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 The leading web portal for pharmacy resources, news, education and careers March 21, 2018
Pharmacy Choice - Cholesterol Disease State Management - March 21, 2018

Cholesterol Disease State Management

Disease Focus: Hypercholesterolemia
by Darrell Hulisz, RPh, PharmD
Associate Professor, Department of Family Medicine
Case Western Reserve University, School of Medicine

It has long been established that coronary heart disease (CHD) is the leading cause of death in the United States in both men and women. More than 14 million Americans suffer from CHD. Each year more than one million Americans will suffer a new or recurrent myocardial infarction. An undisputed, independent risk factor for CHD development is high cholesterol (hypercholesterolemia). According to national consensus guidelines, slightly more than 50% or nearly 105 million American adults older than 20 years have total cholesterol levels 200 mg/dL. Other prominent risk factors for CHD, such as genetics & concurrent disease states (e.g. diabetes) cannot be modified. However, hypercholesterolemia (or dyslipidemia) can be modified through lifestyle changes and pharmacotherapy. Numerous clinical trials have confirmed the benefits of cholesterol reduction for decreasing mortality and CHD events and stroke. This is especially well-established among patients with existing CHD or other cardiovascular disease, such as hypertension and stroke. To a lesser extent, studies have also demonstrated that lowering cholesterol decreases the incidence of CHD events in patients without established coronary disease. Pharmacists are well positioned to improve the care of patients with hyperlipidemia by screening patients at risk for CHD, recommending appropriate lifestyle modifications and/or pharmacotherapy, and monitoring and counseling patients on lipid-lowering drugs.

Total blood cholesterol is composed of subunits called lipoproteins. Low density lipoprotein (LDL) is the atherogenic subunit and is often the main target for lipid lowering therapy. The usual goal for LDL is < 100-140mg/dL, or even as low as < 70 for high risk patients. High-density lipoprotein (HDL) is the beneficial subunit. Increased levels of HDL have been shown to correlate with CHD reduction. The usual goal for HDL in men is > 40mg/dL and > 50mg/dL in women. A high triglyceride level is also considered an independent risk for CHD and should be lowered to > 150mg/dL in most patients. LDL particles contributes to the development of fatty deposits in the arteries and HDL helps to remove excess LDL from the blood.

A number of therapeutic lifestyle changes can be recommended to decrease CHD risk factors, some of which can favorably alter lipoprotein levels. Patients should work to decrease any ongoing CHD risk factors prior to using pharmacotherapy. Examples of these interventions include weight loss, tobacco cessation, reduction of alcohol and sodium intake, increase physical activity, and control of hypertension. A number of dietary interventions include use of canola oil or olive oil for cooking, consuming more fiber, fruits, vegetables, whole grains, oatmeal, oat bran, barley, and dried beans. Patients should be encouraged to more fish (e.g. salmon, tuna), soybeans, flaxseeds, walnuts and almonds. Patients can fortify their foods with spreads and dressing that contain plant sterols or stanols.

Several drug therapy options are available to treat hypercholesterolemia. The HMG-Co-A inhibitors, or statins are generally considered first-line therapy in most patients. Examples include simvastatin and atrovastatin among several others. Statins inhibit the hepatic enzyme responsible for cholesterol synthesis, up-regulating LDL receptor activity to reduce circulating LDL. While these drugs are well tolerated, some patients may develop myalgia, myopathy and increased liver enzymes. Patients should promptly report any unexplained muscle pain and/or weakness, or dark-colored urine while taking a statin. These drugs are Category X for use in pregnancy. Maximum doses of these drugs can yield up to a 40-60% decrease in LDL when used with lifestyle modifications.

Fibric acid derivatives, or fibrates include gemfobrozil and fenofibrate. These drugs increase hepatic fatty acid metabolism and decrease secretion of triglyceride-containing lipoproteins. They are primarily used to treat isolated hypertriglyceridemia.

Niacin is a useful drug to treat mixed hypercholesterolemia. This drug reduces liver synthesis of triglycerides and inhibits the mobilization of free fatty acids. Side effects may include flushing, hyperglycemia, hyperuricemia, dyspepsia and rarely hepatotoxicity. Niacin decreases LDL and triglycerides, but raises HDL levels. The incidence of headache and flushing can be decreased by titrating the dosage up slowly, using a sustained-release preparation, and pre-treating with a prostaglandin inhibitor, such as aspirin or ibuprofen.

Bile acid sequestrants, such as cholestyramine bind bile acids in the intestine, interrupting their enterohepatic circulation and increasing hepatic conversion of cholesterol into bile acids. These drugs cause gastrointestinal complaints, such as constipation, flatulence and bloating.

Ezetimibe is a drug that acts at the brush border of the small intestine and inhibits cholesterol absorption. This results in a decrease in the delivery of intestinal cholesterol to the liver, which decreased hepatic cholesterol stores and increases clearance of cholesterol from circulation. Ezetimibe can be used as an alternative to statins or niacin if patients develop intolerable side effects.
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