Real-World Efficacy of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i) in Heterozygous Familial Hypercholesterolemia Patients Referred for Lipoprotein Apheresis

Abstract

Background A small proportion of familial hypercholesterolemia (FH) patients can adequately control this condition, although achieving the recommended targets for low-density lipoprotein cholesterol (LDL-c) levels remains a challenge. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are new and potent lipid-lowering drugs. However, there is scarce literature on real-world data about their use in patients with FH. Material/Methods We examined the reduction in LDL-c levels from the baseline, after PCSK9i initiation in heterozygous familial hypercholesterolemia patients referred for lipoprotein apheresis in our regional lipid clinic. The study was conducted from March 2018 to September 2019, the period immediately after PCSK9i reimbursement was available in France. PCSK9i was added on top of the patients’ maximal tolerated lipid-lowering regimens. Results The study had 123 patients with heterozygous FH. The mean age of the patients was 59±11 years. The mean baseline LDL-c for all the participants was 277±78 mg/dl. It was 283±81 mg/dl in the PCSK9i monotherapy group (n=83), 247±68 mg/dl in the PCSK9i plus ezetimibe group (n=12), and 264±78 mg/dl in the PCSK9i plus statin and ezetimibe group (n=28). The mean decrease observed in the LDL-c level from baseline was 136±70 mg/dl (n=123), 125±60 mg/dl (n=83), 103±77 mg/dl (n=12), and 175±70 mg/dl (n=28), respectively. Conclusions An overall reduction of 49.1% from the baseline LDL-c was observed in the heterozygous FH population after PCSK9i initiation in a real-world experience. The group treated with PCSK9i ezetimibe plus statin showed further reduction of their LDL-c levels with a better responder rate, achieving the target 50% reduction in LDL-c from the baseline.

Burden of cardiovascular disease in a large contemporary cohort of patients with heterozygous familial hypercholesterolemia

“…Yet, lipid-lowering treatment is henceforward based on 3 major agents: statins, ezetimibe and PCSK9 monoclonal antibodies (which were not available in France at the time of this study). If these 3 treatments were used appropriately, it is highly probable that the therapeutic objective would be achieved in the majority of cases in our registry [ 24 , 25 ].…”

Tratamento Das Dislipidemias: Das Estatinas, Inibidores De Pcsk9 Ao Desenvolvimento De Novos Candidatos a Fármacos Hipolipemiantes

“…A proteína PCSK9 é membro da família protease-serina, que age reduzindo os níveis de receptores celulares das lipoproteínas de baixa densidade. Dessa forma, a sua inibição previne a ligação do c-LDL à PCSK9, a subsequente degradação lisossomal, permitindo o aumento do número de c-LDL na superfície do hepatócito e consequentemente uma diminuição dos níveis séricos de c-LDL (Sabatine et al, 2017;Schwartz et al, 2014;Matta et al, 2021).…”

“…Recentemente, ensaios clínicos e estudos em vários níveis de evidência para benefícios clínicos, apresentaram destaque para o uso dos fármacos inibidores da enzima PCSK9 (iPCSK9), indicados para pacientes que não toleram estatinas e não conseguem atingir os níveis ideais de c-LDL necessários. Os iPCSK9 permitem uma redução significativa e consistente dos valores de c-LDL, além de mostrarem-se eficientes tanto em monoterapia como em terapia combinada, assim também, no tratamento de pacientes com alto risco cardiovascular, como ocorre na presença de Hipercolesterolemia Familiar (HF) (Matta et al, 2021). Já na química medicinal, são extensamente estudados os derivados de ftalimidas, os quais constituem uma importante classe de compostos heteroaromáticos e apresentam diversas atividades biológicas, como a hipolipidêmica (Assis et al, 2013).…”

PCSK9 Inhibitors in Clinical Practice: Experience of a Specialized Lipid Center

“…Аналогичные данные представлены в национальном регистре Дании, где большинство пациентов (68,0%), получающих ингибиторы PCSK9, имели в анамнезе ишемическую болезнь сердца [8]. В одной из липидных клиник Франции частота наличия ишемической болезни у пациентов была ниже -66,7%, однако именно она в значительной мере обуславливала очень высокий ССР у пациентов [10]. Учитывая, что большая доля пациентов очень высокого ССР имела раннее развитее ССЗ, а также исходно высокий уровень ХС ЛПНП, это может говорить о недостаточном лечении пациентов с гиперхолестеринемией.…”

“…Таким образом, для эффективного снижения ХС ЛПНП в большинстве случаев требуется назначение комбинированной гиполипидемической терапии. Суммарное снижение уровня ХС ЛПНП в Липидной клинике «НМИЦ ТПМ» при добавлении к терапии ингибиторов PCSK9 превосходит данные, полученные в одной из липидных клиник Франции, где на тройной гиполипидемической терапии (статин, эзетимиб и ингибитор PCSK9) удалось снизить уровень ХС ЛПНП на 66,3% от исходного [10].…”