{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:09:37Z","timestamp":1790039377741,"version":"4.0.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>We performed a study-level meta-analysis to provide more robust evidence on safety of very low LDL-cholesterol (LDL-C) levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Concerns on the safety of LDL-C values achieved with potent lipid-lowering therapies have been raised.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We searched randomized trials reporting clinical outcomes with intensive lipid-lowering treatments leading to very low (&amp;lt;40\u00a0mg\/dL) LDL-C levels vs. a control group with higher LDL-C levels. Only studies with follow-up duration\u00a0\u2265\u00a03 months were considered. Primary endpoint was the incidence of various safety measures. A total of 10 randomized trials were overall included, with 38\u00a0427 patients being in the very low LDL-C group vs. 70\u00a0668 in the control group. Median follow-up duration was 28.8 months. The incidence of all safety outcomes was similar in the two groups: non-cardiovascular death: OR 1.13, 95% CI 0.87\u20131.45; P\u00a0=\u00a00.36; any adverse events: OR 1.00, 0.90\u20131.11, P\u00a0=\u00a00.94; adverse events leading to drug discontinuation: OR 1.00, 0.87\u20131.15, P\u00a0=\u00a00.99; cancer: OR 1.02, 0.95\u20131.10, P\u00a0=\u00a00.57; haemorrhagic stroke OR 0.89, 0.66\u20131.20, P\u00a0=\u00a00.44; new-onset diabetes: OR 1.16, 0.91\u20131.47, P\u00a0=\u00a00.23; neurocognitive disorders: OR 0.97, 0.91\u20131.04, P\u00a0=\u00a00.41; haepatobiliary disorders: OR 0.99, 0.83\u20131.18, P\u00a0=\u00a00.93; muscle disorders: OR 0.94, 0.77\u20131.13, P\u00a0=\u00a00.49; cataract: OR 1.28, 0.78\u20132.10, P\u00a0=\u00a00.34. The rates of major adverse cardiovascular events were significantly lower in the very low LDL-C group: OR 0.82, 0.72\u20130.94, P\u00a0=\u00a00.005.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This meta-analysis indicates that very low LDL-C levels on intensive lipid-lowering treatments are not associated with any adverse event and maintain a persistent reduction of cardiovascular events.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjcvp\/pvac049","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T15:22:08Z","timestamp":1663168928000},"page":"138-147","source":"Crossref","is-referenced-by-count":45,"title":["Safety and efficacy of very low LDL-cholesterol intensive lowering: a meta-analysis and meta-regression of randomized trials"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5404-3968","authenticated-orcid":false,"given":"Giuseppe","family":"Patti","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, University of Eastern Piedmont , Novara 28100 , Italy"},{"name":"Division of Cardiology, Maggiore della Carit\u00e0 Hospital , Novara 28100 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7980-1737","authenticated-orcid":false,"given":"Enrico Guido","family":"Spinoni","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Eastern Piedmont , Novara 28100 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5277-9907","authenticated-orcid":false,"given":"Leonardo","family":"Grisafi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Eastern Piedmont , Novara 28100 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5546-262X","authenticated-orcid":false,"given":"Roxana","family":"Mehran","sequence":"additional","affiliation":[{"name":"Cardiac Catheterization Laboratory of the Cardiovascular Institute, Mount Sinai Hospital , New York NY 10029 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3795-8787","authenticated-orcid":false,"given":"Marco","family":"Mennuni","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Maggiore della Carit\u00e0 Hospital , Novara 28100 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"2023020208425890000_bib1","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":"2023020208425890000_bib2","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1001\/jamacardio.2018.2258","article-title":"Efficacy and safety of further lowering of low-density lipoprotein cholesterol in patients starting with very low levels: a meta-analysis","volume":"3","author":"Sabatine","year":"2018","journal-title":"JAMA Cardiol"},{"key":"2023020208425890000_bib3","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/j.jacc.2005.04.064","article-title":"Can low-density lipoprotein be too low? 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