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Neurologia. 2019 Apr;34(3):198-203. doi: 10.1016/j.nrl.2017.03.009. Epub 2017 May 24.

Cholesterol and stroke: Roll of PCSK9 inhibitors.

[Article in English, Spanish]

Author information

1
Servicio de Medicina Interna, Unidad de Riesgo Vascular, Hospital Virgen Macarena, Sevilla, España. Electronic address: castillafernandez@hotmail.com.
2
Servicio de Neurología, Hospital de Valme, Sevilla, España.
3
Servicio de Medicina Interna, Unidad de Riesgo Vascular, Hospital Virgen Macarena, Sevilla, España.

Abstract

INTRODUCTION:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the modulation of plasma levels of low density lipoprotein cholesterol (LDLC). PCSK9 binds to the LDL receptor (LDLR), disrupts its endocytic recycling itinerary and directs it to lysosomal degradation. Activation of PCSK9 can thus decrease the expression of LDLR in the liver and inhibit LDL uptake, which leads to hypercholesterolaemia.

DEVELOPMENT:

Currently we now know that different polymorphisms of PCSK9 are associated with the occurrence of ischaemic stroke. On the other hand, PCSK9 inhibitors prevent binding of PCSK9 to LDLR and inhibit degradation of LDLR, which results in increased hepatic uptake of LDL and lower LDL levels in blood. Different phase 2 and 3 studies, including OSLER and ODYSSEY LONG-TERM, have demonstrated the efficacy and safety of the new monoclonal antibodies against PCSK9 such as evolucumab and alirocumab, and the first exploratory analyses have shown evidence of their efficacy in decreasing vascular events, including stroke.

CONCLUSIONS:

Although few strokes have been reported by these studies, new ongoing trials examining the cardiovascular effects of evolucumab (FOURIER study), alirocumab (ODYSSEY OUTCOMES study), and bococizumab (SPIRE-1 and SPIRE-2 studies) will reveal the true potential of these drugs, particularly for the prevention of stroke.

KEYWORDS:

Cholesterol; Colesterol; Ictus; Inhibidores de PCSK9; LDL; PCSK9 inhibitors; Prevención; Prevention; Pro-protein convertase subtilisin kexine type 9; Proproteína convertasa subtilisina kexina tipo 9; Stroke

PMID:
28549755
DOI:
10.1016/j.nrl.2017.03.009
[Indexed for MEDLINE]
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