{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:47:01Z","timestamp":1786978021803,"version":"build-2736575974"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T00:00:00Z","timestamp":1648857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Inclisiran increases the number of low\u2010density lipoprotein surface receptors expressed on hepatocytes using small interfering RNA directed against proprotein convertase subtilisin\/kexin type 9 (PCSK9) mRNA. This novel mechanism can reduce low\u2010density lipoprotein by \u224850%, like reductions achieved with high\u2010intensity statins or PCSK9\u2010inhibiting monoclonal antibodies. Inclisiran is indicated in the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, unable to achieve target LDL concentrations with diet and maximally tolerated statin therapy. It is more expensive than PCSK9\u2010inhibiting monoclonal antibodies and still lacks clinical evidence for the expected reduction in atherosclerotic cardiovascular disease events when added to statin therapy. Although some patients experience injection\u2010site reactions of mild or moderate severity, current evidence suggests a strong safety profile with total and serious adverse events approximating that of placebo. The dosing protocol of inclisiran offers its biggest clinical advantage over PCSK9\u2010inhibiting monoclonal antibodies, being administered only every 6 months after initial baseline and 3\u2010month doses rather than every second or fourth week. Unlike PCSK9\u2010inhibiting monoclonal antibodies, inclisiran has not as yet been noted to induce neutralizing antidrug antibodies that can impact drug efficacy. Thus, inclisirin is a novel small interfering RNA molecule that provides further options in the management of hypercholesterolemia refractory to statins alone. However, cost and evidence considerations suggest it should not supplant adjunctive therapy with the PCSK9\u2010inhibiting monoclonal antibodies, despite having an efficacy, safety, tolerability, and drug interaction profile superior to other antihypercholesterolemic options such as lomitapide, niacin, bile acid sequestrants, and bempedoic acid.<\/jats:p>","DOI":"10.1002\/jcph.2045","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T05:09:35Z","timestamp":1647148175000},"page":"1079-1085","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inclisiran: A Novel Small Interfering RNA Drug for Low\u2010Density Lipoprotein Reduction"],"prefix":"10.1002","volume":"62","author":[{"given":"Kimberly W.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice University of Connecticut School of Pharmacy  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9367-4893","authenticated-orcid":false,"given":"C. Michael","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice University of Connecticut School of Pharmacy  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,2]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"e1082","article-title":"AHA\/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":"139","author":"Grundy SM","year":"2019","journal-title":"Circulation"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1074248418769040"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60367-5"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-017-0259-7"},{"key":"e_1_2_10_6_1","unstructured":"Novartis Pharmaceuticals.Inclisiran package insert.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/214012lbl.pdf. Published 2021. Accessed January 11 2022."},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01473-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa212"},{"issue":"7","key":"e_1_2_10_9_1","first-page":"e16664","article-title":"Can clinicians start prescribing inclisiran for hypercholesterolemia today? A review of clinical studies for internal medicine physicians and endocrinologists","volume":"13","author":"Jahangir A","year":"2021","journal-title":"Cureus"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1913805"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1912387"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.12.058"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001053"},{"key":"e_1_2_10_14_1","unstructured":"LiuAInclisiran now has its cost\u2010effectiveness report from ICER. Should Novartis be concerned? 12\/27\/2021. Fierce Pharma. Accessed January 12 2022.https:\/\/www.fiercepharma.com\/pharma\/icer\u2010outlines\u2010cost\u2010effective\u2010price\u2010range\u2010for\u2010pcsk9\u2010cholesterol\u2010drug\u2010inclisiran\u2010should."},{"key":"e_1_2_10_15_1","unstructured":"Aegerion Pharmaceuticals.Lomitapide package insert.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2012\/203858s000lbl.pdf. Published 2012. Accessed January 13 2022."},{"key":"e_1_2_10_16_1","unstructured":"Abbie Vie Inc.Niaspan package insert.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/020381Orig1s051lbl.pdf. Published April 2015. Accessed January 13 2022."},{"key":"e_1_2_10_17_1","unstructured":"Esperion Pharmaceuticals.Bempedoic acid with ezetimibe package insert.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/211617s000lbl.pdf. Published February 2020. Accessed January 13 2022."},{"key":"e_1_2_10_18_1","unstructured":"Daiichi Sankyo Pharmaceuticals.Colesevelam package insert.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2006\/021176s014lbl.pdf. Published 2006. Accessed January 13 2022."},{"key":"e_1_2_10_19_1","unstructured":"Drugs.com.Nexlizet prices coupons and patient assistance programs.https:\/\/www.drugs.com\/price\u2010guide\/nexlizet. Accessed January 13 2022."},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40256\u2010021\u201000477\u20107"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2021.57.5.3277083"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2045","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.2045","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2045","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:53:42Z","timestamp":1692838422000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.2045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,2]]},"references-count":20,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1002\/jcph.2045"],"URL":"https:\/\/doi.org\/10.1002\/jcph.2045","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,2]]},"assertion":[{"value":"2022-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}