{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T01:17:18Z","timestamp":1784510238386,"version":"3.55.0"},"reference-count":43,"publisher":"IMR Press","issue":"11","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Cardiovasc. Med."],"abstract":"<jats:p>Therapeutic approaches based on gene silencing technologies represent a new opportunity to manage hypercholesterolemia. Inclisiran is a small interfering RNA that targets proprotein convertase subtilisin\/kexin type 9 (PCSK9) mRNA. Clinical studies have demonstrated that inclisiran is effective, safe, and well-tolerated in reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia, atherosclerotic cardiovascular disease, and atherosclerotic cardiovascular disease risk equivalents. A meta-analysis of phase 3 trials demonstrated a 51% reduction in LDL-C levels at 18 months as compared with placebo. Adverse event incidence was found to be comparable in individuals treated with inclisiran and those receiving placebo, though the reactions at the site of injection were more common in patients receiving inclisiran as compared with those receiving placebo. The recommended inclisiran dose is 284 mg administered as a subcutaneous injection to be repeated after three months with a subsequent 6-month maintenance regimen. Overall, since the pharmacological efficacy of inclisiran in LDL-C reduction is comparable to that of monoclonal antibodies against PCSK9, the longer effect duration and the favorable safety profile may favor this newer approach for hypercholesterolemia management.<\/jats:p>","DOI":"10.31083\/j.rcm2311375","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T01:29:46Z","timestamp":1667525386000},"source":"Crossref","is-referenced-by-count":20,"title":["Inclisiran: A New Pharmacological Approach for Hypercholesterolemia"],"prefix":"10.31083","volume":"23","author":[{"given":"Stefania Angela","family":"Di Fusco","sequence":"first","affiliation":[{"name":"Emergency Department, Clinical and Rehabilitation Cardiology Unit, San Filippo Neri Hospital, ASL Roma 1, 00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo Pietro","family":"Maggioni","sequence":"first","affiliation":[{"name":"ANMCO Research Center, Heart Care Foundation, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Bernelli","sequence":"first","affiliation":[{"name":"Cardiology Department, Interventional Cardiology Unit, Ospedale Santa Corona, 17027 Pietra Ligure, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Perone","sequence":"first","affiliation":[{"name":"Cardiac Rehabilitation Unit, Rehabilitation Clinic \u201cVilla delle Magnolie\", Castel Morrone, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"De Marzo","sequence":"first","affiliation":[{"name":"CardioThoracic and Vascular Department, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, 16100 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Conte","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences for Health, IRCCS Ospedale Galeazzi-Sant'Ambrogio, University of Milan, 20161 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Musella","sequence":"first","affiliation":[{"name":"Division of Cardiology, Ospedale Santa Maria delle Grazie Pozzuoli, 80078 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Uccello","sequence":"first","affiliation":[{"name":"Cardiovascula Department, Clinical and Interventional Cardiology Unit, Istituto Clinico Sant'Ambrogio, 20149 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo De","family":"Luca","sequence":"first","affiliation":[{"name":"Dipartimento Cardio-Toraco-Vascolare, U.O.C. Cardiologia, Azienda Ospedaliera San Camillo Forlanini, 00152 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Gabrielli","sequence":"first","affiliation":[{"name":"Dipartimento Cardio-Toraco-Vascolare, U.O.C. Cardiologia, Azienda Ospedaliera San Camillo Forlanini, 00152 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele Massimo","family":"Gulizia","sequence":"first","affiliation":[{"name":"U.O.C. Cardiologia, Ospedale Garibaldi-Nesima, Azienda di Rilievo Nazionale e Alta Specializzazione \u201cGaribaldi\", 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Oliva","sequence":"first","affiliation":[{"name":"De Gasperis Cardio Center, Niguarda Hospital, 20162 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furio","family":"Colivicchi","sequence":"first","affiliation":[{"name":"Emergency Department, Clinical and Rehabilitation Cardiology Unit, San Filippo Neri Hospital, ASL Roma 1, 00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2019; 73: 3168\u20133209.","DOI":"10.1016\/j.jacc.2018.11.002"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association between Lowering LDL-C and Cardiovascular Risk Reduction among Different Therapeutic Interventions. JAMA. 2016; 316: 1289.","DOI":"10.1001\/jama.2016.13985"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. ESC Scientific Document Group. 2019 ESC\/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European Heart Journal. 2020; 41: 111\u2013188.","DOI":"10.1093\/eurheartj\/ehz455"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events. New England Journal of Medicine. 2015; 372: 1500\u20131509.","DOI":"10.1056\/NEJMoa1500858"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events. New England Journal of Medicine. 2015; 372: 1489\u20131499.","DOI":"10.1056\/NEJMoa1501031"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Mourikis P, Zako S, Dannenberg L, Nia AM, Heinen Y, Busch L, et al. Lipid lowering therapy in cardiovascular disease: from myth to molecular reality. Pharmacology & Therapeutics. 2020; 213: 107592.","DOI":"10.1016\/j.pharmthera.2020.107592"},{"key":"ref7","unstructured":"Ray KK, Molemans B, Schoonen WM, Giovas P, Bray S, Kiru G, et al. DA VINCI study. EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study. European Journal of Preventive Cardiology. 202; 28: 1279\u20131289."},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Colivicchi F, Di Fusco SA, Gulizia MM, De Luca L, Geraci G, Nardi F, et al. Risk stratification and secondary prevention post-myocardial infarction: insights from the EYESHOT Post-MI study. Journal of Cardiovascular Medicine. 2021; 22: 478\u2013485.","DOI":"10.2459\/JCM.0000000000001132"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Serban M, Colantonio LD, Manthripragada AD, Monda KL, Bittner VA, Banach M, et al. Statin Intolerance and Risk of Coronary Heart Events and all-Cause Mortality Following Myocardial Infarction. Journal of the American College of Cardiology. 2017; 69: 1386\u20131395.","DOI":"10.1016\/j.jacc.2016.12.036"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL, Goldstein LB, et al. Statin Safety and Associated Adverse Events: A Scientific Statement from the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biology. 2019; 39: e38\u2013e81.","DOI":"10.1161\/ATV.0000000000000081"},{"key":"ref11","unstructured":"Di Fusco SA, Di Michele S, Colivicchi F. [Atherosclerosis prevention: new therapeutic strategies on the horizon]. Giornale Italiano di Cardiologia (Rome). 2021; 22: 922\u2013931."},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Brown CR, Gupta S, Qin J, Racie T, He G, Lentini S, et al. Investigating the pharmacodynamic durability of GalNAc\u2013siRNA conjugates. Nucleic Acids Research. 2020; 48: 11827\u201311844.","DOI":"10.1093\/nar\/gkaa670"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Ray KK, Landmesser U, Leiter LA, Kallend D, Dufour R, Karakas M, et al. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. New England Journal of Medicine. 2017; 376: 1430\u20131440.","DOI":"10.1056\/NEJMoa1615758"},{"key":"ref14","unstructured":"European Medicines Agency. Leqvio 284 mg solution for injection in pre-filled syringe: summary of product characteristics. 2021. Available at: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/leqvio-epar-product-information_en.pdf (Accessed: 1 October 2022)."},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Cupido AJ, Kastelein JJP. Inclisiran for the treatment of hypercholesterolaemia: implications and unanswered questions from the ORION trials. Cardiovascular Research. 2020; 116: e136\u2013e139.","DOI":"10.1093\/cvr\/cvaa212"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Wright RS, Collins MG, Stoekenbroek RM, Robson R, Wijngaard PLJ, Landmesser U, et al. Effects of Renal Impairment on the Pharmacokinetics, Efficacy, and Safety of Inclisiran: An Analysis of the ORION-7 and ORION-1 Studies. Mayo Clinic Proceedings. 2020; 95: 77\u201389.","DOI":"10.1016\/j.mayocp.2019.08.021"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Kallend D, Stoekenbroek R, He Y, Smith PF, Wijngaard P. Pharmacokinetics and pharmacodynamics of inclisiran, a small interfering RNA therapy, in patients with hepatic impairment. Journal of Clinical Lipidology. 2022; 16: 208\u2013219.","DOI":"10.1016\/j.jacl.2022.01.001"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Frank-Kamenetsky M, Grefhorst A, Anderson NN, Racie TS, Bramlage B, Akinc A, et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proceedings of the National Academy of Sciences. 2008; 105: 11915\u201311920.","DOI":"10.1073\/pnas.0805434105"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Fitzgerald K, White S, Borodovsky A, Bettencourt BR, Strahs A, Clausen V, et al. A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. New England Journal of Medicine. 2017; 376: 41\u201351.","DOI":"10.1056\/NEJMoa1609243"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisinkexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. The Lancet. 2014; 383: 60\u201368.","DOI":"10.1016\/S0140-6736(13)61914-5"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Ray KK, Stoekenbroek RM, Kallend D, Leiter LA, Landmesser U, Wright RS, et al. Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins. Circulation. 2018; 138: 1304\u20131316.","DOI":"10.1161\/CIRCULATIONAHA.118.034710"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Ray KK, Stoekenbroek RM, Kallend D, Nishikido T, Leiter LA, Landmesser U, et al. Effect of 1 or 2 Doses of Inclisiran on Low-Density Lipoprotein Cholesterol Levels. JAMA Cardiology. 2019; 4: 1067.","DOI":"10.1001\/jamacardio.2019.3502"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Raal FJ, Kallend D, Ray KK, Turner T, Koenig W, Wright RS, et al. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. New England Journal of Medicine. 2020; 382: 1520\u20131530.","DOI":"10.1056\/NEJMoa1913805"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, et al. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. New England Journal of Medicine. 2020; 382: 1507\u20131519.","DOI":"10.1056\/NEJMoa1912387"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Leiter LA, Teoh H, Kallend D, Wright RS, Landmesser U, Wijngaard PLJ, et al. Inclisiran Lowers LDL-C and PCSK9 Irrespective of Diabetes Status: the ORION-1 Randomized Clinical Trial. Diabetes Care. 2019; 42: 173\u2013176.","DOI":"10.2337\/dc18-1491"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Soffer D, Stoekenbroek R, Plakogiannis R. Small interfering ribonucleic acid for cholesterol lowering \u2013 Inclisiran. Journal of Clinical Lipidology. 2022. (in press)","DOI":"10.1016\/j.jacl.2022.06.009"},{"key":"ref27","unstructured":"A Randomized Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People with Cardiovascular Disease (ORION-4). ClinicalTrials.gov Identifier: NCT03705234. 2022. Available at: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03705234 (Accessed: 1 October 2022)."},{"key":"ref28","unstructured":"A Study of Inclisiran in Participants with Homozygous Familial Hypercholesterolemia (HoFH) (ORION-5). ClinicalTrials.gov Identifier: NCT03851705. Available at: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03851705 (Accessed: 1 October 2022)."},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Khan SA, Naz A, Qamar Masood M, Shah R. Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia. The American Journal of Cardiology. 2020; 134: 69\u201373.","DOI":"10.1016\/j.amjcard.2020.08.018"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Koenig W, Ray KK, Kallend DG, Landmesser U, Leiter LA, Schwartz GG, et al. Efficacy and safety of inclisiran in patients with established cerebrovascular disease: pooled, post hoc analysis of the ORION-9, ORION-10 and ORION-11, phase 3 randomised clinical trials. European Heart Journal. 2021; 42, ehab724.2026.","DOI":"10.1093\/eurheartj\/ehab724.2026"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Koenig W, Ray KK, Kallend DG, Landmesser U, Leiter LA, Schwartz GG, et al. Efficacy and safety of inclisiran in patients with polyvascular disease: pooled, post hoc analysis of the ORION-9, ORION-10 and ORION-11, phase 3 randomised controlled trials. European Heart Journal. 2021; 42: ehab724.2025.","DOI":"10.1093\/eurheartj\/ehab724.2025"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170\u2008000 participants in 26 randomised trials. The Lancet. 2010; 376: 1670\u20131681.","DOI":"10.1016\/S0140-6736(10)61350-5"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Lamb YN. Inclisiran: first Approval. Drugs. 2021; 81: 389\u2013395.","DOI":"10.1007\/s40265-021-01473-6"},{"key":"ref34","unstructured":"LEQVIO\u00ae (inclisiran) prescribing information. Available at: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/214012lbl.pdf (Accessed: 1 October 2022)."},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Santulli G, Jankauskas SS, Gambardella J. Inclisiran: a new milestone on the PCSK9 road to tackle cardiovascular risk. European Heart Journal - Cardiovascular Pharmacotherapy. 2021; 7: e11\u2013e12.","DOI":"10.1093\/ehjcvp\/pvab014"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Landmesser U, Haghikia A, Leiter LA, Wright RS, Kallend D, Wijngaard P, et al. Effect of inclisiran, the small-interfering RNA against proprotein convertase subtilisinkexin type 9, on platelets, immune cells, and immunological biomarkers: a pre-specified analysis from ORION-1. Cardiovascular Research. 2021; 117: 284\u2013291.","DOI":"10.1093\/cvr\/cvaa077"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Desai NR, Campbell C, Electricwala B, Petrou M, Trueman D, Woodcock F, et al. Cost Effectiveness of Inclisiran in Atherosclerotic Cardiovascular Patients with Elevated Low-Density Lipoprotein Cholesterol despite Statin Use: a Threshold Analysis. American Journal of Cardiovascular Drugs. 2022; 22: 545\u2013556.","DOI":"10.1007\/s40256-022-00534-9"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Zlatev I, Castoreno A, Brown CR, Qin J, Waldron S, Schlegel MK, et al. Reversal of siRNA-mediated gene silencing in vivo. Nature Biotechnology. 2018; 36: 509\u2013511.","DOI":"10.1038\/nbt.4136"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Reijman MD, Schweizer A, Peterson ALH, Bruckert E, Stratz C, Defesche JC, Hegele RA, et al. Rationale and design of two trials assessing the efficacy, safety, and tolerability of inclisiran in adolescents with homozygous and heterozygous familial hypercholesterolaemia. European Journal of Preventive Cardiology. 2022; 29: 1361\u20131368.","DOI":"10.1093\/eurjpc\/zwac025"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Di Fusco SA, Arca M, Scicchitano P, Alonzo A, Perone F, Gulizia MM, Gabrielli D, et al. Lipoprotein(a): a risk factor for atherosclerosis and an emerging therapeutic target. Heart. 2022. (in press)","DOI":"10.1136\/heartjnl-2021-320708"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Ruiz I. Twice-yearly inclisiran injections halve LDL-cholesterol levels. Nature Reviews Cardiology. 2020; 17: 321\u2013321.","DOI":"10.1038\/s41569-020-0373-0"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Nordestgaard BG, Nicholls SJ, Langsted A, Ray KK, Tybj\u00e6rg-Hansen A. Advances in lipid-lowering therapy through gene-silencing technologies. Nature Reviews Cardiology. 2018; 15: 261\u2013272.","DOI":"10.1038\/nrcardio.2018.3"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Nambi V, Agha A. Inclisiran: A Game Changer in a Changing Game? Journal of the American College of Cardiology. 2021; 77: 1194\u20131196.","DOI":"10.1016\/j.jacc.2021.01.008"}],"container-title":["Reviews in Cardiovascular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/23\/11\/10.31083\/j.rcm2311375","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T18:22:37Z","timestamp":1732731757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/23\/11\/10.31083\/j.rcm2311375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,3]]},"references-count":43,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022]]}},"alternative-id":["S1530-6550(22)00717-7"],"URL":"https:\/\/doi.org\/10.31083\/j.rcm2311375","relation":{},"ISSN":["1530-6550","2153-8174"],"issn-type":[{"value":"1530-6550","type":"print"},{"value":"2153-8174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,3]]},"article-number":"375"}}