Niacin-based therapy for dyslipidemia: past evidence and future advances

Updated guidelines published recently by the National Cholesterol Education Program place greater emphasis on atherogenic dyslipidemia, characterized by low high-density lipoprotein (HDL) cholesterol; elevated triglycerides; and small, dense, low-density lipoprotein (LDL) particles, as well as the drugs that can alter the condition. Both low HDL cholesterol and elevated triglycerides are independent risk factors for coronary artery disease. Low-density lipoprotein particles can be divided into subclasses with differing atherogenicity. Phenotype A is characterized by large buoyant LDL particles, and phenotype B by small, dense particles associated with increased atherogenicity. The frequency of phenotype B in patients increases as triglyceride levels increase and HDL cholesterol levels decrease. Fibrates and niacin have been shown to improve atherogenic dyslipidemia in clinical trials. Niacin effectively lowers triglycerides, raises HDL cholesterol, and shifts LDL particles to a less atherogenic phenotype (phenotype A). The various niacin formulations available differ in terms of safety and efficacy. When administered alone or in combination with other lipid-modifying agents, niacin prevents progression and promotes regression of coronary atherogenic lesions and reduces coronary risk. Combination therapy is also an effective option for improving multiple lipoprotein abnormalities. In studies, a once-daily, single-tablet combination of niacin extended-release/lovastatin showed additive LDL cholesterol lowering and was more effective than would be anticipated from doubling the component lovastatin dose. Combination products provide a viable strategy for treating the full spectrum of lipid abnormalities seen in some patients, including those with atherogenic dyslipidemia, and will be increasingly used in the treatment of dyslipidemia. Other combination products are currently undergoing clinical testing.