Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical update.
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.
Department of Internal Medicine, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Kispaticeva 12, 10 000 Zagreb, Croatia. Electronic address: zreiner@kbc-zagreb.hr.
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D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D016632:Apolipoprotein A-I / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy; D058607:Fibric Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D009525:Niacin / Q000627:therapeutic use; D009841:Oligonucleotides / Q000627:therapeutic use; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000378:metabolism; D014280:Triglycerides / Q000097:blood*
D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; C473731:BMS201038; D001562:Benzimidazoles; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009841:Oligonucleotides; D014280:Triglycerides; D009525:Niacin; C524142:mipomersen; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
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