{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T17:49:28Z","timestamp":1771264168532,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T00:00:00Z","timestamp":1617580800000},"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>Acute Coronary Syndrome (ACS) remains one of the most frequent causes of morbidity and mortality in the world. Although the age- and gender-adjusted incidence of ACS is decreasing, the mortality associated with this condition remains high, especially 1-year after the acute event. Several studies demonstrated that PCSK9 inhibitors therapy determine a significant reduction of major adverse cardiovascular events (MACE) in post-ACS patients, through a process of plaque modification, by intervening in lipid metabolism and platelet aggregation and finally determining an improvement in endothelial function. In the EVACS (Evolocumab in Acute Coronary Syndrome) study, evolocumab allows &gt;90% of patients to achieve LDL-C &lt; 55 mg\/dL according to ESC\/EAS guidelines compared to 11% of patients who only receive statins. In the EVOPACS (EVOlocumab for Early Reduction of low-density lipoprotein (LDL)-cholesterol Levels in Patients With Acute Coronary Syndromes) study, evolocumab determined LDL levels reduction of 40.7% (95% CI: 45.2 to 36.2; p &lt; 0.001) and allowed 95.7% of patients to achieve LDL levels &lt;55 mg\/dL. In ODYSSEY Outcome trial, alirocumab reduced the overall risk of MACE by 15% (HR = 0.85; CI: 0.78\u20130.93; p = 0.0003), with a reduced risk of all-cause mortality (HR = 0.85; CI: 0.73\u20130.98: nominal p = 0026), and fewer deaths for coronary heart disease (CHD) compared to the control group (HR = 0.92; CI: 0.76\u20131.11; p = 0.38). The present review aimed at describing the beneficial effect of PCSK9 inhibitors therapy early after ACS in reducing LDL circulating levels (LDL-C) and the risk of major adverse cardiovascular events, which was very high in the first year and persists higher later after the acute event.<\/jats:p>","DOI":"10.3390\/jcm10071510","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T11:48:29Z","timestamp":1617623309000},"page":"1510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Inhibitors of Protein Convertase Subtilisin\/Kexin 9 (PCSK9) and Acute Coronary Syndrome (ACS): The State-of-the-Art"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7392-5544","authenticated-orcid":false,"given":"Gabriella","family":"Iannuzzo","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine and Surgery, \u201cFederico II\u201d University, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3744-6375","authenticated-orcid":false,"given":"Marco","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, \u201cFederico II\u201d University, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Bresciani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, A. Cardarelli Hospital, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vania","family":"Mallardo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, \u201cFederico II\u201d University, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, \u201cFederico II\u201d University of Naples, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Merone","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, \u201cFederico II\u201d University of Naples, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluigi","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, \u201cFederico II\u201d University of Naples, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6330-1738","authenticated-orcid":false,"given":"Mario","family":"Pacileo","sequence":"additional","affiliation":[{"name":"Unit of Cardiology and Intensive Care, \u201cUmberto I\u201d Hospital, Viale San Francesco, 84014 Nocera Inferiore, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-8316","authenticated-orcid":false,"given":"Filippo M.","family":"Sarullo","sequence":"additional","affiliation":[{"name":"Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, 90123 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7223-7574","authenticated-orcid":false,"given":"Elio","family":"Venturini","sequence":"additional","affiliation":[{"name":"Cardiac Rehabilitation Unit, Azienda USL Toscana Nord-Ovest, Cecina Civil Hospital, 57023 Cecina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-9145","authenticated-orcid":false,"given":"Antonello","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"Unit of Cardiology and Intensive Care, \u201cUmberto I\u201d Hospital, Viale San Francesco, 84014 Nocera Inferiore, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Vigorito","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, \u201cFederico II\u201d University of Naples, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-9397","authenticated-orcid":false,"given":"Francesco","family":"Giallauria","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, \u201cFederico II\u201d University of Naples, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update from the GBD 2019 Study","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ralapanawa, U., and Sivakanesan, R. (2021). Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: A Narrative Review. J. Epidemiol. Glob. Health.","DOI":"10.2991\/jegh.k.201217.001"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1093\/eurheartj\/ehu505","article-title":"Cardiovascular risk in post-myocardial infarction patients: Nationwide real world data demonstrate the importance of a long-term perspective","volume":"36","author":"Jernberg","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1073\/pnas.051630598","article-title":"An orchestrated gene expression component of neuronal programmed cell death revealed by cDNA array analysis","volume":"98","author":"Chiang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.str.2007.04.004","article-title":"The crystal structure of PCSK9: A regulator of plasma LDL-cholesterol","volume":"15","author":"Piper","year":"2007","journal-title":"Structure"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"600","DOI":"10.7326\/M15-2994","article-title":"Proprotein Convertase Subtilisin\/Kexin Type 9 Monoclonal Antibodies for Acute Coronary Syndrome: A Narrative Review","volume":"164","author":"Navarese","year":"2016","journal-title":"Ann. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Xian, X., Wang, Z., Bi, Y., Chen, Q., Han, X., Tang, D., and Chen, R. (2018). Research Progress on the Relationship between Atherosclerosis and Inflammation. Biomolecules, 8.","DOI":"10.3390\/biom8030080"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.4110\/in.2019.19.e41","article-title":"A Critical Role of PCSK9 in Mediating IL-17-Producing T Cell Responses in Hyperlipidemia","volume":"19","author":"Kim","year":"2019","journal-title":"Immune. Netw."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1089\/ars.2014.6054","article-title":"Hemodynamic shear stress via ROS modulates PCSK9 expression in human vascular endothelial and smooth muscle cells and along the mouse aorta","volume":"22","author":"Ding","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1093\/cvr\/cvz313","article-title":"PCSK9 and inflammation: Role of shear stress, pro-inflammatory cytokines, and LOX-1","volume":"116","author":"Ding","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1161\/01.ATV.0000134621.14315.43","article-title":"Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia","volume":"24","author":"Dubuc","year":"2004","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1161\/ATVBAHA.110.220988","article-title":"Circulating proprotein convertase subtilisin\/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulation in visceral adipose tissue","volume":"31","author":"Roubtsova","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/cvr\/cvw194","article-title":"Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering","volume":"112","author":"Norata","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1161\/CIRCULATIONAHA.120.046290","article-title":"PCSK9 (Proprotein Convertase Subtilisin\/Kexin 9) Enhances Platelet Activation, Thrombosis, and Myocardial Infarct Expansion by Binding to Platelet CD36","volume":"143","author":"Qi","year":"2021","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11811","DOI":"10.1016\/S0021-9258(19)50272-1","article-title":"CD36 is a receptor for oxidized low density lipoprotein","volume":"268","author":"Endemann","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.cmet.2006.06.007","article-title":"A CD36-dependent signaling cascade is necessary for macrophage foam cell formation","volume":"4","author":"Rahaman","year":"2006","journal-title":"Cell Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.freeradbiomed.2019.02.021","article-title":"CD36 signaling in vascular redox stress","volume":"136","author":"Yang","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1182\/bloodadvances.2018025411","article-title":"Platelet CD36 signaling through ERK5 promotes caspase-dependent procoagulant activity and fibrin deposition in vivo","volume":"2","author":"Yang","year":"2018","journal-title":"Blood Adv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.jacc.2017.07.779","article-title":"Exploration of PCSK9 as a Cardiovascular Risk Factor: Is There a Link to the Platelet?","volume":"70","author":"Gurbel","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.ijcard.2016.10.084","article-title":"Association of PCSK9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: The PCSK9-REACT study","volume":"227","author":"Navarese","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.jacc.2017.07.743","article-title":"Relationship of PCSK9 and Urinary Thromboxane Excretion to Cardiovascular Events in Patients with Atrial Fibrillation","volume":"70","author":"Pastori","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/eurheartj\/ehv043","article-title":"European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms: Impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management","volume":"36","author":"Stroes","year":"2015","journal-title":"Eur. Hear. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1056\/NEJMoa1105803","article-title":"Effect of a monoclonal antibody to PCSK9 on LDL cholesterol","volume":"366","author":"Stein","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","unstructured":"The Emerging Risk Factors Collaboration, Erqou, S., Kaptoge, S., Perry, P.L., Di Angelantonio, E., Thompson, A., White, I.R., Marcovina, S.M., Collins, R., and Thompson, S.G. (2009). Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA, 302, 412\u2013423.","DOI":"10.1001\/jama.2009.1063"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1615758","article-title":"Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol","volume":"376","author":"Ray","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1056\/NEJMoa1912387","article-title":"ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol","volume":"382","author":"Ray","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk","volume":"41","author":"Mach","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jacl.2013.12.005","article-title":"An International Atherosclerosis Society Position Paper: Global recommendations for the management of dyslipidemia--full report","volume":"8","author":"Grundy","year":"2014","journal-title":"J. Clin. Lipidol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Guedeney, P., Giustino, G., Sorrentino, S., Claessen, B.E., Camaj, A., Kalkman, D.N., Vogel, B., Sartori, S., De Rosa, S., and Baber, U. (2019). Efficacy and safety of alirocumab and evolocumab: A systematic review and meta-analysis of randomized controlled trials. Eur. Heart J.","DOI":"10.1093\/eurheartj\/ehz430"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e285","DOI":"10.1016\/j.jacc.2018.11.003","article-title":"2018AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"73","author":"Grundy","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1001\/jama.285.13.1711","article-title":"Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial","volume":"285","author":"Schwartz","year":"2001","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1056\/NEJMc1509363","article-title":"Ezetimibe plus a Statin after Acute Coronary Syndromes","volume":"373","author":"Cannon","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.atherosclerosis.2018.06.871","article-title":"Lipid management in ACS: Should we go lower faster?","volume":"275","author":"Gencer","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1001\/jama.2016.13985","article-title":"Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis","volume":"316","author":"Silverman","year":"2016","journal-title":"JAMA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/clc.23160","article-title":"Cardiovascular events and death after myocardial infarction or ischemic stroke in an older Medicare population","volume":"42","author":"Li","year":"2019","journal-title":"Clin. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/clc.22583","article-title":"REACH Registry Investigators. Residual Ischemic Risk and Its Determinants in Patients with Previous Myocardial Infarction and Without Prior Stroke or TIA: Insights From the REACH Registry","volume":"39","author":"Abtan","year":"2016","journal-title":"Clin. Cardiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.amjcard.2019.01.037","article-title":"One-Year Outcomes of Patients with Established Coronary Artery Disease Presenting With Acute Coronary Syndromes","volume":"123","author":"Murphy","year":"2019","journal-title":"Am. J. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1161\/CIRCULATIONAHA.120.046320","article-title":"Effect of Evolocumab on Atherogenic Lipoproteins During the Peri- and Early Postinfarction Period: A Placebo-Controlled, Randomized Trial","volume":"142","author":"Leucker","year":"2020","journal-title":"Circulation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1016\/j.jacc.2019.08.010","article-title":"Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS)","volume":"74","author":"Koskinas","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1801174","article-title":"ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome","volume":"379","author":"Schwartz","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_42","first-page":"1","article-title":"Association between atherogenic index of plasma and carotid intima-media thickness in a cohort of Mediterranean women","volume":"11","author":"Gentile","year":"2020","journal-title":"Acta. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1177\/2047487319884380","article-title":"Lipoprotein (a) is an independent predictor of cardiovascular events in Mediterranean women (Progetto Atena)","volume":"27","author":"Gentile","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1001\/jamacardio.2018.4178","article-title":"Interindividual Variation in Low-Density Lipoprotein Cholesterol Level Reduction With Evolocumab: An Analysis of FOURIER Trial Data","volume":"4","author":"Qamar","year":"2019","journal-title":"JAMA Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"376","DOI":"10.7326\/M17-2485","article-title":"Diagnosing Resistance to a Proprotein Convertase Subtilisin\/Kexin Type 9 Inhibitor","volume":"168","author":"Shapiro","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10557-018-6784-z","article-title":"Assessment of the 1% of Patients with Consistent <15% Reduction in Low-Density Lipoprotein Cholesterol: Pooled Analysis of 10 Phase 3 ODYSSEY Alirocumab Trials","volume":"32","author":"Bays","year":"2018","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jacc.2018.04.054","article-title":"The Evolving Future of PCSK9 Inhibitors","volume":"72","author":"Rosenson","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1161\/CIRCRESAHA.118.311227","article-title":"PCSK9: From Basic Science Discoveries to Clinical Trials","volume":"122","author":"Shapiro","year":"2018","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.thromres.2020.07.049","article-title":"Endothelial function improvement in patients with familial hypercholesterolemia receiving PCSK-9 inhibitors on top of maximally tolerated lipid lowering therapy","volume":"194","author":"Gentile","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.numecd.2020.02.018","article-title":"Changes in carotid stiffness in patients with familial hypercholesterolemia treated with Evolocumab\u00ae: A prospective cohort study","volume":"30","author":"Gentile","year":"2020","journal-title":"Nutr. Metab. Cardiovasc. Dis."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/7\/1510\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:33:52Z","timestamp":1760362432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/7\/1510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,5]]},"references-count":50,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["jcm10071510"],"URL":"https:\/\/doi.org\/10.3390\/jcm10071510","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,5]]}}}