title: Relationship of glycated haemoglobin and reported hypoglycaemia to cardiovascular outcomes in patients with type 2 diabetes and recent acute coronary syndrome events: The EXAMINE trial.
abstract: To investigate relationships between glycated haemoglobin (HbA1c) and reported hypoglycaemia and risk of major adverse cardiovascular events (MACE).
  
  
  
  The EXAMINE trial randomized 5380 patients with type 2 diabetes (T2DM) and a recent acute coronary syndrome (ACS) event, in 49 countries, to double-blind treatment with alogliptin or placebo in addition to standard of care. We used Cox proportional hazards models to analyse relationships among MACE, HbA1c levels and hypoglycaemic events.
  
  
  
  Patients randomized to alogliptin achieved lower HbA1c levels than the placebo group in all baseline HbA1c categories without differences in hypoglycaemia rates. No systematic change was found in MACE rates according to baseline HbA1c (Pinteraction= 0.971) or HbA1c category at 1 month. Patients in the combined treatment groups (n = 5380) who experienced serious hypoglycaemia (n = 34) had higher MACE rates than those who did not (35.3% vs 11.4%, adjusted hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.27-4.60; P = .007), although the association was less strong when analysing only events after the hypoglycaemic event (adjusted HR 1.60, 95% CI 0.80, 3.20).
  
  
  
  There were no relationships between baseline HbA1c levels or HbA1c levels after 1 month of treatment and the risk of MACE. Alogliptin improved glycaemic control without increasing hypoglycaemia. Reported events of hypoglycaemia and serious hypoglycaemia were associated with MACE. These data underscore the safety of alogliptin in improving glycaemic control in T2DM post-ACS. Further study of hypoglycaemia as an independent risk factor for MACE in patients with T2DM and coronary disease is needed.
authors.affiliation: University of Sheffield, Sheffield, UK.
authors.forename: Simon R
authors.identifier: 0000-0002-2425-9565
authors.initials: SR
authors.lastname: Heller
authors.affiliation: International Diabetes Center, Park-Nicollet Clinic, Minneapolis, Minnesota.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bergenstal
authors.affiliation: Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut.
authors.forename: William B
authors.initials: WB
authors.lastname: White
authors.affiliation: Takeda Development Center Americas, Inc, Deerfield, Illinois.
authors.forename: Stuart
authors.initials: S
authors.lastname: Kupfer
authors.affiliation: University of Chicago Medicine, Chicago, Illinois.
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.affiliation: University of Tennessee College of Medicine, Memphis Veterans Affairs Medical Center, Memphis, Tennessee.
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Mehta
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
authors.affiliation: Takeda Development Center Americas, Inc, Deerfield, Illinois.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Wilson
authors.affiliation: Université de Lorraine, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Yuyin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Noah M
authors.initials: NM
authors.lastname: Gourlie
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
mesh_terms: D054058:Acute Coronary Syndrome / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D055502:Secondary Prevention; D012720:Severity of Illness Index; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010880:Piperidines; D014498:Uracil; C517652:hemoglobin A1c protein, human; C520853:alogliptin
keywords: HbA1c; alogliptin; cardiovascular disease; coronary disease; diabetes; hypoglycaemia; myocardial infarction; stroke