Combination therapy in dyslipidemia: where are we now?

Atherosclerosis. 2014 Nov;237(1):319-35. doi: 10.1016/j.atherosclerosis.2014.09.026. Epub 2014 Sep 30.


Lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk of cardiovascular disease: each 1.0 mmol/L (38.7 mg/dL) reduction in LDL-C reduces the incidence of major coronary events, coronary revascularizations, and ischemic stroke by approximately 20%. Statins are a well-established treatment option for dyslipidemia, with LDL-C reduction in the range of 27-55%. Several lipid goal-driven guidelines recommend reducing LDL-C to <2.59 mmol/L (100 mg/dL) or <1.81 mmol/L (70 mg/dL) in very high-risk patients. Many patients treated with statins do not reach these goals, and remain at risk of future cardiovascular events. The 2013 American College of Cardiology/American Heart Association guidelines move away from advocating LDL-C treatment targets with focus placed on identifying patients most likely to benefit from high-intensity or moderate-intensity statin therapy. While increasing the statin dose can prove efficacious in some patients, this approach typically offers limited additional LDL-C lowering, and is associated with increased incidence of adverse side effects. Indeed, this has led to the investigation of statins in combination with other lipid-modifying agents for the treatment of dyslipidemia. This review of the evidence for statin use in combination with fibrates, niacin, bile acid sequestrants, and the cholesterol absorption inhibitor, ezetimibe, in dyslipidemic patients at increased risk of cardiovascular disease, explores the impact of such combination therapies on lipids, attainment of lipid targets, inflammatory markers, and on cardiovascular outcomes and pathology. Additionally, new and emerging dyslipidemia treatments are summarized.

Keywords: Combination therapy; Ezetimibe; Fibrate; LDL-C; Niacin; PCSK9; Statin.

Publication types

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

MeSH terms

  • Azetidines / administration & dosage
  • Bile Acids and Salts / chemistry
  • Cardiovascular Diseases / drug therapy
  • Cholesterol / metabolism
  • Cholesterol, LDL / metabolism
  • Clinical Trials as Topic
  • Dyslipidemias / drug therapy*
  • Ezetimibe
  • Female
  • Fibric Acids / administration & dosage
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Inflammation / blood*
  • Lipids / blood*
  • Male
  • Niacin / administration & dosage
  • Patient Compliance
  • Proprotein Convertase 9
  • Proprotein Convertases / blood
  • Serine Endopeptidases / blood
  • Treatment Outcome


  • Azetidines
  • Bile Acids and Salts
  • Cholesterol, LDL
  • Fibric Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Niacin
  • Cholesterol
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases
  • Ezetimibe