Treating mixed hyperlipidemia and the atherogenic lipid phenotype for prevention of cardiovascular events

Am J Med. 2010 Oct;123(10):892-8. doi: 10.1016/j.amjmed.2010.03.024.


Statins reduce cardiovascular events and cardiovascular and total mortality in persons at risk for and with coronary disease, but there remains a significant residual event rate, particularly in those with the atherogenic lipid phenotype that is characterized by a low high-density lipoprotein (HDL) cholesterol and increase in non-HDL cholesterol. Large outcome trials designed to assess the value of combining statins with other agents to target HDL cholesterol and non-HDL cholesterol will not be completed for a few years, but there is ample evidence for the clinician to consider combination therapy. The choices for therapies to supplement statins include niacin, fibrates, and omega-3 fatty acids. We present the argument that after therapeutic lifestyle changes, the first priority should be the maximally tolerated effective dose of a potent statin. Evidence supports the addition of niacin as the second agent. In some situations, high-dose omega-3 fatty acid therapy could be the first agent added to statins. Although fibrate monotherapy alone or in combination with non-statin low-density lipoprotein cholesterol-lowering agents can be effective in mixed hyperlipidemia when statins are not tolerated, the combination of statin+fibrate should be considered second-line therapy until the efficacy and safety are established.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Atherosclerosis / prevention & control*
  • Cardiovascular Diseases / prevention & control
  • Cholesterol, LDL / blood
  • Clofibric Acid / therapeutic use
  • Drug Therapy, Combination
  • Fatty Acids, Omega-3 / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipidemia, Familial Combined / drug therapy*
  • Hyperlipidemia, Familial Combined / therapy
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Niacin / therapeutic use
  • Phenotype
  • Risk Factors
  • Risk Reduction Behavior


  • Cholesterol, LDL
  • Fatty Acids, Omega-3
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Niacin
  • Clofibric Acid