*Stable Angina Pectoris

Chapter: Stable Angina Pectoris
McMaster Section Editor(s): P.J. Devereaux
Section Editor(s) in Interna Szczeklika: Andrzej Budaj, Wiktoria Leśniak
McMaster Author(s): Tej Sheth
Author(s) in Interna Szczeklika: Tomasz Pasierski, Waldemar Banasiak, Wiktoria Leśniak, Maria Referowska
Additional Information

This chapter addresses symptomatic stable coronary artery disease (CAD).

Definition, Etiology, Pathogenesis Top

Angina pectoris is a clinical syndrome characterized by chest pain (or its equivalent) due to myocardial ischemia, usually developing on exertion or caused by stress and not associated with necrosis of cardiomyocytes. In some patients, the pain may be spontaneous. Angina reflects an inadequate oxygen supply in relation to myocardial demand. Stable angina pectoris is diagnosed in patients with symptoms of angina and no worsening over the prior 2 months.

Etiology and pathogenesis: see Ischemic Heart Disease.

Clinical Features and Natural History Top

1. Symptoms: The clinical diagnosis of angina is based on the history; therefore, a detailed characterization of the symptom complex is critical to the patient assessment.

Anginal chest pain is typically retrosternal in location and may radiate to the neck, jaw, left shoulder, and/or left arm (and usually further along the ulnar nerve to the wrist and fingers), to the epigastrium, or rarely to the interscapular region. The pain is caused by exertion (the threshold may vary from patient to patient) and emotional stress; it usually lasts a few minutes and is relieved by rest or sometimes decreases in the course of continued exercise. The pain is frequently more severe in the morning and may be exacerbated by cold air or a heavy meal. The intensity of the pain is not related to body position or the phase of the respiratory cycle; it usually resolves within 1 to 3 minutes of sublingual administration of nitroglycerin (if the pain resolves after 5-10 minutes, it is probably not related to myocardial ischemia; in such cases, it may be caused, eg, by esophageal disease). The pain may be absent in patients with an anginal “equivalent,” particularly exertional dyspnea; however, it may be challenging to distinguish the anginal equivalent from a pulmonary cause.

Typical angina (1) is substernal and referred in a typical way; (2) is caused by exertion or emotional stress; (3) resolves at rest or after sublingual administration of a nitrate. Atypical angina fulfills 2 of these criteria. Nonanginal pain meets only 1 criterion.

2. Grading of angina based on its severity (Table 1): Grading the severity of angina is helpful in monitoring the course of symptoms and provides a basis for therapeutic decisions. In a significant proportion of patients, the symptoms of angina remain stable for many years. Long-term spontaneous remissions may occur (these are sometimes only apparent and related to the reduction of the patient’s physical activity).

3. Signs: No signs are specific to angina. Signs of atherosclerosis of other arteries (eg, carotid bruit, ankle-brachial index <0.9 or >1.15) increase the risk of coronary artery disease.

Diagnosis Top

Diagnostic Tests

1. Laboratory tests may reveal risk factors for atherosclerosis and disorders that may trigger angina. The baseline tests in a patient with stable coronary disease include:

1) Fasting lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]).

2) Fasting blood glucose and glycated hemoglobin (HbA1c) (and oral glucose tolerance test, when indicated [see Diabetes Mellitus]).

3) Complete blood count.

4) Serum creatinine level and estimated glomerular filtration rate.

Moreover, in patients with clinical indications perform:

1) Measurement of cardiac troponin levels (in the case of suspected acute coronary syndrome).

2) Thyroid function tests.

3) Liver function tests (after starting statin therapy).

4) Measurement of creatine kinase levels (in patients with features of myopathy).

5) B-type natriuretic peptide/N-terminal pro–B-type natriuretic peptide (NT-proBNP) (in the case of suspected heart failure).

2. Resting electrocardiography (ECG) should be performed in every patient with suspected angina. Although the results are normal in the majority of patients, some patients may have significant Q waves, indicating prior myocardial infarction (MI) (even in the absence of a clinical history suggestive of prior MI) or ECG features of myocardial ischemia, mainly ST-segment depression or T-wave inversion.

3. Resting echocardiography is indicated in all patients to detect other diseases that may cause angina, assess impaired myocardial contractility and diastolic function, and measure left ventricular (LV) ejection fraction (LVEF), which is necessary for risk stratification.

4. ECG Holter monitoring rarely provides significant diagnostic information and therefore should not be performed routinely. It can be considered in the case of suspected arrhythmia or vasospastic angina (Prinzmetal variant angina).

Noninvasive Imaging Diagnostic Tests for Coronary Artery Disease

The choice of diagnostic tests depends on the clinical probability of CAD. The probability can be estimated by considering the age and sex of the patient and the nature of discomfort. Clinically useful classification is divided into low (~15%), intermediate (~15%-85%), and high (~>85%) probability (Table 2).

In patients with a high pretest probability (PTP), noninvasive testing is performed to assess the risk of cardiovascular events. However, invasive coronary angiography may be an alternative in many such patients (see below). In patients with a low PTP, a search for other causes should be considered, and noninvasive testing has limited usefulness. In patients with an intermediate PTP, noninvasive testing should be performed to confirm the diagnosis and assess prognosis. There are several noninvasive strategies commonly used in practice (Figure 1).

1. ECG stress test is used in patients with an intermediate PTP who are able to exercise and have an interpretable ECG. The test has only modest sensitivity but very high specificity. It should be considered in patients with a PTP of 15% to 65%. Due to its limited sensitivity, the test is of less value for diagnostic purposes in patients with a PTP of 66% to 85%. The study is also of limited diagnostic value in patients in whom the baseline ECG features make it impossible to interpret the recordings during exercise (left bundle branch block [LBBB], preexcitation syndromes, pacemaker rhythms).

2. ECG stress test with imaging: The addition of imaging to stress testing improves sensitivity, specificity, and prognostic information. Stress imaging is especially useful in assessing patients with a PTP of 66% to 85% with LVEF <50% and in those who have an uninterpretable ECG. The 2 common types of imaging are single-photon emission computed tomography (SPECT) with sestamibi or thallium isotopes and stress echocardiography. Imaging can be performed with pharmacologic stress (persantine or dobutamine) in individuals who are not able to exercise. However, exercise is always preferred whenever possible for the additional prognostic information that it provides.

3. Coronary computed tomography angiography (CCTA) is used in patients with a PTP of 15% to 85% and in intermediate-risk patients in whom stress testing yields equivocal results or is not feasible (due to limited exercise capacity or an uninterpretable ECG). CCTA has a very high negative predictive value, which allows for the exclusion of CAD in lower-risk patients. Specificity and diagnostic accuracy are reduced in the setting of extensive coronary calcification and fast or irregular heart rates.

4. Cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) are the emerging modalities for cardiac imaging. They have value for the assessment of myocardial viability and ventricular function; however, they are not widely used as stress testing modalities.

In patients with an intermediate PTP, clinical outcomes are similar whether an initial strategy with stress testing or CCTA is employed, so either may be used.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of intervention). Douglas PS, Hoffmann U, Patel MR, et al; PROMISE Investigators. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015 Apr 2;372(14):1291-300. doi: 10.1056/NEJMoa1415516. Epub 2015 Mar 14. PubMed PMID: 25773919; PubMed Central PMCID: PMC4473773. SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet. 2015 Jun 13;385(9985):2383-91. doi: 10.1016/S0140-6736(15)60291-4. Epub 2015 Mar 15. Erratum in: Lancet. 2015 Jun 13;385(9985):2354. PubMed PMID: 25788230. The radiation dose with CCTA is lower than with nuclear imaging but higher than with stress echocardiography or stress ECG, where no radiation is administered. In patients investigated with stress testing, the addition of CCTA (in case of a positive result of stress testing) increases diagnostic certainty and leads to fewer angiograms without subsequent revascularization. Therefore, either stress testing or CCTA are recommended in patients with an intermediate PTP. The choice of strategy in an individual patient depends on the patient’s characteristics, local experience, and physician’s preference.

Coronary angiography is the gold standard for demonstrating coronary anatomy, establishing prognosis, and assessing the feasibility of invasive treatment. Coronary angiography should be considered for the diagnosis of CAD in the following situations:

1) High PTP of CAD in patients with severe symptoms or clinical features suggestive of high risk of cardiovascular events. In such cases, it is justified to proceed to early coronary angiography without prior noninvasive imaging with the intention of revascularization.

2) Coexistence of typical angina and systolic LV dysfunction (LVEF <50%).

3) Equivocal diagnosis made on the basis of noninvasive tests or conflicting results of various noninvasive tests (this is an indication for coronary angiography with measurement of functional flow reserve [FFR], if necessary).

4) Unavailability of imaging stress testing, special legal requirements associated with certain professions (eg, aircraft pilots).

Risk Stratification Based on Clinical Data and Noninvasive Imaging Tests

Estimating the subsequent risk of cardiovascular events utilizes data from the clinical evaluation, ventricular function, and results of stress testing or CCTA. Markers of increased risk:

1) Clinical: Increased age, a history of diabetes mellitus, current smoking, hypertension, elevated cholesterol, peripheral vascular disease, and chronic kidney disease (CKD). Evidence of clinical heart failure and ECG abnormalities are additional risk markers.

2) LV function: Ventricular function is the strongest long-term predictor of survival. An LVEF <50% indicates an elevated risk; the risk continues to increase with a lower LVEF.

3) Noninvasive tests for ischemia: High-risk findings include >10% area of ischemia on SPECT or >3 dysfunctional segments on stress echocardiography. Intermediate-risk findings include 1% to 10% area of ischemia on SPECT or 1 to 2 dysfunctional segments on stress echocardiography.

4) Coronary anatomy assessed by noninvasive tests (CCTA): High-risk findings include stenosis in the left main coronary artery, in the proximal section of the left anterior descending artery (LAD), or 3-vessel CAD. Intermediate-risk findings include 1-vessel or 2-vessel disease.

Management based on the estimated risk of a cardiovascular event: Table 3, Figure 2. In all patients with confirmed CAD, an optimum medical therapy should be started. The decision to proceed to coronary angiography and revascularization depends on the estimated risk, symptom control, and patient’s preference (see below).

Differential Diagnosis

Other causes of chest pain: see Chest Pain.

Other causes of ST-segment and T-wave abnormalities: see Standard Electrocardiogram.

Treatment Top

General Considerations

1. Control of the risk factors of atherosclerosis (secondary prevention): see Prevention of Cardiovascular Diseases.

2. Treatment of diseases worsening angina, such as anemia, hyperthyroidism, or tachyarrhythmias.

3. Increasing physical activity (below the threshold of angina): 30 minutes daily, at least 3 days a week.

4. Influenza vaccination: Annually.

5. Optimum medical therapy to improve prognosis and to control the symptoms of angina.

6. Invasive treatment (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG]): In eligible patients.

Optimum Medical Therapy: Treatment to Improve Prognosis

In every patient, the following oral agents should be administered on a lifelong basis:

1) Antiplatelet agents: Acetylsalicylic acid (ASA) 75 mg once daily; in the case of adverse gastrointestinal effects, add an antacid (see Peptic Ulcer Disease). In patients with contraindications to ASA (peptic ulcer disease, coagulopathy, aspirin-induced asthma), use clopidogrel 75 mg once daily (dosage: Table 2 in Non–ST-Segment Elevation Myocardial Infarction); a combination therapy with ASA and clopidogrel is not recommended in stable patients except after stenting (see Choice of Stents and Management After Stent Insertion).Evidence 2Strong recommendation (downsides clearly outweigh benefits; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of intervention). Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86. Erratum in: BMJ 2002 Jan 19;324(7330):141. PubMed PMID: 11786451; PubMed Central PMCID: PMC64503.

2) Statins ([Table 2.4-2 in Hypercholesterolemia]). Make attempts to lower LDL-C levels ≤1.8 mmol/L (70 mg/dL), and if this cannot be achieved, to reduce them by >50% compared with baseline levels.Evidence 3Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of intervention). Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8. PubMed PMID: 21067804; PubMed Central PMCID: PMC2988224. In cases of poor tolerance or ineffectiveness of statins, the use of ezetimibe can be considered.

3) Angiotensin-converting enzyme inhibitors (ACEIs) (or angiotensin-receptor blockers [ARBs]) are indicated in patients with coexisting hypertension, diabetes mellitus, heart failure, or LV systolic dysfunction (dosage: Table 4; agents: Table 5 in Essential Hypertension).Evidence 4Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of intervention). Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000 Jan 20;342(3):145-53. Erratum in: 2000 May 4;342(18):1376. N Engl J Med 2000 Mar 9;342(10):748. PubMed PMID: 10639539. Dagenais GR, Pogue J, Fox K, Simoons ML, Yusuf S. Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet. 2006 Aug 12;368(9535):581-8. Review. PubMed PMID: 16905022.

Optimum Medical Therapy: Treatment to Control Symptoms

1. Acute symptom control and prevention prior to planned exercise: Use a short-acting nitrate—nitroglycerin aerosol (Table 5). Patients should be instructed to use nitroglycerin 3 times at 5-minute intervals. If no relief is achieved, the patient should call an ambulance and should be assessed by medical personnel for acute chest pain. Relative contraindications include hypertrophic cardiomyopathy with outflow tract obstruction, severe aortic stenosis, use of phosphodiesterase-5 (PDE-5) inhibitors (eg, sildenafil). Other drug interactions include alpha-blockers (in male patients with benign prostatic hyperplasia, the combined use of nitrates and a selective alpha-blocker [tamsulosin] is allowed). Adverse effects: headache, facial flushing, dizziness, syncope.

2. Prevention of angina and increasing exercise tolerance:

1) Beta-blockers reduce heart rate, contractility, and atrioventricular (AV) conduction. They are the first-line agents for treatment of angina. Physicians should titrate the dose on the basis of heart rate and blood pressure with a goal to achieve the maximum recommended dose. Typical dosage: Table 6. A beta-blocker may be considered in asymptomatic patients with extensive ischemia (>10% of LV). Absolute contraindications: symptomatic bradycardia, symptomatic hypotension, second-degree or third-degree AV block, sick sinus syndrome, severe decompensated heart failure. Adverse effects: bradycardia, AV block, bronchospasm, peripheral artery spasm, and peripheral hypoperfusion in patients with severe peripheral artery disease; sexual dysfunction and loss of libido; and particularly in the case of propranolol, fatigue, headache, sleep disturbances, insomnia, vivid dreams, depression. Caution should be exercised in combining beta-blockers with verapamil and diltiazem due to their additive effects on AV conduction and heart rate.

2) Calcium channel blockers are smooth muscle vasodilators; they have a negative inotropic effect. They can be used in patients who cannot take beta-blockers or do not respond to monotherapy with a beta-blocker. Typical dosage: Table 6.

a) Diltiazem and verapamil lower the heart rate. They are of value in patients with contraindications to or intolerance of beta-blockers. Contraindications: heart failure, bradycardia, AV conduction disturbances, hypotension. Adverse effects: constipation, bradycardia, AV block, hypotension.

b) Dihydropyridines are vasodilators. Their mechanism of action is complementary to beta-blockers. They can be used in combination with a beta-blocker in patients not responding to a beta-blocker alone. Adverse effects: facial flushing, headache, peripheral edema.

3) Long-acting nitrates are arterial and venous vasodilators; they reduce preload. Isosorbide dinitrate, isosorbide mononitrate, or nitroglycerin are recommended as second-line agents; typical dosage: Table 5. When administered bid, ensure ~10-hour intervals between the doses. The onset of action of nitroglycerin patches occurs a few minutes after they are attached; their antianginal effect is maintained for 3 to 5 hours.

3. Other agents, such as ivabradine, molsidomine, nicorandil, ranolazine, and trimetazidine, are used for their antianginal properties in some countries around the world.

Invasive Angiography and Revascularization

In patients with a diagnosis of stable angina based on noninvasive testing, invasive angiography is indicated for high-risk patients or those with severe or refractory symptoms to assess the potential for revascularization:

1) Invasive coronary angiography (with assessment by the FFR measurement, when necessary) is recommended:

a) For risk stratification in patients with severe stable angina or with a high risk of cardiovascular events, especially if symptoms do not improve with medical therapy.

b) For patients with mild or no symptoms if noninvasive risk stratification suggests a high risk of cardiovascular events and revascularization has the potential to improve the prognosis.

2) Invasive coronary angiography (with FFR measurement) should be considered in patients with inconclusive or conflicting noninvasive test results to obtain a definitive diagnosis and inform the prognosis.

Findings of invasive angiography (the extent and complexity of CAD, LV dysfunction) as well as clinical factors (age, comorbidities, history of diabetes mellitus) dictate the decision to perform revascularization and the choice of the revascularization strategy. In patients with multivessel disease, the angiographic extent and complexity of CAD can be quantified using the SYNTAX score (www.syntaxscore.com). Decisions about the revascularization strategy are usually taken by an interventional cardiologist in consultation with a cardiovascular surgeon as part of the heart team approach.

Choice of Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting

1. PCI is the preferred treatment in patients with:

1) 1-vessel disease (including the proximal section of the LAD) or 2-vessel disease that does not involve the proximal LAD.

2) Anatomical features of a low-risk lesion.

3) First occurrence of restenosis.

4) Comorbidities increasing the risk of cardiac surgery.

2. CABG is preferred in patients with:

1) 3-vessel disease and a SYNTAX score >22 or reduced LV function.

2) Patients with diabetes mellitus and multivessel disease.

3) Left main coronary artery stenosis, either isolated or combined with 2-vessel or 3-vessel disease in patients with a SYNTAX score >32.

3. Anatomic subsets where either PCI or CABG may be considered include patients with 2-vessel disease involving the proximal LAD, 3-vessel disease with a low SYNTAX score (<22), or left main coronary artery stenosis in the ostium or shaft with limited CAD at other sites.

4. Patients after prior revascularization: In patients with prior CABG or with prior PCI presenting with in-stent restenosis, PCI is the preferred treatment option, unless angiographic complexity or the extent of the disease favors bypass surgery.

5. Patients with diabetes mellitus: Patients with diabetes mellitus are at an increased risk of disease progression and cardiovascular events. Patients with diabetes mellitus and multivessel disease have a survival advantage with bypass surgery. PCI with drug-eluting stents (DESs) should be considered in patients with 1-vessel disease.Evidence 5Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of intervention). Farkouh ME, Domanski M, Sleeper LA, et al; FREEDOM Trial Investigators. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012 Dec 20;367(25):2375-84. doi: 10.1056/NEJMoa1211585. Epub 2012 Nov 4. PubMed PMID: 23121323.

6. Patients with CKD: In patients with nonsevere CKD in whom CABG is indicated because of the extent of CAD, the surgical risk is acceptable, and the life expectancy justifies the procedure, consider CABG rather than PCI; in the case of PCI, the use of DESs rather than bare-metal stents (BMSs) may be considered.

7. Intracoronary assessment: For patients without diagnostic noninvasive evidence of ischemia, FFR measurement with administration of intravenous or intracoronary adenosine may be used to guide revascularization decisions, especially in uncertain clinical situations, such as an angiographically moderate coronary stenosis or atypical symptoms. Revascularization is recommended in patients with angina or a positive stress test result with FFR <0.80, but it should be deferred in those with FFR >0.80.

Choice of Stents and Management After Stent Insertion

1. Choice of stents and antiplatelet therapy in patients undergoing elective PCI: Second-generation DESs with thinner struts and biodegradable or more biocompatible polymers have shown superior outcomes compared with first-generation DESs and BMSs. They should be used in all PCI-treated patients who can comply with 12 months of dual antiplatelet therapy.Evidence 6Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of intervention). Bangalore S, Toklu B, Amoroso N, et al. Bare metal stents, durable polymer drug eluting stents, and biodegradable polymer drug eluting stents for coronary artery disease: mixed treatment comparison meta-analysis. BMJ. 2013 Nov 8;347:f6625. doi: 10.1136/bmj.f6625. PubMed PMID: 24212107; PubMed Central PMCID: PMC3898413. BMSs require only 1 month of dual antiplatelet therapy and are chosen in patients who are not candidates for a longer-duration combined therapy. Dual antiplatelet therapy is recommended with aspirin and clopidogrel for patients undergoing elective stenting. Ticagrelor or prasugrel should be considered with aspirin for patients with stent thrombosis while receiving clopidogrel or in other high-risk situations.

2. Antithrombotic treatment is recommended after stenting in patients with atrial fibrillation and a moderate or high risk of thromboembolism in whom the use of vitamin K antagonists or direct oral anticoagulants is necessary ([Table 6-8 in Atrial Fibrillation]). The duration of dual antiplatelet therapy and/or triple therapy should be individualized based on the balance of risks of thrombosis and bleeding.

Follow-Up Top

Regular monitoring of modifiable risk factors: see Prevention of Cardiovascular Diseases. The frequency of follow-up visits depends on the severity of the risk factors and angina: usually every 3 to 4 months in the first year of treatment, and then (in stable patients) every 6 months to 1 year.

Prognosis Top

The annual mortality rate is 1.2% to 3.8%, risk of cardiac death is 0.6% to 1.4%, and risk of nonfatal MI is 0.6% to 2.7%. Adverse prognostic factors include advanced age, more severe angina pectoris (Canadian Cardiovascular Society scale), poor performance status, resting ECG abnormalities, silent myocardial ischemia, LV systolic dysfunction, extensive ischemia documented by noninvasive stress tests, advanced lesions observed in coronary angiography, diabetes mellitus, renal failure, LV hypertrophy, and resting heart rate >70 beats/min.

Tables and FiguresTop


Table 1. Grading of angina pectoris based on its severity according to the Canadian Cardiovascular Society (CCS)

Grade I: Ordinary physical activity (such as walking and climbing stairs) does not cause angina. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation

Grade II: A slight limitation of ordinary activity. Angina occurs when:

– Walking or climbing stairs rapidly

– Walking uphill

– Walking or climbing stairs after meals, in cold, or in wind, or when under emotional stress, or only during the few hours after awakening

– Walking >200 meters or climbing more than 1 flight of stairs at a normal pace and in normal conditions

Grade III: Marked limitation of ordinary physical activity. Angina occurs when walking 100-200 meters or climbing 1 flight of stairs at a normal pace in normal conditions

Grade IV: Inability to carry on any physical activity without discomfort; anginal syndrome may be present at rest

Source: Canadian Cardiovascular Society. Angina pectoris, a CSS Grading Scale. www.ccs.ca/images/Guidelines/Guidelines_POS_Library/Ang_Gui_1976.pdf. Accessed February 12, 2016.

Table 2. Pretest probability of coronary artery disease in patients with stable chest pain depending on age, sex, and type of pain

Type of pain

30-39 years

40-49 years

50-59 years

60-69 years

70-79 years

≥80 years













Typical chest pain

Atypical chest pain

Nonanginal chest pain

PTP of CAD <15% (white boxes) indicates no need for further diagnostics.

In patients with PTP of CAD 15%-65% (grey boxes), ECG stress test may be performed as the first-line test. If well-conducted noninvasive imaging stress testing is available, this is the preferred method because of higher diagnostic yield. In young patients, irradiation must be taken into consideration.

In patients with PTP of CAD 66%-85% (light-blue boxes), CAD should be confirmed using noninvasive imaging stress test, not by ECG stress test.

In patients with PTP of CAD >85% (dark-blue boxes), CAD is diagnosed and the risk of complications should be assessed.

Based on: Genders TS, Steyerberg EW, Alkadhi H, et al. A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension. Eur Heart J. 2011 Jun;32(11):1316-30.

CAD, coronary artery disease; ECG, electrocardiography; F, female patients; M, male patients; PTP, pretest probability.

Table 3. Definitions of risk of cardiovascular events in various diagnostic studies






ECG stress testa

Annual cardiovascular mortality




Imaging studies

Area of ischemia



Coronary CTA

Coronary lesions

Significant stenosisd

Significant stenosise

Normal coronary arteries or atherosclerotic plaques only

a Risk assessment using the Duke treadmill score including the exercise workload in time expressed in metabolic equivalents, ST-T changes during and after exercise, and clinical symptoms (no angina, angina, or angina causing discontinuation of the test). Calculator is available at www.cardiology.org/tools/medcalc/duke.

b >10% in SPECT; the quantitative data for MRI are limited: probably ≥2 segments (out of 16) with new areas of hypoperfusion; ≥3 segments (out of 17) with dysfunction caused by dobutamine; or ≥3 segments (out of 17) with abnormal wall motion observed on stress echocardiography.

c Or any ischemia rated as lower than high-risk on MRI of the heart or stress echocardiography.

d Ie, 3-vessel disease with proximal stenosis of the large coronary arteries, stenosis of the left main coronary artery, or proximal stenosis of the LAD.

e Non–high-risk stenosis of proximal large coronary arteries.

Adapted from: Task Force Members, Montalescot G, Sechtem U, Achenbach S, 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. 2013 Oct;34(38):2949-3003.

CTA, computed tomography angiography; ECG, electrocardiography; LAD, left anterior descending artery; MRI, magnetic resonance imaging; SPECT, single-photon emission computed tomography.

Table 4. Typical dosage of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARB) in angina pectoris


Dosage (oral administration)



10-40 mg once daily or in 2 divided doses


10-80 mg once daily or in 2 divided doses


2.5-5 mg once daily


5-40 mg once daily or in 2 divided doses


20-40 mg once daily or in 2 divided doses


5-20 mg once daily


25-50 mg bid to tid


10-40 mg once daily


7.5-30 mg once daily or in 2 divided doses


4(5)-8(10) mg once daily


2.5-5 mg once daily (max, 10 mg)


2-4 mg once daily



50-100 mg once daily


80-320 mg once daily


8-32 mg once daily


40-80 mg once daily


150-300 mg once daily


600-800 mg once daily


20-40 mg once daily

bid, 2 times a day; tid; 3 times a day.

Table 5. Typical dosage of nitrates in angina pectoris




Duration of action


(INN glyceryl trinitrate)


0.4 mg

1.5-7 min

Transdermal patch

5-20 mg/24 h

(patch should be detached for the night)


Prolonged-release tablets

6.5-15 mg bid

4-8 h

Isosorbide dinitrate


5-10 mg

Up to 60 min

Isosorbide mononitrate


10-40 mg bid

Up to 8 h

Prolonged-release tablets

50-100 mg once daily

12-24 h

Prolonged-release capsules

40-120 mg once daily

a In a long-term bid administration, the second dose should be administered within 8 h of the first dose (eg, 7:00 and 15:00), and the nitroglycerin patches should be detached for 10 h.

bid, 2 times a day; INN, International Nonproprietary Name.

Table 6. Typical dosage of beta-blockers and calcium channel blockers in angina pectoris


Dosage (oral administration)



200-600 mg bid


50-200 mg once daily


10-20 mg once daily


5-10 mg once daily


12.5-25 mg bid


Immediate-release formulations

25-100 mg bid

Extended-release formulations

25-200 mg once daily


2.5-10 mg bid or tid


10-80 mg bid or tid

Dihydropyridine calcium channel blockers


5-10 mg once daily


5-10 mg once daily

Nondihydropyridine calcium channel blockers



Immediate-release formulations

30-90 mg tid

Extended-release formulations

120-480 mg once daily (or in 2 divided doses)


Immediate release formulations

40-160 mg tid

Extended-release formulations

120-480 mg once daily

bid, 2 times a day; tid, 3 times a day.

Figure 1. Proposed diagnostic algorithm in patients with suspected stable coronary artery disease. Adapted from the 2013 European Society of Cardiology guidelines (see Additional Information for details).

Figure 2. Management algorithm in patients with confirmed stable coronary artery disease depending on the risk of cardiovascular events. Adapted from the 2013 European Society of Cardiology guidelines (see Additional Information for details).


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