Fibrates and future PPARalpha agonists in the treatment of cardiovascular disease

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Bart Staels1, Michel Maes, Alberto Zambon

  • 1Department of Atherosclerosis, Institut Pasteur de Lille, UMR545 Inserm, University of Lille 2, Lille, France. bart.staels@pasteur-lille.fr

Nature Clinical Practice. Cardiovascular Medicine
|July 17, 2008
PubMed

Insights

Statins reduce cardiovascular events in diabetics, but residual risk remains. Peroxisome proliferator-activated receptor (PPAR)alpha agonists, like fibrates, address this by improving lipid profiles and other metabolic markers.

Area of Science:

  • Cardiovascular Medicine
  • Endocrinology
  • Pharmacology

Background:

  • Statins are effective for cardiovascular risk reduction in diabetic patients but leave significant residual risk.
  • This residual risk is partly due to statins' limited efficacy on hypertriglyceridemia, low HDL cholesterol, and LDL particle size distribution.
  • The metabolic syndrome and type 2 diabetes are associated with an atherogenic lipid profile contributing to cardiovascular risk.

Purpose of the Study:

  • To evaluate the role of Peroxisome proliferator-activated receptor (PPAR)alpha agonists in managing residual cardiovascular risk in patients with diabetes and metabolic syndrome.
  • To assess the impact of PPARalpha agonists on specific lipid abnormalities like hypertriglyceridemia and LDL particle size.
  • To explore the potential benefits of combining PPARalpha agonists with statins for comprehensive lipid management.

Main Methods:

  • Review of outcome trials and studies investigating PPARalpha agonists (fibrates).
  • Analysis of effects on lipid profiles, including triglycerides, HDL cholesterol, and LDL particle distribution.
  • Examination of impacts on cardiovascular morbidity, metabolic syndrome markers, and diabetic complications.

Main Results:

  • PPARalpha agonists effectively normalize atherogenic lipid profiles, significantly improving hypertriglyceridemia and the ratio of small dense to large buoyant LDL particles.
  • Outcome trials show PPARalpha agonists reduce cardiovascular morbidity in diabetic and metabolic syndrome patients.
  • Benefits include diminished plaque progression, counteraction of diabetic nephropathy/retinopathy, and decreased amputation risk.

Conclusions:

  • PPARalpha agonists are indicated for patients with diabetes experiencing residual dyslipidemia despite statin therapy.
  • They are also suitable for nondiabetic individuals with metabolic syndrome features like insulin resistance, hypertriglyceridemia, low HDL, and inflammation.
  • Combination therapy with fibrates and statins offers further improvement in the overall lipoprotein profile.

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