Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Use for Atherogenic Dyslipidemia in Solid Organ Transplant Patients

Abstract

Dyslipidemia is a widespread risk factor in solid organ transplant patients, due to many reasons, such as the use of immunosuppressive drugs, with a consequent increase in cardiovascular diseases in this population. PCSK9 is an enzyme mainly known for its role in altering LDL levels, consequently increasing cardiovascular risk. Monoclonal antibody PCSK9 inhibitors demonstrated remarkable efficacy in the general population in reducing LDL cholesterol levels and preventing cardiovascular disease. In transplant patients, these drugs are still poorly used, despite having comparable efficacy to the general population and giving fewer drug interactions with immunosuppressants. Furthermore, there is enough evidence that PCSK9 also plays a role in other pathways, such as inflammation, which is particularly dangerous for graft survival. In this review, the current evidence on the function of PCSK9 and the use of its inhibitors will be discussed, particularly in transplant patients, in which they may provide additional benefits.

Features of lipid-lowering therapy in liver transplant recipients

“…Эзетимиб Эзетимиб -ингибитор абсорбции ХС в кишечнике, позволяющий снижать уровень ХС ЛНП на перенесших трансплантацию, особенно с учетом причин, приведших к отмене бокоцизумаба [41]. Однако следует учитывать, что другие типы моноклональных антител с иммуносупрессивным действием уже успешно применяются у реципиентов трансплантатов, и в настоящее время иммуноинтерферирующего действия у человеческих моноклональных антител, алирокумаба и эволокумаба, не выявлено [42]. Для подтверждения этих результатов необходимы дополнительные исследования на более крупных когортах.…”

Dyslipidemia in Transplant Patients: Which Therapy?

“…To date, there is little evidence in transplant recipients [ 147 ], but PCSK9 inhibitors have been shown to be a very effective treatment for dyslipidemia, with a reported reduction in LDL values of up to 50% [ 148 ]. Moreover, PCSK9 seems to be safe in these patients because they are not involved in CYP3A4 or P-gp metabolism; however, reductions in CsA and sirolimus levels have been reported, without negative effects on rejection [ 148 ].…”