Observational data show a consistent association between elevated low density lipoproteins (LDL-C) and cardiovascular disease (CVD). Reduction of LDL-C reduces the risk of CVD as has been shown by many trials. Statins are currently the most effective drugs for lowering LDL-C, but can present side effects which might limit the prescribed dosage and prevent patients from reaching the recommended LDL levels. Although treated with statins important residual cardiovascular event risk remains in patients in primary and secondary prevention for CVD. The discovery of protein convertase subtilisin kexin 9 antibodies is a very promising new hypolipidemic treatment and the aim of this review is to explain their mechanism of action and to discuss safety and efficacy results of some phase III studies.
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Am J Physiol Heart Circ Physiol
January 2025
Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital Taipei, Taiwan.
Cardiovascular disease is one of the foremost causes of morbidity and mortality worldwide, with low-density lipoprotein cholesterol (LDL-C) identified as a significant risk factor for subsequent ischemic events. Elevated LDL-C contributes to vascular injury and fibrosis by upregulating the expression of connective tissue growth factor and collagen IV, which leads to endothelial cell dysfunction that initiates the process of atherosclerotic diseases. Currently, there is an absence of clear, risk-defined criteria to identify patients who are in greater needs for intensive LDL-C reduction, particularly with PCSK9 inhibitors.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning, China.
Objective: The impact of lipid-lowering medications on chronic kidney disease (CKD) remains a subject of debate. This Mendelian randomization (MR) study aims to elucidate the potential effects of lipid-lowering drug targets on CKD development.
Methods: We extracted 11 genetic variants encoding targets of lipid-lowering drugs from published genome-wide association study (GWAS) summary statistics, encompassing LDLR, HMGCR, PCSK9, NPC1L1, APOB, ABCG5/ABCG8, LPL, APOC3, ANGPTL3, and PPARA.
JACC Adv
February 2025
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Background: Lipoprotein(a) [Lp(a)] has been independently associated with increased cardiovascular risk.
Objectives: The authors examined the effect of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) on plasma Lp(a) levels across multiple trials.
Methods: Studies were retrieved comparing the effect of PCSK9i vs placebo on Lp(a) levels.
Mol Diagn Ther
January 2025
Department of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 4288A-1151 Richmond Street North, London, ON, N6A 5B7, Canada.
Clinical endpoints caused by hyperlipoproteinemia include atherosclerotic cardiovascular disease and acute pancreatitis. Emerging lipid-lowering therapies targeting proprotein convertase subtilisin/kexin 9 (PCSK9), lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3 represent promising advances in the management of patients with hyperlipoproteinemia. These therapies offer novel approaches for lowering pathogenic lipid and lipoprotein species, particularly in patients with serious perturbations who are not adequately controlled with conventional treatments or who are unable to tolerate them.
View Article and Find Full Text PDFClin 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.
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