Clinical implications of the IMPROVE-IT trial in the light of current and future lipid-lowering treatment options

Expert Opin Pharmacother. 2016;17(3):369-80. doi: 10.1517/14656566.2016.1118055. Epub 2015 Nov 30.


Introduction: A residual risk of morbidity and mortality from cardiovascular (CV) disease remains despite statin therapy. This situation has generated an interest in finding novel approaches of combining statins with other lipid-lowering agents, or finding new lipid and non-lipid targets, such as triglycerides, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, proprotein convertase subtilisin/kexin type 9 (PCSK9) gene, cholesterol ester transfer protein (CETP), lipoprotein (a), fibrinogen or C-reactive protein.

Areas covered: The recent results from the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated an incremental clinical benefit when ezetimibe, a non-statin agent, was added to simvastatin therapy.

Expert opinion: The results from IMPROVE-IT revalidated the concept that low-density lipoprotein cholesterol (LDL-C) levels are a clinically relevant treatment goal. This trial also suggested that further decrease of LDL-C levels (53 vs. 70 mg/dl; 1.4 vs. 1.8 mmol/l) was more beneficial in lowering CV events. This "even lower is even better" evidence for LDL-C levels may influence future guidelines and the use of new drugs. Furthermore, these findings make ezetimibe a more realistic option to treat patients with statin intolerance or those who cannot achieve LDL-C targets with statin monotherapy.

Keywords: Ezetimibe; IMPROVE-IT; low-density lipoprotein cholesterol; simvastatin; statin.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents / therapeutic use*
  • Cardiovascular Diseases / prevention & control
  • Cholesterol, LDL / blood
  • Drug Therapy, Combination
  • Dyslipidemias / drug therapy*
  • Ezetimibe / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Randomized Controlled Trials as Topic
  • Simvastatin / therapeutic use


  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin
  • Ezetimibe