Extended-Release Niacin (NIASPAN): Now Designated as Do Not Use

Niacin, the active ingredient in niacin extended-release tablets (NIASPAN), belongs to the family of B complex vitamins. Niacin also is known as nicotinic acid or vitamin B3. In doses much higher than the recommended dietary allowance for healthy people, niacin reduces total cholesterol, “bad” low-density lipoprotein cholesterol (LDL) and triglycerides and increases “good” high-density lipoprotein cholesterol (HDL).[1]

Niacin extended-release tablets are approved by the Food and Drug Administration (FDA) to reduce elevated cholesterol levels and to reduce the risk of recurrent, nonfatal heart attacks in patients with histories of previous heart attacks and elevated cholesterol levels.[2] Niacin and other cholesterol-lowering drugs are approved as an adjunct for use when there is an inadequate response to a diet restricted in saturated fat and cholesterol and other nondrug measures.

In 2018, Public Citizen’s Health Research Group changed the designation of niacin extended-release tablets from Limited Use to Do Not Use because of an increasing body of new evidence showing that the drug offers little benefit in terms of preventing cardiovascular disease but does have significant, unique well-documented adverse effects.

Other extended- and sustained-release forms of niacin (lasting longer in the body than extended-release Niaspan) are available as dietary supplements under the brand names NICOBID and SLO-NIACIN, among others. However, they are unregulated dietary supplements that have not been approved by the FDA for lowering cholesterol and also should not be used. Also called modified-release or time-released, these forms of niacin can cause severe liver toxicity that can lead to liver failure.[3]

Lack of cardiovascular benefits

Early evidence suggesting that niacin could help prevent cardiovascular disease came from the Coronary Drug Project, which was completed in 1975.[4] This study was designed to assess the safety and efficacy of niacin and other cholesterol-altering drugs in men 30 to 64 years old with histories of previous heart attacks. Over an observation period of five years, niacin treatment was associated with a small but statistically significant reduction in nonfatal, recurrent heart attacks. The incidence of nonfatal heart attack was 8.9 percent for the 1,119 patients randomized to niacin versus 12.2 percent for the 2,789 patients who received a placebo. However, use of niacin for five years did not decrease the rate of mortality from all causes or the rate of mortality from cardiovascular causes.

In May 2011, the U.S. National Institutes of Health’s (NIH) National Heart, Lung, and Blood Institute prematurely stopped an NIH-funded randomized clinical trial known as the AIM-HIGH trial,[5] which evaluated the use of high-dose, extendedrelease niacin in patients who were taking the statin drug simvastatin (ZOCOR) and who had atherosclerotic cardiovascular disease.[6] The intent of the trial had been to evaluate whether the combination of highdose, extended-release niacin with simvastatin was more effective than simvastatin alone at reducing the risk of adverse cardiovascular events, including death from coronary heart disease, nonfatal heart attacks and ischemic strokes, which can occur when an artery to the brain is blocked.

The AIM-HIGH trial was stopped after enrollment of 3,414 subjects because the combination, despite increasing HDL cholesterol levels and decreasing LDL cholesterol and triglyceride levels, did not reduce the risk of these adverse cardiovascular events in subjects using both drugs compared with the risk in subjects using simvastatin alone. In the group getting both drugs, there also was a small, unexplained increase in ischemic strokes.

A more recent clinical trial, called the HPS2-THRIVE trial, was the largest long-term study of the risks and benefits of niacin in patients with existing cardiovascular disease already taking statins.[7] The study, which enrolled more than 25,000 subjects, showed that niacin, despite increasing HDL cholesterol levels and decreasing LDL cholesterol levels, did not prevent any more deaths or cardiovascular events, such as heart attack or stroke, than did statins alone. Use of niacin, however, did cause a significant increase in the risk of serious adverse events, including worsening diabetes control and new diabetes diagnoses, infections, bleeding, and muscle injury and pain.

In June 2017, the Cochrane Database of Systematic Reviews published a study that analyzed data from 23 randomized clinical trials that evaluated the effectiveness of niacin compared with placebo in more than 39,000 subjects who had, or were at risk of developing, cardiovascular disease.[8] In four of the trials, no subjects received statins, whereas in 12 trials, all subjects received statins. The study authors found moderateto high-quality evidence that niacin did not reduce the risk of death from all causes, death from cardiovascular causes, fatal or non-fatal heart attacks, or non-fatal strokes. The author concluded that it is unlikely that niacin helps to prevent cardiovascular disease.

Adverse effects

The same 2017 Cochrane Database of Systematic Reviews study demonstrated that use of niacin was associated with a significant increase in the risk of side effects, including flushing, itching, rash, headache and gastrointestinal side effects.[9] Subjects in the niacin groups also were more likely to withdraw from the trials because of side effects.

Another study published in 2016 analyzed data from 11 randomized clinical trials of niacin to determine whether niacin treatment was associated with an increased risk of diabetes.[10] Combined, the trials involved more than 26,000 subjects without diabetes at the time of enrollment. Niacin use was associated with a 34 percent increase in the risk of developing new-onset diabetes. This risk was present regardless of whether the subjects were also being treated with a statin. The study authors estimated that for every 43 patients without diabetes who are treated with niacin for five years, one will develop diabetes.

What You Can Do

We recommend that you do not take extended-release niacin to lower your LDL cholesterol level or to raise your HDL cholesterol level. If you already have cardiovascular disease — including coronary artery disease, peripheral vascular disease or a history of stroke — you should take a statin to lower your LDL cholesterol level. If you are having side effects from statins, discuss lowering the dose with your doctor. If you are one of the few patients with cardiovascular disease who cannot take a statin due to side effects or for medical reasons, you can consider cholestyramine (CHOLESTYRAMINE LIGHT, PREVALITE) to lower your LDL cholesterol level or omega-3 fatty acids (EPANOVA, LOVAZA, OMACOR, OMTRYG, VASCEPA) to lower your triglyceride level after discussing the risks of the medications with your doctor.

References

[1] Drug profile: niacin extended-release (NIASPAN). /monographs/view/194. Accessed January 6, 2018.

[2] AbbVie. Label: niacin tablet, extended release (NIASPAN). August 2016. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=35433c7b-556c-49a0-bfb5-0d498359925b&type=pdf&name=35433c7b-556c-49a0-bfb5-0d498359925b. Accessed January 6, 2018.

[3] Drug profile: niacin extended-release (NIASPAN). /monographs/view/194. Accessed January 5, 2018.

[4] The Coronary Drug Project Research Group. Clofibrate and Niacin in Coronary Heart Disease. JAMA. 1975;231(4):360-381.

[5] National Institutes of Health. Press release: NIH stops clinical trial on combination cholesterol treatment. May 26, 2011. https://www.nih.gov/news-events/news-releases/nih-stops-clinical-trial-combination-cholesterol-treatment. Accessed January 6, 2018.

[6] AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011: 365(24):2255-2267.

[7] HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, Hopewell JC, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014 Jul 17;371(3):203-212.

[8] Schandelmaier S, Briel M, Saccilotto R, et al. Niacin for primary and secondary prevention of cardiovascular events. Cochrane Database of Systematic Reviews. 2017; Issue 6. Art. No.: CD009744. DOI: 10.1002/14651858.CD009744.pub2.

[9] Ibid.

[10] Goldie C, Taylor AJ, Nguyen P, et al. Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials. Heart. 2016;102(3):198-203.