Effect of Evolocumab in Patients With Critical Limb Ischemia (Evol-CLI)

Critical limb ischemia (CLI), is the most severe form of peripheral arterial disease (PAD), and clinically is characterized by pain at rest or non-healing ulcers of the lower extremities. Also, is associated with increased risk of cardiovascular death, myocardial infarction (MI), stroke and amputation. Feringa et al. demonstrated in a study of 1,374 patients with PAD that all cause and cardiac related mortality rates were lower in patients at higher statin dose and lower levels of low-density lipoprotein cholesterol (LDL). Patients with CLI statin therapy and lower LDL levels improve amputation-free survival and patency after revascularization procedures. In the FOURIER trial, LDL cholesterol reduction with the PCSK9 inhibitor evolocumab in patients with symptomatic PAD with or without prior myocardial infarction or stroke was associated with improved major adverse cardiac events (MACE) and major adverse limb events (MALE) at 2-years. The effect of evolocumab in patients with CLI , after a recent arterial revascularization and active wounds is not known, also it is not known whether the cholesterol lowering effect of evolocumab in this group of patients is equivalent to that of non-CLI PAD patients and what the effect is on arterial perfusion, wound healing and other biological markers of vascular physiology. This study aims to investigate the effect of evolocumab in patients with CLI on maximally tolerated lipid lowering therapy with a statin for one year after an index CLI event, requiring revascularization.