@article{7f96197cc2ec4117ad42848428fd9601,
title = "Association between glycated haemoglobin levels and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the TECOS randomized clinical trial",
abstract = "Aims: Whether glycaemic control is associated with cardiovascular outcomes in patients with type 2 diabetes (T2D) is unclear. Consequently, we assessed the relationship between glycated haemoglobin (HbA1c) and cardiovascular outcomes in a placebo-controlled randomized trial which demonstrated no cardiovascular effect of sitagliptin in patients with T2D and atherosclerotic vascular disease. Methods and results: Secondary analysis of 14 656 TECOS participants with time to event analyses using multivariable Cox proportional hazard models. During a median 3.0 (interquartile range 2.3–3.8) year follow-up, 456 (3.1% of 14 656) patients had first hospitalization for heart failure (HF), 1084 (11.5%) died, 1406 (9.6%) died or were hospitalized for HF, and 1689 (11.5%) had a non-HF cardiovascular event (cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, or hospitalization for unstable angina). Associations between baseline or time-varying HbA1c and cardiovascular outcomes were U-shaped, with the lowest risk when HbA1c was around 7%. Each one-unit increase in the time-varying HbA1c above 7% was associated with an adjusted hazard ratio (HR) of 1.21 [95% confidence interval (CI) 1.11–1.33] for first HF hospitalization, 1.11 (1.03–1.21) for all-cause death, 1.18 (1.09–1.26) for death or HF hospitalization, and 1.10 (1.02–1.17) for non-HF cardiovascular events. Each one-unit decrease in the time-varying HbA1c below 7% was associated with an adjusted HR of 1.35 (95% CI 1.12–1.64) for first HF hospitalization, 1.37 (1.16–1.61) for death, 1.42 (1.23–1.64) for death or HF hospitalization, and 1.22 (1.06–1.41) for non-HF cardiovascular events. Conclusion: Glycated haemogobin exhibits a U-shaped association with cardiovascular outcomes in patients with T2D and atherosclerotic vascular disease, with nadir around 7%. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT00790205.",
keywords = "Diabetes mellitus, Glycaemic control, Heart failure, Outcomes",
author = "{TECOS Study Group} and McAlister, {Finlay A.} and Yinggan Zheng and Westerhout, {Cynthia M.} and Buse, {John B.} and Eberhard Standl and McGuire, {Darren K.} and {Van de Werf}, Frans and Green, {Jennifer B.} and Armstrong, {Paul W.} and Holman, {Rury R.}",
note = "Funding Information: F.A.M. is supported by the Alberta Health Services Chair in Cardiovascular Outcomes Research. J.B.B. reports that contracted advisory fees are paid to his employer (the University of North Carolina) by Adocia, AstraZeneca, Dance Biopharm, Eli Lilly, MannKind, NovaTarg, NovoNordisk, Senseonics, vTv Therapeutics, and Zafgen; he has received grant support from NovoNordisk, Sanofi, and vTv Therapeutics; served as a consultant to Neurimmune AG; has stock options in Mellitus Health, PhaseBio and Stability Health; and is supported by a grant from the National Institutes of Health (UL1TR002489). E.S. reports personal fees from the Oxford Diabetes Trials Unit, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Menarini, Merck Serono, Excemed, Novartis, NovoNordisk, and Sanofi. Conflict of interest: Funding Information: D.K.M. has received personal fees from Boehringer Ingelheim, Janssen Research and Development LLC, Sanofi US, Merck & Co., Merck Sharp and Dohme Corp., Eli Lilly USA, NovoNordisk, GlaxoSmithKline, AstraZeneca, Lexicon Pharmaceuticals, Eisai, Pfizer, Metavant, Applied Therapeutics, Afimmune and Esperion. F.V.d.W. has received study grants from Merck. J.B.G. has received grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Sanofi, and personal fees from AstraZeneca, Merck, Boehringer‐Ingelheim, Sanofi/Regeneron, and NovoNordisk. P.W.A. has received research grants, personal fees and non‐financial support from Merck; complete disclosures are available at http://thecvc.ca/wp‐content/uploads/2017/01/Financial‐Disclosure‐form‐PWA‐September2018‐Final.pdf . R.R.H. has received 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. All other authors have nothing to disclose. Funding Information: No specific funding for this analysis, but the TECOS trial was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. The funders had no role in the conception, design, analysis, writing, or decision to publish this manuscript. Publisher Copyright: {\textcopyright} 2020 European Society of Cardiology",
year = "2020",
month = nov,
doi = "10.1002/ejhf.1958",
language = "English (US)",
volume = "22",
pages = "2026--2034",
journal = "European Journal of Heart Failure",
issn = "1388-9842",
publisher = "Oxford University Press",
number = "11",
}