title: Very low LDL-C levels may safely provide additional clinical cardiovascular benefit: the evidence to date.
abstract: BACKGROUND
  Cardiovascular disease (CVD) is the leading cause of death in Europe and increased low-density lipoprotein cholesterol (LDL-C) is a major contributor to CVD risk. Extensive evidence from clinical studies of statins has demonstrated a linear relationship between LDL-C levels and CVD risk. It has been proposed that lower LDL-C levels than those currently recommended may provide additional clinical benefit to patients.
  
  
  OBJECTIVE
  This review summarises the genetic and clinical evidence on the efficacy and safety of achieving very low LDL-C levels.
  
  
  METHODS
  Relevant epidemiological and clinical studies were identified using PubMed and by searching abstracts published at major congresses.
  
  
  RESULTS
  Genetic evidence demonstrates that individuals with naturally very low LDL-C levels are healthy and have a low risk of CVD. Clinical evidence has shown that those patients who achieve very low LDL-C levels through using lipid-lowering therapies (LLTs), such as statins, have reduced CVD risk compared with patients who only just achieve recommended target LDL-C levels. These data show that the incidence of adverse events in patients achieving very low LDL-C levels using LLT is comparable to those reaching the recommended LDL-C targets.
  
  
  CONCLUSIONS
  Genetic and clinical evidence supports the concept that reduction in LDL-C levels below current recommended targets may provide additional clinical benefit to patients without adversely impacting patient safety. Statin add-on therapies, such as ezetimibe and the recently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab, allow patients to achieve very low LDL-C levels and are likely to impact on future treatment paradigms.
authors.affiliation: Hull York Medical School, Whitby Group Practice, Spring Vale Medical Centre, Whitby, UK.
authors.forename: Terry
authors.initials: T
authors.lastname: McCormack
authors.affiliation: Amgen (Europe) GmbH, Zug, Switzerland.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Dent
authors.affiliation: Ashgate Medical Practice, Chesterfield, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Blagden
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D008078:Cholesterol, LDL / Q000097:blood* / Q000235:genetics*; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000235:genetics; D012307:Risk Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab; C571059:alirocumab