Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place?

Abstract

Niacin is considered to be a powerful drug for the treatment of lipid and lipoprotein abnormalities connected with “residual cardiovascular risk”, which persist in high-risk patients even when the target goals of LDL-C are achieved with statin therapy. Recent large randomized clinical studies – AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides) and HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) – delivered some disappointing results, leading to the conclusion that no further benefit (decreased parameters of cardiovascular risk) is achieved by adding niacin to existing statin therapy in patients with high cardiovascular risk. Moreover, in these studies, several adverse effects of the treatment were observed; therefore, niacin treatment for hypolipidemias is not recommended. In this paper, we analyze the mechanisms underlying the hypolipidemic and antiatherogenic effects of niacin as well as some limitations of the designs of the AIM HIGH and HP2-THRIVE studies. We also provide the possibilities of rational usage of niacin for specific types of dyslipidemias.

Targeting NAD+ in Metabolic Disease: New Insights Into an Old Molecule

“…The long-known lipid-lowering effects of NA may, at least partly, be NAD+ mediated. This hypothesis is favored because the half maximal effective concentration for the GPR109A receptor is in the nanomolar range [ 215 , 216 ]; however, the therapeutic doses of NA are greatly in excess of this amount [ 71 , 217 ]. Moreover, NR ameliorated hypercholesterolemia in mice without activating the GPR109A receptor [ 54 ].…”

“…Dietary niacin is not associated with side effects because the tolerable upper intake level is not exceeded [ 62 ], whereas pharmacologic NA dosing is commonly associated with undesirable effects, thereby decreasing treatment adherence. NA is a ligand for the G-protein–coupled receptor GPR109A and is coexpressed on the epidermal Langerhans cells mediating prostaglandin formation, which induces troublesome flushing and other vasodilatory effects, such as itching, hypotension, and headaches [ 12 , 71–73 ]. To overcome these problems, the selective antagonist of prostaglandin D2 receptors, laropiprant, was introduced into clinical practice in combination with extended-release NA (extended-release NA-laropiprant) [ 74 ].…”

HDL and type 2 diabetes: the chicken or the egg?

“…NCT00120289) and the HPS2-THRIVE (ClinicalTrials.gov registration no. NCT00461630) clinical trials was very low and highly questionable due to design flaws [26]. Indeed, in the AIM-HIGH trial, Niaspan (extended-release nicotinic acid) was administered in patients receiving maximal intensive lipidlowering therapy with statin and ezetimibe, who already had a median plasma LDL-C level of 1.86 mmol/l (72 mg/dl) and median plasma TAG level of 1.84 mmol/l (163 mg/dl) [27].…”

Effects of an Enriched Extract of Paeoniflorin, a Monoterpene Glycoside used in Chinese Herbal Medicine, on Cholesterol Metabolism in a Hyperlipidemic Rat Model

“…Hyperlipidemia, including hypercholesterolemia and hypertriglyceridemia, is associated with reduced levels of high-density lipoprotein (HDL) [ 1 , 2 ]. Due to changes in lifestyle and diet, hyperlipidemia is associated with obesity, ischemic heart disease, and diabetes mellitus [ 3 ].…”