title: Ischemic cardiac outcomes and hospitalizations according to prior macrovascular disease status in patients with type 2 diabetes and recent acute coronary syndrome from the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care trial.
abstract: BACKGROUND
  Concerns raised regarding adverse cardiovascular (CV) outcomes with new therapies for type 2 diabetes mellitus (T2DM) have led to several large-scale CV outcome trials. The EXAMINE trial confirmed noninferiority of the dipeptidyl dipeptidase 4 inhibitor alogliptin to placebo on major adverse cardiac event rates in a post-acute coronary syndrome (ACS) T2DM population. We present data on additional ischemic cardiac events and CV hospitalizations in EXAMINE.
  
  
  METHODS
  Patients with T2DM and an ACS event in the previous 15 to 90 days were randomly assigned to alogliptin or placebo on a background of standard treatment for diabetes. The incident rates of a 5-component composite end point of CV death, stroke, myocardial infarction, unstable angina, and coronary revascularization as well as CV hospitalization were calculated in all participants and according to macrovascular disease at baseline.
  
  
  RESULTS
  There were no significant differences between alogliptin (n = 2,701) and placebo (n = 2,679) in the event rate of the 5-component composite endpoint with median follow-up 533 days (21.0% vs 21.5%, hazard ratio [HR] 0.98 [0.87-1.10], P = .72). No differences were observed in terms of CV hospitalization (25.0% vs 25.4%, HR 0.98 [0.88-1.09], P = .70) or coronary revascularization (10.6% vs 10.2%, HR 1.05 [0.88-1.09], P = .60). No interactions were observed for treatment and prior macrovascular disease.
  
  
  CONCLUSIONS
  EXAMINE demonstrates that there was no increase in the risk of cardiac ischemic events and CV hospitalizations with alogliptin in a high-risk post-ACS patient population. Because these are major driver of overall health care costs, these data suggest that there would be no adverse impact on health care resource utilization.
authors.affiliation: Harvard Clinical Research Institute, Boston, MA; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address: yshimada@partners.org.
authors.forename: Yuichi J
authors.initials: YJ
authors.lastname: Shimada
authors.affiliation: Harvard Clinical Research Institute, Boston, MA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: Harvard Clinical Research Institute, Boston, MA; Department of Biostatistics, Boston University, Boston, MA.
authors.forename: Yuyin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Takeda Development Center Americas, Deerfield, IL.
authors.forename: Craig
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Takeda Development Center Americas, Deerfield, IL.
authors.forename: Stuart
authors.initials: S
authors.lastname: Kupfer
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Venu
authors.initials: V
authors.lastname: Menon
authors.affiliation: University of Tennessee College of Medicine, Memphis Veterans Affairs Medical Center, Memphis, TN.
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.affiliation: Harvard School of Public Health, Boston, MA.
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Mehta
authors.affiliation: University of Chicago Medicine, Chicago, IL.
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.affiliation: Institut Lorrain du Coeur et des Vaisseaux, Centre d'Investigation Clinique Inserm, Université de Lorraine and CHU, Vandoeuvre-Les-Nancy, France.
authors.forename: Faeiz
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT.
authors.forename: William B
authors.initials: WB
authors.lastname: White
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000628:therapy; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology / Q000628:therapy; D009204:Myocardial Revascularization / Q000379:methods / Q000706:statistics & numerical data; D010043:Outcome and Process Assessment, Health Care; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment; D059039:Standard of Care; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000628:therapy; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D007004:Hypoglycemic Agents; D010880:Piperidines; D014498:Uracil; C520853:alogliptin