21

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Table 12-5

Calcium-Channel Blockers in Anginal Syndromes

Drug Name FDA Approved

a

Usual Dose for Chronic

Stable Angina

b Product Availability

Dihydropyridines

Amlodipine Angina, hypertension 2.5–10 mg every day 2.5, 5, 10 mg tab

Felodipine Hypertension 5–20 mg every day 5, 10 mg ER tab

Isradapine Hypertension 2.5–10 mg BID 2.5, 5 mg IR cap

5–10 mg every day 5, 10 mg CR tab

Nicardipine Angina (IR only),

hypertension

20–40 mg TID 20, 30 mg IR cap

30–60 mg BID 30, 45, 60 mg SR cap

Nifedipine Angina, hypertension 10–30 mg TID 10, 20 mg IR cap

30–180 mg every day 30, 60, 90 mg ER tab

Nisoldipine Hypertension 20–60 mg every day 10, 20, 30, 40 mg ER tab

Diphenylalkylamines

Verapamil Angina, hypertension,

SVT

30–120 mg TID/QID 40, 80, 120 mg IR tab

120–240 mg BID 120, 180, 240 mg SR tab

120–480 mg every HS 180, 240 mg DR, ER tab

120, 180, 240, 360 mg ER

cap

100, 200, 300 mg DR, ER

tab

Benzothiazepines

Diltiazem Angina, hypertension,

SVT

30–120 mg TID/QID 30, 60, 90, 120 mg IR tab

60–180 mg BID 60, 90, 120, 180 mg SR

cap

120–480 mg every day 120, 180, 240, 300, 360 mg

cap

120, 180, 240 mg ER cap

120, 180, 240, 300, 360,

420 mg ER cap

aFDA-approved indications vary among IR and ER products. However, most all have been used clinically for both

angina and hypertension. Avoid IR products in hypertension.

bBecause of short half-lives, most of these drugs are given TID if using IR tabs or caps. Amlodipine has a long

half-life and is given once daily.

BID, 2 times a day; cap, capsules; CD, controlled diffusion; CR, controlled-release; DR, delayed-release; ER,

extended-release; FDA, US Food and Drug Administration; HS, bedtime; IR, immediate-release; QID, four times

a day; SR, sustained-release; SVT, supraventricular including atrial fibrillation, atrial flutter, and re-entry; tab,

tablets; TID, three times a day.

Despite the availability of data regarding the relative effects of PCI, CABG, and

medical management on morbidity and mortality, there has been a dramatic increase

in the use of PCI in recent years. CABG remains the preferred strategy for patients

with three-vessel disease or who have multi-vessel disease plus left ventricular

dysfunction. In patients with less severe CAD, PCI can be expected to provide

similar benefits in mortality as compared to CABG, but may not be as effective at

reducing symptoms or the need for repeat revascularization procedures. Recent

investigations have indicated that aggressive medical treatment, including intensive

lipid-lowering therapy, may be as effective as PCI at improving prognosis over the

long term, but may be inferior at reducing symptoms of angina.

1,43,44 These trials are

significant in that they highlight the importance of implementing effective strategies,

which reduce the progression of CAD, regardless of whether revascularization

therapy is utilized. Relevant issues facing pharmacists today not only include

optimizing the medical management of CAD but also providing effective

pharmacotherapy to prevent complications of PCI.

CLINICAL PRESENTATION OF CHRONIC

STABLE ANGINA

CASE 12-1

QUESTION 1: J.P., a 62-year-old dairy farmer, is hospitalized for evaluation of chest pain. About 3 weeks

before admission, he noted substernal chest pain brought on by lifting heavy objects or walking uphill. He

describes a crushing or viselike pain that never occurs at rest and is not associated with meals, emotional stress,

or a particular time of day. When J.P. stops working, the pain subsides in about 5 minutes.

J.P.’s mother and brother died of a heart attack at ages 62 and 57, respectively; his father, who is alive at

age 86, has survived one heart attack and one stroke. Family history (except for J.P.)

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is negative for diabetes mellitus. J.P. is 5 feet 10 inches tall and weighs 235 pounds; he drinks two or three

beers a day and does not smoke or chew tobacco.

J.P.’s other medical problems include a 10-year history of hypertension and diabetes for 4 years. Until 3

weeks ago, J.P. could perform all his farm chores without difficulty, including heavy labor. He follows a noadded-salt diet, but consistently eats at fast-food establishments with his favorite meal consisting of two

cheeseburgers and French fries.

J.P.’s medication history reveals the following: lisinopril 10 mg once daily, metformin 500 mg BID and

hydrochlorothiazide 25 mg once daily. He rarely uses over-the-counter medications. He has an allergy to

sulfamethoxazole.

On admission to the cardiac ward, J.P. appears his stated age and is in no apparent distress. Resting vital

signs include supine BP, 145/95 mm Hg (last ambulatory visit, 130/85 mm Hg); regular pulse, 84 beats/minute

(last ambulatory visit, 78 beats/minute), and respiratory rate, 12 breaths/minute. He has no peripheral edema or

neck vein distension, and lung auscultation is within normal limits. Abdominal examination is unremarkable and

he is alert and oriented × 3. Cardiac auscultation reveals a regular rate and rhythm with a normal S1

and S2

;

third or fourth heart sounds and murmurs are not noted. A 12-lead ECG reveals normal sinus rhythm at a rate

of 84 beats/minute without evidence of previous MI. All intervals are within normal limits.

Admitting laboratory values include the following:

Hct, 43.5%

White blood cell (WBC) count, 5,000/μL

Sodium (Na), 140 mEq/L

Potassium (K), 4.7 mEq/L

Magnesium (Mg), 1.9 mEq/L

Random blood glucose, 132 mg/dL

Hgb A1c 7.4%

Blood urea nitrogen, 27 mg/dL

Serum creatinine, 1.4 mg/dL

Urinary albumin–creatinine ratio, 27 mg/mmol

Chest radiograph is within normal limits.

What signs and symptoms does J.P. exhibit that are consistent with the diagnosis of chronic stable angina?

J.P.’s description of his chest pain includes several common characteristics of

angina pectoris (Table 12-2).

1–3 The substernal location of J.P.’s chest pain is

typical, although some patients describe pain radiating down the left arm or pain that

is referred to the shoulder area or jaw. J.P.’s pain is described as crushing or

viselike in quality, which also is common; a fullness in the throat or jaw may occur

simultaneously or in lieu of chest pain. In some cases, the patient may not consider

these sensations as pain, describing them instead as a sense of pressure or heaviness.

Many patients complain of SOB. J.P.’s symptoms are related to exercise and exertion

—both known precipitating factors of angina. Most episodes of exertional angina last

several minutes in duration and are relieved with rest. Because J.P. has never sought

medical attention for his chest pain, his response to NTG cannot be determined.

After getting a detailed description of J.P.’s symptoms, his physician can

characterize his chest pain and make a global assessment. Initially, the chest pain

should be classified as either typical angina, atypical angina, or noncardiac chest

pain. Furthermore, angina should also be classified as either stable or unstable. This

distinction is important because it indicates whether his short-term risk of an acute

coronary event could be life-threatening. Attempts to categorize J.P.’s anginal

symptoms on an objective measurement scale (e.g., Canadian Cardiovascular Society

Grading Scale) can be misleading.

45 For example, a sedentary 65-year-old patient’s

class II symptoms may be tolerable, but the same symptoms could significantly

disable an active 50-year-old patient.

J.P.’s chest pain is of a quality and duration characteristic of angina, provoked by

exertion, and relieved by rest; therefore, J.P.’s constellation of symptoms can be

classified as typical chest pain. J.P.’s symptoms do not occur at rest; however, they

should be classified as stable angina.

1–3

CASE 12-1, QUESTION 2: Assess J.P.’s physical examination. What signs and symptoms are relevant to

the angina?

The physical examination typically provides little information about the presence

of CAD. The most useful findings pertain to the cardiovascular system where heart

rate and BP can be increased during an acute anginal episode. J.P.’s physical

examination is characteristic of a man of his age with angina.

3 He is obese and

hypertensive, but his cardiac examination is normal. The presence of murmurs would

have required further workup; the absence of a third heart sound suggests that the left

ventricle may be functioning normally. (See Chapter 14, Heart Failure, for a

description of third heart sounds.) The absence of a fourth heart sound in J.P. is

indicative of a low probability of cardiac end-organ damage resulting from systemic

hypertension. His chest radiograph, which is normal, does not present evidence of

other complications commonly associated with myocardial ischemia (e.g., enlarged

heart, HF).

J.P.’s physical examination should also evaluate the possibility of the presence of

atherosclerosis in other major vascular beds (peripheral vascular disease,

cerebrovascular disease, abdominal aortic aneurysm). The presence of xanthomas

would suggest severe hypercholesterolemia, but these were not noted in J.P.

Diagnostic Procedures

CASE 12-1, QUESTION 3: What other objective diagnostic procedures are helpful to confirm CAD and

angina in J.P?

A 12-lead ECG indicates there is no ongoing ischemia at this time. As such, it

does not help confirm the diagnosis of CAD. An echocardiogram could be used to

better assess cardiac structure and function, including ruling out other potential

causes for myocardial ischemia such as valvular dysfunction or pericardial disease,

but would not definitively confirm the presence of CAD. Electron bean computed

tomography or CCTA could be used to detect the presence of coronary

atherosclerosis, but in J.P. would not offer vital prognostic information available

with other testing modalities.

1

Given J.P’s current lifestyle and activity level, he would likely be able to tolerate

exercise treadmill testing. Treadmill testing would be an appropriate initial

diagnostic modality in J.P. due to its noninvasive nature, reliability with established

protocols, as well as the ability to offer prognostic information regarding the risk of

MI and death for J.P. Therefore stress testing, in this case with exercise treadmill

versus pharmacologic means, is an excellent initial diagnostic modality to use in J.P.

CASE 12-1, QUESTION 4: Should J.P. undergo cardiac catheterization? How will the results of this invasive

procedure influence future therapy?

Coronary catheterization and angiography is the best test for the definitive

diagnosis of CAD. In addition, angiography is the most accurate means of identifying

less common causes of chronic stable angina, such as coronary artery spasm.

1

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p. 218

Although angiography is effective at identifying flow-limiting atherosclerotic

plaques in the coronary vasculature, it cannot provide information on whether those

lesions are causing clinical symptoms. Stress testing is often a more appropriate

initial modality to first characterize the myocardial ischemia that takes place with

exertion. Patients with significant ischemia via stress testing should then undergo

cardiac catheterization to determine the nature and extent of disease. The results of

angiography will be useful in determining the risk of death or MI in J.P. and,

subsequently, the course of needed treatment. For example, patients who have a

significant stenosis in the left main coronary artery are at high risk of death and

should undergo CABG.

20

Risk Stratification and Prognosis

CASE 12-1, QUESTION 5: After having a positive treadmill stress test and undergoing subsequent cardiac

catheterization, J.P. is found to have two-vessel CAD with obstructive lesions of 55% and 70% in the right

coronary artery (RCA) and circumflex arteries, respectively; the LAD coronary artery is not involved. What is

his prognosis?

The prognosis of patients with stable angina is variable and dependent on the

presence of other factors and comorbid conditions. The extent of CAD, quantification

of ventricular function, the response to stress testing, as well as the initial clinical

evaluation all help to provide an estimate of risk in a given patient. Developing a

level of risk for a particular patient helps determine the appropriate treatment

strategy.

1,2

J.P.’s history and physical examination suggest he does not have HF; poor LV

function would be an ominous concurrent finding. J.P. also does not have threevessel disease or blockage of the LAD artery. J.P. does have type 2 diabetes, which

elevates his risk for future cardiovascular events. The absence of other major

comorbid conditions, myocardial dysfunction, along with the current extent of CAD

indicates that J.P.’s prognosis at this time is favorable provided he initiate

appropriate treatment strategies demonstrated to reduce morbidity and mortality in

patients with CAD.

1,2

Medical Management of Chronic Stable Angina

CASE 12-1, QUESTION 6: How should J.P. be managed at this time? Should he undergo revascularization

with PCI or CABG, or be managed medically?

As discussed previously, goals for managing CAD and angina in J.P. include relief

of symptoms and reduction of myocardial ischemia to improve quality of life, as well

as prevention of major complications of CAD such as acute MI and death.

1

Depending on the patient, both goals may be accomplished through surgical

revascularization, medical management, or both. Regardless of the treatment strategy

chosen to relieve ischemic symptoms, therapies that prevent death (vasculoprotective

agents) should receive priority.

Presently, CABG is not the best option for J.P. because the usual indications for

surgical therapy include presence of left main CAD, presence of three-vessel disease

(especially if LV function is impaired), or ineffectiveness of medical therapy.

1,20

However, revascularization with PCI is a potential option along with medical

management alone. Although PCI would offer no mortality advantage over medical

therapy at this time, it has been shown to decrease the incidence of recurrent

symptoms in the short term (1 year).

1

If J.P. can implement aggressive lifestyle

modifications and control of risk factors, progression of CAD and control of

ischemic symptoms will be similar to PCI within a 5-year time frame.

42 Both

strategies, including the pros and cons of PCI or medical management alone, should

be offered to J.P. so that an informed decision can be made in accord with his

wishes. Overall, J.P. will probably do well with medical therapy. His life

expectancy depends on progression of the disease and development of other

complications of CHD (HF, MI, sudden cardiac death).

RISK FACTORS AND LIFESTYLE MODIFICATIONS

CASE 12-1, QUESTION 7: What independent risk factors for CAD are present in J.P.? Which of these may

be altered?

The first step in the treatment of any patient with chronic stable angina or CAD

should be the modification of any existing risk factors and the adoption of a healthy

lifestyle. By addressing the underlying circumstances, which likely led to the

development of CAD, a significant impact can be made at halting the progression of

the disease and preventing complications of CAD. Current recommendations for the

goals for risk factor management are listed in Table 12-3.

23,25,26

In addition to specific

risk factor goals, attention should be paid to evidence that favors specific drug

therapies that have evidence supporting reductions in morbidity and mortality.

Examples would include the use of HMG-CoA reductase inhibitors in the treatment

of hyperlipidemia,

1,2 as well as the use of ACE inhibitors for the treatment of

hypertension.

25,26

J.P. has several risk factors for CAD, some of which cannot be altered, such as

middle age, male sex, and a strong family history of CAD. Risk factors, such as

hypertension, obesity, hypercholesterolemia, smoking, and possibly stress, can

potentially be modified to decrease the likelihood of adverse sequelae for J.P. His

hypertension should be controlled and statin therapy should be initiated (see Chapter

8, Dyslipidemias, Atherosclerosis, and Coronary Heart Disease). A fasting Hgb A 1c

should be drawn with a goal of less than 7% (see Chapter 53, Diabetes Mellitus).

Dietary modification and weight reduction for J.P. are mandatory, because they

positively influence several risk factors. J.P., however, does not smoke cigarettes,

which would significantly increase his cardiovascular risk.

1,22 J.P.’s active lifestyle

may influence his prognosis favorably.