title: A study in high-risk, maximally pretreated patients to determine the potential use of PCSK9 inhibitors at various thresholds of total and LDL cholesterol levels.
abstract: OBJECTIVE
  Statins and ezetimibe reduce low-density lipoprotein cholesterol (LDL-c) and cardiovascular disease (CVD) risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-c by 50%-70% and might be useful in refractory patients. The National Institute for Health and Care Excellence (NICE) technology appraisal guidance (TAG) recommends use of these drugs in secondary prevention and familial hypercholesterolaemia (FH) at differing LDL-c thresholds. We have estimated the proportion of patients in whom this third-line drug might be useful.
  
  
  METHODS
  We used data from a lipid-lowering audit programme to study 72 with FH and/or CVD of 271 patients referred over 12 months who failed to achieve target total cholesterol (TC) and LDL-c levels. All 72 patients were treated with ezetimibe, and 69 cases also received statins. We used LDL-c thresholds 1.5-5.5 mmol/L to estimate how many of these refractory patients could benefit from PCSK9 inhibitors.
  
  
  RESULTS
  In 72 patients, TC and LDL-c targets were not met by 64 and 53 patients, respectively. We judged using the NICE TAG that only one patient (1.4% ezetimibe requiring and 0.4% total referrals) required a PCSK9 inhibitor.
  
  
  CONCLUSIONS
  We determined that the proportion of patients eligible for a PCSK9 inhibitor at various TC and LDL-c levels is modest. This may reflect the use of all available statins in UK lipid clinics often at non-daily frequency. We suggest that cost-effective use of PCSK9 inhibitors requires prescribing being restricted to clinicians working in specialised lipid clinics.
authors.affiliation: Department of Clinical Biochemistry, Heart of England Foundation NHS Trust, Sutton Coldfield, UK.
authors.forename: Carl
authors.initials: C
authors.lastname: Groves
authors.affiliation: Department of Clinical Biochemistry, Worcestershire Acute Hospitals NHS Trust, Worcester, Worcestershire, UK.
authors.forename: Chandrashekar
authors.initials: C
authors.lastname: Shetty
authors.affiliation: Institute for Science and Technology in Medicine, Keele University Medical School, Stoke-on-Trent, Staffordshire, UK.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Strange
authors.affiliation: Department of Clinical Biochemistry, University Hospitals of North Midlands, Stoke-on-Trent, Staffordshire, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Waldron
authors.affiliation: Department of Clinical Biochemistry, Heart of England Foundation NHS Trust, Sutton Coldfield, UK.|Department of Clinical Biochemistry, University Hospitals of North Midlands, Stoke-on-Trent, Staffordshire, UK.|Faculty of Health Sciences, Staffordshire University, Stoke-on-Trent, Staffordshire, UK.
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Ramachandran
mesh_terms: D000924:Anticholesteremic Agents / Q000191:economics / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D003362:Cost-Benefit Analysis; D000069438:Ezetimibe / Q000191:economics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D000091362:PCSK9 Inhibitors; D010818:Practice Patterns, Physicians' / Q000191:economics / Q000706:statistics & numerical data*; D055502:Secondary Prevention / Q000191:economics; D006113:United Kingdom; D000071449:Proprotein Convertase 9
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D000069438:Ezetimibe; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Dyslipidaemia targets; Ezetimibe; PCSK9 inhibitors; PREVENTIVE MEDICINE; Statins