title: Cardiovascular Outcomes of Patients in SAVOR-TIMI 53 by Baseline Hemoglobin A1c.
abstract: BACKGROUND
  The effect of saxagliptin on cardiovascular outcomes according to different hemoglobin A1c (HbA1c) levels has not been described. Thus, we analyzed the SAVOR-TIMI 53 trial to compare the cardiovascular effects of saxagliptin vs placebo according to baseline HbA1c.
  
  
  METHODS
  A total of 16,492 patients with type 2 diabetes (HbA1c 6.5%-12.0% in the 6 months before randomization) and either a history of established cardiovascular disease or multiple risk factors for atherosclerosis were randomized to saxagliptin or placebo in addition to usual care. Patients were followed for a median of 2.1 years. The primary endpoint was cardiovascular death, myocardial infarction, or ischemic stroke.
  
  
  RESULTS
  Patients were stratified by HbA1c at randomization into the following prespecified groups: <7%, 7%-<8%, 8%-<9%, and ≥9%. Baseline HbA1c ≥7% was associated with increased risk of cardiovascular death, myocardial infarction, or ischemic stroke (adjusted hazard ratio [HR(adj)] 1.35; 95% confidence interval [CI], 1.17-1.58) but not hospitalization for heart failure (HR(adj) 1.09; 95% CI, 0.88-1.36). Saxagliptin neither increased nor decreased the risk of cardiovascular death, myocardial infarction, or ischemic stroke in patients with HbA1c <7% (HR 1.01; 95% CI, 0.78-1.31), 7%-<8% (HR 0.98; 95% CI, 0.80-1.20), 8%-<9% (HR 1.09; 95% CI, 0.85-1.39), ≥9% (HR 0.95; 95% CI, 0.77-1.18) (P-interaction = .89).
  
  
  CONCLUSIONS
  Baseline HbA1c is associated with increased risk of macrovascular events but not hospitalization for heart failure. There was no heterogeneity in the effect of saxagliptin on cardiovascular events by baseline HbA1c, with cardiovascular death, myocardial infarction, or ischemic stroke neither increased nor decreased across the spectrum of baseline HbA1c values.
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Heart and Vascular Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cavender
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Heart and Vascular Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.affiliation: Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.affiliation: FACT, DHU FIRE, Université Paris-Diderot, Sorbonne Paris-Cité, LVTS INSERM U-1148, Hôpital Bichat, HUPNVS, AP-HP, Paris, France; NHLI, Imperial College, Royal Brompton Hospital, London, United Kingdom.
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.affiliation: Division of Endocrinology and Metabolism, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, ON, Canada.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: AstraZeneca Research and Development, Gaithersburg, Md.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Jaime
authors.initials: J
authors.lastname: Davidson
authors.affiliation: Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Avivit
authors.initials: A
authors.lastname: Cahn
authors.affiliation: Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Ofri
authors.initials: O
authors.lastname: Mosenzon
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Heart and Vascular Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass.
authors.forename: KyungAh
authors.initials: K
authors.lastname: Im
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Heart and Vascular Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Heart and Vascular Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass. Electronic address: dlbhattmd@post.harvard.edu.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004151:Dipeptides / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006333:Heart Failure / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D012306:Risk; D020521:Stroke / Q000453:epidemiology*
chemical_list: D000218:Adamantane; D004151:Dipeptides; D006442:Glycated Hemoglobin; D054795:Incretins; C517652:hemoglobin A1c protein, human; C502994:saxagliptin
keywords: Coronary artery disease; Diabetes mellitus; Glycated hemoglobin assay; Randomized clinical trials