Death Knell For Niacin For Lipids Sounded by FDA?

The skeptical cardiologist stopped writing new prescriptions for niacin extended release tablets in 2011. For any patient who was taking niacin, I recommended stopping it.
Because niacin had favorable effects on the cholesterol profile, physicians had been utilizing it for many years in high risk patients on statins who had low HDL  (good cholesterol) and/or high triglycerides.
The rationale was that, since high HDL was associated with lower risk of heart attacks, raising the HDL would lower that risk. Similarly, lowering the triglycerides would improve cardiovascular risks.
While niacin certainly improved the cholesterol profile, there was no good evidence that starting it in a patient already on statin would improve cardiovascular outcomes. The cholesterol profile is a surrogate endpoint: the actual treatment goal is reducing cardiovascular disease.
In 2011, the AIM-HIGH study proved there was no benefit to adding niacin to good statin therapy despite increasing HDL from 35 to 42 mg/dl, lowering triglycerides and lowering LDL. This and other studies showing no benefit of niacin therapy (and worrisome adverse effects) should have resulted in the total cessation of niacin prescriptions, especially  in patients on statins.
Unfortunately, old habits die hard amongst physicians, and the allure of raising HDL and lowering triglycerides with niacin persisted despite a lack of evidence of any benefit in lowering cardiovacular risk.
Yesterday, the FDA announced it was removing from the market two  drugs made by Abbvie, Advicor and Simcor, which are combinations of extended release niacin plus lovastatin or simvastatin, and removed its approved indication for niacin ER plus statin for lowering CHD risk stating:

“Based on the collective evidence from several large cardiovascular outcome trials (Refs. 1-3), the Agency has concluded that the totality of the scientific evidence no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL-cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events. Consistent with this conclusion, FDA has determined that the benefits of niacin ER tablets and fenofibric acid DR capsules for coadministration with statins no longer outweigh the risks, and the approvals for this indication should be withdrawn.”

This is good news for patients whose physicians were keeping them on the unproven brand name combination drugs, Advicor and Simcor.
There are still legitimate uses of niacin to prevent vitamin deficiencies but If you are still taking some form of niacin ER for the purpose of preventing heart disease with or without a statin I recommend presenting your doctor with the link to the FDA pronouncement above and having a good discussion with him about the rationale for staying on it.
The other drug mentioned in the announcement, fenofibric acid,  is far less often prescribed and is not available as a combination. It is the most effective drug we have for extremely high triglyceride levels over 500 mg/dl which can cause pancreatitis. I have a few patients on the generic fenofibric acid strictly for the purpose of lowering their dangerously high triglycerides but not for the indication of lowering their cardiovascular risk.
Nonsurrogateingly Yours


13 thoughts on “Death Knell For Niacin For Lipids Sounded by FDA?”

  1. I think there were many issues with AIM-HIGH when reading between the lines. The study design appears highly biased from the get-go to show no benefit from Niacin.
    Participants were men and women 50 to 80 years of age and had a history of myocardial infarction, cerebrovascular disease, peripheral arterial disease, or diabetes mellitus with evidence of symptomatic coronary disease.
    Participants were already at goal before the niacin was given so, of course, they would not receive added benefit from niacin. Participants initially received simvastatin at a dose of 40 mg daily; if this dose was not as effective as their prior treatment or if their total cholesterol level was 135 mg per deciliter (3.50 mmol per liter) or higher after 4 weeks, ezetimibe at a dose of 10 mg daily was added. I am curious why would the researchers even bother to treat people who were already at goal?? Obvious answer is that they should treat people who weren’t at goal.
    After participants had their LDL cholesterol lowered with Simvastatin and ezetimibe, they received a combination tablet containing 1-gram of extended-release niacin and 20 mg of laropiprant daily for 4 weeks, followed by two tablets daily providing a total of 2-gram of niacin and 40 mg of laropiprant for 3 to 6 weeks. Participants who did not report clinically significant adverse effects with this treatment and who remained eligible were randomly assigned to receive two niacin–laropiprant combination tablets (a total of 2 g of niacin and 40 mg of laropiprant) daily or matching placebo.
    The study also never looked at people like me with sky high Lp(a). I was in the 95th perc nailed for Lp(a). 1,500 MG of Endur-Acin (extended release niacin) and 5 MG of Rosuvastatin lowered my Lp(a) by 75% to normal levels. There are many other benefits of niacin.
    The trial was finally stopped early because of the toxic effects of the laropiprant which subsequently was taken off the market. It was not stopped due to the niacin.
    The moral of my story is that if someone wants to make sure a trial will fail then just treat people who don’t need the therapy in the first place and you will see no benefit.
    Here is the full study: “Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients”

    • You are confusing and conflating two separate trials. The AIM-High trial did not use Laropiprant and the protocol is different from your description.-
      “Patients in the niacin group received niacin at a dose of 1500 to 2000 mg per day plus simvastatin. Patients in the placebo group received simvastatin plus a matching placebo that contained a small dose (50 mg) of immediate-release niacin in each 500-mg or 1000-mg tablet to mask the identity of the blinded treatment to patients and study personnel. In both groups, the dose of simvastatin was adjusted according to an algorithm specified in the protocol to achieve and maintain the LDL cholesterol level during treatment in the range of 40 to 80 mg per deciliter (1.03 to 2.07 mmol per liter). Subjects in both groups could receive ezetimibe, at a dose of 10 mg per day, to achieve the target LDL cholesterol level. ”
      The goal was to get patients to LDL goal and then see if niacin and HDL raising had any benefit in this population. It was a very well designed study.
      This is the link for AIM-HIGH
      It is a totally different study than the study you are referencing.
      niacin does lower Lipoprotein (a) but there is no evidence that is a beneficial action. We need randomized trials of patients with high lipoprotein (a).
      Just because a drug modifies a biomarker favorably does not mean it lowers
      risk of heart attack. For example, several studies now have shown that drugs that raise HDL don’t lower risk of atherosclerotic CV disease and may actually increase the risk.

    • Thanks for your comments. I have reviewed HPS2-Thrive. Although Europeans did better than Chinese with niacin this was nonsignificant. Most participants were male and they fared a little better with niacin but again this was a nonsignificant difference.
      With multiple subgroup analyses the possibility of a chance difference becomes much more likely.
      The authors concluded that any subgroup differences were not clinically significant.
      Reviewing the study again I’m struck by the marked increase in side effects in patients receiving niacin, the lack of benefit in reducing vascular events and although, not quite reaching significant the 9% increase in total mortality on patients receiving niacin.
      After that study I stopped writing niacin prescriptions and stopped the drug on patients taking it and nothing since then has changed my practice pattern.

      • Dr., I don’t see how the Aim & Thrive conclusions on niacin relate to people like me who’ve never taken a statin.
        I’m 55. My hdl was in the high 20s & low 30s & was increased into the 40s; another time, the 50s; & this most recent time taking Niacin for six months into the mid 40s by taking 500mg niacin once or twice a day. It lowered my ldl from 140 to 118 over this latest six-month period.
        I’m 45 pounds overweight, 5’6″, weighing 184. I don’t exercise & sit most of the day.
        Is there something wrong with taking Niacin to keep my hdl in the good range & ldl not so bad? I’ve never had a high homocysteine level.
        In my early 40s, my hdl was 25 & ldl 150. Every time I’ve taken niacin it’s resulted in almost ideal ldl, which they say would be below 100, but really importantly, I thought, HDL in the 40s & 50s. I’m not clear on why this isn’t a good thing. Thanks a lot!
        Be well.

  2. Thanks for the post Dr. Pearson. I’m curious what your view is for patients that are statin intolerant. My experience with a variety of statins was miserable. The solution, in terms of lowering my LDL (I won the lottery in the FH contest!), was Zetia and Niacin. These two medicines have lowered my LDL from 150ish to 80ish. However, your comment about the “actual treatment goal is reducing cardiovascular disease.” hits the mark. I’ve taken the approach of “doubling down;” using a low carb diet to reduce the “insulin hit” and taking the zetia/niacin combo. But, as an “N of one” (and having a cardiologist who is open to alternative solutions), I’m very interested on better treatment approaches. Thanks for you comments.

    • Based on some intriguing findings from the GAUSS-3 trial at the recent ACC meetings (mentioned in a previous post) I have revisited muscle related statin intolerance and was hoping to write a post on it soon. I will assume your side effect from statins is muscle ache.
      I will also assume you have taken at least two statins and developed significant muscle ache on them that resolved within two weeks of stopping. The GAUSS trial showed a large number of patients developing muscle ache on placebo, the so-called nocebo effect.
      My approach is as follows in a patient who really needs cholesterol lowering therapy (see my posts on detecting subclinical atherosclerosis)
      -trial of crestor 5 mg twice weekly or livalo 2 mg twice weekly. In the past I have added coq10 and checked Vit D levels. If symptoms develop on this then I give up on statins
      -I offer patients zetia (see my post on finally seeing data that this drug lowers CV risk after 12 years on the market) or cholestyramine.
      -I don’t prescribe niacin, no data on outcomes.

  3. Many Neuroendocrine Tumour patients take Niacin supplements as they are risk of a deficiency due to their surgery and or treatment (this in turn has the potential to cause malabsorption of key nutrients. I personally don’t but I know many who do. I was therefore interested in your statement “If you are still taking some form of niacin ER with or without a statin …….” Do you have any views on the use of Niacin supplements for those with potential nutrient deficiencies or has this aspect of Niacin got nothing to do with the FDA action? Thanks in advance,


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