The First Report of a Real-world Experience With a PCSK9 Inhibitor in a Large Familial Hyperlipidemia and Very-high-risk Middle Eastern Population

• Published in: Clinical therapeutics 2022-10, Vol.44 (10), p.1297-1309
• Main Authors: Iqbal, Sajid, Sabbour, Hani Mohamed, Siddiqui, Mohsin Sohail, Tikriti, Alia Al, Santos, Raul D., Buckley, Adam
• Format: Article
• Language: English
• Subjects: Adult; Adverse events; Angina pectoris; Anticholesteremic Agents - adverse effects; Arteriosclerosis; Atherosclerosis; Atherosclerosis - drug therapy; atherosclerotic cardiovascular disease; Cardiology; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Cholesterol, LDL; Codes; Diabetes; Diabetes mellitus; Disease prevention; evolocumab; familial hypercholesterolemia; Female; Health services; Heart attacks; Heterogeneity; High density lipoprotein; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hypercholesterolemia; Hyperlipidemia; Hyperlipidemias - drug therapy; Hyperlipoproteinemia Type II - drug therapy; Indication; Inhibitors; Intolerance; Kexin; Laboratories; LDL-C; Lipids; Lipoproteins; Low density lipoprotein; Male; Middle Aged; Monoclonal antibodies; Patients; PCSK9 inhibitor; Prevention; Proprotein Convertase 9; Proprotein convertases; real-world experience; Reduction; Retrospective Studies; Statistical analysis; Subtilisin; Transient ischemic attack; Triglycerides; Vein & artery diseases
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2022.08.005

Evolocumab, a monoclonal inhibitor of proprotein convertase subtilisin/kexin 9, has been shown to reduce proatherogenic lipoproteins in patients with or without familial hypercholesterolemia (FH), diabetes mellitus, or atherosclerotic cardiovascular disease (ASCVD). We explored the safety profile and clinical effectiveness of evolocumab in an outpatient population of Emirati individuals with FH diagnosed per Dutch Lipid Clinic Network criteria, previous ASCVD, or statin intolerance. This study was a retrospective review of patients initiating evolocumab treatment for any indication at Imperial College London Diabetes Centre between 2017 and 2020. All individuals followed up for at least 90 days or with at least one lipid panel postinitiation were included. Participants were subclassified into primary prevention (no previous ASCVD event, n = 81) and secondary prevention (any prior clinical ASCVD event, n = 102) groups. Evolocumab was initiated in 183 individuals (mean [SD] age, 51.5 [12.4] years; 51% male); 108 (59%) had a clinical or genetic FH diagnosis, and 70.5% had diabetes mellitus. Statin intolerance was a treatment indication in 60 (32.8%) individuals. At 90 days, substantial reductions in serum LDL-C, triglycerides (TG), and total cholesterol:HDL-C (TC:HDL-C) were observed in both the primary and secondary prevention groups, and both FH and non-FH individuals. In the primary prevention group, median (interquartile range) reduction in LDL-C was 43.7% (10.8%; 63.0%); TG, 15.0% (7.2%; 35.3%); and TC:HDL-C, 31.5% (11.1%; 46.0%). In the secondary prevention group, median (interquartile range) reduction in LDL-C was 48.3% (22%; 70%); TG, 19.6% (1.2%; 32.5%); and TC:HDL-C, 32.6% (14.6%; 46.3%) (all, P < 0.0001). American College of Cardiology/American Heart Association LDL-C targets were consistently achieved in 114 (62.3%) patients during a follow-up of 359 (79-639) days. Nonattainment of the LDL-C target was attributed to nonadherence in 36 (52.2%) patients and discontinuation of treatment in 14 (20.3%) patients. Evolocumab was discontinued in 4 patients because of adverse events. This study is the first from the Middle East and North Africa region that reports the real-world efficacy of evolocumab in a mixed risk population of individuals with FH and other non-FH indications. Clinically meaningful and sustained reductions in LDL-C, TG, and cholesterol ratios were observed after evolocumab initiation. Few adverse events were reported in this predominant