{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T18:28:25Z","timestamp":1765477705401,"version":"3.48.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Swiss National Science Foundation","award":["33IC30_193052"],"award-info":[{"award-number":["33IC30_193052"]}]},{"name":"The Swiss National Science Foundation","award":["32003B_205067"],"award-info":[{"award-number":["32003B_205067"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Statin-associated muscle symptoms (SAMS) are an obstacle in the prevention of cardiovascular events. A systematic assessment of the evidence of interventions in the setting of SAMS is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the evidence of strategies of statin-based vs non-statin based therapies in patients with a history of SAMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MEDLINE, EMBASE, Cochrane Central Register of Controlled Clinical Trials, Scopus, Clinicaltrials.gov and Proquest databases were searched from inception up to February 2024.We included randomized controlled trials (RCTs) and non-randomized studies involving patients with history of prior SAMS, comparing statin-based therapy to a comparator. We followed the PRISMA guideline with multiple authors involved at each stage. A random-effect model was used in the meta-analysis. We defined the primary outcome as incidence of muscle symptoms. The secondary outcomes were proportion of statin discontinuation of statin-based therapy within patients with history of SAMS. The protocol was registered on PROSPERO (CRD42020202619).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 23 studies (13 RCTs, 2 prospective and 8 retrospective studies) there were in total 1868 participants in RCTs and 47\u2019628 participants in non-RCTs (follow-up 12 weeks \u2013 31 months). Our confidence in the body of evidence using GRADE was moderate for the primary outcome and low-moderate for the secondary outcome. In RCTs among patients with history of SAMS, there was high heterogeneity in the statin regimens and controls (placebo\/non-daily dosing\/ezetimibe\/PCSK9 inhibitors). In RCTs, the meta-analysis showed no difference between statin-based and control groups in the incidence of muscle symptoms (OR 1.19, 95%CI 0.86\u20131.64, I\n                      <jats:sup>2<\/jats:sup>\n                      : 46.3%)). Therapy discontinuation due to muscle symptoms in RCTs was higher in the statin-based than the comparator groups (OR 1.48, 95%CI 1.03\u20132.12, I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200917.6%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that patients with a history of SAMS can be re-challenged with statins. More high-quality evidence is needed to strengthen guidelines regarding the management of SAMS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0338575","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T18:24:27Z","timestamp":1765477467000},"page":"e0338575","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety outcomes of statin vs non-statin lipid-lowering interventions in patients with prior statin-associated muscle symptoms: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2034-9793","authenticated-orcid":true,"given":"Philipp 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Giovane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baris","family":"Gencer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Rodondi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel R.","family":"Blum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"issue":"2","key":"pone.0338575.ref001","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1001\/jama.1996.03530260042029","article-title":"Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia","volume":"275","author":"RG 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