TY - JOUR
T1 - Sitagliptin does not reduce the risk of cardiovascular death or hospitalization for heart failure following myocardial infarction in patients with diabetes
T2 - Observations from TECOS
AU - Nauck, Michael A.
AU - McGuire, Darren K.
AU - Pieper, Karen S.
AU - Lokhnygina, Yuliya
AU - Strandberg, Timo E.
AU - Riefflin, Axel
AU - Delibasi, Tuncay
AU - Peterson, Eric D.
AU - White, Harvey D.
AU - Scott, Russell
AU - Holman, Rury R.
N1 - Funding Information:
MAN has been a member of advisory boards or consulted for AstraZeneca (moderate), Boehringer Ingelheim (moderate), Eli Lilly & Co. (significant), Fractyl (moderate), GlaxoSmithKline (moderate), Intarcia (moderate), Menarini/ Berlin Chemie (moderate), Merck, Sharp & Dohme (significant), and NovoNor-disk (significant). His institution has received grant support from AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Intarcia, Menarini/ Berlin-Chemie, Merck, Sharp & Dohme, Novartis Pharma, and Novo Nordisk A/S. He has also served on the speakers’bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Menarini/Berlin Chemie (all moderate), Merck, Sharp & Dohme, and Novo Nordisk A/S (both significant). DKM has provided clinical trial leadership for AstraZeneca, Sanofi Aventis, Janssen, Boehringer Ingelheim, Merck & Co, Pfizer, Lilly US, Novo Nordisk, Lexicon, Eisai, GlaxoSmithKline, and Esperion, and consultancy for AstraZeneca, Sanofi Aventis, Lilly US, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Applied Therapeutics, Afimmune and Metavant. KSP has no disclosures. YL has received grants from Merck, Janssen Research & Development, AstraZeneca, GlaxoSmithKline, and Bayer HealthCare AG. TES reports personal fees from several companies (incl. Amgen, AstraZeneca, Merck, NovoNordisk, Pfizer, Orion, Bayer, Boehringer-Ingelheim) and owns a minor amount of stock in Orion-Pharma. AR has no disclosures. TD has no disclosures. EDP has received grants from Janssen, Merck, Sanofi, AstraZeneca, Genentech, and Amgen, and has consulting associations with Janssen, Bayer, Merck, and Sanofi. HDW reports research grants from GlaxoSmithKline, Sanofi-Aventis, Eli Lilly and Company, National Institute of Health, Merck Sharp & Dohme, George Institute, Omthera Pharmaceuticals, Pfizer New Zealand, Intarcia Therapeutics Inc., Elsai Inc., Daiichi-Sankyo, DalCor Pharmaceuticals; Advisory board/lecture fees from AstraZeneca, Acetelion, Sirte and he is a Steering Board member for Luitpold Pharmaceuticals Ltd and CSL Behring LLC. RS has no disclosures. RRH reports receiving grants from AstraZeneca during the conduct of the study and grants and personal fees from Bayer, Boehringer Ingelheim and Merck Sharp&Dohme Corp., a subsidiary of Merck & Co., Inc.; personal fees from Novartis, Amgen, and Servier; and financial support from Elcelyx, GlaxoSmithKline, Janssen, and Takeda outside the submitted work.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/9/3
Y1 - 2019/9/3
N2 - Background: To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods: TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. Results: During TECOS, 616 participants had ≥ 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. Conclusions: In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205
AB - Background: To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods: TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. Results: During TECOS, 616 participants had ≥ 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. Conclusions: In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205
KW - Acute myocardial infarction
KW - Cardiovascular outcomes
KW - Sitagliptin
KW - Type 2 diabetes
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U2 - 10.1186/s12933-019-0921-2
DO - 10.1186/s12933-019-0921-2
M3 - Article
C2 - 31481069
AN - SCOPUS:85071775016
SN - 1475-2840
VL - 18
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
IS - 1
M1 - 116
ER -