incretins and Peripheral-Arterial-Disease

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).. 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.. 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];. 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.

Topics: Aged; Cause of Death; Diabetes Mellitus, Type 2; Double-Blind Method; Exenatide; Female; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome

Diabetes mellitus (DM) is a known risk factor for myocardial infarction (MI); however, data regarding MI subtypes in people with diabetes are limited. In the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial (n = 9,340), liraglutide significantly reduced the risk of major adverse cardiovascular (CV) events (composite of CV death, nonfatal MI, or nonfatal stroke) versus placebo in patients with type 2 DM and high CV risk. Liraglutide also reduced risk of first MI (292 events with liraglutide vs 339 with placebo). This post hoc analysis characterized MIs (first and recurrent) occurring in LEADER, by treatment arm and regarding incidence, outcome, subtype, and troponin levels. A total of 780 MIs (first and recurrent) were reported, with fewer in the liraglutide-treatment group than in the placebo-treatment group (359 vs 421, p = 0.022). Numerically fewer MIs were associated with CV death with liraglutide than with placebo (17 vs 28 fatal MIs, p = 0.28). Symptomatic MIs in both arms were mainly non-ST-segment elevation MI (555/641) and spontaneous MI (518/641). Numerically greater proportions of symptomatic MIs were associated with troponin levels ≤5× or ≤10× the upper reference limit with liraglutide versus placebo (p = 0.16 and p = 0.42, respectively). At baseline, more liraglutide-treated patients than placebo-treated patients with MI during the trial had a history of coronary artery bypass graft (p = 0.008), and fewer had peripheral arterial disease in the lower extremities (p = 0.005) and >50% stenosis of the coronary artery, the carotid artery, or other arteries (p = 0.044). In conclusion, this analysis showed that liraglutide reduces the incidence of MIs in patients with type 2 DM at high CV risk and may impact the clinical outcomes of MI.

Topics: Carotid Stenosis; Coronary Stenosis; Diabetes Mellitus, Type 2; Double-Blind Method; Humans; Incidence; Incretins; Liraglutide; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peripheral Arterial Disease; ST Elevation Myocardial Infarction; Troponin