Effectiveness and safety of PCSK9 inhibitor therapy in patients with familial hypercholesterolemia within a therapeutic program in Poland: Preliminary multicenter data.

BACKGROUND: In Poland, treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has become available free of charge in a therapeutic program. Assessed herein, is the efficacy and safety of alirocumab and evolocumab in patients with heterozygous familial hypercholesterolemia (FH). METHODS: Data of 55 adult FH patients who participated in the program were analyzed upon meeting the criteria established by the Ministry of Health (low density lipoprotein cholesterol [LDL-C] above 160 mg/dL on max. tolerated statin dose and ezetimib). The efficacy of PCSK9 inhibitors in reducing LDL-C with drug administration every 2 weeks was assessed after 3 months and 1 year of therapy. A safety profile evaluation was performed at each visit. 48 patients completed the 3-month and 21 for the 1-year observation periods (34 patients treated with alirokumab and 14 with evolocumab). RESULTS: The mean concentration of direct-measured LDL-C decreased from the initial level of 215.1 ± 74.5 mg/dL to 75.3 ± 64.1 mg/dL, i.e., by 65 ± 14% following 3 months of treatment. This effect was stable in 1-year observation (77.7 ± 72.8 mg/dL). Adverse effects were flu-like symptoms (13.0%), injection site reactions (11.1%), fatigue (5.6%) and musculoskeletal symptoms (5.6%). Seven patients failed to complete the 3-month treatment period due to side effects or non-compliance, and 1 patient failed to complete the 1-year treatment due to myalgia. CONCLUSIONS: This study confirmed high effectiveness of PCSK9 inhibitors in reducing LDL-C levels in patients with FH. Due to restrictive inclusion criteria with LDL-C threshold level > 160 mg/dL (> 4.1 mmol/L) required for participation in the therapeutic program, a relatively small number of FH patients were eligible for treatment.

Long-term lipoprotein apheresis in the treatment of severe familial hypercholesterolemia refractory to high intensity statin therapy: Three year experience at a lipoprotein apheresis centre.

BACKGROUND: Severe familial hypercholesterolemia (FH) individuals, refractory to conventional lipidlowering medications are at exceptionally high risk of cardiovascular events. The established therapeutic option of last choice is lipoprotein apheresis (LA). Herein, it was sought to investigate the clinical usefulness of LA in a highly selected group of severe heterozygous FH (HeFH), as recently described by the International Atherosclerosis Society (IAS), for their efficacy in lipid reduction and safety. METHODS: Efficacy and safety of LA were investigated in 318 sessions of 7 severe HeFH females with cardiovascular disease, over a mean period of 26.9 ± 6.5 months. Relative reduction of low density lipoprotein cholesterol (LDL-C) ≥ 60%, clinical complications and vascular access problems were evaluated and compared between the direct adsorption of lipoproteins (DALI) and lipoprotein filtration (Membrane Filtration Optimized Novel Extracorporeal Treatment [MONET]). Additionally, lipoprotein (a) [Lp(a)], total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fibrinogen concentrations were investigated. RESULTS: The relative reduction of LDL-C, TC, TG and Lp(a) were 69.4 ± 12.9%, 59.7 ± 9.1, 51.5 ± ± 14.2% and 71.3 ± 14.4%, respectively. A similar efficacy was found in both systems in LDL-C removal. DALI system led to larger depletions of Lp(a) (80.0 [76-83]% vs. 73.0 [64.7-78.8]%; p < 0.001). The frequency of clinical side effects and vascular access problems were low (8.5%). CONCLUSIONS: Long-term LA in severe HeFH individuals is safe and efficiently reduces LDL-C and Lp(a). Higher efficacy of the DALI system than MONET in Lp(a) removal may indicate the need for individualized application of the LA system in severe HeFH individuals.