{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:06:47Z","timestamp":1791410807233,"version":"4.3.3"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Lowering low\u2010density lipoprotein cholesterol (LDL\u2010C) levels is a primary strategy to reduce ASCVD risk. Although statin therapy remains the initial therapy of choice to reduce LDL\u2010C and ASCVD risk, statin intolerance and suboptimal LDL\u2010C lowering response prompts the need for additional non\u2010statin therapies. Ezetimibe and bempedoic acid are reasonable options but they modestly reduce LDL\u2010C levels (15% to 25%). Therapies directed at the proprotein convertase subtilisin\/kexin type 9 (PCSK9) enzyme, however, reduce LDL\u2010C levels by 50%\u201360% when added to background statin therapy. PCSK9 is an enzyme synthesized by the liver that facilitates the degradation of LDL receptors and prevents their recycling to the hepatocyte surface to remove LDL\u2010C from circulation. Approaches to inhibit this effect have centered on monoclonal antibodies (mAbs) (alirocumab, evolocumab) targeting PCSK9 functionality and small interfering RNA (siRNA) therapies (inclisiran) targeting the hepatic synthesis of PCSK9. Randomized controlled trials have demonstrated beneficial cardiovascular outcomes of PCSK9 mAbs, but such evidence is not yet available for inclisiran. Current clinical practice guidelines generally recommend PCSK9\u2010directed therapies for higher\u2010risk patients with established ASCVD and those with familial hypercholesterolemia. This approach is, in part, due to their cost and uncertain economic value, but also because these therapies require subcutaneous administration, which is not preferred by some patients. Oral therapies targeting PCSK9 are, however, in development. This scoping review covers the development of current and emerging PCSK9\u2010directed therapies, their efficacy, safety, and role in clinical practice.<\/jats:p>","DOI":"10.1002\/phar.4635","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T06:50:33Z","timestamp":1734331833000},"page":"54-65","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Current and emerging PCSK9\u2010directed therapies to reduce LDL\u2010C and ASCVD risk: A state\u2010of\u2010the\u2010art review"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6554-9318","authenticated-orcid":false,"given":"Candice L.","family":"Garwood","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University  Detroit Michigan USA"},{"name":"Department of Pharmacy Harper University Hospital, Detroit Medical Center  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6831-1804","authenticated-orcid":false,"given":"Katherine P.","family":"Cabral","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Albany College of Pharmacy &amp; Health Sciences  Albany New York USA"},{"name":"Capital Cardiology Associates  Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0627-9132","authenticated-orcid":false,"given":"Roy","family":"Brown","sequence":"additional","affiliation":[{"name":"Health Sciences Library Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-9521","authenticated-orcid":false,"given":"Dave L.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy &amp; Outcomes Science Virginia Commonwealth University School of Pharmacy  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"Cardiovascular Diseases (CVDs) Word Health Organization.2021.https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/cardiovascular\u2010diseases\u2010(cvds). 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Norvartis.2024.https:\/\/www.leqviohcp.com\/. Accessed November 11 2024."},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1701488"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614062"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac594"},{"key":"e_1_2_13_25_1","unstructured":"A randomized trial assessing the effects of Inclisiran on clinical outcomes among people with cardiovascular disease (ORION\u20104).clinicaltrials.gov\/study\/NCT03705234. Accessed November 11 2024."},{"key":"e_1_2_13_26_1","unstructured":"A study of Inclisiran to Prevent Cardiovascular (CV) events in participants with established cardiovascular disease (VICTORION\u20102P).https:\/\/clinicaltrials.gov\/study\/NCT05030428. 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