{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:49:50Z","timestamp":1791510590746,"version":"4.3.4"},"reference-count":100,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"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>Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and\/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated \u201cgame-changer\u201d trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and\/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact.<\/jats:p>","DOI":"10.3390\/jcm12082922","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T01:36:45Z","timestamp":1681781805000},"page":"2922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Soluble PCSK9 Inhibition: Indications, Clinical Impact, New Molecular Insights and Practical Approach\u2014Where Do We Stand?"],"prefix":"10.3390","volume":"12","author":[{"given":"Michele","family":"Bellino","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7265-7613","authenticated-orcid":false,"given":"Gennaro","family":"Galasso","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-8092","authenticated-orcid":false,"given":"Angelo","family":"Silverio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Tedeschi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Formisano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Romei","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Paolo","family":"Cancro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Vassallo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0480-907X","authenticated-orcid":false,"given":"Giulio","family":"Accarino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6506-8397","authenticated-orcid":false,"given":"Monica","family":"Verdoia","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ospedale Degli Infermi, ASL Biella, 13900 Biella, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Maria","family":"Di Muro","sequence":"additional","affiliation":[{"name":"Structural Interventional Cardiology, Department of Clinical and Experimental Medicine, Clinica Medica, Careggi University Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Vecchione","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy"},{"name":"Vascular Physiopathology Unit, IRCCS Neuromed Mediterranean Neurological Institute, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6031-2899","authenticated-orcid":false,"given":"Giuseppe","family":"De Luca","sequence":"additional","affiliation":[{"name":"Division of Cardiology, AOU \u201cPoliclinico G. Martino\u201d, Department of Clinical and Experimental Medicine, University of Messina, 98166 Messina, Italy"},{"name":"Division of Cardiology, IRCCS Hospital Galeazzi-Sant\u2019Ambrogio, 20161 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e005375","DOI":"10.1161\/CIRCOUTCOMES.118.005375","article-title":"Mortality From Ischemic Heart Disease","volume":"12","author":"Nowbar","year":"2019","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Silverio, A., Di Maio, M., Citro, R., Esposito, L., Iuliano, G., Bellino, M., Baldi, C., De Luca, G., Ciccarelli, M., and Vecchione, C. (2021). Cardiovascular risk factors and mortality in hospitalized patients with COVID-19: Systematic review and meta-analysis of 45 studies and 18,300 patients. BMC Cardiovasc. 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