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.

中文翻译：

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2型糖尿病和周围动脉疾病患者的临床结果：来自EXSCEL试验的结果。

背景技术最近的试验已经确定了降低主要不良心血管事件（MACE）发生率的抗糖尿病药物，尽管降低了下肢截肢（LEA）的发生率。患有外周动脉疾病（PAD）的患者发生糖尿病的可能性更高，并有LEA风险，这促使在EXSCEL试验（心血管事件降低的艾塞那肽研究）中对糖尿病和PAD患者的临床结局进行了调查。方法EXSCEL评估了每周一次艾塞那肽（一种GLP-1 [胰高血糖素样肽-1]受体激动剂）与安慰剂对患者主要复合MACE终点（心血管死亡，心肌梗塞或中风）发生率的影响2型糖尿病。在此事后分析中，我们评估了基线PAD与MACE，LEA，和艾塞那肽与安慰剂对有或没有PAD的患者的影响。结果EXSCEL包括2800例PAD患者（占试验人群的19％）。与没有PAD的患者相比，这些个体的未调整和调整后的MACE率更高（分别为13.6％和11.4％），以及较高的调整后风险比（调整后风险比为1.13 [95％CI，1.00-1.27]； P = 0.047）。PAD患者的全因死亡率较高（调整后的危险比1.38 [95％CI，1.20-1.60]； P <0.001）和LEA发生率较高（调整后的危险比5.48 [95％CI，4.16-7.22]； P <0.001 ）。不论PAD状态如何，接受艾塞那肽或安慰剂治疗的患者的MACE和LEA发生率均相似。结论与没有PAD的参与者相比，患有PAD的EXSCEL参与者的全因死亡率和LEA发生率更高。艾塞那肽与安慰剂相比，MACE或LEA率无差异。临床试验注册网址：https：//www.clinicaltrials.gov。唯一标识符：NCT01144338。