BACKGROUND: Large studies in patients with diabetes mellitus (DM) have identified agents that lower major adverse cardiovascular (CV) event (MACE) rates, but certain agents increase rates of lower extremity amputation (LEA). Patients with peripheral artery disease (PAD) have greater incidence of DM and risk for LEA, thus prompting this subgroup analysis of EXSCEL.
METHODS: EXSCEL tested the effects of the GLP-1 agonist exenatide vs. placebo on the rates of the primary composite MACE endpoint (CV death, myocardial infarction, or stroke). In this post hoc analysis, we assessed the association of PAD with rates of MACE, LEA, and the effects of exenatide vs. placebo in patients with and without PAD.
RESULTS: EXSCEL included 2,800 patients with PAD. Patients with PAD had higher unadjusted rates of MACE compared with patients without PAD (uHR 1.36, 95% CI 1.21-1.52; P <0.001); there was no statistically significant difference after adjusting for baseline characteristics (aHR 1.07, 95% CI 0.95-1.20; P=0.29). PAD patients had higher all-cause mortality (aHR 1.39, 95% CI 1.21-1.61; P <0.001), and more LEA (aHR 5.02, 95% CI 3.83-6.57; P<0.001). Exenatide treatment effects vs. placebo for the primary composite, key secondary, and limb-specific endpoints (Figure) did not differ based on PAD status.
CONCLUSIONS: EXSCEL participants with PAD had higher crude rates of MACE, all-cause mortality and LEA compared with those without PAD. There were no differential rates of MACE or LEA comparing exenatide with placebo.