Efficacy and Safety of Alirocumab and Evolocumab as Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors in Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis.

BACKGROUND Familial hypercholesterolemia (FH) is a prevalent and potentially fatal illness that causes a substantial elevation in low-density lipoprotein cholesterol (LDL-C). OBJECTIVE The aim of this study was to investigate the effects of monoclonal antibodies alirocumab and evolocumab on LDL-C and other lipid parameters, as well as their safety in familial hypercholesterolemia patients. METHODS A comprehensive search was done on PubMed/MEDLINE, EMBASE, Web of Science (WOS/ ISI), Scopus, ClinicalTrials (www. CLINICALTRIALS gov), and conferences/ congress research papers. Random effect models were used to calculate mean differences (%) and risk ratios (RRs), and confidence intervals (95%). RESULTS Ten studies (n=1489 patients) were included in this study. PCSK9 inhibitors decreased the levels of LDL-C by -49.59% (95%CI -55.5%, -43.67%) as compared to placebo. They also didn't alter the Treatment-Emergent Adverse Event (TEAE) and neuronal events by RR 0.92 (0.75, 1.13) and 1.31 (0.66, 2.59), respectively. PCSK9 inhibitors were effective and safe in treating patients with FH. CONCLUSION There was high-quality evidence showing that monoclonal antibodies (alirocumab & evolocumab) lower LDL-C (GRADE: high), lipoprotein (a) (GRADE: High), triglycerides (TG) (GRADE: High), total cholesterol (GRADE: High), non-high-density lipoprotein cholesterol (nonHDL-C) (GRADE: Moderate), and apolipoprotein B (GRADE: High), and increase the HDL-C (GRADE: High) as well as apolipoprotein A1 (GRADE: High). Comparing PCSK9 inhibitors against placebo, neither TEAE (GRADE: high) nor neuronal events (GRADE: moderate) were changed. Registration number PROSPERO-CRD42022334035