{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:28:39Z","timestamp":1790818119127,"version":"4.1.0"},"reference-count":127,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Lipoprotein(a) [Lp(a)] is a low-density lipoprotein-like particle that contains a unique apolipoprotein(a) [apo(a)] component covalently bound to apolipoprotein B-100. Elevated levels of Lp(a) have been identified as a well-established and genetically determined risk factor for atherosclerotic cardiovascular disease, including coronary artery disease, stroke, and calcific aortic valve stenosis. In contrast to other lipids, Lp(a) concentrations are minimally influenced by lifestyle or traditional lipid-lowering therapies, emphasizing the necessity for novel treatment approaches. This narrative review summarizes current and emerging therapeutic strategies for reducing Lp(a) levels. Such strategies include traditional agents such as niacin and PCSK9 inhibitors, as well as innovative therapies such as antisense oligonucleotides, RNA interference-based molecules, and small-molecule inhibitors. The mechanisms of action of these agents, in addition to clinical trial data and their capacity to modify cardiovascular outcomes, are explored in further detail. Furthermore, the current status of clinical guidelines and the evolving role of Lp(a)-targeted therapies in cardiovascular risk stratification are reviewed. A particular emphasis is placed on therapies that are in the advanced stages of clinical development. These include late-phase outcome trials and orally administered agents, which have the potential to significantly impact future clinical practice. The integration of mechanistic data with ongoing and completed clinical studies has been undertaken in order to provide a comprehensive framework for understanding the therapeutic potential of Lp(a) in the context of cardiovascular prevention.<\/jats:p>","DOI":"10.3390\/jcm15062179","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:27:51Z","timestamp":1773332871000},"page":"2179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Existing and Potential Therapeutic Strategies for Lowering Lipoprotein(a) Levels: An Update"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2293-8553","authenticated-orcid":false,"given":"Igor","family":"Doma\u0144ski","sequence":"first","affiliation":[{"name":"Clinical Department of Diabetology, Hypertension and Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3807-4678","authenticated-orcid":false,"given":"Aleksandra","family":"Kozie\u0142","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Liver Disease and Acquired Immune Deficiencies, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-8062","authenticated-orcid":false,"given":"Jurand","family":"Doma\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Preclinical Sciences, Pharmacology and Medical Diagnostics, Wroclaw University of Science and Technology, 58-376 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3951-205X","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Trocha","sequence":"additional","affiliation":[{"name":"Clinical Department of Diabetology, Hypertension and Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/00041433-200404000-00009","article-title":"Structure-function relationships in apolipoprotein(a): Insights into lipoprotein(a) assembly and pathogenicity","volume":"15","author":"Koschinsky","year":"2004","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1194\/jlr.R071233","article-title":"Lipoprotein (a) as a cause of cardiovascular disease: Insights from epidemiology, genetics, and biology","volume":"57","author":"Nordestgaard","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1172\/JCI113849","article-title":"Changes of genetic apolipoprotein phenotypes caused by liver transplantation. Implications for apolipoprotein synthesis","volume":"83","author":"Kraft","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.1016\/S0021-9258(18)83643-2","article-title":"Rhesus monkey apolipoprotein(a). Sequence, evolution, and sites of synthesis","volume":"264","author":"Tomlinson","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1172\/JCI117292","article-title":"The inverse association of plasma lipoprotein(a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate","volume":"93","author":"Rader","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1194\/jlr.M036566","article-title":"Inhibition of plasminogen activation by apo(a): Role of carboxyl-terminal lysines and identification of inhibitory domains in apo(a)","volume":"55","author":"Romagnuolo","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1515\/CCLM.2004.205","article-title":"In vitro inhibition of fibrinolysis by apolipoprotein(a) and lipoprotein(a) is size- and concentration-dependent","volume":"42","author":"Knapp","year":"2004","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/330132a0","article-title":"cDNA sequence of human apolipoprotein(a) is homologous to plasminogen","volume":"330","author":"McLean","year":"1987","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0009-3084(94)90164-3","article-title":"Lp(a): An acute-phase reactant?","volume":"67\u201368","author":"Noma","year":"1994","journal-title":"Chem. Phys. Lipids"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1194\/jlr.P094763","article-title":"Potent reduction of plasma lipoprotein (a) with an antisense oligonucleotide in human subjects does not affect ex vivo fibrinolysis","volume":"60","author":"Boffa","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sticchi, E., Magi, A., Kamstrup, P.R., Marcucci, R., Prisco, D., Martinelli, I., Mannucci, P.M., Abbate, R., and Giusti, B. (2016). Apolipoprotein(a) Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149427"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1161\/CIRCULATIONAHA.116.020838","article-title":"Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans","volume":"134","author":"Bekkering","year":"2016","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S207","DOI":"10.1194\/jlr.R800074-JLR200","article-title":"The role of oxidized phospholipids in atherosclerosis","volume":"50","author":"Berliner","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Oskolkova, O.V., Birukova, A.A., Birukov, K.G., and Bochkov, V.N. (2022). Oxidized phospholipids are biomarkers, drug targets, and drug leads. Front. Drug Discov., 2.","DOI":"10.3389\/fddsv.2022.1043708"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1056\/NEJMoa043175","article-title":"Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery Disease","volume":"353","author":"Tsimikas","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jacc.2013.05.105","article-title":"Elevated Expression of Lipoprotein-Associated Phospholipase A2 in Calcific Aortic Valve Disease","volume":"63","author":"Mahmut","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/CIRCULATIONAHA.115.016757","article-title":"Autotaxin Derived from Lipoprotein(a) and Valve Interstitial Cells Promotes Inflammation and Mineralization of the Aortic Valve","volume":"132","author":"Bouchareb","year":"2015","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa1109034","article-title":"Genetic Associations with Valvular Calcification and Aortic Stenosis","volume":"368","author":"Thanassoulis","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/s41569-018-0153-2","article-title":"Oxidized phospholipids as a unifying theory for lipoprotein(a) and cardiovascular disease","volume":"16","author":"Boffa","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1373\/clinchem.2010.146779","article-title":"Lipoprotein(a) and Risk of Type 2 Diabetes","volume":"56","author":"Mora","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"332","DOI":"10.2337\/db13-1144","article-title":"The Association Between Circulating Lipoprotein(a) and Type 2 Diabetes: Is It Causal?","volume":"63","author":"Ye","year":"2014","journal-title":"Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Polo-Barranco, A., Rebolledo-Maldonado, C., Esquiaqui-Rangel, V., Nu\u00f1ez-Mejia, A., Rambal-Torres, J., Barraza-Ahumada, V., Vargas-Cantillo, S., Benavides-De la Cruz, W., Li\u00f1\u00e1n-Mart\u00ednez, V., and Rada-Obeso, V. (2025). Diabetes Mellitus and Lipoprotein(a): A Determinant Interaction in Micro- and Macrovascular Damage. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202511.1215.v1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jacl.2017.10.001","article-title":"Effect of atorvastatin, cholesterol ester transfer protein inhibition, and diabetes mellitus on circulating proprotein subtilisin kexin type 9 and lipoprotein(a) levels in patients at high cardiovascular risk","volume":"12","author":"Arsenault","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhu, L., Fang, Y., Gao, B., Jin, X., Zheng, J., He, Y., and Huang, J. (2022). Effect of an increase in Lp(a) following statin therapy on cardiovascular prognosis in secondary prevention population of coronary artery disease. BMC Cardiovasc. Disord., 22.","DOI":"10.1186\/s12872-022-03027-4"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105275","DOI":"10.1016\/j.phrs.2020.105275","article-title":"Effect of different types and dosages of statins on plasma lipoprotein(a) levels: A network meta-analysis","volume":"163","author":"Wang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1567-5688(11)70887-X","article-title":"Pitavastatin: Novel effects on lipid parameters","volume":"12","author":"Chapman","year":"2011","journal-title":"Atheroscler. Suppl."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jacl.2023.02.002","article-title":"Effects of bempedoic acid on CRP, IL-6, fibrinogen and lipoprotein(a) in patients with residual inflammatory risk: A secondary analysis of the CLEAR harmony trial","volume":"17","author":"Ridker","year":"2023","journal-title":"J. Clin. Lipidol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17887","DOI":"10.1038\/s41598-018-36204-7","article-title":"Impact of ezetimibe on plasma lipoprotein(a) concentrations as monotherapy or in combination with statins: A systematic review and meta-analysis of randomized controlled trials","volume":"8","author":"Sahebkar","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s40265-018-0870-1","article-title":"Effect of Ezetimibe Monotherapy on Plasma Lipoprotein(a) Concentrations in Patients with Primary Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"78","author":"Awad","year":"2018","journal-title":"Drugs"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"888","DOI":"10.5551\/jat.5918","article-title":"Ezetimibe, Oxidized Low Density Lipoprotein, Lp (a), and Dyslipidemia","volume":"17","author":"Fonseca","year":"2010","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.21037\/jtd.2017.04.32","article-title":"Long-term statin therapy could be efficacious in reducing the lipoprotein (a) levels in patients with coronary artery disease modified by some traditional risk factors","volume":"9","author":"Xu","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.5551\/jat.1651","article-title":"Effects of Ezetimibe on Remnant-Like Particle Cholesterol, Lipoprotein (a), and Oxidized Low-Density Lipoprotein in Patients with Dyslipidemia","volume":"17","author":"Nozue","year":"2010","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1194\/jlr.P065334","article-title":"PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: An analysis of 10 clinical trials and the LDL receptor\u2019s role","volume":"57","author":"Raal","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1161\/CIRCULATIONAHA.118.037184","article-title":"Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk","volume":"139","author":"Fazio","year":"2019","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1801174","article-title":"Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome","volume":"379","author":"Schwartz","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jacc.2019.10.057","article-title":"Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome","volume":"75","author":"Bittner","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1161\/CIRCULATIONAHA.116.025253","article-title":"Effects of PCSK9 Inhibition with Alirocumab on Lipoprotein Metabolism in Healthy Humans","volume":"135","author":"Pavlyha","year":"2017","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1093\/eurheartj\/ehy122","article-title":"Controlled study of the effect of proprotein convertase subtilisin-kexin type 9 inhibition with evolocumab on lipoprotein(a) particle kinetics","volume":"39","author":"Watts","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jacbts.2016.06.006","article-title":"PCSK9 Modulates the Secretion but Not the Cellular Uptake of Lipoprotein(a) Ex Vivo","volume":"1","author":"Villard","year":"2016","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"The HPS2-THRIVE Collaborative Group (2014). Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients. N. Engl. J. Med., 371, 203\u2013212.","DOI":"10.1056\/NEJMoa1300955"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1001\/jama.284.10.1263","article-title":"Effect of Niacin on Lipid and Lipoprotein Levels and Glycemic Control in Patients with Diabetes and Peripheral Arterial Disease","volume":"284","author":"Elam","year":"2000","journal-title":"JAMA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e001696","DOI":"10.1161\/CIRCGEN.117.001696","article-title":"Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study","volume":"11","author":"Parish","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1016\/S0735-1097(23)03757-9","article-title":"Niacin treatment effective for reducing Lp(a) levels","volume":"81","author":"Echeverry","year":"2023","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.atherosclerosissup.2015.02.008","article-title":"Lowering of lipoprotein(a) level under niacin treatment is dependent on apolipoprotein(a) phenotype","volume":"18","author":"Artemeva","year":"2015","journal-title":"Atheroscler. Suppl."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/j.clinthera.2019.06.012","article-title":"Serious Adverse Effects of Extended-release Niacin\/Laropiprant: Results from the Heart Protection Study 2\u2013Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial","volume":"41","author":"Haynes","year":"2019","journal-title":"Clin. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1080\/15563650500394928","article-title":"Treatment advice on the internet leads to a life-threatening adverse reaction: Hypotension associated with Niacin overdose","volume":"44","author":"Mularski","year":"2006","journal-title":"Clin. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.japh.2018.04.033","article-title":"Hepatotoxicity upon using niacin to pass a drug test: A case report","volume":"58","author":"Durham","year":"2018","journal-title":"J. Am. Pharm. Assoc."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"AIM-HIGH Investigators (2011). Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy. N. Engl. J. Med., 365, 2255\u20132267.","DOI":"10.1056\/NEJMoa1107579"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1161\/CIRCULATIONAHA.113.002432","article-title":"Lipoprotein Apheresis in Patients with Maximally Tolerated Lipid-Lowering Therapy, Lipoprotein(a)-Hyperlipoproteinemia, and Progressive Cardiovascular Disease","volume":"128","author":"Leebmann","year":"2013","journal-title":"Circulation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1038\/s41598-024-51782-5","article-title":"Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a)","volume":"14","author":"Kuchta","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.atherosclerosissup.2015.02.013","article-title":"Efficacy, safety, and tolerability of long-term lipoprotein apheresis in patients with LDL- or Lp(a) hyperlipoproteinemia: Findings gathered from more than 36,000 treatments at one center in Germany","volume":"18","author":"Heigl","year":"2015","journal-title":"Atheroscler. Suppl."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1016\/j.jacc.2013.07.081","article-title":"Mipomersen, an Apolipoprotein B Synthesis Inhibitor, Reduces Atherogenic Lipoproteins in Patients with Severe Hypercholesterolemia at High Cardiovascular Risk","volume":"62","author":"Thomas","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.jacc.2009.11.069","article-title":"Efficacy and Safety of Mipomersen, an Antisense Inhibitor of Apolipoprotein B, in Hypercholesterolemic Subjects Receiving Stable Statin Therapy","volume":"55","author":"Akdim","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.atherosclerosis.2018.11.017","article-title":"Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia","volume":"280","author":"Reeskamp","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_55","unstructured":"European Medicines Agency (2012). Questions and Answers on the Refusal of the Marketing Authorisation for Kynamro (Mipomersen), EMA. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/smop-initial\/questions-and-answers-refusal-marketing-authorisation-kynamro-mipomersen_en.pdf."},{"key":"ref_56","unstructured":"Fierce Biotech (2026, January 04). FDA Approves New Orphan Drug Kynamro to Treat Inherited Cholesterol Disorder. Available online: https:\/\/www.fiercebiotech.com\/biotech\/fda-approves-new-orphan-drug-kynamro-to-treat-inherited-cholesterol-disorder."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/0016-6480(82)90152-6","article-title":"Effects of in vivo corticosterone treatment on the in vitro metabolism of testosterone in the comb and brain of the young male chicken","volume":"48","author":"Deviche","year":"1982","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_58","first-page":"16372","article-title":"Oxidized phospholipids associated with lipoprotein(a) contribute to hypofibrinolysis in severe aortic stenosis","volume":"132","author":"Kopytek","year":"2022","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1056\/NEJMoa2211023","article-title":"Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease","volume":"387","author":"Rosenson","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s11883-021-00968-7","article-title":"RNA Silencing in the Management of Dyslipidemias","volume":"23","author":"Henney","year":"2021","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.atherosclerosis.2022.04.020","article-title":"Existing and emerging strategies to lower Lipoprotein(a)","volume":"349","author":"Schwartz","year":"2022","journal-title":"Atherosclerosis"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s12265-014-9605-1","article-title":"Development of Lipoprotein(a) siRNAs for Mechanism of Action Studies in Non-Human Primate Models of Atherosclerosis","volume":"8","author":"Robinson","year":"2015","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1001\/jama.2024.21957","article-title":"Zerlasiran\u2014A Small-Interfering RNA Targeting Lipoprotein(a)","volume":"332","author":"Nissen","year":"2024","journal-title":"JAMA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1056\/NEJMoa2415818","article-title":"Lepodisiran\u2014A Long-Duration Small Interfering RNA Targeting Lipoprotein(a)","volume":"392","author":"Nissen","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1001\/jama.2023.21835","article-title":"Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a)","volume":"330","author":"Nissen","year":"2023","journal-title":"JAMA"},{"key":"ref_66","unstructured":"ClinicalTrials.gov (2026, January 05). Study Details|NCT06292013|A Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults with Elevated Lipoprotein(a)-ACCLAIM-Lp(a), Available online: https:\/\/clinicaltrials.gov\/study\/NCT06292013."},{"key":"ref_67","unstructured":"ClinicalTrials.gov (2026, January 05). Study Details|NCT05537571|Evaluate SLN360 in Participants with Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05537571."},{"key":"ref_68","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT04914546|A Study of LY3819469 in Healthy Participants, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04914546."},{"key":"ref_69","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05932446|A Study to Compare Two Formulations of LY3819469 in Healthy Participants, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05932446."},{"key":"ref_70","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05565742|A Study of LY3819469 in Participants with Elevated Lipoprotein(a) [Lp(a)], Available online: https:\/\/clinicaltrials.gov\/study\/NCT05565742."},{"key":"ref_71","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05841277|A Study of LY3819469 in Participants with Impaired and Normal Renal Function, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05841277."},{"key":"ref_72","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06916078|A Study of Lepodisiran (LY3819469) in Participants with Normal, Mild, Moderate, or Severe Liver Function, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06916078."},{"key":"ref_73","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT04270760|Olpasiran Trials of Cardiovascular Events and LipoproteiN(a) Reduction-DOSE Finding Study, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04270760?cond=Olpasiran&rank=1."},{"key":"ref_74","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05581303|Olpasiran Trials of Cardiovascular Events and Lipoprotein(a) Reduction (OCEAN(a))-Outcomes Trial, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05581303?cond=Olpasiran&rank=2."},{"key":"ref_75","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06411860|A Study to Assess the Effect of Olpasiran on QT\/QTc Intervals in Healthy Participants, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06411860?cond=Olpasiran&rank=3."},{"key":"ref_76","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT04987320|A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Olpasiran in Chinese Participants with Elevated Serum Lipoprotein(a), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04987320?cond=Olpasiran&rank=4."},{"key":"ref_77","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05481411|A Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Participants with Various Degrees of Hepatic Impairment, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05481411?cond=Olpasiran&rank=5."},{"key":"ref_78","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05489614|A Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Participants with Normal Renal Function and Participants with Various Degrees of Renal Impairment, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05489614?cond=Olpasiran&rank=6."},{"key":"ref_79","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT04606602|Study to Investigate Safety, Tolerability, PK and PD Response of SLN360 in Subjects with Elevated Lipoprotein(a), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04606602."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"100723","DOI":"10.1016\/j.jlr.2024.100723","article-title":"Measuring Lp(a) particles with a novel isoform-insensitive immunoassay illustrates efficacy of muvalaplin","volume":"66","author":"Swearingen","year":"2025","journal-title":"J. Lipid Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/s41586-024-07387-z","article-title":"Discovery of potent small-molecule inhibitors of lipoprotein(a) formation","volume":"629","author":"Diaz","year":"2024","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1001\/jama.2024.24017","article-title":"Oral Muvalaplin for Lowering of Lipoprotein(a)","volume":"333","author":"Nicholls","year":"2025","journal-title":"JAMA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1001\/jama.2023.16503","article-title":"Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation","volume":"330","author":"Nicholls","year":"2023","journal-title":"JAMA"},{"key":"ref_84","unstructured":"ClinicalTrials.gov (2026, January 05). Study Details|NCT07157774|Assessing the Impact of Muvalaplin on Major Cardiovascular Events in Adults with Elevated Lipoprotein(a), Available online: https:\/\/clinicaltrials.gov\/study\/NCT07157774."},{"key":"ref_85","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT04472676|A Study of LY3473329 in Healthy Participants, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04472676."},{"key":"ref_86","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05038787|A Study of LY3473329 in Healthy Japanese Participants, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05038787."},{"key":"ref_87","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06342596|A Study of Carbon-14-Labelled [14C] LY3473329 in Healthy Male Participants, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06342596."},{"key":"ref_88","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05778864|A Study of LY3473329 in Participants with Impaired and Normal Renal Function, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05778864."},{"key":"ref_89","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05563246|A Study of LY3473329 in Adult Participants with Elevated Lipoprotein(a) at High Risk for Cardiovascular Events, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05563246."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1161\/ATVBAHA.117.309114","article-title":"Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits","volume":"37","author":"Zhang","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1016\/j.jacc.2012.07.045","article-title":"Genetic Inhibition of CETP, Ischemic Vascular Disease and Mortality, and Possible Adverse Effects","volume":"60","author":"Johannsen","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1038\/s41591-022-01936-7","article-title":"Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: A randomized phase 2 trial","volume":"28","author":"Nicholls","year":"2022","journal-title":"Nat. Med."},{"key":"ref_93","unstructured":"ClinicalTrials.gov (2026, January 05). Study Details|NCT06005597|Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06005597."},{"key":"ref_94","unstructured":"ClinicalTrials.gov (2026, January 05). Study Details|NCT05202509|Cardiovascular Outcome Study to Evaluate the Effect of Obicetrapib in Patients with Cardiovascular Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05202509."},{"key":"ref_95","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06496243|Impact of Obicetrapib and Obicetrapib Plus Repatha on Lp(a) Levels, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06496243."},{"key":"ref_96","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT04770389|Randomized Study of Obicetrapib in Combination with Ezetimibe, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04770389."},{"key":"ref_97","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05972278|Investigating the Effect of Obicetrapib on Lipoprotein Metabolism, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05972278."},{"key":"ref_98","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT04753606|Randomized Study of Obicetrapib as an Adjunct to Statin Therapy, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04753606."},{"key":"ref_99","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06050291|Investigating the Effect of Food on the Bioavailability of a Fixed Dose Combination of Obicetrapib and Ezetimibe, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06050291."},{"key":"ref_100","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06250205|Evaluate the Pharmacokinetics of a Combined Oral Contraceptive (COC) with and Without Obicetrapib, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06250205."},{"key":"ref_101","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06547359|A Study to Evaluate Drug-Drug Interactions of Obicetrapib Tablets and Ezetimibe Tablets in Healthy Adult Subjects, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06547359."},{"key":"ref_102","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06982508|Evaluation of Obicetrapib on Antioxidant Levels in Plasma and HDL Particles of Healthy Volunteers, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06982508."},{"key":"ref_103","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06305559|A CCTA Imaging Trial to Evaluate the Effect of Obicetrapib\/Ezetimibe on Coronary Plaque, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06305559."},{"key":"ref_104","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06081166|A Drug-Drug Interaction Study Evaluating the PK Effects of Obicetrapib on Atorvastatin and Rosuvastatin, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06081166."},{"key":"ref_105","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05142722|Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05142722."},{"key":"ref_106","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06048302|PK and Safety in Participants Taking Obicetrapib with Moderate Hepatic Impairment Relative to Normal Hepatic Function, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06048302."},{"key":"ref_107","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05266586|Study to Evaluate the Effect of Obicetrapib in Combination with Ezetimibe as an Adjunct to HIS Therapy, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05266586."},{"key":"ref_108","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05425745|Evaluate the Effect of Obicetrapib in Patients with HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05425745."},{"key":"ref_109","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05421078|A Dose-Finding Study in Japanese Patients to Evaluate the Effect of Obicetrapib as an Adjunct to Stable Statin Therapy, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05421078."},{"key":"ref_110","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05161715|Proof-of-Concept, Open-Label Study in Patients with Early Alzheimer\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05161715."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1007\/s11239-023-02818-6","article-title":"On-treatment platelet reactivity through the thromboxane A2 or P2Y12 platelet receptor pathways is not affected by pelacarsen","volume":"56","author":"Li","year":"2023","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.jacc.2021.12.032","article-title":"Effect of Pelacarsen on Lipoprotein(a) Cholesterol and Corrected Low-Density Lipoprotein Cholesterol","volume":"79","author":"Yeang","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jacl.2022.12.001","article-title":"Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects","volume":"17","author":"Lesogor","year":"2023","journal-title":"J. Clin. Lipidol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ahj.2025.03.019","article-title":"Design and Rationale of Lp(a)HORIZON Trial: Assessing the Effect of Lipoprotein(a) Lowering with Pelacarsen on Major Cardiovascular Events in Patients with CVD and Elevated Lp(a)","volume":"287","author":"Cho","year":"2025","journal-title":"Am. Heart J."},{"key":"ref_115","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT07000695|Managed Access Programs for TQJ230, Pelacarsen, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07000695."},{"key":"ref_116","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06875973|Pelacarsen Roll-Over Extension Program, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06875973."},{"key":"ref_117","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT04993664|Influence of Pelacarsen on Patients After Myocardial Infarction with High Lp(a) Values (PEMILA), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04993664."},{"key":"ref_118","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05900141|An Open Label Extension (OLE) Study to Evaluate Long-Term Safety and Tolerability of Pelacarsen (TQJ230), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05900141."},{"key":"ref_119","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT04023552|Assessing the Impact of Lipoprotein (a) Lowering with Pelacarsen (TQJ230) on Major Cardiovascular Events in Patients with CVD, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04023552."},{"key":"ref_120","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06813911|Lp(a) Lowering Study of Pelacarsen (TQJ230) with Background Inclisiran in Participants with Elevated Lp(a) and Established ASCVD, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06813911."},{"key":"ref_121","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05337878|A Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Pelacarsen (ISIS 681257) in Healthy Japanese Participants, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05337878."},{"key":"ref_122","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05026996|Study to Assess the Pharmacokinetics of Pelacarsen (TQJ230) in Participants with Mild Hepatic Impairment Compared to Matched Healthy Participants, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05026996."},{"key":"ref_123","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05646381|A Multicenter Trial Assessing the Impact of Lipoprotein(a) Lowering with Pelacarsen (TQJ230) on the Progression of Calcific Aortic Valve Stenosis, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05646381."},{"key":"ref_124","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT06267560|Lp(a) Lowering Study of Pelacarsen (TQJ230) in US Black\/African American and Hispanic Participants with Elevated Lp(a) and Established ASCVD, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06267560."},{"key":"ref_125","unstructured":"ClinicalTrials.gov (2026, January 06). Study Details|NCT05305664|A Multicenter Trial Assessing the Impact of Lipoprotein(a) Lowering with Pelacarsen (TQJ230) on the Rate of Weekly Lipoprotein Apheresis Sessions in Patients with Hyperlipoproteinemia(a) and Established Cardiovascular Disease in Germany, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05305664."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1093\/eurheartj\/ehac361","article-title":"Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement","volume":"43","author":"Kronenberg","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e308","DOI":"10.1016\/j.jacl.2024.03.001","article-title":"A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice","volume":"18","author":"Koschinsky","year":"2024","journal-title":"J. Clin. Lipidol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/6\/2179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:44:14Z","timestamp":1773333854000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/6\/2179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":127,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["jcm15062179"],"URL":"https:\/\/doi.org\/10.3390\/jcm15062179","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]}}}