TRIPASS XR تري باس

 

1

Diagnosis and Risk Assessment

The evaluation of a patient presenting with chest pain suspected to be due to CAD

should begin with a detailed history of ischemic symptoms and physical examination.

Once this information is available, an estimate can be made of the probability of

CAD being present (low, intermediate, high).

1 The probability estimate will often

help direct which diagnostic tests are appropriate. Given that many symptoms

associated with chronic stable angina are nonspecific, several noninvasive and

invasive testing modalities are available to assist in the diagnosis and risk

assessment of CAD.

1,2

It is important to discern as soon as possible whether the

patient’s reported chest discomfort is consistent with chronic stable angina, or

represents the presence of ACS. Patients presenting with ACS often are at high shortterm risk of MI or death and warrant hospitalization with aggressive treatment

strategies.

16,17 Lipid parameters, renal function, and fasting blood glucose levels

should be obtained in all patients with suspected or established CAD to screen for

metabolic abnormalities. Other biochemical markers such as high-sensitivity Creactive protein, lipoprotein(a), lipoprotein-associated phospholipase A2

, and

apolipoprotein B are not routinely recommended.

3

Table 12-2

Characteristics of Angina Pectoris

1–3

Symptoms

Sensation of pressure or heavy weight on chest alone or with pain

Pain described variably as feelings of tightness, burning, crushing, squeezing, vicelike, aching, or “deep”

Gradual increase in intensity followed by gradual fading away (distinguished from esophagealspasm)

a

Shortness of breath with feeling of constriction about the larynx of upper trachea

Duration of Symptoms

0.5–30 minutes

Location of Pain or Discomfort

Over the sternum or very near to it

Anywhere between epigastrium and pharynx

Occasionally limited to left shoulder and left arm

Rarely limited to right arm

Lower cervical or upper thoracic spine

Left interscapular or suprascapular area

Radiation of Pain

Medial aspect of left arm

Left shoulder

Jaw

Occasionally, right arm

Electrocardiogram

ST-segment depression >2 mm

T-wave inversion

Precipitating Factors

Mild, moderate, or heavy exercise, depending on patient

Effort that involves use of arms above the head

Cold environment

Walking against the wind

Walking after a large meal

Emotions: fright, anger, or anxiety

Coitus

Nitroglycerin Relief

a

Relief of pain occurring within 45 seconds to 5 minutes of taking nitroglycerin

aEsophagealspasm and other gastrointestinal disorders occasionally mimic anginal pain and also can be relieved by

nitroglycerin.

A 12-lead ECG reading should be obtained in all patients with symptoms

suggestive of angina pectoris. Although not useful

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in establishing a definitive diagnosis of CAD, the ECG will be useful at detecting

important information regarding conduction abnormalities, left ventricular

hypertrophy, ongoing ischemia, or evidence of a previous MI. Chest radiography is

not routinely recommended except in patients with an abnormal ECG, history of MI,

symptoms of HF, or ventricular arrhythmias.

1 Cardiac computed tomography

angiography (CCTA) is a reasonable option to determine risk in patients whose ECG

cannot be interpreted, who are unable to exercise to an appropriate workload, unable

to perform stress testing, or alternatively to invasive coronary angiography in

moderate- to high-risk patients with unknown coronary anatomy.

1

STRESS TESTING

The induction of stress via exercise or pharmacologic means is a common and highly

useful procedure in the diagnosis of CAD. The test would be indicative of CAD if

angina, ECG signs of ischemia, arrhythmias, abnormal heart rate, or abnormal blood

pressure (BP) response develops. The product of the heart rate and systolic BP (i.e.,

the rate–pressure or double product) correlates well with myocardial oxygen

demand. The rate–pressure product normally rises progressively during exercise,

with the peak value best describing the cardiovascular response to stress. Often,

patients with stable angina experience chest pain at a consistent rate–pressure

product.

18

Abnormal responses of either BP or heart rate may signal CAD. A normal BP

response to exercise is a gradual rise in systolic BP with the diastolic BP remaining

unchanged. A rise or fall of diastolic BP greater than 10 mm Hg is considered

abnormal. A fall in systemic BP during exercise is especially ominous because this

indicates that the cardiac output cannot increase sufficiently to overcome the

vasodilation in the skeletal muscle vascular bed.

18

Stress imaging studies, either echocardiographic or nuclear, are preferred over the

exercise tolerance test in patients with left bundle-branch block, electronically paced

ventricular rhythm, prior revascularization (percutaneous coronary intervention [PCI]

or coronary artery bypass surgery [CABG]), preexcitation syndrome, greater than 1

mm ST-segment depression at rest, or other ECG conduction abnormalities. In

addition, many patients are not able to exhibit an appropriate level of cardiac stress

through exercise; pharmacologic stress testing is preferred in these patients.

1,18

Pharmacologic stress may be achieved through the use of dipyridamole, adenosine,

or dobutamine. Each of these agents is used to induce changes in the balance between

myocardial oxygen supply and demand, similar to walking on a treadmill during the

exercise stress test. Vasodilators (dipyridamole and adenosine) promote vasodilation

in normal coronary segments, but have no effect in arteries affected by

atherosclerosis. The net result is shunting of blood away from diseased coronary

arteries and the development of ischemia that may be detected by changes in BP,

heart rate, or ECG changes. These agents are typically used in conjunction with

myocardial perfusion scintigraphy. Stress thallium-201 myocardial perfusion imaging

provides a dynamic picture of the heart. The radionuclide is injected at peak stress

and an image is obtained within several minutes. A defect in myocardial uptake of the

thallium indicates an area of ischemia or possible infarction.

19

Dobutamine is a positive inotrope and typically is used with echocardiography.

Administration of dobutamine leads to an increase in myocardial oxygen demand

secondary to increases in heart rate and contractility. If demand exceeds available

oxygen supply, ischemia develops. Subsequent to the infusion of dobutamine, defects

or decreases in the wall motion or thickening of the left ventricle are indicative of

ischemia.

19

CARDIAC CATHETERIZATION

CAD can be diagnosed definitively by coronary catheterization and angiography. In

addition, angiography is the most accurate means of identifying less common causes

of chronic stable angina, such as coronary artery spasm.

1 Cardiac catheterization is a

procedure used to provide vascular access to the coronary arteries. Once access is

gained with an intravascular catheter, a number of procedures (angiography,

ventriculography, PCI) can be performed. Access to the vasculature is usually

obtained percutaneously through the radial, brachial, or femoral arteries. From this

point, the catheter is advanced through the vasculature until the coronary arteries are

accessible. After the tip of the catheter is advanced into the coronary arteries, dye is

injected into the coronary arteries and the location and extent of atherosclerosis can

be determined. Approximately 75% of patients with chronic stable angina are noted

to have one-vessel, two-vessel, or three-vessel disease by this procedure (equally

divided).

3

The results of angiography can be useful in determining the risk of death or MI in

patients with CAD 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.

20,21

OVERVIEW OF DRUG AND NONDRUG THERAPY

The goals of therapy for chronic stable angina are to reduce or eliminate the

symptoms of angina, to maintain or improve the quality of life, halt the progression of

atherosclerosis and prevent complications of the disease, such as MI and death while

minimizing healthcare costs. Both pharmacologic and non-pharmacologic

interventions, in addition to myocardial revascularization procedures, are utilized

simultaneously to achieve each of these goals.

1

Vasculoprotective Therapy

LIFESTYLE MODIFICATIONS

Lifestyle modifications should always constitute a significant portion of any treatment

plan for patients with chronic stable angina. Lifestyle modification should include

adoption of a heart-healthy diet, smoking cessation/avoidance of second-hand smoke,

adequate physical activity, weight control, and maintenance of an acceptable waist

circumference.

1,22,23 Dietary recommendations typically consist of limiting saturated

fat, total fat, cholesterol, sodium, sugar-sweetened beverages, and red meat while

consuming a diet high in fruits, vegetables, whole grains, omega-3 fatty acids, and

fiber

22

(see Chapter 8, Dyslipidemias, Atherosclerosis, and Coronary Heart

Disease). Adoption of a healthy dietary pattern reflective of these components has

been demonstrated to have positive effects on cardiovascular risk factors.

1,22

Smoking cessation is a crucial intervention as cigarette smoking (including

second-hand smoke exposure) has been identified as the single most preventable

cause of death due to CAD.

24 Clinicians should routinely assess the smoking status of

patients with chronic stable angina and provide information regarding effective

options to aid in smoking cessation. Nicotine replacement products, bupropion, and

varenicline have been demonstrated as effective in assisting cessation efforts (see

Chapter 91, Tobacco Use and Dependence). In addition to the avoidance of cigarette

smoke, it is reasonable to recommend the avoidance of air pollution in patients with

chronic stable angina. Unless contraindicated, it is appropriate to recommend

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one alcoholic beverage in women and one to two alcoholic beverages in men.

1

A body mass index (BMI) of 18.5 to 24.9 kg/m2 and a waist circumference less

than 40 inches in men and 35 inches in women should be achieved or maintained.

Adequate exercise facilitates both weight loss and better control of cardiovascular

risk factors. Patients with chronic stable angina should be encouraged to engage in

moderate-intensity exercise for 30 to 60 minutes/day for at least 5 days/week, but

ideally each day. Weight loss can be facilitated through appropriate caloric

restriction, as well as the adoption of healthy dietary eating patterns.

1

RISK FACTOR MODIFICATION

In addition to appropriate lifestyle modifications, optimization of cardiovascular risk

factors should be achieved. Although the lifestyle modifications may help improve

risk factor control, pharmacotherapy may be required. Table 12-3 provides

appropriate targets for risk factor optimization. Appropriate identification and

treatment of risk factors helps prevent the development of CAD and disease

progression in patients with existing CAD. Select drug therapies for each risk factor

may be preferred due to their positive effects on the pathophysiology of

atherosclerosis. Although several different classes of lipid-modifying drugs exist, 3-

hydroxy-3-methylglutaryl co-enzyme A inhibitors (HMG-CoA reductase inhibitors,

or statins) have been demonstrated in multiple trials to significantly reduce the

progression of atherosclerosis, as well as reduce the incidence of death and MI.

25

In

patients who require additional BP control after antianginal therapy has been

optimized, angiotensin-converting enzyme (ACE) inhibitors may be preferred due to

their theoretical potential to reduce the progression of CAD by improving endothelial

function. Data suggest that angiotensin receptor blockers (ARBs) may provide

similar benefits in patients who cannot tolerate ACE inhibitors.

1,26 The presence of

diabetes has been shown to be a significant risk factor for the development and

progression of atherosclerosis; however, the majority of clinical trials demonstrate

that tight glycemic control did not have a positive effect on the progression of

atherosclerosis or reduce the risk of hard end points such as MI.

27

Information from

the Diabetes Control and Complications Trial indicates that tight glycemic control

with intensive insulin therapy in patients with type 1 diabetes significantly reduces

the risk for MI and cardiovascular death.

28 Similar effects have not been seen in large

randomized trials in patients with type 2 diabetes. In one large trial involving

patients with CVD and type 2 diabetes, the use of intensive insulin therapy reduced

nonfatal MI at 5 years, but total mortality was increased.

29 Given the available

information, intensive glucose lowering cannot be recommended for patients with

CAD and type 2 diabetes. Patients with type 2 diabetes should target a glycosylated

hemoglobin (Hgb A1c

) less than 7%.

27

Table 12-3

AHA/ACC Guidelines for Secondary Prevention for Patients with Coronary and

Other Atherosclerotic Vascular Disease

23,25,26

Risk Factor Intervention and Goal

Smoking Complete cessation

No exposure to environmental tobacco smoke

Blood pressure <140/90 mm Hg

Lipid management High intensity statin

Diabetes Hemoglobin A1c <7%

Physical activity At least 30 minutes of moderate-intensity aerobic

activity (e.g., brisk walking) for minimum of 5

days/week

Weight management BMI between 18.5 and 24.9 kg/m

2

Waist circumference, men <40 inches

Waist circumference, women <35 inches

Influenza vaccination Patients with CAD should have an annual influenza

vaccination

BMI, body mass index; CAD, coronary artery disease; HDL-C, high-density lipoprotein cholesterol; LDL-C, lowdensity lipoprotein cholesterol.

ANTIPLATELET THERAPY

Antiplatelet therapy has a central place in the treatment of patients with CAD.

Aspirin (acetylsalicylic acid [ASA]) therapy has demonstrated a reduction in the

incidence of MI and sudden cardiac death in patients with chronic stable angina.

Aspirin’s clinical efficacy in chronic stable angina, coupled with its minimal cost

and demonstrated efficacy after MI, have made it the gold standard for antiplatelet

monotherapy in patients with CAD. Current national guidelines from the American

College of Cardiology (ACC)/AHA recommend an ASA dose of 75 to 162 mg daily

for the prevention of MI and death. Although higher doses have been investigated in

clinical studies, they have not shown increased efficacy, but do increase the risk for

adverse effects.

23

Clopidogrel represents a suitable alternative antiplatelet agent to prevent MI and

death in chronic stable angina patients unable to take ASA. The Clopidogrel versus

Aspirin in Patients at Risk of Ischemic Events trial (CAPRIE) demonstrated that

clopidogrel significantly reduced the incidence of stroke, MI, or vascular death in

patients with atherosclerotic vascular disease (previous MI, stroke, or peripheral

arterial disease [PAD]) compared with ASA. In addition, clopidogrel was well

tolerated with the major adverse effects noted to be gastrointestinal (GI) intolerance

and rash. Despite the significant results, the absolute difference in the primary

outcome between the two strategies was quite small (0.4%, number need to treat =

200).

30 As such, clopidogrel remains a second-line choice behind ASA in patients

with CAD. Clopidogrel should be administered at a dosage of 75 mg/day.

The approach of dual antiplatelet therapy (DAPT), combining ASA with a P2Y12

antagonist (clopidogrel, prasugrel, or ticagrelor), has been demonstrated to improve

morbidity and mortality in a number of high-risk patients with CVD.

16,17 Given the

different mechanisms of antiplatelet effect, combining aspirin with a P2Y12 antagonist

might be expected to provide additional protection from MI and death in patients

with stable CAD as compared to monotherapy. The Clopidogrel for High

Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance trial

assessed the utility of long-term DAPT in patients with documented CAD or with

multiple cardiovascular risk factors. The combination of ASA plus clopidogrel for

28 months did not reduce the risk of death, MI, stroke, or coronary revascularization

as compared to ASA alone. However, dual therapy did increase the risk of

bleeding.

31

A post hoc analysis revealed a reduction in ischemic risk in patients with prior MI

suggesting that some patients may benefit from long-term DAPT.

31 The Pegasus-TIMI

54 trial evaluated the role of DAPT (low-dose ASA plus either ticagrelor 90 mg BID

or 60 mg BID vs. ASA alone) in patients with a prior MI in the previous 1 to 3

years.

32 The median time from MI to randomization was 1.7 years. In over 21,000

patients with a median follow-up of 33 months, ASA plus both doses of ticagrelor

reduced the primary

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end point (cardiovascular death, MI, stroke) compared to ASA monotherapy. This

reduction came at the expense of an increased risk of bleeding, with TIMI major

bleeding occurring at a rate of 2.6% and 2.3% in the groups receiving ticagrelor 90

mg and 60 mg BID, as compared to 1.06% in patients receiving placebo.

32

In a separate investigation, patients who received an additional 18 months of

DAPT as compared to the standard duration of 12 months in patients who received

drug-eluting stents (DES) had a lower rate of stent thrombosis (0.4% vs. 1.4%, p <

0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs.

5.9%, p < 0.001), which included a reduction in MI.

33 There was an increase in

moderate to severe bleeding (2.5% vs. 1.6%, p = 0.001). Up to 40% of the 9,961

patients underwent PCI due to chronic stable angina, and DAPT either consisted of

ASA plus clopidogrel, or ASA plus prasugrel.