Pharmacy Times

Multistep Approach to the Treatment of CAD

Author: Yvette C. Terrie, BSPharm, RPh

Coronary artery disease (CAD) is the most prevalent type of heart disease, affecting approximately 13 million individuals in the United States. It is considered to be the number-1 killer among both men and women.1 It is the end result of atherosclerosis, which occurs when the arteries that supply blood to the heart muscle become hardened and narrowed as the result of an accumulation of plaque in the inner walls or the lining. The flow of blood to the heart is diminished due to this narrowing, and thus the supply of oxygen to the myocardial tissue is decreased. Over time, the plaque can completely obstruct blood flow to the myocardial tissue or cause the formation of blood clots that can lead to myocardial infarction (MI).

CAD can begin as early as childhood and can develop over many years. The major complications of CAD, in addition to MI, are angina pectoris, unstable angina, and arrhythmias, which may cause sudden death. Yet, 25% to 30% of all individuals in the early stages of CAD are asymptomatic and are experiencing "silent ischemia."2

CAD is very prevalent in individuals over the age of 70, and it is often thought to be misdiagnosed or underdiagnosed in this patient population.3 The risks of developing CAD are not exclusively an unavoidable result of the aging process but are directly related to lifestyle and environmental factors. The likelihood of developing CAD is dependent on certain risk factors, some of which can be controlled whereas others cannot (Tables 1 and 2).

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Figure

Signs and Symptoms

The signs and symptoms of CAD can vary. In some individuals, an MI is the first sign of CAD. Other common signs include chest pain or angina, dyspnea upon exertion, or episodes of fatigue. Signs of angina in men may include pain felt behind the breastbone that may radiate up to the left arm, neck, shoulder, elbow, jaw, or back. Some individuals may exhibit atypical symptoms such as indigestion, excessive sweating, or nausea. Atypical symptoms are very common in women.

Diagnosis

Various diagnostic tests are used to determine whether an individual has CAD, along with an evaluation of the individual's symptoms, risk factors, and genetic history. The tests typically performed include the following:

Recently, the FDA approved the marketing of the PLAC test, a laboratory blood test that, when used in conjunction with a clinical evaluation, can predict an individual's risk of CAD. Because nearly 50% of individuals who have heart attacks have normal low-density lipoprotein (LDL) levels, this test can be beneficial in predicting risks. The PLAC test measures lipoprotein- associated phospholipase (A2, Lp-PLA2). Any sign of elevation indicates an increased risk of CAD.4

Goals of Treatment

Pharmacists can play an effective role in the management of CAD by having a thorough understanding of both the pathophysiology and the pharmacology of CAD. A multistep approach often is utilized in the treatment of CAD, which includes pharmacologic agents, lifestyle modifications, and special invasive procedures. The goals of treatment include the following:

Pharmacologic Therapies

The choice of pharmacologic therapies is dependent on the patient's medical history and the extent of CAD. In the geriatric population, decreased hepatic and renal functions should be considered when selecting appropriate pharmacologic therapies and dosing regimens to reduce the incidence of adverse effects and/or toxicity. Because these patients tend to have multiple drug regimens and other disease states, they should be screened for potential drug?drug interactions and contraindications.

Nitrates

Currently, various nitrate products are available for the treatment of angina. Long-term usage of nitrates may lead to the development of tolerance to their pharmacologic effects. This tolerance may be prevented by establishing "nitrate-free" periods. Abrupt withdrawal should be avoided so as to decrease the chances of precipitating an angina attack. Tapering the dose over time is recommended.

Beta-Blockers

Beta-blockers have been in use since the 1970s and have been very advantageous in the treatment of CAD. They exert their therapeutic effect by competitive inhibition of betaadrenergic receptors, thus causing reduction in cardiac rate and contractibility and therefore de-creasing myocardial oxygen demand. Beta-blockers should be avoided particularly in elderly populations and in those with chronic obstructive pulmonary disease, diabetes, and congestive heart failure (CHF). Otherwise, beta-blockers tend to be well-tolerated by other patient populations.

Calcium Channel Blockers

Calcium channel blockers such as verapamil, diltiazem, and nifedipine aid in treating CAD because they cause peripheral dilation, producing a decrease in afterload and hence a reduction in myocardial oxygen demand. In general, adverse effects associated with calcium channel blockers stem from their therapeutic effect and may include peripheral edema, hypotension, and constipation. In the elderly population, constipation tends to be troublesome and needs to be monitored.

Antiplatelet Drugs/Anticoagulants

Antiplatelet drugs such as aspirin, glycoprotein IIb/IIIa inhibitors, thienopyridines, and anticoagulants (eg, warfarin and heparin) are very beneficial in preventing the formation of thrombi or emboli. Low-dose aspirin is the first line of defense in preventing MIs in patients with stable angina or in those with risk factors. Aspirin alone has been reported to reduce the risk of an MI by 25% to 50% in men.5 These therapies also pose the risk of bleeding disorders, however.

Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are very useful in treating hypertension and usually are recommended as an agent of choice in individuals with diabetes, CHF, and renal abnormalities. They exert therapeutic action by inhibiting the breakdown of bradykinin, thus inhibiting the conversion of angiotensin I to angiotensin II. They work by vasodilation without producing tachycardia. Due to the breakdown of bradykinin, a dry hacking cough is a common adverse effect. ACE inhibitors also can cause hyperkalemia.

Cholesterol-Lowering Agents

Because there is a strong correlation between hypercholesterolemia and CAD, the usage of antihyperlipidemic agents such as ezetimibe (Zetia; Merck/Schering-Plough), the fibrates (gemfibrozil), resins (cholestyramine), and niacin products commonly are used to reduce lipoprotein levels.

In the past few years, the management of CAD has been enhanced by the addition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly known as statins. These drugs include atorvastatin (Lipitor; Parke-Davis); pravastatin (Pravachol; Bristol-Myers Squibb); rosuvastatin (Crestor; AstraZeneca); simvastatin (Zocor; Merck); and lovastatin. These agents have been utilized for both primary and secondary prevention of CAD. They exert their pharmacologic effect by inhibiting HMG-CoA reductase, the rate-timing enzyme in cholesterol synthesis, thus reducing LDL levels. Statins also can cause reductions in triglyceride levels and small elevations of high-density lipoprotein. Common adverse effects include gastrointestinal discomfort, headaches, and nausea. Periodic hepatic-function monitoring is recommended, because these agents can cause elevation of serum transaminase levels. Statins, however, have demonstrated their effectiveness in reducing mortality rates in relation to CAD.

Combination Therapy

In some cases of CAD, monotherapy is insufficient for controlling symptoms. Combining various pharmacologic therapies may be necessary to slow the progression of CAD and to decrease the incidence of cardiac events.

Invasive Procedures

In some cases of severe CAD, the use of pharmacologic agents and lifestyle modifications are not effective and symptoms are not controlled. In these cases, angioplasty or coronary artery bypass surgery may be needed.

Conclusion

A thorough knowledge of the clinical management of CAD can aid pharmacists in educating patients about reducing risk, improving outcomes by being compliant with their medication regimen, and committing to lifestyle modifications. Pharmacists also can encourage younger patients to make conscious decisions to reduce the progression of this cardiovascular morbidity, through modifying any controllable risk factors and taking proactive measures to decrease risk.

Ms. Terrie is a clinical pharmacy writer based in Slidell, La.

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