patients on an antiplatelet agent, a beta-blocker, and a statin, and add a calcium channel blocker for further symptom prevention if needed.
Consider revascularization if significant angina persists despite pharmacologic therapy or if lesions noted during angiography indicate high risk of mortality.
Do coronary angiography when revascularization (percutaneous intervention or coronary artery bypass grafting) is being considered.
Initiate ongoing risk modification in all patients with stable angina, including smoking cessation, blood pressure control, weight control, glycemic control, exercise, and use of statins and antiplatelet agents.
Drug Information for the Topic
