Treatment with PCSK9 inhibitors in patients with chronic kidney disease at very high cardiovascular risk

Abstract Background and Aims Proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitors may be an option in the treatment of dyslipidaemia in patients with chronic kidney disease (CKD) who do not reach therapeutic targets or who do not tolerate statins at maximal doses. However, studies in this population are scarce. The aim of our study is to analyse the efficacy and safety of iPCSK9 in patients with CKD. Method Retrospective cohort study of patients with CKD, defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, who started treatment with iPCSK9 in our centre between 2016 and 2020. All patients had at least 2 years of follow-up. We compared total cholesterol, LDL cholesterol (c-LDL), triglycerides and eGFR at baseline, 6, 12 and 24 months after iPCSK9 prescription. Adverse effects were collected. Results During the study period, 278 patients started treatment with iPCSK9 in our centre, of whom 41 had CKD and a follow-up of more than 2 years. Of these, 21 were on treatment with Alirocumab and 20 with Evolocumab. Of these, 51.2% were men with a mean age of 70.6 ± 9.4 years and 87.8% had G3a or G3b stage. One patient was on peritoneal dialysis. Acquired dyslipidaemia was present in 82.9% and 87.8% had suffered from coronary events. 53.7% of iPCSK9 prescriptions were for failure to achieve c-LDL targets, while in the remaining patients the reason was non-tolerance of maximum statin doses. After 6 months of treatment, a significant reduction in total cholesterol (226.7 ± 52.9 mg/dL vs. 142.1 ± 46.17 mg/dL; p<0.001), c-LDL (147.8 ± 48.8 mg/dL vs. 62.9 ± 37.1 mg/dL; p<0.001) and triglycerides (229.8 ± 112.4 mg/dL vs. 192.4 ± 119.2 mg/dL; p = 0.025) was observed, and these differences were maintained at 2 years of treatment (p = 0.016, p<0.001, p = 0.004). 48.8% of patients achieved c-LDL targets (≤ 55 mg/dL) at 6 months of treatment and 48.8% at 12 months of treatment. Renal function remained stable during follow-up. No side effects or cardiovascular events were documented. Conclusion iPCSK9 reduce cholesterol, c-LDL and triglycerides in patients with CKD, allowing therapeutic targets to be achieved while maintaining stable renal function. Due to the apparent advantages of this drug in CKD patients, we believe that conducted clinical trials should be designed for this population.