New Analysis Re-Affirms IR-Niacin as Evidence-Based Therapy for Dyslipidemia

Mar 01, 2016, 08:00 ET from Arizona Pharmaceuticals, LLC

PHOENIX, March 1, 2016 /PRNewswire/ -- In a clarifying analysis [1], University of Pennsylvania Lipidologist Richard Dunbar, M.D., affirms immediate-release (IR) niacin maintains its trail-blazing status as a cardioprotective drug, whereas an alternative form of niacin failed to prove such benefits. Analysis was done in conjunction with a clinical trial sponsored by Arizona Pharmaceuticals, LLC. 

The long-running Coronary Drug Project [2] clearly showed IR-niacin:

  • Significantly reduces recurring heart attacks within 5 years, and
  • Significantly reduces overall mortality within 15 years

This established 1 gram thrice daily (i.e. 3 grams/day) as the first cardioprotective lipid regimen

An extended-release (ER) alternative was later developed to mitigate flushing from niacin.  Critically, the ER alternative has not proven cardioprotective, and appears severely handicapped by a strict dose limit not to exceed 2 grams/day.  Thus, a critical test for the alternative was whether it might nevertheless echo some of the benefits of the more potent cardioprotective regimen established by IR niacin at 3 grams/day.  Two recent studies suggest the weaker ER alternative is in fact powerless to prevent heart attacks and reduce overall mortality:  

  • HPS2-THRIVE [3] studied the ER alternative + laropiprant or placebo added to simvastatin, failing to demonstrate a decisive benefit to the ER alternative in an already-healthy test population
  • AIM-HIGH [4] studied the ER alternative or low-dose IR-niacin added to simvastatin, also failing to demonstrate any benefit from the ER alternative

Dr. Dunbar and Dr. Harsh Goel conducted a new meta-analysis that combines all of the cardiovascular outcomes studies to date.  They affirmed the established regimen of 3 grams/day prevents major cardiovascular events, with an odds ratio of 0.75 pooling two studies of the established regimen, indicating a substantial benefit.  Disappointingly, pooling the two studies of the much lesser dose of 2 grams/day showed the ER alternative had an odds ratio of 1.0, indicating no benefit whatsoever.  Taking this a step further, they conducted a meta-regression analysis implying the weaker regimen represented by the ER alternative likely failed because it had little ability to lower cholesterol, whereas the established regimen doubled or nearly tripled the drop in cholesterol. 

The authors warn that failing to carefully distinguish the alternative regimen from the "gold standard" might tempt doctors to falsely conclude that all niacin regimens lack benefits.  This would be ironic, since the Coronary Drug Project was the first outcomes study to prove that lowering cholesterol prevented heart attacks, an observation that was foundational to cholesterol treatment. 

Accordingly, Dunbar and Goel argue that the gold standard regimen of 1 gram thrice daily remains the only cardioprotective niacin regimen backed by a large coronary heart disease outcomes trial, whereas the ER alternative with its weaker dose consistently failed to live up to that standard.  They also point out that several companies are developing novel drugs to replicate niacin's cardioprotective benefits while bypassing the apparent problems with the ER alternative. 

"We are excited to participate in the new and growing field of innovative IR-Niacin compounds and mimetics. NIALOR® builds on the established science of niacin, and we look forward to completion of efficacy trials." said Ron Javor, President and Founder of Arizona Pharmaceuticals, LLC. 

Disclosure:
Arizona Pharmaceuticals, LLC and University of Pennsylvania are collaborating on a niacin-based clinical trial (reference: https://clinicaltrials.gov/ct2/show/NCT01984073).

NIALOR is a registered trademark of Arizona Pharmaceuticals, LLC. U.S. Patent 7,879,375

References:

  1. Current Atherosclerosis Reports http://link.springer.com/article/10.1007/s11883-016-0563-8  (Open Access)
  2. Coronary Drug Project: http://www.ncbi.nlm.nih.gov/pubmed/3782631
  3. HPS2-THRIVE: http://www.nejm.org/doi/full/10.1056/NEJMoa1300955
  4. AIM-HIGH:  http://www.nejm.org/doi/full/10.1056/NEJMoa1107579

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SOURCE Arizona Pharmaceuticals, LLC