Search

Niacin or nicotinic acid is a soluble vitamin with hypolipidemic properties. Niacin reduces triglycerides (20 50%), LDL-c (5-25%), and raises HDL-c (15-35%). The Coronary Drug Project study showed that the use of niacin was associated with reduction on coronary events and total mortality, and more recently it has been demonstrated that niacin combined with other hypolipidemic drugs can attenuate the progression of coronary atherosclerosis. Niacin appears to reduce the mobilization of free fatty acids from the adipocytes, acting on specific receptors, diminishing the liver formation of triglyceride-rich lipoproteins. There are two forms of niacin, one of rapid absorption (crystalline), more commonly associated with flushing, and another of extended release, recently reported to be better tolerated. The use of niacin can be associated with dyspepsia, increased plasma levels of liver enzymes and also with a modest elevation in glucose and uric acid plasma levels, at least using the extended-release preparation up to 2 g/d.

Liver disease following the use of hypolipidemic drugs has been reported as a cellular damage (increases in AST or ALT enzymes) without cholestatic alterations (bilirubin and or alkaline phosphatase increases). Six mechanisms were proposed for hepatotoxicity: 1. High energy reactions on P450 cytochrome impairing calcium homeostasis with rupture of intracellular fibrils and hepatocyte lysis. 2. Impairment of transporter proteins related to the bile acids flux (mechanism proposed for fibrate liver toxicity). 3. Immune reactions due to the formation of metabolites linked to enzymes following liver metabolism of hypolipidemic drugs. 4. Hepatotoxicity by T cells with additional inflammation mediated by neutrophils. 5. Apoptosis mediated by TNF and Fas (immune mediated). 6. Oxidative stress due to damage of intracellular organelles. In addition, advanced age, alcohol in excess, high doses of hypolipidemic drugs, interaction with other drugs, and previous active liver disease might increase liver toxicity.

Combination of statins with niacin appears to be an attractive association, in the presence of mixed dyslipidemia with low HDL-c levels, when monotherapy is insufficient to achieve target lipid levels. Clinical benefits were observed by the combination of statins with niacin in the FATS, HATS and ARBITER 2 trials, showing attenuation of atherosclerosis development and/or reduction in coronary events following favorable lipid changes. In general, this combination can be well-tolerated. Recommendations for appropriate monitoring of liver and muscle enzymes are important to reduce the rate of side effects. In addition, careful titration of each drug is recommended.