What is the role of proprotein convertase subtilisin/kexin type 9 inhibitors in treating dyslipidemia in CKD?
Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is an enzyme that binds to the LDL receptor, reduces its cell surface density, and leads to hypercholesterolemia. In recent years, a number of studies of antibodies inhibiting PCSK-9 have been shown to effectively treat hypercholesterolemia and reduce CVD events in persons already being treated with maximal statin therapy.
Data suggests that levels of PCSK-9 are elevated in kidney disease, are removed by dialysis, and are lowered after kidney transplantation.
The recently completed Long-term Safety and Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM) trial enrolled 174 patients with an eGFR <60 mL/min per 1.73 m 2 at baseline.
In this sub-group, treatment with aliroucumab was associated with 62% reduction in LDL cholesterol levels, compared to 8% elevation in the placebo arm ( P value, .02).
This study was not powered to evaluate the effect of the intervention on clinical outcomes, and further studies are needed that include a larger number of patients with CKD.
Whether these drugs offer the same degree of lipid reduction and cardiovascular benefit in patients not taking statins, for instance those with statin intolerance, remains unknown.
