Stable Ischemic Heart Disease

Stable Ischemic Heart Disease

Gharibyan Rosie Jasper

James C. Blankenship



Coronary artery disease (CAD) remains the leading cause of death and morbidity worldwide. Cardiovascular disease (CVD) remains the number one cause of death in the United States, accounting for one in three deaths, and it claims more lives than all cancers and pulmonary diseases combined.1 The overall CAD prevalence is 6.7% (18.2 million) in US adults over 20 years of age and is higher in men (7.4%) than in women (6.2%). Over the past two decades, the incidence of CAD declined from 3.9 to 2.2 per 1000 person-years in people without diabetes and from 11.1 to 5.4 per 1000 person-years among those with diabetes.2 The lifetime risk of developing CAD in 40-year-old persons is greater than 40% in men and greater than 30% in women. Of note, the incidence of angina rises continuously with age in women. Stable angina or stable ischemic heart disease (SIHD) is the most common presentation of CAD in women, compared to acute myocardial infarction (MI) and sudden coronary death in men. The direct and indirect costs of heart disease in 2014 to 2015 were estimated at $219 billion in the United States, 42% of which was spent on persons over 60 years of age. Chronic CAD and MI were two of the 10 most expensive conditions treated in US hospitals and accounted for 14% of total health expenditures in 2014 to 2015.2

Risk Factors

The traditional risk factors for atherosclerosis include age, sex, smoking, hypertension, hyperlipidemia, obesity, metabolic syndrome, diabetes mellitus, sedentary lifestyle, and family history. Nontraditional risk factors include socioeconomic and psychosocial stress, autoimmune diseases, malignancy and its therapies, infections, sleep apnea, and pregnancy-related complications.


Angina pectoris is the result of myocardial ischemia caused by an imbalance between myocardial blood supply and oxygen demand. Myocardial ischemia typically results from a reduction of coronary blood flow caused by fixed and/or dynamic epicardial coronary artery stenosis. Less commonly, it may be due to abnormal constriction (or deficient relaxation) of coronary microcirculation, markedly increased myocardial oxygen demands (ie, malignant hypertension, severe aortic stenosis), or reduced oxygen-carrying capacity of the blood (ie, severe anemia, carboxyhemoglobin).

Coronary stenosis is typically caused by atherosclerosis, affecting large and medium size arteries. Atherosclerosis begins in young adulthood, as demonstrated by an incidence of coronary atherosclerosis of 45% to 75% in soldiers killed in combat.3 The disease progresses in an indolent fashion and is usually clinically silent for many decades.


Common Signs and Symptoms

Identifying individuals with cardiac chest pain or SIHD requires careful evaluation of the patient’s history, examination, testing, and risk. Traditionally, “typical angina” is described as substernal chest discomfort with: (1) ischemic quality and duration; (2) exacerbation by exercise and/or emotional stress; and (3) relief by rest and/or nitrates. “Atypical angina” meets two of the above three characteristics, whereas “non-anginal chest pain” meets only one or none. It is generally safe to assume symptoms are noncardiac if the symptoms meet criteria for “non-anginal” and an alternative diagnosis is readily apparent (eg, chest pain reproducible by palpation in a trauma patient). A diagnosis of “non-anginal chest pain,” with only one of the three characteristics present, carries intermediate risk for CAD in women older than 60 years and men older than 40 years.

Angina pectoris is characterized by pain in the retrosternal and/or surrounding areas, often radiating to the jaw, epigastrium, and left shoulder and arm. It is often described as a pressure-like, constricting, burning, or squeezing sensation. It may be accompanied by dyspnea, fatigue, and nausea. The Canadian Cardiovascular Society classification is widely used to grade the severity of typical angina (Table 4.1).4

Diabetic patients with coronary disease are more likely to have “noncardiac” chest pain compared to nondiabetics. However, diabetics and nondiabetics have similar ratios of “typical” to “atypical” angina, and most diabetics have typical angina when they present with symptomatic SIHD.

Physical Examination Findings

The physical examination is often unremarkable in stable CAD. Physical examination findings, which are nonspecific, but may accompany CAD, include the presence of S4, S3, mitral regurgitation murmur, rales, carotid bruit, diminished pedal pulse,
retinal exudates, and xanthomas. Reproducible chest wall pain/pressure in two studies of nontrauma patients significantly correlated with a noncardiac etiology of chest pain. Chest pain that is reproduced by coughing, deep inspiration, lying supine, moving arms and shoulders, rotating the torso, or swallowing is usually not due to myocardial ischemia

Differential Diagnosis

The majority of patients presenting with chest pain in an outpatient setting have noncardiac etiologies, and these conditions should be considered in the differential diagnosis of chest pain or SIHD (Table 4.2).


Medical Approach

The treatment goals in stable CAD are to:

(1) reduce premature cardiovascular death; (2) prevent complications (ie, heart failure and MI); (3) maintain optimal functional capacity; (4) eliminate or decrease ischemic symptoms; and (5) minimize health care costs by eliminating unnecessary tests, procedures, and hospitalizations.8

Clinicians are obligated to help patients understand their disease etiology, clinical manifestations, and signals of worsening disease. Patients should be empowered to make shared decisions regarding revascularization options and actively participate in risk reduction, behavioral modification, and medication adherence.11

Antianginal Therapies

Nitrates. All patients with stable CAD should be prescribed sublingual nitroglycerin or a nitroglycerin spray for immediate relief of angina (Class Ib).9 Long-acting formulations are recommended when an initial anginal therapy with maximum tolerated beta-blocker is not effective in preventing angina. Failure of nitrate therapy is often due to nitrate tolerance. Therefore, depending on nitrate formulation used, a 10- to 14-hour nitrate-free interval is indicated.

Beta-blockers. Beta-blockers should be prescribed as a first-line therapy for relief of ischemic symptoms in patients with stable CAD (Class I).9 In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, patients with stable CAD and coronary stenosis greater than 70% on angiography who received a beta-blocker reported a 22% improvement in symptoms of angina, similar to results following percutaneous coronary intervention (PCI).12 Similarly, in the Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) trial, PCI did not improve exercise angina after medical therapy with beta-blockers was optimized.13 All beta-blockers have similar efficacy in patients with angina. The dose of beta-blocker is titrated for a goal heart rate of 55 to 60 beats per minute. An abrupt discontinuation of beta-blockers may be poorly tolerated and is discouraged, as it can worsen angina and precipitate an acute coronary syndrome (ACS) (9).

Calcium Channel Blockers. The calcium channel blockers (CCBs) are as effective as beta-blockers in relieving angina and increasing angina-free exercise time. CCBs can be used alone as antianginal therapy, though their combination with nitrates and beta-blockers exerts a more potent antianginal effect. All CCB classes are equally efficacious in treating angina, and selection of a specific agent should be based on drug interactions and potential side effects. Dihydropyridine (DHP) CCBs or long-acting nitrates should be prescribed in combination with beta-blockers for relief of anginal symptoms (Class Ib).9 Alternatively, long-acting non-DHP CCBs (ie, diltiazem or verapamil) can be considered instead of beta-blockers as initial therapy (Class IIa).9

Ranolazine. Ranolazine is a selective late sodium channel inhibitor that reduces sodium-dependent calcium currents in ischemic myocardium. It is administered orally in doses of 500 to 2000 mg daily to reduce angina and increase symptom-free exercise capacity. Ranolazine has antianginal efficacy when used as a monotherapy or in combination with first- and second-line antianginal agents and shows a more potent effect in diabetic patients with elevated hemoglobin A1C levels. Ranolazine can be useful as a substitute for beta-blockers for relief of angina in
stable CAD (Class IIb) or in combination with beta-blockers (Class IIa).9,10

Ivabradine. Ivabradine was approved in the United States in 2015 for the treatment of heart failure with reduced ejection fraction (EF). Although it has not been approved in the United States for angina, it has been reported to have antianginal properties. Ivabradine as monotherapy improves treadmill test performance and decreases frequency of angina attacks with efficacy similar to that of beta-blockers and amlodipine.14

Other Antianginal Therapies. Nicorandil and trimetazidine are antianginal therapies not available in the United States but are used in Europe and other countries.10

Nonpharmacologic Therapies for Refractory Angina in Stable Ischemic Heart Disease

Individuals with refractory angina constitute approximately 10% of stable CAD patients. Refractory angina is defined as angina despite maximal medical therapy because of CAD that is not amenable to revascularization. Nonpharmacologic therapies may be considered in patients to improve quality of life.6 These new therapies attempt to either (1) improve myocardial perfusion or (2) modulate afferent and efferent pain pathways to change perception of ischemic pain.15

Angiogenesis. Intracoronary or transendocardial injection of autologous cells (CD34+, CD133+) that activate myocardial angiogenesis can improve exercise capacity. Their therapeutic use for refractory angina is currently under review.16

Enhanced External Counterpulsation. The Food and Drug Administration (FDA) approved the use of enhanced external counterpulsation (EECP) in 1995 for the treatment of refractory angina. The full treatment course consists of 1-hour treatments, 5 days per week, for 35 sessions. Contraindications include heart failure, severe peripheral arterial disease (PAD), and aortic regurgitation. Studies have shown some benefit of EECP for treatment of refractory angina not responsive to conventional antianginal therapies.15 EECP has a Class IIb (may be considered for refractory angina) indication for angina therapy per the ACCF/AHA 2014 guidelines.6,15

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May 8, 2022 | Posted by in CARDIOLOGY | Comments Off on Stable Ischemic Heart Disease
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