Metformin-Induced Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition Further Decreases Low-Density Lipoprotein Cholesterol Following Statin Treatment in Patients With Coronary Artery Disease and Without Diabetes.
J Cardiovasc Pharmacol
; 84(2): 261-269, 2024 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-38922587
ABSTRACT
ABSTRACT In vitro investigations have established metformin's capacity to downregulate proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, suggesting a potential beneficial effect on atherogenic lipoprotein particles when combined with metformin therapy. Our objective was to assess whether metformin could mitigate statin-induced adverse effects on PCSK9, thereby improving lipid profiles in patients with coronary artery disease (CAD) but without diabetes. Employing an open-label, placebo-controlled, randomized trial, we randomized patients with CAD but without diabetes into CLA (cholesterol-lowering agents alone atorvastatin ± ezetimibe, n = 38) and Met + CLA groups (metformin plus CLA, n = 33) in a 11 ratio. The primary end point was the therapeutic impact of 1-month metformin combination treatment on low-density lipoprotein cholesterol (LDL-C) and PCSK9 levels. Baseline LDL-C and PCSK9 levels were 76.18 mg·dL -1 and 80.54 ng·mL -1 , respectively. After 1 month, metformin significantly reduced LDL-C (-20.81%, P < 0.001), enabling 72% of patients to attain guideline-recommended LDL-C goals. Noteworthy reductions in PCSK9 levels (-15.03%, P < 0.001) were observed. Moreover, Met + CLA markedly reduced LDL particle number more than CLA alone (-10.65% vs. 1.45%, P = 0.009), primarily due to diminished small-dense LDL particle count. Mechanistically, our study demonstrated metformin's inhibition of statin-induced PCSK9 expression in human hepatocellular cells. In summary, a 1-month metformin combination regimen reduced LDL-C levels in patients with CAD but without diabetes by inhibiting PCSK9 expression. TRIAL REGISTRATION Chinese Clinical Trial Registry identifier ChiCTR1900026925 (26/10/2019).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
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Biomarcadores
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Inibidores de Hidroximetilglutaril-CoA Redutases
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Quimioterapia Combinada
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Pró-Proteína Convertase 9
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Inibidores de PCSK9
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LDL-Colesterol
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Metformina
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Cardiovasc Pharmacol
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J. cardiovasc. pharmacol
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Journal of cardiovascular pharmacology
Ano de publicação:
2024
Tipo de documento:
Article