title: Evaluating bococizumab, a monoclonal antibody to PCSK9, on lipid levels and clinical events in broad patient groups with and without prior cardiovascular events: Rationale and design of the Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Lipid Lowering and SPIRE Cardiovascular Outcomes Trials.
abstract: BACKGROUND
  Although statins significantly reduce vascular event rates, residual cholesterol risk remains high in many patient groups, including those with known vascular disease as well as in the setting of high-risk primary prevention. Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), prolongs the half-life of hepatic low-density lipoprotein (LDL) receptors, and reduces circulating atherogenic cholesterol levels.
  
  
  METHODS
  The SPIRE program comprises 6 lipid-lowering studies and 2 cardiovascular outcomes trials, each comparing bococizumab (150 mg subcutaneously every 2 weeks) to matching placebo. The 6 SPIRE lipid-lowering studies include 3 parallel 12-month assessments of bococizumab on atherogenic lipids among statin-treated individuals at high residual risk (SPIRE-HR, SPIRE-LDL, SPIRE-LL), one 12-month study of bococizumab among individuals with familial hypercholesterolemia (SPIRE-FH), one 6-month study of bococizumab among those with statin intolerance (SPIRE-SI), and one 3-month study of bococizumab delivery using an auto-injector device (SPIRE-AI). The SPIRE-1 and SPIRE-2 event-driven cardiovascular outcome trials will assess the efficacy and safety of bococizumab in the prevention of incident vascular events in high-risk populations with and without clinically evident cardiovascular disease who have directly measured entry LDL cholesterol levels ≥70 mg/dL (SPIRE-1, n = 17,000) or ≥100 mg/dL (SPIRE-2, n = 11,000).
  
  
  CONCLUSIONS
  The SPIRE trials, inclusive of more than 30,000 participants worldwide, will ascertain the magnitude of reduction in atherogenic lipids that accrue with bococizumab and determine whether the addition of this PCSK9 inhibitor to standard treatment significantly reduces cardiovascular morbidity and mortality in high-risk patients, including those without a history of clinical cardiovascular events.
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors: Paul M
authors: PM
authors: Ridker
authors: Paris-Diderot, Sorbonne University, Paris, France.
authors: Pierre
authors: P
authors: Amarenco
authors: Pfizer Inc, New York, NY.
authors: Robert
authors: R
authors: Brunell
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors: Robert J
authors: RJ
authors: Glynn
authors: Leiden University Medical Center, Leiden, the Netherlands.
authors: J Wouter
authors: JW
authors: Jukema
authors: Academic Medical Center of the University of Amsterdam, Amsterdam, Netherlands.
authors: John J P
authors: JJ
authors: Kastelein
authors: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors: Wolfgang
authors: W
authors: Koenig
authors: Cleveland Clinic Foundation, Cleveland, OH.
authors: Steven
authors: S
authors: Nissen
authors: Pfizer Inc, New York, NY.
authors: James
authors: J
authors: Revkin
authors: Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.
authors: Raul D
authors: RD
authors: Santos
authors: Pfizer Inc, New York, NY.
authors: Pamela F
authors: PF
authors: Schwartz
authors: Pfizer Inc, New York, NY.
authors: Carla
authors: C
authors: Yunis
authors: Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors: Jean-Claude
authors: JC
authors: Tardif
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000097:blood
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; C000598888:bococizumab