PHARMACOTHERAPY OF DYSLIPIDEMIA

HMG-CoA Reductase Inhibitors
Lovastatin, pravastatin, simvastatin fluvastatin atorvastatin (Lipitor) and cerivastatin are HMG-CoA reductase inhibitors, or statins, that inhibit cholesterol synthesis. To varying degrees, all of these agents lower total, LDL and triglyceride cholesterol components and slightly raise the HDL fraction. While these agents are generally well tolerated, a small percentage of patients (less than 1 percent) may develop elevated hepatic transaminase levels, which may necessitate discontinuation of the drug.21 Other adverse effects include myopathy (fewer than 0.1 percent of cases) and gastrointestinal complaints. The gastrointestinal effects often subside with continued therapy. Evidence suggests that these agents reduce untoward cardiovascular events and work by mechanisms beyond the simple reduction in the LDL cholesterol level. The results of the Primary Prevention of Coronary Heart Disease with Pravastatin trial demonstrated reductions of 31 percent in first myocardial infarctions, 32 percent in cardiovascular mortality, 22 percent in total mortality and 37 percent in the need for revascularization procedures (Shepherd J, Cobbe SM, 1995) HMG-CoA reductase inhibitors, or statins, are well tolerated and cost-effective, and have been shown to reduce coronary events as well as the need for revascularization procedures. There are differences among the statins. For example, atorvastatin has a slightly different side effect profile than the other statins. It may exert a greater effect on lowering LDL cholesterol, total cholesterol and triglycerides, but higher doses of other statins may produce the same response. However, atorvastatin as a single agent may obviate the need for multiple drug therapy in high-risk patients. (Nawrocki JW, Weiss SR, Davidson MH, 1995). In view of the numerous other mechanisms being investigated, such as plaque stabilization, antiplatelet aggregation activity and anti-arterial spasmodic effects, this particular difference may be less important than other factors. To date, no comparative studies of the statins have been performed to delineate all of the clinically important differences. However, analysis of the Scandanavian Simvastatin Survival Study showed that hospitalization costs for patients hospitalized because of cardiovascular disease were reduced by approximately 31 percent, making statins quite cost-effective. (Pedersen TR, Kjekshus J, Berg K, 1996) Statins should generally be taken in a single dose with the evening meal or at bedtime to maximize the LDL lowering effect.
Bile Acid Binding Resins
The anion exchange resins cholestyramine (Questran) and colestipol (Colestid) bind cholesterol-containing bile acids in the intestines, producing an insoluble complex that prevents reabsorption. This results in increased hepatic oxidation of cholesterol to bile acids, fecal cholesterol excretion and LDL receptor activity. (Snyder S. 1990)These agents decrease LDL cholesterol levels by up to 20 percent. They may be a good choice in patients with hepatic disease because they do not affect hepatic metabolism. They are also a good choice in very young patients and women of childbearing age.. (Atkins D, Garber AM. 1996)

Nicotinic Acid
Nicotinic acid, or niacin, decreases the synthesis of LDL cholesterol by reducing the hepatic synthesis of VLDL cholesterol, by increasing the synthesis of HDL cholesterol, by inhibiting lipolysis in adipose tissue and by increasing lipase activity. This agent increases the HDL level by 15 to 35 percent, reduces total and LDL cholesterol levels by 10 to 25 percent, and decreases the triglyceride level by 20 to 50 percent. Side effects of nicotinic acid include flushing, pruritus, gastrointestinal discomfort, hyperuricemia, gout, elevated liver function tests and glucose intolerance. Taking 325 mg of aspirin 30 minutes before the drug is ingested may minimize flushing. (Jungnickel PW, Maloley PA, 1997).
Fibric Acid Derivatives
Fibric acid derivatives, or fibrates, increase the clearance of VLDL cholesterol by enhancing lipolysis and reducing hepatic cholesterol synthesis. These agents have been reported to lower triglyceride levels by 20 to 50 percent, raise HDL levels by up to 20 percent and reduce LDL levels by approximately 5 to 15 percent.( Carlson LA, Rosenhamer G. 1988) Some patients with hypertriglyceridemia may have an increase in LDL levels, so such patients should be very closely monitored if fibrates are used. Gemfibrozil is particularly useful in patients with diabetes and familial dysbetalipoproteinemia.
Side effects of gemfibrozil include nausea, bloating, flatulence, abdominal distress and mild liver-function abnormalities. Myositis, gallstones and elevation of the LDL cholesterol level have also been reported. Clofibrate has been associated with formation of gallstones and serious gastrointestinal disease, including hepatic malignancy, (Cohen JD, Pearson TA, 1996) and therefore should only be used in certain select patients with types II, IV or V hyperlipidemia. In addition, clofibrate has not been shown to prevent coronary heart disease. Fibrates should generally not be used with HMG-CoA reductase inhibitors because the risk of severe myopathy is greatly increased. (National Cholesterol Education Program. Cholesterol lowering in the patient with coronary heart disease 1997).
COMPLEMENTARY AND ALTERNATIVE THERAPIES FOR THE MANAGEMENT OF DYSLIPIDEMIA
Randomized controlled trials were found for omega-3-fatty acids, policosanol, plant stanols and sterols, flaxseed, red yeast rice, guggulipid, garlic, fiber, almonds, and soy. Studies for each of these agents report varying degrees of lipid reduction. Based on published data, effective therapeutic options for lipid-lowering include intake of fiber, intake of plant stanols/sterols, replacement of animal protein with soy protein, and substitution of foods high in saturated fat with those with monounsaturated fatty acids (e.g., dry roasted almonds). Adding omega-3-fatty acids is effective for reducing triglycerides in patients with hypertriglyceridemia. Well-designed studies with long-term outcome data are necessary to further define the role for guggul, red yeast rice, policosanol, garlic, and flaxseed in the management of dyslipidemia.