TY - JOUR
T1 - Cardiovascular Outcomes of Patients in SAVOR-TIMI 53 by Baseline Hemoglobin A1c
AU - Cavender, Matthew A.
AU - Scirica, Benjamin M.
AU - Raz, Itamar
AU - Gabriel Steg, Ph
AU - McGuire, Darren K
AU - Leiter, Lawrence A.
AU - Hirshberg, Boaz
AU - Davidson, Jaime
AU - Cahn, Avivit
AU - Mosenzon, Ofri
AU - Im, Kyungah
AU - Braunwald, Eugene
AU - Bhatt, Deepak L.
N1 - Funding Information:
Funding: SAVOR-TIMI 53 was funded by AstraZeneca and Bristol-Myers Squibb.
Funding Information:
Conflict of Interest: The TIMI Study Group has received significant research grant support from Amgen, Astra-Zeneca, Athera, Beckman Coulter, BG Medicine, Bristol-Myers Squibb, Buhlmann Laboratories, Daiichi Sankyo, Eli Lilly and Co, Eisai, Glaxo Smith Kline, Johnson & Johnson, Merck and Company, Nanosphere, Novartis Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Randox, Roche Diagnostics, Sanofi-Aventis, Siemens, and Singulex. MAC reports consulting fees from AstraZeneca and Merck. BMS reports consulting fees from AstraZeneca, Gilead, GE Healthcare, Lexicon, Arena, Eisai, St. Jude's Medical, Bristol-Myers Squibb, Forest Pharmaceuticals, Boston Clinical Research Institute, University of Calgary, Elsevier Practice Update Cardiology, and Forest Pharmaceuticals. IR reports grants from Astra Zeneca, grants from Bristol Myers Squibb, during the conduct of the study; scientific board membership from Novo Nordisk, MSD, Eli Lilly and Co, Sanofi, Medscape, Andromeda, Insuline; payment for lectures, including service on speakers bureaus, for lectures from Eli Lilly, Novo Nordisk, Johnson & Johnson, Sanofi, MSD, Novartis; and stock options in Insuline. GS reports personal fees from AstraZeneca during the conduct of the study; personal fees from Amarin, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck-Sharpe-Dohme, Novartis, Otsuka, Pfizer, Roche, The Medicines Company, and Vivus. He has received grants and personal fees from Sanofi and Servier. DKM reports personal fees from Brigham and Women's Hospital during the conduct of the study; personal fees from Boehringer Ingelheim, Janssen Research and Development LLC, Sanofi Aventis Groupe, Genentech, Inc, Merck Sharp and Dohme Corp., Medscape Cardiology, Pri-Med Institute, The Brigham and Women's Hospital, Duke Clinical Research Institute, The Cleveland Clinic Coordinating Center for Clinical Research, The University of Oxford, Daiichi Sankyo, Lilly USA, Novo Nordisk, F Hoffmann La Roche, Axio Research, Premier Research, INC Research LLC, Glaxo Smith Kline, Takeda Pharmaceuticals North America, Bristol-Myers Squibb, Astra Zeneca, Lexicon Pharmaceuticals, GlaxoSmithKline, Eisai, Omthera, and Regeneron. He reports nonfinancial support from Gilead Sciences. LAL reports receiving research funding from, having provided CME on behalf of, and/or have acted as a consultant to: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novo Nordisk, Sanofi, Servier, and Takeda. BH reports employment by AstraZeneca and having stock/stock options in AstraZeneca. JD reports personal fees from the TIMI Study Group during the conduct of the study. AC reports receipt of consulting fees and payment for lectures from AstraZeneca, Boehringer Ingelheim, Elli Lilly, Merck, Novartis, Novo Nordisk and Sanofi. OM reports grants from AstraZeneca and Bristol-Myers Squibb during the conduct of the study; consulting fees from AstraZeneca and Bristol-Myers Squibb; support for travel to meetings for the study from AstraZeneca and Bristol-Myers Squibb; scientific advisory board membership from Novo Nordisk, Eli Lilly, Sanofi, Norvartis, speakers bureaus for Novo Nordisk, Eli Lilly, Sanofi, Norvartis, and Merck, Sharpe and Dohme. EB reports grants from Duke University, personal fees from Eli Lilly, Merck, CVRx, CV Therapeutics (now Gilead), Daiichi Sankyo, Menarini International, Medscape, Bayer, Genzyme, The Medicines Company, Sanofi Aventis. DLB discloses the following relationships: advisory board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; board of directors for Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair of the American Heart Association Get With The Guidelines Steering Committee; data monitoring committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); other: Clinical Cardiology (Deputy Editor); research funding: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company; Site Co-Investigator: Biotronik, St. Jude Medical; trustee: American College of Cardiology; Unfunded Research: FlowCo, PLx Pharma, Takeda.
Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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 [HRadj] 1.35; 95% confidence interval [CI], 1.17-1.58) but not hospitalization for heart failure (HRadj 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.
AB - 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 [HRadj] 1.35; 95% confidence interval [CI], 1.17-1.58) but not hospitalization for heart failure (HRadj 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.
KW - Coronary artery disease
KW - Diabetes mellitus
KW - Glycated hemoglobin assay
KW - Randomized clinical trials
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U2 - 10.1016/j.amjmed.2015.09.022
DO - 10.1016/j.amjmed.2015.09.022
M3 - Article
C2 - 26524706
AN - SCOPUS:84958053809
SN - 0002-9343
VL - 129
SP - 340.e1-340.e8
JO - American Journal of Medicine
JF - American Journal of Medicine
IS - 3
ER -