Lipid Management in Chronic Kidney Disease: Systematic Review of PCSK9 Targeting.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and CKD is considered a coronary artery disease risk equivalent. So far, statins have been the mainstay of primary and secondary prevention of cardiovascular disease in the general population. However, their benefit on outcomes is limited and controversial in CKD patients and new therapeutic approaches to reduce cardiovascular risk are needed. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) in high-risk populations and cardiovascular events in secondary prevention. We now review the limitations of the current approach to lipid management in CKD and information on CKD patients from clinical trials of anti-PCSK9 monoclonal antibodies alirocumab and evolocumab. In CKD sub-group analysis, ODYSSEY COMBO I and ODYSSEY COMBO II studies demonstrated significant superiority of alirocumab on LDL-cholesterol lowering in comparison to placebo and ezetimibe, respectively, when added to statins, and case reports have shown efficacy in nephrotic syndrome. A detailed analysis of CKD subgroups in general population trials of anti-PCSK9 strategies addressing events is needed, given the limited efficacy of statins in CKD both in terms of lipid lowering and events, the high rate of statin non-compliance in these patients, and the high lipoprotein(a) levels. This information should guide the design of trials addressing the safety profile and efficacy on cardiovascular outcomes of PCSK9-targeted therapies in CKD patients.