Effect of evolocumab in patients with chronic limb threatening ischemia (Evol-CLI study)

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: CLTI; Evolocumab; PAD; PCSK-9 inhibitors.