The role of niacin in lipid-lowering treatment: are we aiming too high?

The clinically most relevant medications for lipid management are the statins, which constitute in the majority of the cases the basis of any lipid-modulating therapy. However, other agents are often needed to either reduce low-density cholesterol to target levels and/or to treat residual serum lipoprotein abnormalities. Niacin is currently the most potent available agent to increase high-density lipoprotein and reduce lipoprotein(a), both independent risk factors for cardiovascular disease. Niacin also has been found to reduce inflammatory markers like C-reactive protein (CRP) and lipoprotein-associated phospholipase-A2 (Lp-PLA2) and to decrease small-dense LDL and increase large-particle LDL, all potentially anti-atherosclerotic properties. Through its action on the GPR109A receptor niacin seems to also exert various pleiotropic effects such as improvement of endothelial function and reduction of inflammation and oxidative stress. However, niacin is often underused in the clinical setting, mainly due to either potentially preventable or disproportionally feared side effects such as flushing, hyperglycemia, and hyperuricemia, respectively. Even though the results of the AIM-HIGH trial were negative, the results of the larger end point trial HPS2-THRIVE are still pending. Based on the totality of existing evidence, niacin should in the mean time remain high in the list of lipid-modulating agents to be used in clinical practice, second after statins.