FDA Ends Niacin and Fenofibric Acid Combinations With Statins

–“In the absence of benefits, there remain only harms.”

The FDA is putting an end to the combined use of statins with two once-popular lipid drugs, niacin and fenofibric acid. On Monday the FDA will announce in the Federal Register that it is withdrawing its approval for indications for coadministration of these drugs with statins and the removal from the market of two niacin-statin combination products.

“The FDA actions are appropriate and important,” said Steve Nissen (Cleveland Clinic). “There is no evidence for any meaningful benefit for addition of niacin or fibric acid derivatives to statins. There are also significant harms associated with these drugs. In the absence of benefits, there remain only harms. Unfortunately, these drugs continue to be prescribed to large numbers of patients. Hopefully FDA’s actions will significantly reduce inappropriate use.”

The two combination products that are being withdrawn from the market are Advicor and Simcor, which combine niacin extended-release with lovastatin and simvastatin, respectively. Both are manufactured by AbbVie. The withdrawn indications for coadminstration with statins involve Niaspan (niacin extended-release) tablets from AbbVie and its generic equivalents and Trilipix (fenofibric acid) DR, also from AbbVie, and its generic equivalents.

The FDA said that the changes were “based on the collective evidence from several large cardiovascular outcome trials,” including ACCORD, AIM-HIGH, and HPS2-THRIVE. The FDA said 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.”

The FDA move signals the final stage of a dramatic reversal of fortune for lipid drugs using niacin and fibrates. The AbbVie drugs, in particular, had been enormously successful, though their use diminished as a result of the large clinical trials cited by the FDA.

​”This action by the FDA seems appropriate and is consistent with the recent disappointing randomized controlled trial evidence,” said Michael Blaha (Johns Hopkins). “We might ask – why were the indications for these drugs granted in the first place? This shows how far we have come in the evaluation of lipid-lowering drugs. It is now firmly established that improvements in the simple lipid profile are not enough, and that clear evidence of benefit on clinical outcomes is needed for routine use of lipid-lowering drugs as add-on to statin therapy.”

The FDA announcements were released on Friday (here and here) and are scheduled to be published on Monday in the Federal Register.

Comments

  1. I wonder why FDA took this long to act on this issue?

    Going forward, I have a humble recommendation to the FDA: No new drugs should be approved for the treatment of diabetes, hypertension, and high cholesterol to prevent atherosclerotic cardiovascular disease just on the basis of improvement in surrogate risk markers and risk factors, without outcome studies showing definite statistical significance that can be reproduced.

    Do we have more money to waste like this any more to support the self-serving medical industrial complex? Hope, FDA pays attention to the lessons we learned from the past!

  2. Paul D. Rosenblit MD says:

    Treating dyslipidemia can be more complex than implied by the FDA logic; management may not simply be a 1- or 2-step process for all patients at-risk.
    When triglycerides (TGs) are in the average range, as in the design utilized for most clinical trials, using combinations of agents that target only LDL-C to a very-low goal may be all that is needed to adequately reduce ASCVD. But when TGs are elevated >200 mg/dL, considerable cryptic ‘atherogenic cholesterol’ resides in TG-rich remnants. Clearing the TGs with TG-lowering agents, i.e. fenofibrate or fenofibric acid, prescription-grade omega-3 fatty acids, niacin, (and statins) and combinations of these classes aim to expose additional atherogenic cholesterol in TGRL remnants (i.e. VLDL-C), in need of further (emphasis added) treatment (i.e. Non-HDL-C and LDL-C lowering); the third step. While such a trial demonstrating this has not been designed, lowering both non-HDL-C and LDL-C lowers event rates.
    In other words, when the LDL-C has been lowered to 200 mg/dL, relatively small subgroups, less than 20% of the cohorts in these trials, but nevertheless groups with consistently higher ASCVD event rates that the cohort as a whole or the subgroups with TG <200 mg/dL.
    AIM-HIGH and HPS2-THRIVE were designed to evaluate the 'HDL-C raising' hypothesis, i.e. raising the cholesterol content of HDL particles. The control groups received higher statin concentrations and ezetimibe to minimize LDL-C changes (both manuevers lower LDL-C and raise HDL-C in controls); and successfully resulted in nominal changes in any lipid parameter including HDL-C; the between-group LDL-C difference in AIM-High was 5 mg/dL and in HPS2-THRIVE was 10 mg/dL, differences which do not meet threshold for significant ASCVD risk reduction, even in statin trials.
    Pulling approval for niacin or fibrate for lowering TGs in patients with hypertriglyceridemia as a 'penultimate' step, for ultimately additional lowering of atherogenic cholesterol, is a denial of the patho-physiology of atherosclerosis, as well as, many well-designed combinations trials carried out in the past and many at-risk patients will be harmed.

    • Pardon the intrusion, but as a senior woman with every known high risk factor and diagnosed cardiovascular disease, I want to see studies that focus on statin effects with a similar population before I take them, just as it is difficult to be convinced that cardiac catheterization is worth the risk in women. But add to all that, cardiologists who do not monitor patients. It is also difficult to reduce one’s risk factors when anxiety regarding getting the right care, and taking the right medications exacerbates, but I’m sure you know that. Thank you.

  3. Why WERE the indications for the combination drugs granted in the first place without sufficient validation.

Leave a Reply

%d bloggers like this: