Clinical Outcomes in Patients with Type 2 Diabetes Mellitus and Peripheral Artery Disease: Results from the EXSCEL Trial
Year: 2020
Type: article
Abstract: Background: Recent trials have identified anti-diabetes mellitus agents that lower major adverse cardiovascular event (MACE) rates, although some increase rates of lower-extremity amputation (LEA). Patients with peripheral artery disease (PAD) have greater incidence of diabetes mellitus and risk for LEA, prompting this investigation of clinical outcomes in patients with diabetes mellitus and PAD in the EXSCEL trial (Exenatide Study of Cardiovascular Event Lowering). Methods: EXSCEL evaluated the effects of once-weekly exenatide (a GLP-1 [glucagon-like peptide-1] receptor agonist) versus placebo on the rates of the primary composite MACE end point (cardiovascular death, myocardial infarction, or stroke) among patients with type 2 diabetes mellitus. In this post hoc analysis, we assessed the association of baseline PAD with rates of MACE, LEA, and the effects of exenatide versus placebo in patients with and without PAD. Results: EXSCEL included 2800 patients with PAD (19% of the trial population). These individuals had higher unadjusted and adjusted rates of MACE compared with patients without PAD (13.6% versus 11.4%, respectively) as well as a higher adjusted hazard ratio (adjusted hazard ratio, 1.13 [95% CI, 1.00-1.27]; P=0.047). Patients with PAD had higher all-cause mortality (adjusted hazard ratio 1.38 [95% CI, 1.20-1.60]; P<0.001) and more frequent LEA (adjusted hazard ratio 5.48 [95% CI, 4.16-7.22]; P<0.001). Patients treated with exenatide or placebo had similar rates of MACE and LEA, regardless of PAD status. Conclusions: EXSCEL participants with PAD had higher rates of all-cause mortality and LEA compared with those without PAD. There were no differences in MACE or LEA rates with exenatide versus placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01144338.
DOI: 10.17615/ks7q-gz23
Authors: Goodman, S.G., Sattar, N., Katona, B., Patel, M.R., Buse, J.B., Mentz, R.J., Jones, S.W., Badjatiya, A., Merrill, P., Hernandez, A.F., Holman, R.R., Pagidipati, N.J., Iqbal, N.
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: American Heart Association, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Amylin Pharmaceuticals, AstraZeneca, GlaxoSmithKline, Sanofi, CSL Behring, Boston Scientific Corporation, Regeneron Pharmaceuticals, MannKind Corporation, Luitpold Pharmaceuticals, Tenax Therapeutics, Zafgen, Verily Life Sciences, University of Alberta, University of Oxford, University of Glasgow, University of Toronto, Novo Nordisk, Servier, National Institutes of Health, Agency for Healthcare Research and Quality, School of Medicine, Duke University, Department of Medicine, University of Toronto, Daiichi Sankyo Europe
OpenAlex ID: W3200394566