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Lowering LDL cholesterol by PCSK9 inhibition: a new era of gene silencing, RNA, and alternative therapies.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Institute of Pharmacy, Nirma University, Gujarat, 382481, India.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) discovery has added a new paradigm to our understanding of cholesterol homeostasis and lipid metabolism. Since its discovery, PCSK9 inhibitors have become a widely investigated therapeutic class for lipid management in cardiovascular diseases and hypercholesterolemia. Scientists have explored different approaches for PCSK9 inhibition, such as monoclonal antibodies (mAbs), gene silencing and gene editing techniques, vaccines, mimetic peptides, and small molecules.
View Article and Find Full Text PDFEfficacy and safety of PCSK9 inhibitors in real life.
Clin Investig Arterioscler
January 2025
Unidad de Lípidos y Riesgo Vascular, Servicio de Endocrinología y Nutrición, Hospital del Mar, Barcelona, España. Electronic address:
Objective: To confirm the effectiveness and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in daily clinical practice.
Methods: Retrospective observational study of patients from hospital registry of PCSK9 inhibitor treatment with a follow-up ≥ 6 months. The lipid-lowering effect and safety were evaluated.
Bempedoic Acid: A Review in Cardiovascular Risk Reduction in Statin-Intolerant Patients.
Am J Cardiovasc Drugs
January 2025
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Oral bempedoic acid (NEXLETOL in the USA; Nilemdo in the EU) and the fixed dose combination (FDC) of bempedoic acid/ezetimibe (NEXLIZET in the USA; Nustendi in the EU) are approved to reduce cardiovascular (CV) risk in statin-intolerant patients who are at high risk for, or have, CV disease. A first-in-class therapy, bempedoic acid inhibits the adenosine triphosphate-citrate lyase enzyme in the cholesterol biosynthesis pathway. In the multinational phase III CLEAR Outcomes trial in statin-intolerant patients, once-daily bempedoic acid 180 mg significantly reduced the risk of the primary endpoint (a four-component major adverse CV event composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) compared with placebo.
View Article and Find Full Text PDFFamilial hypercholesterolemia - Targeted whole gene sequencing as a diagnostic approach.
Atheroscler Plus
March 2025
Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Background And Aims: Familial hypercholesterolemia (FH) and other disorders with similar features are common genetic disorders that remain underdiagnosed and undertreated, due in part to the cost of screening. The aim of this study was to design and implement a whole gene targeted NGS panel for the molecular diagnosis of FH and statin intolerance with an emphasis on high quality variant calling, including copy number analysis.
Methods: A whole gene panel for hybridisation-based short read NGS was designed for the dominant FH-genes low density lipoprotein receptor (), apolipoprotein B (APOB), proproteinconvertas subtilisin/kexin type 9 (PCSK9), apolipoprotein E (APOE) and the recessive FH-genes low density lipoprotein receptor adaptor protein 1 (), ATP binding cassette subfamily member 5/8 (ABCG5/8) and lipase A, lysosomal acid type (), as well as solute carrier organic anion transporter family member 1B1 (), not an FH gene but linked to statin intolerance.
Cutting-edge lipid-lowering pharmacological therapies: Improving lipid control beyond statins.
Hipertens Riesgo Vasc
January 2025
Hospital Pharmacist Manager, Pharmaceutical Department, Asl Napoli 3 Sud., Italy. Electronic address:
Statins are crucial for both the prevention and management of atherosclerotic cardiovascular disease (ASCVD). However, even with optimized statin therapy, a significant residual risk of ASCVD remains, highlighting the need for innovative approaches to lipid-lowering therapies (LLT) that more effectively target low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipoproteins. Recently, novel pharmacologic agents have been introduced for the management of dyslipidemia.
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