title: Evidence-based goals in LDL-C reduction.
abstract: The evidence from trials of statin therapy suggests that benefits in cardiovascular disease (CVD) event reduction are proportional to the magnitude of low-density lipoprotein cholesterol (LDL-C) lowering. The lack of a threshold at which LDL-C lowering is not beneficial, in terms of CVD prevention observed in these trials, is supported by epidemiological and genetic studies reporting the cardio-protective effects of lifelong low exposure to atherogenic cholesterol in a graded fashion. Providing that intensive LDL-C lowering is safe, these observations suggest that many individuals even at current LDL-C treatment targets could benefit. Here, we review recent safety and efficacy data from trials of adjunctive therapy, with LDL-C lowering beyond that achieved by statin therapy, and their potential implications for current guideline targets. Finally, the application of current guidance in the context of pre-treatment LDL-C concentration and deployment of statin therapy is also discussed. The number of patients requiring treatment to prevent a CVD event with statin treatment has been shown to differ markedly according to the pre-treatment LDL-C concentration even when absolute CVD risk is similar. It produces more likelihood of benefit when absolute LDL-C reduction is greater which is largely dependent on pre-treatment LDL-C concentration. This also has to be taken in consideration when deploying new agents like proprotein convertase subtilisin/kexin type 9 monoclonal antibodies. Patients with highest LDL-C concentration despite maximum statin and ezetimibe therapy will attain most absolute LDL-C reduction when treated with proprotein convertase subtilisin/kexin type 9 monoclonal antibodies, hence benefit most in term of CVD risk reduction.
authors.affiliation: Cardiovascular Research Group, School of Biomedicine, University of Manchester, Core Technology Facility, Manchester, UK. Handrean.Soran@cmft.nhs.uk.|Cardiovascular Trials Unit, University Department of Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. Handrean.Soran@cmft.nhs.uk.
authors.forename: Handrean
authors.initials: H
authors.lastname: Soran
authors.affiliation: Amgen (Europe) GmbH, Zug, Switzerland.|Esperion Therapeutics Inc., Ann Arbor, MI, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Dent
authors.affiliation: Cardiovascular Research Group, School of Biomedicine, University of Manchester, Core Technology Facility, Manchester, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Durrington
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood*; D004359:Drug Therapy, Combination; D006040:Goals; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D012307:Risk Factors
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Ezetimibe; LDL cholesterol; PCSK9; Residual risk; Statin