Management of Coronary Artery Disease and Chronic Stable Angina

Yesenia Camero, PharmD, BCPS; Jinwi Ghogomu, PharmD, BCPS, CPh

Disclosures

US Pharmacist. 2017;42(2):27-31. 

In This Article

Medications to Relieve Symptoms (Anti-ischemics)

Beta-Blockers:

As stated above, beta-blockers are considered first-line therapy for management of SIHD symptoms, particularly exercise-induced angina. Because beta-blockers reduce BP and heart rate during exercise, the onset of angina or ischemic threshold is delayed or avoided altogether.[6] Any beta-blocker may be used for treatment, although it is important to consider the beta-blocker's selectivity, dosing requirements, and cost. Selective beta-blockers such as metoprolol and atenolol are commonly used. If a beta-blocker is being considered in a patient with vasospastic or variant (Prinzmetal's) angina, one with alpha-blocking properties, such as carvedilol or labetalol, should be used because unopposed alpha blockade in these patients can potentially induce coronary vasospasm. The beta-blocker dose should be adjusted to limit the resting heart rate to about 55 bpm because higher resting heart rates have been associated with higher rates of mortality.[6]

Adherence to beta-blocker therapy may be limited by adverse effects. Although the majority of patients tolerate beta-blockers, some patients may experience fatigue, sexual dysfunction, lethargy, or sleep disturbances. If a patient is unable to tolerate beta-blocker therapy, the next option would be a calcium channel blocker or a long-acting nitrate for relief of symptoms.[6]

Calcium Channel Blockers

Calcium channel blockers are generally added to beta-blocker therapy when initial treatment with a beta-blocker does not adequately improve symptoms; they are also used as an alternative when beta-blocker use is contraindicated. However, beta-blockers have been shown to more effectively alleviate anginal symptoms and improve exercise tolerance, and they have an added survival benefit in patients who have HF or have had an MI.[6]

Dihydropyridine (e.g., nifedipine, amlodipine) and nondihydropyridine (e.g., verapamil, diltiazem) calcium channel blockers produce coronary vasodilation, a reduction in myocardial contractility, and a decrease in myocardial oxygen demand. Both classes are effective in managing anginal symptoms, so decisions about which one to use should be made on a case-by-case basis, with particular attention paid to drug interactions, adverse effects, and other patient-specific factors. Calcium channel blockers are the drugs of choice for patients with Prinzmetal's angina, along with nitrates used alone or in combination.[6]

Nondihydropyridines depress cardiac pacemaker rates and slow conduction, which can lead to sinus bradycardia; therefore, dihydropyridines are preferred in patients with cardiac-conduction defects such as sick sinus syndrome and sinus bradycardia. Combining diltiazem or verapamil with beta-blockers generally should be avoided because of enhanced effects on slowed heart rate and contractility, unless combination therapy is needed to achieve heart-rate control, particularly in patients with atrial fibrillation.[6]

Major adverse effects of dihydropyridines include headache, palpitations, flushing, and peripheral edema due to excessive arterial vasodilation. Verapamil can cause significant constipation, especially in elderly patients.[6]

Nitrates

Nitrates, which are effective at managing all forms of angina, are first-line therapy for the management of acute anginal symptoms. They relax vascular smooth muscle and reduce myocardial oxygen demand by inducing systemic vasodilation. By dilating veins, nitrates reduce the pressure of the blood returning to the heart (preload), and by dilating arteries, they reduce the pressure against which the heart has to pump (afterload). Both of these effects lead to a decrease in oxygen demand.[14]

Long-acting nitrates, such as isosorbide dinitrate, isosorbide mononitrate, and nitroglycerin, are recommended when beta-blockers or calcium channel blockers are not tolerated or are contraindicated, or when additional therapy is needed to achieve symptom control.[6] Despite differences in dosing and formulation, all nitrates seem to be roughly equivalent. Nitrates should be dosed and titrated using the lowest dose possible to alleviate symptoms and reduce the incidence of adverse effects such as headache, flushing, and tolerance. Nitrate tolerance is defined by the loss of antianginal effects after repeated dosing, necessitating increasingly higher doses to achieve a clinical effect. Therefore, a nitrate-free interval of 10 to 14 hours must be maintained to avoid tolerance. The use of long-acting nitrates does not lead to tolerance to sublingual products.[6]

All patients with SIHD should be prescribed sublingual nitroglycerin tablets or spray for acute episodes of angina. Most patients respond within 5 minutes of taking these products, but if relief does not occur, the patient should be advised to seek medical attention immediately. These products also may be used for prevention of exercise-induced angina; their effect lasts 30 to 40 minutes.[6]

Ranolazine

Ranolazine (Ranexa) is another therapy for chronic angina. It works by inhibiting the late inward sodium current in heart muscle and reducing sodium-dependent calcium levels, leading to a reduction in heart-wall tension and a decrease in oxygen consumption. Because ranolazine does not cause significant changes in heart rate or BP, it is an attractive alternative for patients with bradycardia or hypotension.[15] It can be used in combination with beta-blockers when relief of symptoms has not been successful, or as an alternative therapy if beta-blockers are contraindicated.[6]

Ranolazine prolongs the QTc interval in a dose-dependent manner; however, there is little experience with coadministration of other QT-prolonging agents. Of note, studies have shown a lower incidence of arrhythmias such as ventricular tachycardia, bradycardia, and atrial fibrillation with ranolazine compared with placebo. Ranolazine also may lower HbA1cin patients with diabetes. Its use is contraindicated in patients with clinically significant hepatic impairment. The most common adverse effects are constipation, dizziness, headache, and nausea.[15]

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