Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical update

Nutr Metab Cardiovasc Dis. 2013 Sep;23(9):799-807. doi: 10.1016/j.numecd.2013.05.002. Epub 2013 Aug 9.

Abstract

Cardiovascular disease (CVD) is a significant cause of death in Europe. In addition to patients with proven CVD, those with type 2 diabetes (T2D) are at a particularly high-risk of CVD and associated mortality. Treatment for dyslipidaemia, a principal risk factor for CVD, remains a healthcare priority; evidence supports the reduction of low-density lipoprotein cholesterol (LDL-C) as the primary objective of dyslipidaemia management. While statins are the treatment of choice for lowering LDL-C in the majority of patients, including those with T2D, many patients retain a high CVD risk despite achieving the recommended LDL-C targets with statins. This 'residual risk' is mainly due to elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. Following statin therapy optimisation additional pharmacotherapy should be considered as part of a multifaceted approach to risk reduction. Fibrates (especially fenofibrate) are the principal agents recommended for add-on therapy to treat elevated TG or low HDL-C levels. Currently, the strongest evidence of benefit is for the addition of fenofibrate to statin treatment in high-risk patients with T2D and dyslipidaemia. An alternative approach is the addition of agents to reduce LDL-C beyond the levels attainable with statin monotherapy. Here, addition of fibrates and niacin to statin therapy is discussed, and novel approaches being developed for HDL-C and TG management, including cholesteryl ester transfer protein inhibitors, Apo A-1 analogues, mipomersen, lomitapide and monoclonal antibodies against PCSK9, are reviewed.

Keywords: ACCORD; AIM-HIGH; ARBITER; Action to Control Cardiovascular Risk in Diabetes; Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol; Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes; BIP; Bezafibrate Infarction Prevention; CTT; Cardiovascular diseases; Cholesterol Treatment Trialists; EAS; ERASE; ESC; Effect of reconstituted HDL on Atherosclerosis-Safety and Efficacy; European Atherosclerosis Society; European Society of Cardiology; FIELD; Fenofibrate Intervention and Event Lowering in Diabetes; Fibrates; HPS2-THRIVE; Heart Protection Study 2: Treatment of HDL to Reduce the Incidence of Vascular Events; Hypertriglyceridaemia; ILLUMINATE; Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events; Nicotinic acid; SCORE; Statins; Study of the Effect of Dalcetrapib on Atherosclerotic Disease in Patients with Coronary Artery Disease; Systemic Coronary Risk Estimation; Triglycerides; dal-OUTCOMES.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Anticholesteremic Agents / therapeutic use
  • Apolipoprotein A-I / therapeutic use
  • Benzimidazoles / therapeutic use
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / drug therapy*
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors
  • Cholesterol Ester Transfer Proteins / metabolism
  • Cholesterol, HDL / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy
  • Fibric Acids / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Niacin / therapeutic use
  • Oligonucleotides / therapeutic use
  • Proprotein Convertase 9
  • Proprotein Convertases / antagonists & inhibitors
  • Proprotein Convertases / metabolism
  • Risk Factors
  • Serine Endopeptidases / metabolism
  • Triglycerides / blood*

Substances

  • Antibodies, Monoclonal
  • Anticholesteremic Agents
  • Apolipoprotein A-I
  • BMS201038
  • Benzimidazoles
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Fibric Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Oligonucleotides
  • Triglycerides
  • Niacin
  • mipomersen
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases