Evaluating the Options in Correcting Dyslipidemia

Charles A. Reasner, MD.

In This Article

Lipid-Lowering Medications

Four classes of lipid-lowering drugs are available: the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (the "statins"), the fibrates (gemfibrozil, clofibrate, and fenofibrate), niacin/nicotinic acid, and the bile acid binding resins (colestipol and cholestyramine) (Table 1).[3]

The HMG-CoA reductase inhibitors work by inhibiting a key step in hepatic cholesterol synthesis, leading to decreased levels of total cholesterol. Decreased total cholesterol may lead to an increased number of low-density lipoprotein (LDL) receptors, increasing catabolism of LDL and clearing LDL from the circulation. The statins are very efficacious in lowering LDL cholesterol (LDL-C), and they sometimes elevate high-density lipoprotein cholesterol (HDL-C) levels as well. They are more likely to lower triglycerides when the levels are markedly elevated. The statins require periodic liver function monitoring, as elevation in liver enzymes (alanine aminotransferase and aspartate aminotransferase) may occur and may require dose adjustment or cessation of these medications. The FDA recommends dose adjustment or cessation when these liver enzymes reach three times the upper limit of normal levels. Because of their once-a-day dosing, minimal side effects, and efficacy, the statins are considered a first-line drug therapy for dyslipidemias.

The fibrates work preferentially on the liver to reduce triglyceride synthesis and very low-density lipoprotein (VLDL) production. Fibrates also stimulate the uptake and metabolism of VLDL from the plasma, which can lead to increased LDL levels in patients who have very high baseline triglyceride levels. They can reduce triglyceride levels markedly, and often produce a modest increase in HDL-C. However, they usually are dosed multiple times per day and may produce side effects, such as gallstones and gastrointestinal (GI) disturbances, including nausea and rash. However, for patients who predominantly have elevated triglycerides (type IV and V hyperlipidemias), they are considered first-line agents. Fibric acid derivatives should not be prescribed if a patient is receiving a statin.

Niacin (also known as nicotinic acid or vitamin B 3 but not niacinamide) is a vitamin that lowers total cholesterol and triglycerides at high doses, and it can also produce an increase in HDL-C. However, niacin may also raise glucose and uric acid levels, making it a less than ideal choice for diabetic patients. The intermediate-release form is often associated with an uncomfortable prostaglandin-mediated cutaneous flush and pruritis, side effects that are minimized with the newer sustained-release forms or by premedication with low doses of aspirin (which may be beneficial in itself for patients with cardiovascular disease).

Bile acid sequestering resins (cholestipol and cholestyramine) bind bile acids in the small intestine, preventing their return to the liver by enterohepatic circulation. The bile acid resins carry the bound cholesterol out in the stool. Decreased bile acid concentration increases conversion of cholesterol to bile acid, thereby reducing cholesterol levels.

Resins have little effect on HDL-C but may raise triglyceride levels. They may also bind to many other substances and medications and may impair absorption of fat-soluble vitamins and folate and interfere with absorption of drugs such as phenobarbital, digoxin, and warfarin. They are somewhat clumsy to take -- they come as a powder and have to be mixed with juice -- and have a marked dose-response curve; doses up to 16 g bid have been shown to significantly lower LDL-C and reduce cardiovascular mortality,[4] but none of the reported clinical trials have included a population of patients with diabetes. Side effects include constipation and nausea.


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