Chronic coronary syndrome: Overview of care

INTRODUCTION — Ischemic heart disease, also referred to as coronary heart disease, is the term associated with an inadequate supply of blood to the myocardium due to obstruction of the epicardial coronary arteries, usually from atherosclerosis (see "Pathogenesis of atherosclerosis"). Patients may have chronic (stable) or acute (unstable) disease.

Most patients can be given the diagnosis of chronic coronary syndrome (CCS), also referred to as stable ischemic heart disease (SIHD), based on a classic history of angina pectoris in the presence of either risk factors for or known atherosclerotic cardiovascular disease [1]. Angina pectoris, or angina for short, refers to chest discomfort that occurs when myocardial oxygen demand exceeds oxygen supply. Stable angina refers to chest discomfort that occurs predictably and reproducibly at a certain level of exertion and is relieved with rest or nitroglycerin. The prevalence of anginal symptoms varies and is thought to be lower among community-dwelling patients than trial participants [2,3]. (See "Approach to the patient with suspected angina pectoris", section on 'Evaluation of suspected stable angina'.)

Other patients may have stable disease but not experience classic anginal symptoms. They may have atypical chest pain, non-anginal symptoms related to reduced cardiac blood flow such as dyspnea on exertion, or silent ischemia (particularly in patients with diabetes mellitus). In such patients, the diagnosis of CCS can be confirmed by stress testing or, if that is ambivalent, an anatomic assessment of the coronary arteries, either with coronary computed tomography angiography (CTA) or an invasive coronary angiogram. (See "Outpatient evaluation of the adult with chest pain", section on 'Evaluation for stable myocardial ischemia' and "Stress testing for the diagnosis of obstructive coronary heart disease".)

Multiple pathophysiologic mechanisms may cause CCS. The most common is atherosclerotic epicardial coronary artery obstruction. However, as many as one-third of patients may have no significant epicardial disease and often have microvascular disease as the underlying pathophysiology.  

This topic will provide an overview of the key components of care in patients with atherosclerotic epicardial coronary artery obstruction. Patients with microvascular disease are discussed separately. (See "Microvascular angina: Angina pectoris with normal coronary arteries".)

The care of patients with acute coronary syndromes is discussed elsewhere:

●(See "Overview of the acute management of non-ST-elevation acute coronary syndromes".)

●(See "Acute coronary syndrome: Terminology and classification".)

●(See "Overview of the nonacute management of unstable angina and non-ST-elevation myocardial infarction".)

●(See "Risk stratification after non-ST elevation acute coronary syndrome".)

●(See "Evaluation of emergency department patients with chest pain at low or intermediate risk for acute coronary syndrome".)

●(See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)

●(See "Overview of the acute management of ST-elevation myocardial infarction".)

●(See "Overview of the nonacute management of ST-elevation myocardial infarction".)

DETERMINING DISEASE SEVERITY — A determination of disease severity is important for guiding treatment and establishing prognosis. This includes assessment of the extent of coronary disease for all patients and assessment of left ventricular function for selected patients.

The combination of results of tests to determine severity and individual patient characteristics influences the therapeutic approach. Low- and intermediate-risk patients whose symptoms are controlled on medical therapy can be managed without intervention, while high-risk patients or those with angina refractory to medical therapy undergo coronary angiography and revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). (See 'Identifying patients for angiography and revascularization' below.)

Assessing severity of coronary disease — The extent and severity of coronary disease can be assessed by stress testing, cardiac imaging, and angiography. Stress testing is the most common method.

We recommend that patients with known or suspected chronic coronary syndrome (CCS), also referred to as stable ischemic heart disease (SIHD), undergo stress testing, if not already performed, to secure the diagnosis, determine disease severity, and gain prognostic information [4]. Testing should be performed soon after the diagnosis and when there has been a significant change in symptom status.

Evaluation for coronary disease usually begins with a functional study such as stress testing with exercise electrocardiogram (ECG), exercise with imaging, or pharmacologic stress testing with imaging. The choice of test may be influenced by the patient's resting ECG, the patient's physical ability to perform exercise, local clinician expertise, and available technologies. (See "Selecting the optimal cardiac stress test" and "Stress testing for the diagnosis of obstructive coronary heart disease".)

An initial noninvasive anatomic assessment of coronary disease with coronary computed tomography angiography (CTA) is becoming more common, especially in patients who are not candidates for exercise or pharmacologic stress testing, but CTA is associated with increased costs and no change in mortality when compared with stress testing [5]. The choice of this modality is discussed elsewhere. (See "Selecting the optimal cardiac stress test".)

In certain situations, invasive coronary angiography may also be used to determine disease severity, for example in patients with atypical symptoms and equivocal findings on stress testing in whom a diagnosis needs to be established.

Measurement of left ventricular systolic function — Measurement of left ventricular systolic function is useful in most patients to determine optimal medical therapy, the role of interventional or surgical therapy, or recommendations about activity level, rehabilitation, and work status. Echocardiography can also identify patients who have had a silent infarction in the past and evaluate valvular function.

We suggest that the following patients with CCS merit an assessment of left ventricular systolic function (generally with the use of transthoracic echocardiography):

●Prior myocardial infarction, diagnosed either by history or pathologic Q waves on an electrocardiogram

●Symptoms or signs of heart failure

●Undiagnosed heart murmur

●Complex ventricular arrhythmias

The methodology for the measurement of left ventricular systolic function is discussed separately. (See "Tests to evaluate left ventricular systolic function".)

IDENTIFYING PATIENTS FOR ANGIOGRAPHY AND REVASCULARIZATION — The patient’s clinical characteristics and the results of noninvasive testing are used to identify patients likely to benefit from coronary angiography followed by revascularization of appropriate lesions [6,7]. In patients with chronic coronary syndrome (CCS), there are two primary indications for this:

●Angina that significantly interferes with a patient's lifestyle despite maximal tolerable medical therapy.

●Patients with clinical characteristics and results of noninvasive testing that indicate a high likelihood of severe ischemic heart disease (eg, imaging or strongly positive treadmill test suggesting a large amount of viable myocardium at risk).

Additionally, patients with depressed left ventricular systolic function (ejection fraction <50 percent) and moderate risk criteria on noninvasive testing with demonstrable ischemia may benefit from coronary angiography.

Revascularization is performed in appropriate patients in whom angiography reveals anatomy for which revascularization has a proven benefit or in whom medical therapy has failed. Indications for angiography and revascularization and the choice of technique are discussed elsewhere. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention" and "Chronic coronary syndrome: Indications for revascularization", section on 'Indications' and "Chronic coronary syndrome: Indications for revascularization", section on 'Summary and recommendations'.)

ANTIANGINAL THERAPY — There are three classes of antiischemic drugs commonly used in the management of angina pectoris: beta blockers, calcium channel blockers, and nitrates. Ranolazine is a newer addition. Often, a combination of these agents is used for control of symptoms. These agents are also used for patients who have anginal-equivalent symptoms, such as dyspnea on exertion.

Treatments to prevent angina

Initial beta-blocker monotherapy — We recommend beta blockers as first-line therapy to reduce anginal episodes and improve exercise tolerance [8]. The use of these agents in patients with chronic coronary syndrome (CCS) is discussed in detail elsewhere. (See "Beta blockers in the management of chronic coronary syndrome".)

However, beta blockers should not be used in patients with vasospastic or variant (Prinzmetal) angina. In such patients, they are ineffective and may increase the tendency to induce coronary vasospasm from unopposed alpha-receptor activity. (See "Vasospastic angina".)

Beta blockers reduce anginal symptoms by decreasing both heart rate and contractility. Since beta blockers reduce the heart rate-blood pressure product during exercise, the onset of angina or the ischemic threshold during exercise is delayed or avoided. All types of beta blockers appear to be equally effective in exertional angina.

In addition, beta blockers are the only antianginal drugs proven to prevent reinfarction and to improve survival in patients who have sustained a myocardial infarction [9]. (See "Acute myocardial infarction: Role of beta blocker therapy".)

Alternative monotherapy — In patients who cannot tolerate a beta blocker, alternative initial therapies include calcium channel blockers or long-acting nitrates. Calcium channel blockers are more convenient and better tolerated but should not be used in patients with significant left ventricular dysfunction.

Calcium channel blockers — Calcium channel blockers can be used as monotherapy as an alternative to beta blockers or in combination therapy. (See "Calcium channel blockers in the management of chronic coronary syndrome" and 'Combination therapy for persistent symptoms' below.)

Long-acting diltiazem or verapamil or a second-generation dihydropyridine (amlodipine or felodipine) are preferred. Short-acting dihydropyridines, especially nifedipine, should be avoided unless used in conjunction with a beta blocker in the management of CCS because of evidence of an increase in mortality after a myocardial infarction and an increase in acute myocardial infarction in hypertensive patients. (See "Major side effects and safety of calcium channel blockers".)

These agents improve anginal symptomatology by causing coronary and peripheral vasodilatation and reducing contractility, although the degree to which these changes occur varies with the type of calcium channel blocker given [10].

Long-acting nitrates — Long-acting nitrates can be used as monotherapy as an alternative to beta blockers or in combination therapy. (See "Nitrates in the management of chronic coronary syndrome" and 'Combination therapy for persistent symptoms' below.)

In patients with exertional stable angina, chronic nitrate therapy using oral or dermal preparations improves exercise tolerance, time to onset of angina, and ST-segment depression during exercise testing. However, the long-term utility of nitrates can be limited by the induction of nitrate tolerance.

Combination therapy for persistent symptoms — Combination therapy is commonly used in the treatment of CCS for patients who have continued symptoms on monotherapy. In general, any combination of a beta blocker, calcium channel blocker, and long-acting nitrate can be appropriate. However, some patients may not tolerate the combination of a beta blocker and calcium channel blocker due to hypotension or bradycardia. Ranolazine, a late sodium channel blocker can be added as a third medication, if needed [8]. (See "New therapies for angina pectoris".)

The efficacy of combination therapy was illustrated in a study that randomly assigned 397 patients to four weeks of monotherapy with felodipine or metoprolol or a combination of felodipine and metoprolol [11]. Combination therapy was more effective for increasing exercise duration and better tolerated than monotherapy.

Acute symptom management

Short-acting nitrates — Nitrates, usually in the form of a sublingual preparation, are the first-line therapy for the treatment of acute anginal symptoms. Patients should be instructed to use them at the onset of angina or for prophylaxis of anginal episodes. The use of nitrates as well as their side effects, including nitrate tolerance, is discussed elsewhere. (See "Nitrates in the management of chronic coronary syndrome".)

Reducing exacerbating factors — Treatment of any underlying medical conditions that might aggravate myocardial ischemia, such as hypertension, fever, tachyarrhythmias (eg, atrial fibrillation), thyrotoxicosis, anemia or polycythemia, hypoxemia, or valvular heart disease, should be undertaken. Asymptomatic low-grade arrhythmias are not treated routinely but may require therapy under certain circumstances, such as left ventricular dysfunction.

PREVENTING DISEASE PROGRESSION — The optimal management of patients with stable angina requires more than antianginal therapy. Therapies aimed at preventing cardiovascular events are central to long-term care [8]. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

We recommend that all patients with chronic coronary syndrome (CCS) receive education and counseling about issues such as medication compliance, control of risk factors, and regular exercise [8]. In addition, there are several medical therapies which can reduce the risk of cardiovascular events and disease progression.

Antiplatelet therapy — In the absence of a contraindication, all patients should be treated with aspirin. We believe that doses of aspirin from 75 to 325 mg daily are associated with the best risk/benefit ratio. Some experts prefer to stay within the 75 to 162 mg per day range. Clopidogrel is an alternative in patients who are allergic to aspirin. (See "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease".)

Lipid-lowering therapy — We recommend that all patients with CCS be treated with evidence-based doses of a high-intensity statin regardless of the baseline low-density lipoprotein (LDL) cholesterol. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

ACE inhibitors or ARBs in select patients — Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have known benefits for a subset of patients with CCS, such as those with hypertension, diabetes mellitus, decreased left ventricular ejection fraction (less than 40 percent), or chronic kidney disease. However, in the absence of these indications, whether ACE inhibitors or ARBs have a cardioprotective effect beyond their effect on blood pressure control is uncertain. This is discussed in detail elsewhere. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'ACE inhibitors or ARBs'.)

Other risk factor reduction — Risk factor reduction should be a central component of the management of patients with stable angina. Elements include treatment of hypertension, cessation of smoking, weight reduction, and glycemic control in diabetics. In addition to contributing to chronic progression of atherosclerosis, smoking and hypertension can precipitate acute coronary ischemia by increasing oxygen demands and reducing oxygen supply [12,13]. The specific goals are described elsewhere. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk" and "Cardiovascular risk of smoking and benefits of smoking cessation" and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease" and "Goal blood pressure in adults with hypertension".)

Stress reduction should also be encouraged and treatment of underlying depression and anxiety should be considered, if appropriate. The impact of these interventions in patients with chronic coronary heart disease and stable angina is unknown, although their role in patients with a prior myocardial infarction is better established. (See "Psychosocial factors in coronary and cerebral vascular disease" and "Psychosocial factors in acute coronary syndrome".)

Participation in regular exercise is likely beneficial, although patients may want to avoid more strenuous exercise in cold weather or after a meal. Recommendations for referral to cardiac rehabilitation programs and routine physical activity for patients with stable angina pectoris are discussed separately. (See "Cardiac rehabilitation programs" and "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease".)

Patients with type 2 diabetes mellitus — Glycemic control in patients with diabetes mellitus is important in coronary artery disease risk reduction. Certain medications (eg, sodium-glucose cotransporter 2 [SGLT2] inhibitors and glucagon-like peptide 1 [GLP1] receptor agonists) may decrease adverse cardiovascular outcomes and are favored as adjunctive therapy to be used along with first-line treatments. (See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Established cardiovascular or kidney disease'.)

●In a trial of 7020 patients with diabetes mellitus, treatment with 10 or 25 mg of empagliflozin (an SGLT2 inhibitor) resulted in a lower rate of the composite outcome (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) compared with placebo (10.5 versus 12.1 percent, hazard ratio [HR] 0.86, 95% CI 0.74-0.99), as well as a lower rate of cardiovascular death (3.7 versus 5.9 percent, HR 0.62, 95% CI 0.49-0.77) [14]. A second SGLT2 agent, canagliflozin, has shown similar results but with an increased risk of limb amputation [15].

●In a trial of over 9000 patients with diabetes mellitus, those treated with liraglutide (a GLP1 receptor agonist) had a lower rate of first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke compared with those in the placebo group (13.0 versus 14.9 percent, HR 0.87, 95% CI 0.78-0.97) [16].

CONSIDERATIONS IN OLDER ADULTS — Individuals over the age of 65 years represent a growing proportion of patients with chronic coronary syndrome (CCS) [17,18]. However, recognition of disease can be more challenging in this population due to a higher prevalence of atypical symptoms, including exertional dyspnea or silent myocardial ischemia.

The approach to the management of angina in older adults is essentially the same as for younger patients. However, the efficacy of therapies for coronary heart disease in older adults is often unrecognized or underestimated, in part because older adults have been underrepresented in trials [19]. All of the drugs used in younger patients for the control of anginal symptoms are appropriate for older adults, although older adults may experience more side effects, particularly hypotension from nitrates and calcium channel blockers and central nervous system effects from beta blockers. These patients may need to be started on lower doses.

FOLLOW-UP — Patients with chronic stable angina require follow-up on a regular basis. We suggest follow-up every 6 to 12 months. At each visit, a detailed history should be obtained and physical examination performed. In particular, it is important to establish:

●A change in physical activity

●Any change in the frequency, severity, or pattern of angina

●Tolerance of and compliance with the medical program

●Modification of risk factors

●The development of new or worsened comorbid illnesses

In addition to laboratory studies such as blood glucose or a lipid profile, an electrocardiogram should be obtained if medications are altered or if the history or physical examination have changed.

All patients with chronic coronary syndrome (CCS) should receive an annual influenza vaccine, unless contraindicated.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary prevention of cardiovascular disease" and "Society guideline links: Secondary prevention of cardiovascular disease" and "Society guideline links: Chronic coronary syndrome".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see "Patient education: Coronary artery disease (The Basics)" and "Patient education: Cardiac catheterization (The Basics)" and "Patient education: Medicines for angina (chest pain) (The Basics)" and "Patient education: Stenting for the heart (The Basics)" and "Patient education: Treatment choices for angina (chest pain) (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Goals of care – The principal goals in the care of patients with chronic coronary syndrome (CCS), also referred to as stable ischemic heart disease (SIHD), are to secure the diagnosis, assess the extent of disease, relieve symptoms, and prevent future cardiac events such as acute coronary syndromes, revascularization, or death. (See 'Introduction' above.)

●Determining disease severity – Most patients with CCS should undergo some form of stress testing or cardiac imaging (eg, coronary computed tomography [CT] angiography) to either secure the diagnosis or evaluate disease severity. (See 'Determining disease severity' above and "Stress testing for the diagnosis of obstructive coronary heart disease" and "Cardiac imaging with computed tomography and magnetic resonance in the adult".)

●Identifying patients for angiography and revascularization – Patients with significant anginal symptoms despite maximal medical therapy or those with a high likelihood of severe ischemic heart disease based on stress testing should undergo coronary angiography with potential revascularization. (See 'Identifying patients for angiography and revascularization' above and "Chronic coronary syndrome: Indications for revascularization".)

●Symptom management

•Beta blockers are preferred for initial treatment and prevention of anginal symptoms. (See 'Antianginal therapy' above and "Beta blockers in the management of chronic coronary syndrome".)

•Calcium channel blockers and long-acting nitrates are alternatives if beta blockers are contraindicated or cause side effects; they can also be added as combination therapy if monotherapy is not successful. (See "Calcium channel blockers in the management of chronic coronary syndrome" and "Nitrates in the management of chronic coronary syndrome".)

•Short-acting nitrates are used for immediate angina relief. (See "Nitrates in the management of chronic coronary syndrome".)

●Preventing disease progression – Therapies known to reduce the incidence of adverse cardiovascular events such as death and myocardial infarction should be started. These include aspirin, lipid-lowering therapy, smoking cessation, control of blood pressure and excess weight, and optimal management of diabetes mellitus. Regular exercise and stress reduction are also recommended. (See 'Preventing disease progression' above.)

●Follow-up – The optimal management of these patients also requires periodic evaluation (every 6 to 12 months) of the patient's clinical status, using the history, physical examination, and on occasion the electrocardiogram (ECG). (See 'Follow-up' above.)