Richard A. Lange, MD, MBA

1. Can a patient with new-onset chest pain have chronic stable angina?

    The term “chronic stable angina” refers to angina that has been stable in frequency and severity for at least 2 months and with which the episodes are provoked by exertion or stress of similar intensity. Chronic stable angina is the initial manifestation of coronary artery disease (CAD) in about half of patients; the other half initially experience unstable angina, myocardial infarction (MI), or sudden death.

2. What causes chronic stable angina?

    Angina occurs when myocardial oxygen supply is inadequate to meet the metabolic demands of the heart, thereby causing myocardial ischemia. This is usually caused by increased oxygen demands (i.e., increase in heart rate, blood pressure, or myocardial contractility) that cannot be met by a concomitant increase in coronary arterial blood flow, due to narrowing or occlusion of one or more coronary arteries.

3. How is chronic stable angina classified or graded?

    The most commonly used system is the Canadian Cardiovascular Society system, in which angina is graded on a scale of I to IV. These grades and this system are described in Table 16-1. This grading system is useful for evaluating functional limitation, treatment efficacy, and stability of symptoms over time.

4. What tests should be obtained in the patient with newly diagnosed angina?

    After a careful history and physical examination, the laboratory tests for the patient with suspected angina should include a measurement of hemoglobin, hemoglobin A1c, fasting lipids (i.e., serum concentrations of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol), and a 12-lead electrocardiogram (ECG).

5. What are the goals of treatment in the patient with chronic stable angina?

6. What therapies improve symptoms?

7. What is the initial approach to the patient with chronic stable angina?

    The initial approach should be focused on eliminating unhealthy behaviors such as smoking and effectively promoting lifestyle changes that reduce CV risk, such as maintaining a healthy weight, engaging in physical activity, and adopting a healthy diet. In addition, annual influenza vaccination reduces mortality (by approximately 35%) and morbidity in patients with underlying CAD. Tight glycemic control was thought to be important in the diabetic, but this approach actually increases the risk of CV death and complications.

8. What is first-line drug therapy for the treatment of stable angina?

    When considering medications, β-blockers decrease myocardial oxygen demands by reducing heart rate, myocardial contractility, and blood pressure. They are first-line therapy in the treatment of chronic CAD, as they delay the onset of angina and increase exercise capacity in subjects with stable angina.

9. Is any β-blocker better than the others?

    Although the various β-blockers have different properties (i.e., cardioselectivity, vasodilating actions, concomitant α-adrenergic inhibition, and partial β-agonist activity [Table 16-2]), they appear to have similar efficacy in patients with chronic stable angina. β-blockers prevent reinfarction and improve survival in survivors of MI, but such benefits have not been demonstrated in patients with chronic CAD without previous MI.

10. What is the proper dose of β-blocker?

    The dose of β-blocker is titrated to achieve a resting heart rate of 55 to 60 beats per minute and an increase in heart rate during exercise that does not exceed 75% of the heart rate response associated with the onset of ischemia. β-blockers are contraindicated in the presence of severe bradycardia, high-degree atrioventricular block, sinus node dysfunction, and uncompensated heart failure. They are also contraindicated in the patient with vasospastic angina, in whom they may worsen angina as a result of unopposed α-adrenergic stimulation; calcium channel blockers are preferred in these patients.

11. Calcium channel blocker versus β-blocker: is one more effective than the other?

    Calcium channel blockers and β-blockers are similarly effective at relieving angina and improving exercise time to the onset of angina or ischemia. Calcium channel blockers can be used as monotherapy in patients with chronic stable angina, although combination therapy with a β-blocker or nitrate relieves angina more effectively than does their use alone. In this regard, β-blockers may be particularly useful in blunting the reflex tachycardia that occurs with dihydropyridine calcium channel blocker use.

12. When should a peripherally acting calcium channel blocker (i.e., a dihydropyridine, such as amlodipine or felodipine) be used versus one that has effects on both the heart and the periphery (e.g., verapamil, diltiazem)?

    Amlodipine and felodipine are used primarily as second- or third-line antianginal agents in patients already on β-blockers (and often, also long-acting nitrates). They act mainly as vasodilators, lowering blood pressure and likely having some coronary vasodilating effects. Verapamil and diltiazem, in addition to having vasodilating effects, have negative chronotropic and inotropic effects. Thus, they are used in patients with contraindications or intolerance to β-blockers. They are usually avoided in the patient with an ejection fraction below 40% or who is on a β-blocker, because of their negative inotropic effects.

13. Should sublingual nitroglycerin (NTG) or NTG spray be prescribed to all chronic stable angina patients?

    Yes. This is the standard of care. Patients should be instructed on how to use sublingual NTG—generally one pill every 5 minutes, up to a maximum of three tablets. They should be instructed to call 911 and seek immediate medical attention if their angina is not relieved after three pills or 15 minutes.

14. When is a long-acting nitrate prescribed?

    Long-acting nitrates are often prescribed along with β-blockers or nondihydropyridine calcium channel blocker (i.e., verapamil or diltiazem) as the initial treatments in patients with chronic stable angina (Table 16-3). Continuous exposure to NTG can result in tolerance to its vasodilating effects. Nitrate tolerance can be avoided by providing the patient with a “nitrate-free” period for 4 to 6 hours per day.

15. When is ranolazine added?

    It’s use is reserved for individuals with angina that is refractory to maximal doses of other antianginal medications. Ranolazine targets the underlying derangements in sodium and calcium that occur during myocardial ischemia; it does not affect resting heart rate or blood pressure. Its antianginal efficacy is not related to its effect on heart rate, the hemodynamic state, the inotropic state, or coronary blood flow, as with other currently available agents.

    In randomized trials, ranolazine increased exercise tolerance, decreased anginal frequency, and decreased sublingual NTG use, when used as monotherapy or in combination with β-blockers or calcium channel blockers in subjects with chronic stable angina. Randomized long-term trials evaluating its impact on mortality in stable CAD have not been performed.

    Because ranolazine prolongs the QTc interval, it should not be used in patients with baseline QT prolongation or those on other medications that can prolong the QT interval. Furthermore, patients initiated on this drug should have their QT duration monitored periodically with 12-lead ECGs.

16. What medications prevent MI or death in patients with stable chronic angina?

17. What’s the proper dose of aspirin?

    An aspirin dose of 75 to 162 mg daily is equally as effective as 325 mg, but with a lower risk of bleeding. Doses less than 75 mg have less proven benefit. In patients with chronic CAD, aspirin treatment is associated with a 33% reduction in the risk of vascular events (nonfatal MI, nonfatal stroke, and vascular death). Over the course of a couple of years of treatment, aspirin would be expected to prevent about 10 to 15 vascular events for every 1000 people treated.

18. Should patients with chronic stable angina be on clopidogrel?

    Clopidogrel is a reasonable alternative in the patient with stable CAD who is allergic to or cannot tolerate aspirin. However, the use of aspirin and clopidogrel in combination is no more effective than aspirin alone at reducing vascular events in patients with stable CAD.

19. Should patients with chronic stable angina be treated with an ACE inhibitor?

    The addition of an ACE inhibitor to standard therapy does not reduce the risk of CV events In “low-risk” stable CAD patients (i.e., those with normal ejection fraction in whom CV risk factors are well controlled and revascularization has been performed). Conversely, in “high-risk” patients, ACE inhibitors reduce the incidence of MI, stroke, or CV death by approximately 20%. Thus, ACE inhibitors are started and continued indefinitely in all patients with a left ventricular ejection fraction (LVEF) of 0.40 or below, and in those with hypertension, diabetes, or chronic kidney disease, unless contraindicated.

20. What’s the proper statin dose for the patients with chronic stable angina?

    The dose of statin is gradually increased until the target serum LDL cholesterol concentration is achieved. The goal for patients with stable CAD or a CAD equivalent is less than 100 mg/dL, and for those at “very high risk” (i.e., established CAD and multiple risk factors), the LDL cholesterol goal is less than 70 mg/dL.

21. Which patients with chronic stable angina should be referred for stress testing?

    The two purposes of stress testing are diagnosis of CAD and prognosis in patients with presumed or known CAD. Stress testing performed for diagnostic purposes is usually performed with the patient off antianginal therapy, whereas stress testing performed for prognostic purposes may sometimes be performed with the patient on antianginal agents.

    An estimation of the pretest probability of CAD—based on an assessment of the patient’s chest pain and his or her risk factors for atherosclerosis—is essential in determining if further testing is warranted. In general, diagnostic testing is appropriate for the patient with an intermediate pretest probability of CAD, but it is not recommended for those with a low (10% or less pretest probability) or high (90% or more pretest probability) risk.

    For example, an abnormal exercise test in a 35-year-old woman with atypical chest pain and no risk factors for atherosclerosis (pretest probability of clinically significant CAD is less than 5%) is likely to be falsely positive, thereby prompting the use of unnecessary medications or invasive diagnostic testing; a negative test would simply support a low clinical suspicion of CAD. Similarly, testing of high-risk patients is unlikely to provide information that will alter the diagnosis of CAD. A positive exercise test will only confirm the high clinical suspicion of CAD; a negative result would only lower the estimate of likelihood of CAD into the moderate range and would not exclude the diagnosis.

    The results of noninvasive diagnostic testing are most likely to influence subsequent decisions when the pretest probability of CAD is in the intermediate range. For example, a positive exercise test in a 55-year-old man with atypical chest pain and no risk factors for atherosclerosis (pretest probability of clinically significant CAD, approximately 50%) substantially increases the likelihood of clinically important CAD (posttest probability, 85%), whereas a negative exercise test dramatically reduces the likelihood (posttest probability, 15%).

    The chronic stable angina guidelines advocate obtaining a stress test for prognostic reasons in many cases—if the stress test reveals low-risk findings, then the patient can be managed medically, whereas if the stress test reveals high-risk findings, the patient is usually referred for cardiac catheterization.

22. Which patients with chronic stable angina should have a cardiac catheterization?

23. Which patients with chronic stable angina should be referred for revascularization?

    In most individuals, survival with optimal medical therapy is similar to that observed following revascularization. In the patient with stable angina and preserved ejection fraction receiving optimal medical therapy, percutaneous coronary intervention (PCI) does not reduce the incidence of subsequent MI or cardiac death. Although PCI-treated patients initially may experience a greater improvement in symptom control and quality of life, these salutary effects largely disappear within 24 months. Hence intensive medical therapy and lifestyle intervention are appropriate as initial therapy for most patients with chronic stable angina.

    Revascularization should be reserved for those with (1) symptoms that interfere with the patient’s lifestyle despite optimal medical therapy or (2) coronary anatomic findings that indicate that revascularization would provide a survival benefit, including

The optimal method of revascularization—coronary artery bypass graft (CABG) or PCI—is selected based on the coronary angiographic findings, the likelihood of success (or complications) of each procedure, and the subject’s preferences. Ideally, both an interventional cardiologist and cardiac surgeon should review the patient’s data (including the angiogram) and reach agreement on which procedure(s) should be offered, after which the patient is presented with the advantages and disadvantages of each and allowed to choose between them. Among subjects with left main CAD (or in those with extensive 2- or 3-vessel CAD), either procedure could be considered, but the weight of published evidence supports the more durable benefit afforded by CABG (mortality reduction and lower incidence of repeat revascularization).

24. Is there an easy way to remember how to manage the patient with chronic stable angina?

    The “ABCDEs” of treatment for patients with chronic stable angina

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