nicotinic acid analogues

Last reviewed 04/2021

These drugs include:

• acipimox
• synthetic nicotinic acid

Actions (and proposed mechanisms) include:

• inhibition of synthesis and secretion of VLDL - reduces the rate of mobilisation of free fatty acids from adipose tissue to the liver and therefore a reduction in hepatic synthesis of of VLDL
• increases the rate of VLDL breakdown
• reduction in plasma cholesterol, triglycerides, VLDL, LDL - as VLDL is a precursor to LDL, the effects of nicotinic acid on VLDL also lead to a reduction in LDL
• increases HDL - the pathway by which nicotinic acid increases HDL is thought to be via the binding of HDL to apoA-1 - nicotinic acid decreases the rate of removal of apoA-1 by the liver but does not seem to effect the rate of synthesis of this protein - this means that HDL particles can persist for extended periods leading to an increase in HDL levels
• reduces Lp (a) - the mechanism for this is currently unknown - it is not directly related to the decrease in LDL as neither statins or fibrates decrease Lp (a)
• a meta-analysis has evaluated the effect of nicotinic acid on lipid profile (1):
  • 10% reduction in total cholesterol
  • 20% reduction in triglycerides
  • 14% reduction in low-density lipoprotein cholesterol
  • 16% increase in HDL-C for fibrates and niacin, respectively. Apart from flushes in the niacin group, both fibrates and niacin were shown to be well-tolerated and safe

Side effects include:

• flushing - may be reduced if a small dose of aspirin (or another prostaglandin inhibitor) is taken before nicotinic acid treatment
  • modified-relase nicotinic acid is administered as a once-daily dose in the evening or at bedtime - it is associated with a lower rate of flushing than immediate-release nicotinic acid, and a lower risk of hepatotoxicity in comparison with sustained release nicotinic acid (1,2)
• other possible side effects include
  • hepatitis, exacerbation of peptic ulcer disease, gastritis
  • hyperglycaemia - there is evidence that modified-release nicotinic acid can be used safely in patients with controlled type 2 diabetes (1,3) - modified-release nicotinic acid has been shown to be an appropriate treatment for dyslipidaemia associated with type 2 diabetes and metabolic syndrome (1)
    
  • hyperuricaemia - treatment with nicotinic acid has been associated with hyperuricaemia - it should therefore be used with caution in patients with gout, pre-existing hyperuricaemia or those receiving other treatments that may increase uric acid levels

Combination with statins:

• the combination of modified-release nicotinic acid/statin therapy has been shown to have complimentary lipid-modulating effects, and is safe and effective even in patients with diabetic dyslipidaemia, despite earlier concerns about hyperglycaemia (2)

Synthetic nicotinic acid can be used to treat deficiency states such as pellagra.

Notes:

• nicotinic acid plus the prostaglandin D2 receptor 1 antagonist laropiprant (LRP) (Tredaptive)
  
  
  • MSD announced on 21/1/2013 that 'Treatment with TREDAPTIVE should be discontinued'
    • preliminary results from HPS2-THRIVE failed to show a statistically significant effect of TREDAPTIVE on the reduction of major vascular events. The study also showed an increase in the incidence of some types of non-fatal serious adverse events in the group that received TREDAPTIVE. Consequently the balance of risks and benefits is no longer considered to be favourable
    • tredaptive should no longer be prescribed
    • doctors should review their patients' treatment in order to discontinue treatment with Tredaptive, which will no longer be available from 18/1/13

The summary of product characteristics should be consulted before prescribing this drug.

Reference:

• 1. Birjmohun RS et al. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2005;45:185-97.
• 2. British Journal of Cariology (2003), 10(6), 462-8
• 3. JAMA. 1994 Mar 2; 271(9): 672-7
• 4. MSD (letter to UK Health Professionals, 21/1/2013). Treatment with Tredaptive should be discontinued.