Dhillon Ashwat S, Caro Jorge, Choi Jongkyu, Caro Jorge A, Rowe Vincent, Kumar S Ram, Shavelle David M, Matthews Ray V, Clavijo Leonardo C
Division of Cardiovascular Medicine, Samaritan Health Services, Corvallis, OR, USA.
Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Cardiovasc Revasc Med. 2025 Jul;76:91-97. doi: 10.1016/j.carrev.2024.10.006. Epub 2024 Nov 28.
Chronic limb-threatening ischemia (CLTI) is associated with increased risk of major adverse cardiac and limb events (MACLE). In patients with peripheral arterial disease (PAD), evolocumab is associated with decreased MACLE, improved maximal walking time, increased vascular flow-mediated dilation (FMD), and decreased carotid intima-media thickness (IMT). We investigated the additive effect of evolocumab in patients with CLTI on maximally tolerated lipid lowering therapy after an index revascularization for non-healing wounds.
This double-blind, prospective, randomized, single-center, placebo-controlled study investigated the effect of monthly evolocumab for 6 months compared to placebo in patients with CLTI, with recent revascularization, and on maximally tolerated statin therapy. The primary endpoint was the reduction of low-density lipoprotein cholesterol (LDL-C) at 6 months of therapy. Secondary endpoints included evaluation of FMD and carotid IMT.
N = 13 in the evolocumab arm and N = 14 in the placebo arm. The evolocumab arm had a lower mean LDL-C level at 3 months and 6 months compared to baseline (mean 82 mg/dL at baseline, 26 mg/dL at 3 months, and 34 mg/dL at 6 months, p = 0.017). The placebo arm had no significant difference in LDL-C at 3 and 6 months compared to baseline. Treatment with evolocumab resulted in increased FMD of the brachial artery and decrease in carotid IMT at 6 months. There was no deleterious effect on wound healing.
Evolocumab was associated with a decrease in LDL-C, decreased carotid IMT, and improved FMD in CLTI patients who were on evolocumab therapy in addition to maximally tolerated statin. There was no adverse effect on wound healing with further reduction in LDL-C.
慢性肢体威胁性缺血（CLTI）与主要不良心脏和肢体事件（MACLE）风险增加相关。在周围动脉疾病（PAD）患者中，依洛尤单抗与MACLE减少、最大步行时间改善、血管血流介导的扩张（FMD）增加以及颈动脉内膜中层厚度（IMT）减小有关。我们研究了依洛尤单抗在CLTI患者中对因伤口不愈合进行初次血运重建后最大耐受降脂治疗的附加作用。
这项双盲、前瞻性、随机、单中心、安慰剂对照研究调查了与安慰剂相比，每月一次依洛尤单抗治疗6个月对CLTI患者、近期接受血运重建且接受最大耐受他汀治疗的效果。主要终点是治疗6个月时低密度脂蛋白胆固醇（LDL-C）的降低。次要终点包括FMD和颈动脉IMT的评估。
依洛尤单抗组N = 13，安慰剂组N = 14。与基线相比，依洛尤单抗组在3个月和6个月时的平均LDL-C水平较低（基线时平均82mg/dL，3个月时26mg/dL，6个月时34mg/dL，p = 0.017）。安慰剂组在3个月和6个月时的LDL-C与基线相比无显著差异。依洛尤单抗治疗导致肱动脉FMD增加，6个月时颈动脉IMT减小。对伤口愈合没有有害影响。
在CLTI患者中，除了最大耐受他汀治疗外，接受依洛尤单抗治疗与LDL-C降低、颈动脉IMT减小和FMD改善相关。进一步降低LDL-C对伤口愈合没有不良影响。
