TY - JOUR
T1 - Antiplatelet effects of pcsk9 inhibitors in primary hypercholesterolemia
AU - Pęczek, Piotr
AU - Leśniewski, Mateusz
AU - Mazurek, Tomasz
AU - Szarpak, Lukasz
AU - Filipiak, Krzysztof J.
AU - Gąsecka, Aleksandra
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel group of hypolipidemic drugs that are recommended particularly for high-risk hypercholesterolemia patients, including those with primary hypercholesterolemia (PH), where lifelong exposure to high low-density lipoprotein (LDL) cholesterol levels results in an elevated risk of atherosclerosis at an early age. The onset and progression of atherosclerosis is significantly influenced by activated platelets. Oxidized LDL influences platelet activation by interacting with their surface receptors and remodeling the composition of their cell membrane. This results in platelet aggregation, endothelial cell activation, promotion of inflammation and oxidative stress, and acceleration of lipid accumulation in atherosclerotic plaques. PCSK9 inhibitors reduce platelet activation by both significantly lowering LDL levels and reducing the LDL receptor-mediated activation of platelets by PCSK9. They also work synergistically with other hypolipidemic and antithrombotic drugs, including statins, ezetimibe, acetylsalicylic acid, clopidogrel, and ticagrelor, which enhances their antiplatelet and LDL-lowering effects. In this review, we summarize the currently available evidence on platelet hyperreactivity in PH, the effects of PCSK9 inhibitors on platelets, and their synergism with other drugs used in PH therapy.
AB - Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel group of hypolipidemic drugs that are recommended particularly for high-risk hypercholesterolemia patients, including those with primary hypercholesterolemia (PH), where lifelong exposure to high low-density lipoprotein (LDL) cholesterol levels results in an elevated risk of atherosclerosis at an early age. The onset and progression of atherosclerosis is significantly influenced by activated platelets. Oxidized LDL influences platelet activation by interacting with their surface receptors and remodeling the composition of their cell membrane. This results in platelet aggregation, endothelial cell activation, promotion of inflammation and oxidative stress, and acceleration of lipid accumulation in atherosclerotic plaques. PCSK9 inhibitors reduce platelet activation by both significantly lowering LDL levels and reducing the LDL receptor-mediated activation of platelets by PCSK9. They also work synergistically with other hypolipidemic and antithrombotic drugs, including statins, ezetimibe, acetylsalicylic acid, clopidogrel, and ticagrelor, which enhances their antiplatelet and LDL-lowering effects. In this review, we summarize the currently available evidence on platelet hyperreactivity in PH, the effects of PCSK9 inhibitors on platelets, and their synergism with other drugs used in PH therapy.
KW - Atherosclerosis
KW - LDL-cholesterol
KW - PCSK9 inhibitors
KW - Platelets
KW - Primary hypercholesterolemia
KW - Treatment
UR - http://www.scopus.com/inward/record.url?scp=85107518659&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/life11060466
DO - https://doi.org/10.3390/life11060466
M3 - Review article
C2 - 34071103
SN - 2075-1729
VL - 11
JO - Life (Basel, Switzerland)
JF - Life (Basel, Switzerland)
IS - 6
M1 - 466
ER -