title: Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors to treat hypercholesterolemia: Effect on stroke risk.
abstract: OBJECTIVE
  A reduction of cardiovascular events has been reported in phase 2 and 3 trials of the proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors alirocumab and evolocumab. We aimed to investigate the effect PCSK9 inhibition on stroke risk in a meta-analysis involving data from randomized studies with alirocumab and evolocumab.
  
  
  METHODS
  Data from pre-specified combined analysis of 4465 patients who completed phase 2 or 3 studies of evolocumab over a period of 1year and a randomized trial on alirocumab including 2341 patients with hyperlipidemia on maximally tolerated statin who were at high risk for coronary heart disease over a period of 1.5years were used.
  
  
  RESULTS
  The number of patients having an ischemic stroke was small in both trials. PCSK9 inhibition showed no significant effect on stroke rate (risk ratio 1.43; 95% CI, 0.45-4.57, p=0.55). No significant differences in stroke risk were evident when transient ischemic attacks were included in the analysis (risk ratio 0.65; 95% CI, 0.25-1.68, p=0.37). No hemorrhagic strokes were reported in either study.
  
  
  CONCLUSIONS
  Although a benefit towards reduction of cardiovascular events in the overall has been documented, longer exposure is warranted to be able to evaluate the effect on stroke risk.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece. Electronic address: hmilioni@uoi.gr.
authors.forename: Haralampos
authors.initials: H
authors.lastname: Milionis
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
authors.forename: Fotios
authors.initials: F
authors.lastname: Barkas
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Thesaly, Larissa, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Ntaios
authors.affiliation: Leeds Teaching Hospitals NHS Trust, UK.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Papavasileiou
authors.affiliation: Hellenic Stroke Organisation, Athens, Greece.
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Vemmos
authors.affiliation: Centre Cerebrovasculaire, Service de Neurologie, Departement des Neurosciences Cliniques CHUV, Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Michel
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications* / Q000188:drug therapy*; D000091362:PCSK9 Inhibitors; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000453:epidemiology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; C577155:evolocumab; C571059:alirocumab
keywords: Alirocumab; Evolocumab; Hypercholesterolemia; Ischemic stroke; Lipid lowering; PCSK9 inhibitors