Cardiovascular Prevention and Pharmacotherapy

Review Articles

Apolipoprotein CIII (APOC3) and angiopoietin-like protein 3 (ANGPTL3) inhibitors: current evidence and future directions: Jee Hee Yoo; Cardiovasc Prev Pharmacother. 2025;7(4):146-154. Published online October 23, 2025; DOI: https://doi.org/10.36011/cpp.2025.7.e19

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Familial chylomicronemia syndrome (FCS) and homozygous familial hypercholesterolemia (HoFH) are rare genetic disorders characterized by profound dyslipidemia and high residual cardiovascular risk, for which conventional therapies have demonstrated limited efficacy. Recent advances in antisense oligonucleotide and small interfering RNA (siRNA)–based therapies targeting apolipoprotein CIII (APOC3) and angiopoietin-like protein 3 (ANGPTL3) have introduced promising treatment options. APOC3 inhibitors such as volanesorsen and olezarsen have been shown to markedly reduce triglyceride (TG) levels and lower the incidence of pancreatitis in individuals with FCS and severe hypertriglyceridemia. siRNA-based plozasiran has produced durable TG-lowering effects with favorable tolerability, although mild hyperglycemia has been observed in individuals with diabetes. In parallel, ANGPTL3 inhibition through monoclonal antibodies (e.g., evinacumab) or RNA inhibitor-based agents (e.g., zodasiran) enables low-density lipoprotein (LDL) receptor–independent LDL cholesterol reduction, offering a valuable therapeutic option for people with HoFH. These agents may help mitigate residual atherosclerotic cardiovascular disease risk in populations insufficiently managed by traditional lipid-lowering therapies. Nevertheless, cardiovascular outcome trials remain unavailable, and long-term benefits have yet to be established. Furthermore, high costs and restricted access pose additional barriers, especially in countries such as Korea, where regulatory approval and importation are pending. To maximize their global impact, cost-effective strategies and equitable access must be prioritized.

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Efficacy and Safety of Apolipoprotein C‐III Inhibitors in Hypertriglyceridemia: A Network Meta‐Analysis of Randomised Controlled Trials
Mohammed A. Elbahloul, Aliaa Gamal, Odai Maihoub, Moustafa M. Elbaz Hassan, Manar Khaled Attia, Ahmed M. Salah, Toka Elboraay, Ayman K. Awad, Atef Akoum, Ahmed Elazab, Islam Y. Elgendy
Diabetes, Obesity and Metabolism.2026;[Epub] CrossRef

Next-generation PCSK9 inhibitors: clinical evidence and future directions for cardiovascular prevention: Hyun-Jin Kim; Cardiovasc Prev Pharmacother. 2025;7(4):141-145. Published online October 22, 2025; DOI: https://doi.org/10.36011/cpp.2025.7.e17

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Abstract PDF

Low-density lipoprotein cholesterol (LDL-C) is a causal and modifiable risk factor for atherosclerotic cardiovascular disease, and intensive reduction of LDL-C is central to prevention strategies. Meta-analyses have shown that each 1 mmol/L (approximately 38.7 mg/dL) decrease in LDL-C confers about a 22% relative risk reduction in major vascular events, independent of baseline LDL-C levels. Despite the proven efficacy of statins and ezetimibe, many patients fail to reach recommended LDL-C targets due to inadequate response, intolerance, or poor adherence to daily therapy. The development of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has transformed lipid management, providing substantial LDL-C reduction. Recently, next-generation agents with extended dosing intervals have emerged, including recaticimab, a fully human monoclonal antibody, and inclisiran, a small interfering RNA therapy. Recaticimab binds circulating PCSK9, preventing degradation of the low-density lipoprotein receptor, and achieves sustained LDL-C reductions of about 50% with dosing every 8 to 12 weeks. Inclisiran employs N-acetylgalactosamine (GalNAc)-mediated hepatocyte delivery to silence PCSK9 messenger RNA, producing comparable LDL-C reductions with twice-yearly maintenance dosing after an initial loading dose. Their extended dosing schedules offer potential benefits in adherence and long-term lipid control, particularly for high-risk patients who struggle with frequent dosing or have statin intolerance. As outcome data accumulate, these therapies may further reduce residual atherosclerotic cardiovascular disease risk and become increasingly important in comprehensive prevention strategies.

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Safety and Efficacy of Recaticimab in Dyslipidemia: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Mohammed R. Abdeldayem, Ahmed Elsherbeeny
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy.2026;[Epub] CrossRef

Original Article

Glucagon-like peptide-1 receptor agonists improve cholesterol metabolism by inhibiting SREBP-2 via SIRT6-AMPK pathway in HepG2 cells treated with palmitic acid: Jinmi Lee, Eun-Jung Rhee, Yu-Mi Lim, Seok-Woo Hong, Won-Young Lee; Cardiovasc Prev Pharmacother. 2025;7(3):61-72. Published online July 24, 2025; DOI: https://doi.org/10.36011/cpp.2025.7.e11

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Abstract PDF Supplementary Material

Background
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exhibit not only hypoglycemic effects but also protective effects against nonalcoholic fatty liver disease and cardiovascular diseases, conditions that are associated with dyslipidemia.
Methods
To evaluate the beneficial effects of GLP-1RAs on hepatic cholesterol metabolism, HepG2 cells were exposed to palmitic acid (PA) and subsequently treated with or without the GLP-1RAs, exendin-4 and liraglutide. Cholesterol levels and the expression of cholesterol metabolism-related factors were measured.
Results
Exendin-4 and liraglutide reduced cholesterol levels in both cell lysates and culture media of PA-treated HepG2 cells. They also decreased the expression of genes involved in cholesterol synthesis (ACAT1, SREBP-2, HMGCR, and SQLE), bile acid synthesis (LXRα and CYP7A1), and PCSK9, while increasing the expression of genes involved in the reverse cholesterol transport pathway (ABCA1 and SR-B1) and low-density lipoprotein cholesterol uptake (LDLR). SREBP-2 inhibition by small interfering RNA in GLP-1RAs treated cells amplified the reduction in the expression of HMGCR, SQLE, LXRα, CYP7A1, and PCSK9 genes and HMGCR protein, as well as the increase in expression of the LDLR gene. However, inhibition of SIRT6 and AMPK, which were increased by GLP-1RAs, reversed the suppression of SREBP-2 and its downstream factor genes and amplified the increase in expression of the LDLR gene in PA-treated HepG2 cells.
Conclusions
These findings demonstrate that GLP-1RAs improve cholesterol metabolism through activation of the SIRT6-AMPK pathway, resulting in the inhibition of SREBP-2 in PA-treated HepG2 cells. Moreover, the upregulation of LDLR gene expression in cells treated with GLP-1RAs occurs through both SREBP-2-dependent and SREBP-2-independent pathways.

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Clinical Considerations in Managing Obesity and Obesity-Related Comorbidities
Hyojin Park, Sun Hyun Kim
Korean Journal of Family Practice.2025; 15(4): 186. CrossRef

Review Articles

Re-evaluating the PCSK9 guidelines for low-density lipoprotein cholesterol targets: weighing the benefits against the risks: Terry Gbaa, John Bolodeoku; Cardiovasc Prev Pharmacother. 2024;6(3):85-91. Published online July 30, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e11

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Abstract PDF: Cardiovascular disease management has made significant progress with lipid-lowering interventions, primarily statin therapy. However, statins' side effects, combined with their variable efficacy, have sparked interest in alternative treatments, particularly proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies. These biologics, approved by the US Food and Drug Administration and the European Medicines Agency, have shown a significant impact on lipid levels, particularly low-density lipoprotein cholesterol (LDL-C), resulting in a 50% to 60% reduction. Despite the benefits of PCSK9 inhibitors, the guidelines for their use differ, with specific thresholds determining eligibility. The National Institute for Health and Care Excellence recommends starting PCSK9 therapy for patients with LDL-C levels above 3.5 mmol/L and lipid levels above 5.0 mmol/L who do not have cardiovascular disease. This rigid framework, while cost-effective, may exclude a subset of patients who do not meet these criteria despite having a high cardiovascular risk. The limited scope of these guidelines presents a challenge for specialists managing patients excluded as a result of LDL-C levels that fall just below the threshold but still show signs of significant cardiovascular risk. Recent audits revealed that a significant proportion of patients fall into this grey area, emphasizing the importance of re-evaluating LDL targets for PCSK9 inhibitor initiation. Biological variations, pharmacogenomics, and other factors all contribute to this challenge, highlighting the importance of personalized medicine.

Lipid variability in patients with diabetes mellitus: Jeongmin Lee, Seung-Hwan Lee; Cardiovasc Prev Pharmacother. 2023;5(4):126-133. Published online October 25, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e18

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Abstract PDF

Diabetic dyslipidemia is characterized by hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), elevated low-density lipoprotein cholesterol (LDL-C), and the predominance of small dense LDL particles caused by insulin resistance in patients with type 2 diabetes mellitus (DM) or insulin deficiency in patients with type 1 DM. Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease in individuals with DM, and lowering lipid levels can reduce the associated morbidity and mortality. The current guidelines for dyslipidemia management recommend an LDL-C goal lower than 55 to 100 mg/dL, depending on the underlying risk factors. However, greater visit-to-visit variability in cholesterol levels might be an independent predictor of major adverse cardiovascular events, high incidence of atrial fibrillation, poor renal outcomes, and cognitive dysfunction in patients with DM. This review focuses on the clinical implications of lipid variability in patients with DM.

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Antidiabetic and Toxicological Evaluation of Ehretia asperula Leaf Extract in Diabetic Mice
Yen D. H. Nguyen, Tran Chi Linh, Nguyen Trong Tuan, Luu Thai Danh, Dai Thi Xuan Trang
Chemistry & Biodiversity.2026;[Epub] CrossRef
Visit-to-visit lipid variability and adverse kidney events in real-world type 2 diabetes patients
Hsuan-Yu Su, Yi-Hsin Chang, Chen-Yi Yang, Wei-Hung Lin, Huang-Tz Ou
Diabetes Research and Clinical Practice.2025; 222: 112093. CrossRef
The use of statins in patients with type 2 diabetes mellitus
Vera Morari, Carolina Andriuta, Elena Babalau, Mariana Malevan, Natalia Porcereanu
Public Health, Economy and Management in Medicine.2024; (5(102)): 59. CrossRef

Original Article

Changes in Target Achievement Rates after Statin Prescription Changes at a Single University Hospital: Seon Choe, Jiwon Shinn, Hun-Sung Kim, Ju Han Kim; Cardiovasc Prev Pharmacother. 2020;2(3):103-111. Published online July 31, 2020; DOI: https://doi.org/10.36011/cpp.2020.2.e14

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Abstract PDF

Background
We investigated the changes in low-density lipoprotein cholesterol (LDL-C) target achievement rates (<70 and <100 mg/dL) when the prescription changed from various statins to Lipilou^®, a generic formulation of atorvastatin.
Methods
This was a retrospective cohort study of patients who had been prescribed Lipilou^® for more than 3 months at Seoul National University Hospital from 2012 to 2018. For patients who were treated with a previous statin before the prescription of Lipilou^®, changes in target achievement rates of LDL-C less than 70 and less than 100 mg/dL were confirmed 3–6 months after the prescription of Lipilou^®.
Results
Among the 683 enrolled patients, when their prescription was changed to Lipilou^®, the target achievement rate of LDL-C significantly increased for LDL-C less than 70 mg/dL (from 22.1% to 66.2%, p<0.001) and less than 100 mg/dL (from 26.8% to 75.3%, p<0.001). In particular, when a moderate-low potency statin was changed to Lipilou^® (10 mg), the target achievement rates for LDL-C less than 70 mg/dL (from 28.9% to 66.7%, p<0.001) and less than 100 mg/dL (from 42.2% to 86.7%, p<0.001) significantly increased. The change from a moderate-high potency statin to Lipilou^® (20 mg) showed an increased target achievement rates for LDL-C <70 mg/dL (from 33.3% to 80.0%, p=0.008) and 100 mg/dL (from 40.0% to 73.3%, p<0.025).
Conclusions
We cannot simply conclude that Lipilou^® is superior to other statins. However, when the target LDL-C was not reached with previous statin treatments, a high target achievement rate could be achieved by changing the prescription to Lipilou^®. Physicians should always consider aggressive statin prescription changes for high target achievement rates.

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Understanding and Utilizing Claim Data from the Korean National Health Insurance Service (NHIS) and Health Insurance Review & Assessment (HIRA) Database for Research
Dae-Sung Kyoung, Hun-Sung Kim
Journal of Lipid and Atherosclerosis.2022; 11(2): 103. CrossRef

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