title: Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: Rationale and design of the ACCELERATE trial.
abstract: BACKGROUND
  Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease.
  
  
  METHODS
  ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients qualified for enrollment if they have experienced an acute coronary syndrome within the prior 30 to 365 days, cerebrovascular accident, or transient ischemic attack; if they have peripheral vascular disease; or they have diabetes with coronary artery disease. A total of 12,092 patients were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to first event of CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Treatment will continue until 1,670 patients reached the primary end point; at least 700 patients reach the key secondary efficacy end point of CV death, myocardial infarction, and stroke, and the last patient randomized has been followed up for at least 1.5 years.
  
  
  CONCLUSIONS
  ACCELERATE will establish whether the cholesteryl ester transfer protein inhibition by evacetrapib improves CV outcomes in patients with high-risk vascular disease.
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research and Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH.
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.affiliation: University of New South Wales, Sydney, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.affiliation: Medstar Research Institute, Hyattsville, MD.
authors.forename: H Bryan
authors.initials: HB
authors.lastname: Brewer
authors.affiliation: University of Edinburgh, Edinburgh, Scotland.
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.affiliation: Harvard Medical School, Boston, MA.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Christopher
authors.initials: C
authors.lastname: Grainger
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research and Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Menon
authors.affiliation: Pitie-Salpetriere University Hospital, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.affiliation: University of Pennsylvania, Philadelphia, PA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rader
authors.affiliation: Columbia University, New York City, NY.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Tall
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research and Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH.
authors.forename: Ellen
authors.initials: E
authors.lastname: McErlean
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Riesmeyer
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Vangerow
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Ruotolo
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Govinda J
authors.initials: GJ
authors.lastname: Weerakkody
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research and Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D016491:Peripheral Vascular Diseases / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D018570:Risk Assessment
chemical_list: D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D001569:Benzodiazepines; C568301:evacetrapib