Niacin for dyslipidemia

Niacin is one of our options for managing cholesterol in patients with dyslipidemia.  The benefits of high doses of niacin are well established in reducing triglycerides by 20-50%, reducing LDL by 10-25%, and increasing HDL by 10-30%.  What is not well established, however, are the clinically beneficial endpoints of niacin. 

• The Coronary Drug Project¹ in 1975 showed niacin to reduce MIs and CVAs in patients with prior MIs but did not reduce death (it’s worth noting that because this was done in 1975, many proven therapies were not used by study participants ie. antiplatelet agents, ACE inhibitors, beta-blockers, statins). 
• More recently, the reliability of surrogate markers such as carotid intima-media thickness (which niacin does improve) has come into question.² 
• The AIM-HIGH study³ in 2011 assigned more than 3,400 patients to either high dose extended release niacin (branded in the US as Niaspan) or placebo with both groups receiving simvastatin 40 or 80 mg per day.  The group receiving niacin did have lower triglycerides and LDL and higher HDL but neither the composite endpoint nor any of its components were different between groups (that means no difference in death from coronary heart disease, nonfatal MI, ischemic stroke, hospitalization for ACS, symptom-driven revascularization, and some others).  More patients discontinued the niacin due to side effects. 
• The HPS2-THRIVE study⁴ looked at more than 25,000 patients who received niacin/laropiprant versus placebo and has reported side effects and reasons for stopping niacin.  More patients reported skin reactions, gastrointestinal effects, diabetes effects, and musculoskeletal effects.  For a summary of the final results of this study, see the later post "Update on niacin - results from the HPS2-THRIVE study".

Niacin background

Niacin (or nicotinic acid) is a water-soluble B vitamin that is available in the United States as both an unapproved OTC supplement and also as a prescription.  It has multiple biologic effects which are not fully understood.  The most notable adverse reactions are flushing and pruritus which are dose related.  These effects can be improved by splitting the dose over the course of the day, taking it with meals, and using the extended release formulation.  To achieve an LDL reduction of 20-25%, the dosing needs to be increased to 2-3 grams per day which should be accomplished with a gradual upward titration over months pending the patient’s tolerability.  If using Niaspan, the maximum should be 2 grams per day since this extended release formulation is associated with more hepatotoxicity than the immediate release (3 grams daily of Niaspan has reported rates of hepatotoxicity of up to 50% - while 2 grams of Niaspan has rates <1%).  Gastrointestinal intolerances such as peptic ulcers, nausea, and vomiting occur, in addition to consistently increasing blood glucose and uric acid (Niaspan is “Contraindicated” with active peptic ulcer disease).  Musculoskeletal complaints, myopathy, and rhabdomyolysis also occur with increased frequency when used concurrently with statins.

Take home points:

• Niacin improves the cholesterol panel but has no robust evidence for reducing CV events
• Common adverse effects include skin reactions (flushing pruritus), GI intolerance (contraindicated with active PUD), musculoskeletal, worsening diabetes, and gout
• Avoid if suspicion for hepatotoxicity though it usually occurs at high doses

References:

1.  Clofibrate and niacin in coronary heart disease.  JAMA 1975;231:360-81.

2.  Polak JF, Pencina MJ, Pencina KM, et al.  Carotid-wall intima-media thickness and cardiovascular events.  N Engl J Med 2011;365(3):213-21.

3.  AIM-HIGH Investigators.  Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy.  2011;365(24):2255-67.

4.  HPS2-THRIVE Collaborative Group.  HPS2-THRIVE randomized placebo-controlled trial in 25,673 high-risk patients of ER niacin/laropiprant.  Eur Heart J 2013;34(17):1279-91.

photo by Garrett Ammon