LDL-cholesterol reduction in chronic kidney disease: options beyond statins.

PURPOSE OF REVIEW: Individuals with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) events. LDL cholesterol (LDL-C) is a key modifiable cause of ASCVD and lowering LDL-C with statins reduces the risk of ASCVD events in a wide range of populations, including those with CKD. This review considers the utility of recently developed nonstatin LDL-C-lowering therapies in CKD.

RECENT FINDINGS: The cholesterol absorption inhibitor, ezetimibe, reduces LDL-C by 15-20% and is well tolerated in CKD. Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) reduce LDL-C by 50-60% and reduce the risk of ASCVD events. However, these agents require self-administration by subcutaneous injection every 2-4 weeks. The PCSK9 synthesis inhibitor, inclisiran, is administered approximately 6 monthly and may be more suitable for widespread use, although outcome trials are awaited. These PCSK9 targeting therapies require no dose adjustment in CKD and have no drug interactions.

SUMMARY: Statins and ezetimibe are safe and reduce ASCVD risk in CKD populations. PCSK9 targeting agents may be useful in high-risk CKD patients, including those with prior ASCVD.