title: Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo.
abstract: BACKGROUND
  Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated.
  
  
  METHODS
  ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy.
  
  
  RESULTS
  Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events.
  
  
  CONCLUSIONS
  ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk.
authors.affiliation: Department of Medicine/Diabetes Unit, Massachusetts General Hospital, Boston, MA. Electronic address: rbentleylewis@partners.org.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bentley-Lewis
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX.
authors.forename: David
authors.initials: D
authors.lastname: Aguilar
authors.affiliation: Department of Medicine, Oregon Health & Science University, Portland, OR.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Riddle
authors.affiliation: Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Boston MA.
authors.forename: Brian
authors.initials: B
authors.lastname: Claggett
authors.affiliation: Estudios Cardiologicos Latinoamerica, Rosario, Santa Fe, Argentina.
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.affiliation: University of Bergen, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dickstein
authors.affiliation: Department of Medicine and Population Health Research Institute, McMaster University & Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.affiliation: Sanofi-Aventis, Bridgewater, NJ.
authors.forename: Peter
authors.initials: P
authors.lastname: Johnston
authors.affiliation: The Heart Centre, Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Lars V
authors.initials: LV
authors.lastname: Køber
authors.affiliation: Sanofi-Aventis, Bridgewater, NJ.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lawson
authors.affiliation: Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Boston MA.
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.affiliation: ANMCO Research Center, Florence, Italy.
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Sanofi-Aventis, Bridgewater, NJ.
authors.forename: Lin
authors.initials: L
authors.lastname: Ping
authors.affiliation: Department of Medicine/Cardiology, University of Washington Medical Center, Seattle, WA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Probstfield
authors.affiliation: Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Boston MA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Québec, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.affiliation: Sanofi-Aventis, Bridgewater, NJ.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Boston MA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D002318:Cardiovascular Diseases; D004311:Double-Blind Method; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012107:Research Design; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D052216:Glucagon-Like Peptide 1; D010455:Peptides; D010919:Placebos; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor