In patients with very high-risk PAD, which would be those with intermittent claudication and ABI <0.85, or with a history of revascularization or amputation, lipid-lowering therapy should include the maximum tolerated doses of statins and ezetimibe before considering treatment with proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-I). The gene discussed is PCSK9; the disease is peripheral arterial disease.