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Angina Pectoris

by James Wayne Warnica, MD

Angina pectoris is a clinical syndrome of precordial discomfort or pressure due to transient myocardial ischemia without infarction. It is typically precipitated by exertion or psychologic stress and relieved by rest or sublingual nitroglycerin. Diagnosis is by symptoms, ECG, and myocardial imaging. Treatment may include aspirin, nitrates, β-blockers, Ca channel blockers, ACE inhibitors, statins, and coronary angioplasty or coronary artery bypass graft surgery.


Angina pectoris occurs when cardiac workload and resultant myocardial O 2 demand exceed the ability of coronary arteries to supply an adequate amount of oxygenated blood, as can occur when the arteries are narrowed. Narrowing usually results from atherosclerosis but may result from coronary artery spasm or, rarely, coronary artery embolism. Acute coronary thrombosis can cause angina if obstruction is partial or transient, but it usually causes MI.

Because myocardial O 2 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 result whether atherosclerosis is present or not. These disorders can also decrease relative myocardial perfusion because myocardial mass is increased (causing decreased diastolic flow).

A decreased O 2 supply, as in severe anemia or hypoxia, can precipitate or aggravate angina.


In stable angina, the relationship between workload or demand and ischemia is usually relatively predictable. However, 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. Also, abnormal endothelial function may contribute to variations in arterial tone; eg, in endothelium damaged by atheromas, stress of a catecholamine surge causes vasoconstriction rather than dilation (normal response).

As the myocardium becomes ischemic, coronary sinus blood pH falls, cellular K 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 exact mechanism by which ischemia causes discomfort is unclear but may involve nerve stimulation by hypoxic metabolites.

Symptoms and Signs

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. The discomfort of angina is never above the ears or below the umbilicus.

Some patients have atypical angina (eg, bloating, gas, abdominal distress), often ascribing symptoms to indigestion; belching may even seem to relieve the symptoms. Others 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. Because ischemic symptoms require a minute or more to resolve, brief, 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, BP is often elevated, heart sounds become more distant, and the apical impulse is more diffuse. The 2nd heart sound may become paradoxical because LV ejection is more prolonged during an ischemic attack. A 4th heart sound is common, and a 3rd heart sound 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.

Angina pectoris 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 ( Canadian Cardiovascular Society Classification System of Angina Pectoris).

Canadian Cardiovascular Society Classification System of Angina Pectoris


Activities Triggering Chest Pain


Strenuous, rapid, or prolonged exertion

Not usual physical activities (eg, walking, climbing stairs)


Walking rapidly

Walking uphill

Climbing stairs rapidly

Walking or climbing stairs after meals



Emotional stress


Walking, even 1 or 2 blocks at usual pace and on level ground

Climbing stairs, even 1 flight


Any physical activity

Sometimes occurring at rest

Adapted from Braunwald E, Antman EM, Beasley JW, et al: ACC/AHA Guidelines for the management of patients with unstable angina and non-ST segment elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the management of patients with unstable angina). Journal of American College of Cardiology 36:970–1062, 2000.

Attacks may vary from several a day to symptom-free intervals of weeks, months, or years. They may increase in frequency (called crescendo angina) to a fatal outcome or gradually decrease or disappear if adequate collateral coronary circulation develops, if the ischemic area infarcts, or if heart failure or intermittent claudication supervenes and limits activity.

Nocturnal angina may occur if a dream causes striking changes in respiration, pulse rate, and BP. 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 O 2 demand.

Angina may occur spontaneously during rest (called angina decubitus). It is usually accompanied by a modestly increased heart rate and a sometimes markedly higher BP, which increase O 2 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 O 2 demand increases further, making MI more likely.

Unstable angina

Because angina characteristics are usually predictable for a given patient, any changes (ie, rest angina, new-onset angina, increasing angina) should be considered serious, especially when the angina is severe (ie, Canadian Cardiovascular Society class 3). Such changes are termed unstable angina and require prompt evaluation and treatment.

Unstable angina is classified based on severity and clinical situation ( Braunwald Classification of Unstable Angina*). Also considered are whether unstable angina occurs during treatment for chronic stable angina and whether transient changes in ST-T waves occur during angina. If angina has occurred within 48 h and no contributory extracardiac condition is present, troponin levels may be measured to help estimate prognosis; troponin-negative indicates a better prognosis than troponin-positive.

Braunwald Classification of Unstable Angina*






New onset of severe angina or increasing angina

No angina during rest


Angina during rest within past month but not within preceding 48 h

Subacute angina at rest


Angina during rest within 48 h

Acute angina at rest

Clinical situation


Develops secondary to an extracardiac condition that worsens myocardial ischemia

Secondary UA


Develops when no contributory extracardiac condition is present

Primary UA


Develops within 2 wk of acute MI

Post-MI UA

*Basic classification consists of a Roman numeral and a letter.

Angina occurs more frequently, is more severe, lasts longer, or is triggered by less exertion.

For patients with class IIIB, troponin status (negative or positive) is determined to estimate prognosis.

UA = unstable angina.

Adapted from Hamm CW, Braunwald E: APACHE II: A classification of unstable angina revisited. Circulation 102:118–122, 2000.


  • Typical symptoms

  • ECG

  • Stress testing with ECG or imaging (echocardiographic or nuclear)

  • Coronary angiography for significant symptoms or positive stress test

Diagnosis is suspected if chest discomfort is typical and is precipitated by exertion and relieved by rest. Presence of significant risk factors for coronary artery disease (CAD) in the history adds weight to reported symptoms. Patients whose chest discomfort lasts > 20 min or occurs during rest or who have syncope or heart failure are evaluated for an acute coronary syndrome (see Acute Coronary Syndromes (ACS)). Chest discomfort may also be caused by GI disorders (eg, reflux, esophageal spasm, indigestion, cholelithiasis), costochondritis, anxiety, panic attacks, hyperventilation, and other cardiac disorders (eg, pericarditis, mitral valve prolapse, supraventricular tachycardia, atrial fibrillation), even when coronary blood flow is not compromised (see Chest Pain).


If typical exertional symptoms are present, ECG is indicated. Because angina resolves quickly with rest, ECG rarely can be done during an attack except during stress testing. If done during an attack, 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, and arrhythmia (usually ventricular extrasystoles). Between attacks, the ECG (and usually LV function) at rest is normal in about 30% of patients with a typical history of angina pectoris, even those with extensive 3-vessel disease. In the remaining 70%, the ECG shows evidence of previous infarction, hypertrophy, or nonspecific ST-segment and T-wave (ST-T) abnormalities. An abnormal resting ECG alone does not establish or refute the diagnosis.

Stress testing

More specific tests include stress testing with ECG or with myocardial imaging (eg, echocardiography, radionuclide imaging, MRI) and coronary angiography. Further testing is needed to confirm the diagnosis, evaluate disease severity, determine appropriate exercise levels for the patient, and help predict prognosis. If the clinical or working diagnosis is unstable angina, early stress testing is contraindicated.

Noninvasive tests are considered first. For CAD, the most accurate tests are stress echocardiography and myocardial perfusion imaging with single-photon emission CT (SPECT) or PET. However, these tests are more expensive than simple stress testing with ECG.

If a patient has a normal resting ECG and can exercise, exercise stress testing with ECG is done. In men with chest discomfort suggesting angina, stress ECG testing has a specificity of 70%; sensitivity is 90%. Sensitivity is similar in women, but specificity is lower, particularly in women < 55 (< 70%). However, women are more likely than men to have an abnormal resting ECG when CAD is present (32% vs 23%). Although sensitivity is reasonably high, exercise ECG can miss severe CAD (even left main or 3-vessel disease). In patients with atypical symptoms, a negative stress ECG usually rules out angina pectoris and CAD; a positive result may or may not represent coronary ischemia and indicates need for further testing.

When the resting ECG is abnormal, false-positive ST-segment shifts are common on the stress ECG, so patients should have stress testing with myocardial imaging. Exercise or pharmacologic stress (eg, with dobutamine or dipyridamole infusion) may be used. The choice of imaging technique depends on institutional availability and expertise. Imaging tests 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.


Coronary angiography (see also Angiography) is the standard for diagnosing CAD 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 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, obstruction is assumed to be physiologically significant when the luminal diameter is reduced > 70%. This reduction correlates well with the presence of angina pectoris unless spasm or thrombosis is superimposed.

Intravascular ultrasonography provides images of coronary artery structure. An ultrasound probe on the tip of a catheter is inserted in the coronary arteries during angiography. This test can provide more information about coronary anatomy than other tests; it is indicated when the nature of lesions is unclear or when apparent disease severity does not match symptom severity. Used with angioplasty, it can help ensure optimal placement of stents.

Guidewires with pressure or flow sensors can be used to estimate blood flow across stenoses. Blood flow is expressed as fractional flow reserve (FFR), which is the ratio of maximal flow through the stenotic area to normal maximal flow. These flow measurements are most useful when evaluating the need for angioplasty or CABG in patients with lesions of questionable severity (40 to 70% stenosis). An FFR of 1.0 is considered normal, while an FFR < 0.75 to 0.8 is associated with myocardial ischemia. Lesions with an FFR > 0.8 are less likely to benefit from stent placement.


Electron beam CT can detect the amount of Ca present in coronary artery plaque. The Ca score (from 1 to 100) is roughly proportional to the risk of subsequent coronary events. However, because Ca may be present in the absence of significant stenosis, the score does not correlate well with the need for angioplasty or CABG. Thus, the American Heart Association recommends that screening with electron beam CT should be done only for select groups of patients and is most valuable when combined with historical and clinical data to estimate risk of death or nonfatal MI. These groups may include asymptomatic patients with an intermediate Framingham 10-yr risk estimate of 10 to 20% and symptomatic patients with equivocal stress test results. It is particularly useful in ruling out significant CAD in patients presenting to the emergency department with atypical symptoms, normal troponin levels, and a low probability of hemodynamically significant coronary disease. These patients may have noninvasive testing as outpatients.

Multidetector row CT (MDRC T) coronary angiography can accurately identify coronary stenosis and has a number of advantages. The test is noninvasive, can exclude coronary stenosis with high accuracy, can establish stent or bypass graft patency, can visualize cardiac and coronary venous anatomy, and can assess calcified and noncalcified plaque burden. However, radiation exposure is significant, and the test is not suitable for patients with a heart rate of > 65 beats/min, those with irregular heart beats, and pregnant women. Patients must also be able to hold their breath for 15 to 20 sec, 3 to 4 times during the study.

Evolving indications for MDRCT coronary angiography include

  • Asymptomatic high-risk patients or 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

Cardiac MRI has become invaluable 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.

Current indications for cardiac MRI include evaluation of cardiac structure and function, assessment of myocardial viability, and possibly diagnosis and risk assessment of patients with either known or suspected CAD.


The main adverse outcomes are unstable angina, MI, and sudden death due to arrhythmias. Annual mortality rate is about 1.4% in patients with angina, no history of MI, a normal resting ECG, and normal BP. However, women with CAD tend to have a worse prognosis. Mortality rate is about 7.5% when systolic hypertension is present, 8.4% when the ECG is abnormal, and 12% when both are present. Type 2 diabetes about doubles the mortality rate for each scenario.

Prognosis worsens with increasing age, increasingly severe anginal symptoms, presence of anatomic lesions, and poor ventricular function. 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.


  • Modification of risk factors (smoking, BP, lipids)

  • Antiplatelet drugs (aspirin and/or clopidogrel or ticagrelor)

  • β-Blockers

  • Nitroglycerin and Ca channel blockers for symptom control

  • Revascularization if symptoms persist despite medical therapy

  • ACE inhibitors and statins

Reversible risk factors are modified as much as possible (see also Atherosclerosis : Treatment). Smokers should stop smoking; 2 yr after stopping smoking, risk of MI is reduced to that of people who never smoked. Hypertension is treated diligently because even mild hypertension increases cardiac workload. Weight loss alone often reduces the severity of angina. Sometimes treatment of mild LV failure markedly lessens angina. Paradoxically, digitalis occasionally intensifies angina, presumably because increased myocardial contractility increases O 2 demand, arterial tone is increased, or both. Aggressive reduction of total and LDL cholesterol (via diet plus drugs as necessary) slows the progression of CAD, may cause some lesions to regress (see Dyslipidemia : Treatment), and improves endothelial function and thus arterial response to stress. An exercise program emphasizing walking often improves the sense of well-being, reduces risk of acute ischemic events, and improves exercise tolerance.


The main goals are to relieve acute symptoms, prevent or reduce ischemia ( Drugs for Coronary Artery Disease), and prevent future ischemic events. For an acute attack, sublingual nitroglycerin is the most effective drug.

To prevent ischemia, all patients diagnosed with CAD or at high risk of developing CAD should take an antiplatelet drug daily. β-Blockers, unless contraindicated or not tolerated, are given to most patients. For some patients, prevention of symptoms requires Ca channel blockers or long-acting nitrates.

Antiplatelet drugs inhibit platelet aggregation. Aspirin binds irreversibly to platelets and inhibits cyclooxygenase and platelet aggregation. Clopidogrel blocks adenosine diphosphate–induced platelet aggregation. Either drug can reduce risk of ischemic events (MI, sudden death), but the drugs are most effective when given together. Patients unable to tolerate one should receive the other drug alone.

β-Blockers limit symptoms and prevent infarction and sudden death better than other drugs. β-Blockers block sympathetic stimulation of the heart and reduce systolic BP, heart rate, contractility, and cardiac output, thus decreasing myocardial O 2 demand and increasing exercise tolerance. They also increase the threshold for ventricular fibrillation. Most patients tolerate these drugs well. Many β-blockers are available and effective. Dose is titrated upward as needed until limited by bradycardia or adverse effects. Patients who cannot tolerate β-blockers are given a Ca channel blocker with negative chronotropic effects (eg, diltiazem, verapamil). Those at risk of β-blocker intolerance (eg, those with asthma) may be tried on a cardioselective β-blocker (eg, bisoprolol) perhaps with pulmonary function testing before and after drug administration to detect drug-induced bronchospasm.

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 O 2 need. Sublingual nitroglycerin is given for an acute attack or for prevention before exertion. Dramatic relief usually occurs within 1.5 to 3 min, is complete by about 5 min, and lasts up to 30 min. The dose may be repeated every 4 to 5 min 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 drug deteriorates quickly, small amounts should be obtained frequently.

Long-acting nitrates (oral or transdermal) are used if symptoms persist after the β-blocker dose is maximized. If angina occurs at predictable times, a nitrate is given to cover those times. Oral nitrates include isosorbide dinitrate and mononitrate (the active metabolite of the dinitrate). They are effective within 1 to 2 h; their effect lasts 4 to 6 h. 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 drug for a prolonged effect; exercise capacity improves 4 h after patch application and wanes in 18 to 24 h. Nitrate tolerance may occur, especially when plasma concentrations are kept constant. Because MI risk 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-h respite period seems sufficient. Isosorbide may require a 12-h respite period. If given once/day, sustained-release isosorbide mononitrate does not appear to elicit tolerance.

Ca channel blockers may be used if symptoms persist despite use of nitrates or if nitrates are not tolerated. Ca channel blockers are particularly useful if hypertension or coronary spasm is also present. Different types of Ca channel blockers have different effects. Dihydropyridines (eg, nifedipine, amlodipine, felodipine) have no chronotropic effects and vary substantially in their negative inotropic effects. Shorter-acting dihydropyridines may cause reflex tachycardia and are associated with increased mortality in CAD patients; 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 β-blocker. In this group, amlodipine has the weakest negative inotropic effects; it may be used in patients with LV systolic dysfunction. Diltiazem and verapamil, other types of Ca channel blockers, have negative chronotropic and inotropic effects. They can be used alone in patients with β-blocker intolerance or asthma and normal LV systolic function but may increase cardiovascular mortality in patients with LV systolic dysfunction.

Drugs for Coronary Artery Disease




ACE inhibitors












All patients with CAD, especially those with large infarctions, heart failure, hypertension, or diabetes

Contraindications including hypotension, renal failure, bilateral renal artery stenosis, and known allergy

Angiotensin II receptor blockers








An effective alternative for patients who cannot tolerate ACE inhibitors (eg, because of cough); currently, not first-line treatment after MI

Contraindications including hypotension, renal failure, bilateral renal artery stenosis, and known allergy



350 mcg/kg (IV bolus) followed by 25 mcg/kg/min (IV infusion)

Patients with ACS and a known or suspected history of heparin-induced thrombocytopenia as an alternative to heparin


0.75 mg/kg (IV bolus) followed by 1.75 mg/kg/h infusion


2.5 mg sc q 24 h


30 mg IV (bolus) followed by 1 mg/kg sc q 12 h (maximum, 100 mg)

Patients with unstable angina or NSTEMI

Patients < 75 yr receiving tenecteplase

Almost all patients with STEMI as an alternative to unfractionated heparin (unless PCI is indicated and can be done in < 90 min); drug continued until PCI or CABG is done or patient is discharged

Unfractionated heparin

60–70 units/kg IV (maximum, 5000 units; bolus), followed by 12–15 units/kg/h (maximum, 1000 units/h) for 3–4 days or until PCI is complete

Patients with unstable angina or NSTEMI as an alternative to enoxaparin

60 units/kg IV (maximum, 4000 units; bolus) given when alteplase, reteplase, or tenecteplase is started, then followed by 12 units/kg/h (maximum,1000 units/h) for 48 h or until PCI is complete

Patients who have STEMI and undergo urgent angiography and PCI or patients > 75 yr receiving tenecteplase


Oral dose adjusted to maintain INR of 2.5–3.5

May be useful long-term in patients at high risk of systemic emboli (ie, with large anterior MI, known LV thrombus, or atrial fibrillation)

Antiplatelet drugs


For stable angina: 75 or 81 mg po once/day (enteric-coated)

All patients with CAD or at high risk of developing CAD, unless aspirin is not tolerated or is contraindicated; used long-term

For ACS: 160–325 mg po chewed (not enteric-coated) on arrival at emergency department and once/day thereafter during hospitalization and 81 mg po once/day long-term after discharge

Clopidogrel (preferred)

75 mg po once/day

Used with aspirin or, in patients who cannot tolerate aspirin, alone

For patients undergoing PCI: 300–600 mg po once, then 75 mg po once/day for 1–12 mo

For patients undergoing PCI, clopidogrel loading dose to be administered only in cardiac catheterization laboratory after angiography has confirmed that coronary anatomy is amenable to PCI (so as not to delay CABG if indicated)

Maintenance therapy required for at least 1 mo for bare-metal stents and for at least 12 mo for drug-eluting stents


60 mg po once, followed by 10 mg po once/day

Only for patients with ACS undergoing PCI

Not used in combination with fibrinolytic therapy


For patients undergoing PCI: 180 mg po once before the procedure, followed by 90 mg po bid


250 mg po bid

Rarely used routinely because neutropenia is a risk and WBC count must be monitored regularly

Glycoprotein IIb/IIIa inhibitors


0.25 mcg/kg bolus, then 10 mcg/min

Some patients with ACS, particularly those who are having PCI with stent placement and high-risk patients with unstable angina or NSTEMI

Therapy started at least 6 h before PCI and continued for 18 to 24 h thereafter


180 mcg/kg bolus, then 2 mcg/kg/min


0.4 mcg/kg/min for 30 min, then 0.1 mcg/kg/min



50 mg po q 12 h acutely; 50–100 mg po bid long-term

All patients with ACS, unless a β-blocker is not tolerated or is contraindicated, especially high-risk patients; used long-term


2.5–5 mg po once/day, increasing to 10–15 mg once/day depending on heart rate and BP response


25 mg po bid (in patients with heart failure or other hemodynamic instability, the starting dose should be as low as 1.625–3.125 mg bid and increased very slowly as tolerated)


1–3 boluses of 5 mg given 2–5 min apart as tolerated (up to 15 mg); then 25–50 mg po q 6 h, beginning 15 min after last IV dose and continued for 48 h; then 100 mg bid or 200 mg once/day given long term

Calcium channel blockers


5–10 mg po once/day

Patients with stable angina if symptoms persist despite nitrates use or if nitrates are not tolerated

Diltiazem (extended-release)

180–360 po once/day


2.5–20 mg po once/day

Nifedipine (extended-release)

30–90 mg po once/day

Verapamil (extended-release)

120–360 mg po once/day









Patients with CAD to achieve a target LDL of 70 mg/dL (1.81 mmol/L)

Nitrates: Short acting

Sublingual nitroglycerin (tablet or spray)

0.3–0.6 mg q 4–5 min up to 3 doses

All patients for immediate relief of chest pain; used as needed

Nitroglycerin as continuous IV drip

Started at 5 mcg/min and increased 2.5–5.0 mcg every few minutes until required response occurs

Selected patients with ACS:

During the first 24 to 48 h, those with heart failure (unless hypotension is present), large anterior MI, persistent angina, or hypertension (BP is reduced by 10–20 mm Hg but not to < 80–90 mm Hg systolic)

For longer use, those with recurrent angina or persistent pulmonary congestion

Nitrates: Long acting

Isosorbide dinitrate

10–20 mg po tid; can be increased to 40 mg tid

Patients who have unstable angina or persistent severe angina and continue to have anginal symptoms after the β-blocker dose is maximized

A nitrate-free period of 8–10 h (typically at night) recommended to avoid tolerance

Isosorbide dinitrate (sustained-release)

40–80 mg po bid (typically given at 8 am and 2 pm )

Isosorbide mononitrate

20 mg po bid, with 7 h between 1st and 2nd doses

Isosorbide mononitrate (sustained-release)

30 or 60 mg once/day, increased to 120 mg or, rarely, 240 mg

Nitroglycerin patches

0.2–0.8 mg/h applied between 6:00 and 9:00 am and removed 12–14 h later to avoid tolerance

Nitroglycerin ointment 2% preparation (15 mg/2.5 cm)

1.25 cm spread evenly over upper torso or arms q 6 to 8 h and covered with plastic, increased to 7.5 cm as tolerated, and removed for 8–12 h each day to avoid tolerance



2–4 mg IV, repeated as needed

All patients with chest pain due to ACS to relieve pain (but ischemia may persist)

Best used after drug therapy has been started or the decision to do revascularization has been made

*Of low molecular weight heparins (LMWHs), enoxaparin is preferred.

Higher doses of aspirin do not provide greater protection and increase risk of adverse effects.

ACS = acute coronary syndromes; CABG = coronary artery bypass grafting; CAD = coronary artery disease; LV = left ventricular; NSTEMI = non–ST-segment elevation MI; PCI = percutaneous intervention; STEMI = ST-segment elevation MI.


Revascularization, either with PCI (eg, angioplasty, stenting) or CABG should be considered if angina persists despite drug therapy and worsens quality of life or if anatomic lesions (noted during angiography) put a patient at high risk of mortality. The choice between PCI and CABG depends on extent and location of anatomic lesions, the experience of the surgeon and medical center, and, to some extent, patient preference.

PCI is usually preferred for 1- or 2-vessel disease with suitable anatomic lesions and is increasingly being used for 3-vessel disease. Lesions that are long or near bifurcation points are often not amenable to PCI. However, as stent technology improves, PCI is being used for more complicated cases.

CABG is very effective in selected patients with angina. The ideal candidate has severe angina pectoris and localized disease, or diabetes mellitus. About 85% of patients have complete or dramatic symptom relief. Exercise stress testing shows positive correlation between graft patency and improved exercise tolerance, but exercise tolerance sometimes remains improved despite graft closure.

CABG improves survival for patients with left main disease, those with 3-vessel disease and poor LV function, and some patients with 2-vessel disease. However, for patients with mild or moderate angina (CCS class 1 or 2) or 3-vessel disease and good ventricular function, CABG appears to only marginally improve survival. For patients with 1-vessel disease, outcomes with drug therapy, PCI, and CABG are similar; exceptions are left main disease and proximal left anterior descending disease, for which revascularization appears advantageous.

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.

  • Do stress testing with ECG for patients with normal resting ECG or with myocardial imaging (eg, echocardiography, radionuclide imaging, MRI) for patients with abnormal resting ECG.

  • Do coronary angiography when revascularization (percutaneous intervention or coronary artery bypass grafting) is being considered.

  • Give nitroglycerin for immediate relief of angina

  • Maintain patients on an antiplatelet drug, a β-blocker, and a statin, and add a Ca channel blocker for further symptom prevention if needed.

  • Consider revascularization if significant angina persists despite drug therapy or if lesions noted during angiography indicate high risk of mortality.

Variant Angina

Variant angina is angina pectoris secondary to epicardial coronary artery spasm (Prinzmetal angina).

Most patients with variant angina have significant fixed proximal obstruction of at least one major coronary artery. Spasm usually occurs within 1 cm of the obstruction (often accompanied by ventricular arrhythmia).

Symptoms are anginal discomfort occurring mainly during rest, often at night, and only rarely and inconsistently during exertion (unless significant coronary artery obstruction is also present). Attacks tend to occur regularly at certain times of day.

Diagnosis is suspected if ST-segment elevation occurs during the attack. Between anginal attacks, the ECG may be normal or show a stable abnormal pattern. Confirmation is by provocative testing with ergonovine or acetylcholine, which may precipitate coronary artery spasm, identified by significant ST-segment elevation or by observation of a reversible spasm during cardiac catheterization. Testing is done most commonly in a cardiac catheterization laboratory and occasionally in a coronary care unit.

Average survival at 5 yr is 89 to 97%, but mortality risk is greater for patients with both variant angina and atherosclerotic coronary artery obstruction. Usually, sublingual nitroglycerin promptly relieves variant angina. Ca channel blockers may effectively prevent symptoms. Theoretically, β-blockers may exacerbate spasm by allowing unopposed α-adrenergic vasoconstriction, but this effect has not been proved clinically. Oral drugs most commonly used are sustained-release diltiazem 120 to 540 mg once/day, sustained-release verapamil 120 to 480 mg once/day (dose must be reduced in patients with renal or hepatic dysfunction), or amlodipine 15 to 20 mg once/day (dose must be reduced in elderly patients and patients with hepatic dysfunction). In refractory cases, amiodarone may be useful. Although these drugs relieve symptoms, they do not appear to alter prognosis.

Syndrome X

Syndrome X is cardiac microvascular dysfunction or constriction causing angina (microvascular angina).

Some patients with typical angina that is relieved by rest or nitroglycerin have normal coronary arteriograms (eg, no atherosclerosis, embolism, or inducible arterial spasm). Some of these patients have ischemia detected during stress testing; others do not. In some patients, the cause of ischemia seems to be reflex intramyocardial coronary constriction and reduced coronary flow reserve. Other patients have microvascular dysfunction within the myocardium: The abnormal vessels do not dilate in response to exercise or other cardiovascular stressors; sensitivity to cardiac pain may also be increased. Prognosis is good, although symptoms of ischemia may recur for years. In many patients, β-blockers relieve symptoms. This disorder should not be confused with variant angina due to epicardial coronary spasm or with another disorder called syndrome X, which refers to the metabolic syndrome (see Metabolic Syndrome).

Silent Ischemia

Patients with CAD (particularly patients with diabetes) may have ischemia without symptoms. Ischemia is evidenced by transient asymptomatic ST-T abnormalities seen during 24-h Holter monitoring. Radionuclide studies can sometimes document asymptomatic myocardial ischemia during physical or mental stress (eg, mental arithmetic). Silent ischemia and angina pectoris may coexist, occurring at different times. Prognosis depends on severity of CAD.

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