title: Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial.
abstract: Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on coronary atherosclerosis have not been evaluated.
  
  
  
  To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients.
  
  
  
  The GLAGOV multicenter, double-blind, placebo-controlled, randomized clinical trial (enrollment May 3, 2013, to January 12, 2015) conducted at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia, and South Africa and enrolling 968 patients presenting for coronary angiography.
  
  
  
  Participants with angiographic coronary disease were randomized to receive monthly evolocumab (420 mg) (n = 484) or placebo (n = 484) via subcutaneous injection for 76 weeks, in addition to statins.
  
  
  
  The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to week 78, measured by serial intravascular ultrasonography (IVUS) imaging. Secondary efficacy measures were nominal change in normalized total atheroma volume (TAV) and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated.
  
  
  
  Among the 968 treated patients (mean age, 59.8 years [SD, 9.2]; 269 [27.8%] women; mean LDL-C level, 92.5 mg/dL [SD, 27.2]), 846 had evaluable imaging at follow-up. Compared with placebo, the evolocumab group achieved lower mean, time-weighted LDL-C levels (93.0 vs 36.6 mg/dL; difference, -56.5 mg/dL [95% CI, -59.7 to -53.4]; P < .001). The primary efficacy parameter, PAV, increased 0.05% with placebo and decreased 0.95% with evolocumab (difference, -1.0% [95% CI, -1.8% to -0.64%]; P < .001). The secondary efficacy parameter, normalized TAV, decreased 0.9 mm3 with placebo and 5.8 mm3 with evolocumab (difference, -4.9 mm3 [95% CI, -7.3 to -2.5]; P < .001). Evolocumab induced plaque regression in a greater percentage of patients than placebo (64.3% vs 47.3%; difference, 17.0% [95% CI, 10.4% to 23.6%]; P < .001 for PAV and 61.5% vs 48.9%; difference, 12.5% [95% CI, 5.9% to 19.2%]; P < .001 for TAV).
  
  
  
  Among patients with angiographic coronary disease treated with statins, addition of evolocumab, compared with placebo, resulted in a greater decrease in PAV after 76 weeks of treatment. Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes.
  
  
  
  clinicaltrials.gov Identifier: NCT01813422.
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia2Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.affiliation: Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Todd
authors.initials: T
authors.lastname: Anderson
authors.affiliation: The Methodist DeBakey Heart and Vascular Center, Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
authors.forename: Leslie
authors.initials: L
authors.lastname: Cho
authors.affiliation: Academic Medical Center, Department of Vascular Medicine, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany7DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany8Department of Internal Medicine, University of Ulm Medical Center, Ulm, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Ransi
authors.initials: R
authors.lastname: Somaratne
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Helina
authors.initials: H
authors.lastname: Kassahun
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Wasserman
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Robert
authors.initials: R
authors.lastname: Scott
authors.affiliation: Department of Cardiology, University of Szeged, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Ungi
authors.affiliation: Department of Interventional Cardiology, Cardiology Institute, Jagiellonian University, College of Medicine and the John Paul II Hospital, Krakow, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Podolec
authors.affiliation: Department of Cardiology, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands.
authors.forename: Antonius Oude
authors.initials: AO
authors.lastname: Ophuis
authors.affiliation: Department of Cardiology, Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Borgman
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Brennan
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL / Q000097:blood*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D000091362:PCSK9 Inhibitors; D015990:Placebo Effect; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000473:pathology; D012074:Remission Induction; D013997:Time Factors; D014463:Ultrasonography; D000071449:Proprotein Convertase 9
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab