{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:14:24Z","timestamp":1792599264989,"version":"4.5.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Current proprotein convertase subtilisin\/kexin type 9 (PCSK9) inhibitors (the monoclonal antibodies evolocumab and alirocumab, and the siRNA inclisiran) require parenteral administration, which may limit long-term adherence. Orally active PCSK9 inhibitors could improve convenience and treatment accessibility. This meta-analysis evaluates LDL-C reduction and other lipid changes reported in randomized controlled trials (RCTs) of oral PCSK9 inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>RCTs comparing oral PCSK9 inhibitors with placebo and reporting LDL-C changes were identified through PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials.gov up to November 2025. Pooled mean percentage changes in lipid parameters were calculated using random- and fixed-effects models. Serious adverse events (SAEs) were analysed using risk ratios (RRs) with 95% confidence intervals (CIs). Five RCTs on three different molecules (enlicitide, NNC0385-0434, and laroprovstat), including a total of 3295 participants with hypercholesterolaemia receiving stable doses of background lipid-lowering therapy prior to study initiation, met the inclusion criteria. Treatment durations ranged from 8 to 24 weeks. Pooled analysis showed a significant LDL-C reduction of \u201359.31% (95% CI \u201362.33 to \u201356.28) compared with placebo. Additional lipid parameters also improved: apolipoprotein B (\u221249.53%, 95% CI \u201354.19 to \u201344.79), non-HDL cholesterol (\u221255.41%, 95% CI \u221257.35 to \u221253.48), and lipoprotein(a) (\u221222.74%, 95% CI \u221226.67 to \u221218.81). The pooled RR for SAEs was 0.84 (95% CI 0.68\u20131.03; P = 0.41), indicating no increased risk vs. placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oral PCSK9 inhibitors demonstrate potent LDL-C\u2013lowering efficacy, comparable to parenteral PCSK9i, with favourable effects on other atherogenic lipids and a reassuring short-term safety profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwag273","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:42:23Z","timestamp":1779363743000},"source":"Crossref","is-referenced-by-count":5,"title":["Efficacy and safety of oral Pcsk9 inhibitors: insights from a meta-analysis of RCTs"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7107-243X","authenticated-orcid":false,"given":"Elena","family":"Olmastroni","sequence":"first","affiliation":[{"name":"Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan , Milan 20133 ,","place":["Italy"]},{"name":"IRCCS MultiMedica, Sesto San Giovanni , Milan 20099 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sining","family":"Xie","sequence":"additional","affiliation":[{"name":"Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan , Milan 20133 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Galimberti","sequence":"additional","affiliation":[{"name":"IRCCS MultiMedica, Sesto San Giovanni , Milan 20099 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberico L","family":"Catapano","sequence":"additional","affiliation":[{"name":"Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan , Milan 20133 ,","place":["Italy"]},{"name":"IRCCS MultiMedica, Sesto San Giovanni , Milan 20099 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5124-5361","authenticated-orcid":false,"given":"Manuela","family":"Casula","sequence":"additional","affiliation":[{"name":"Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan , Milan 20133 ,","place":["Italy"]},{"name":"IRCCS MultiMedica, Sesto San Giovanni , Milan 20099 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