Fibrate

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In medicine, fibrates are antilipemic agents for treating hyperlipidemia. Fibrates lower triglycerides by being agonists of peroxisome proliferator-activated receptor alpha (PPAR alpha)[1] Examples include:

Clinical use

A systematic review of randomized controlled trials of fibrates concluded "In addition to improving lipid profiles, fibrates are associated with an important decrease in nonfatal myocardial infarction, but do not substantially affect all-cause mortality."[2]

A narrative review concluded that "the benefit of adding a fibrate to statin therapy in reducing the risk of cardiovascular events in patients with type 2 diabetes remains unproven. The possibility of important clinical benefit among patients with diabetes who have elevated triglyceride and low HDL cholesterol levels cannot be ruled out."[3]

Drug toxicity

Drug toxicity includes acute kidney injury.[4]

Research in synergy

There has been interest in the synergistic use of alpha and gamma PPAR agonists. Trials with dual agonists, the glitazars, were stopped for safety reasons. [5] The PROactive trial had better results using a fibrate with a thiazolidinedione, pioglitazone, but the risk-benefit is not clear in patients with dyslipidemia and diabete. [6]

References

  1. Barter PJ, Rye KA (2006). "Cardioprotective properties of fibrates: which fibrate, which patients, what mechanism?". Circulation 113 (12): 1553-5. DOI:10.1161/CIRCULATIONAHA.105.620450. PMID 16567579. Research Blogging.
  2. Abourbih S, Filion KB, Joseph L, Schiffrin EL, Rinfret S, Poirier P et al. (2009). "Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review.". Am J Med 122 (10): 962.e1-8. DOI:10.1016/j.amjmed.2009.03.030. PMID 19698935. Research Blogging.
  3. Goldfine (2011 [last update]). Fibrates in the Treatment of Dyslipidemias — Time for a Reassessment — NEJM. nejm.org. Retrieved on 10 August 2011.
  4. Zhao YY, Weir MA, Manno M, Cordy P, Gomes T, Hackam DG et al. (2012). "New fibrate use and acute renal outcomes in elderly adults: a population-based study.". Ann Intern Med 156 (8): 560-9. DOI:10.1059/0003-4819-156-8-201204170-00003. PMID 22508733. Research Blogging.
  5. Deane Conlon (3 October 2006), "Goodbye Glitazars?", The British Journal of Diabetes and Vascular Disease
  6. Dormandy JA, Charbonnel B, Eckland DJA et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (prospective pioglitazone clinical trial in macrovascular events): a randomised controlled trial. Lancet 2005;366:1279-89.