{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:13:45Z","timestamp":1772216025110,"version":"3.50.1"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 114917"],"award-info":[{"award-number":["MOP 114917"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 114917"],"award-info":[{"award-number":["MOP 114917"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 114917"],"award-info":[{"award-number":["MOP 114917"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Statin-associated muscle symptoms (SAMS) are frequently reported. Nevertheless, few data on objective measures of muscle function are available. Recent data suggesting an important nocebo effect with statin use could confound such effects. The objective was to assess if subjective and objective measures of muscle function improve after drug withdrawal in SAMS reporters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients (59 men, 33 women, 50.3\u00b19.6 yrs.) in primary cardiovascular prevention composed three cohorts: statin users with (SAMS, n = 61) or without symptoms (No SAMS, n = 15), and controls (n = 16) (registered at clinicaltrials.gov, NCT01493648). Force (F), endurance (E) and power (P) of the leg extensors (\n                      <jats:sc>ext<\/jats:sc>\n                      ) and flexors (\n                      <jats:sc>fle<\/jats:sc>\n                      ) and handgrip strength (F\n                      <jats:sc>hg<\/jats:sc>\n                      ) were measured using isokinetic and handheld dynamometers, respectively. A 10-point visual analogue scale (VAS) was used to self-assess SAMS intensity. Measures were taken before and after two months of withdrawal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following withdrawal, repeated-measures analyses show improvements for the entire cohort in E\n                      <jats:sc>ext<\/jats:sc>\n                      , E\n                      <jats:sc>fle<\/jats:sc>\n                      , F\n                      <jats:sc>fle<\/jats:sc>\n                      , P\n                      <jats:sc>ext<\/jats:sc>\n                      and P\n                      <jats:sc>fle<\/jats:sc>\n                      (range +7.2 to +13.3%, all p\u22640.02). Post-hoc analyses show these changes to occur notably in SAMS (+8.8 to +16.6%), concurrent with a decrease in subjective perception of effects in SAMS (VAS, from 5.09 to 1.85). F\n                      <jats:sc>hg<\/jats:sc>\n                      was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (-1.7 to -4.2%) (all p = 0.02).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Whether suffering from \u201ctrue\u201d SAMS or nocebo, those who reported SAMS had modest but relevant improvements in muscle function concurrent with a decrease in subjective symptoms intensity after drug withdrawal. Greater attention by clinicians to muscle function in frail statin users appears warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      This study is registered in clinicaltrials.gov (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01493648\" xlink:type=\"simple\">NCT01493648<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0281178","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T13:32:58Z","timestamp":1686749578000},"page":"e0281178","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of statin withdrawal on perceived and objective muscle function"],"prefix":"10.1371","volume":"18","author":[{"given":"Paul","family":"Peyrel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascale","family":"Mauri\u00e8ge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00f4me","family":"Frenette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Laflamme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karine","family":"Greffard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien S.","family":"Dufresne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Huth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Bergeron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9699-0616","authenticated-orcid":true,"given":"Denis R.","family":"Joanisse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,6,14]]},"reference":[{"issue":"25","key":"pone.0281178.ref001","first-page":"e1082","article-title":"2018 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":"SM Grundy","year":"2019","journal-title":"Circulation"},{"issue":"25","key":"pone.0281178.ref002","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1016\/j.jacc.2013.08.1626","article-title":"How do statins work?: changing paradigms with implications for statin allocation","volume":"62","author":"MJ Blaha","year":"2013","journal-title":"J Am Coll Cardiol"},{"issue":"12","key":"pone.0281178.ref003","first-page":"1109","article-title":"Statin intolerance and associated muscular dysfunctions","volume":"31","author":"A Boulanger-Piette","year":"2015","journal-title":"Med Sci (Paris)"},{"issue":"20","key":"pone.0281178.ref004","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1016\/j.jacc.2016.02.071","article-title":"Statin-Associated Side Effects","volume":"67","author":"PD Thompson","year":"2016","journal-title":"J Am Coll Cardiol"},{"issue":"6","key":"pone.0281178.ref005","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s10557-005-5686-z","article-title":"Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients\u2014the PRIMO study","volume":"19","author":"E Bruckert","year":"2005","journal-title":"Cardiovasc Drugs Ther"},{"issue":"3","key":"pone.0281178.ref006","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1080\/1744666X.2018.1440206","article-title":"Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations","volume":"14","author":"A Selva-O\u2019Callaghan","year":"2018","journal-title":"Expert Rev Clin Immunol"},{"issue":"17","key":"pone.0281178.ref007","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/eurheartj\/ehv043","article-title":"Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management","volume":"36","author":"ES Stroes","year":"2015","journal-title":"Eur Heart J"},{"key":"pone.0281178.ref008","doi-asserted-by":"crossref","first-page":"104201","DOI":"10.1016\/j.phrs.2019.03.010","article-title":"Mechanisms of statin-associated skeletal muscle-associated symptoms","volume":"154","author":"J Bouitbir","year":"2020","journal-title":"Pharmacol Res"},{"issue":"4","key":"pone.0281178.ref009","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1007\/s13311-018-0670-z","article-title":"Statin-Associated Muscle Disease: Advances in Diagnosis and Management","volume":"15","author":"BA Taylor","year":"2018","journal-title":"Neurotherapeutics"},{"issue":"1","key":"pone.0281178.ref010","doi-asserted-by":"crossref","DOI":"10.3390\/jcm9010022","article-title":"Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components","volume":"9","author":"RM Turner","year":"2019","journal-title":"J Clin Med"},{"issue":"26","key":"pone.0281178.ref011","first-page":"459","article-title":"Nocebo phenomena in medicine: their relevance in everyday clinical practice","volume":"109","author":"W Hauser","year":"2012","journal-title":"Dtsch Arztebl Int"},{"issue":"10","key":"pone.0281178.ref012","first-page":"1059","article-title":"Myalgia and statins: Separating the true from the false","volume":"48","author":"J Blacher","year":"2019","journal-title":"Presse Med"},{"issue":"7","key":"pone.0281178.ref013","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1080\/14740338.2019.1615053","article-title":"Muscle and statins from toxicity to the nocebo effect","volume":"18","author":"J Pedro-Botet","year":"2019","journal-title":"Expert Opinion on Drug Safety"},{"issue":"5","key":"pone.0281178.ref014","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.pcad.2019.10.005","article-title":"New insights into managing symptoms during statin therapy","volume":"62","author":"JG Robinson","year":"2019","journal-title":"Progress in Cardiovascular Diseases"},{"issue":"3","key":"pone.0281178.ref015","doi-asserted-by":"crossref","first-page":"207","DOI":"10.5551\/jat.RV17030","article-title":"Diagnosis and Management of Statin Intolerance","volume":"26","author":"R Alonso","year":"2019","journal-title":"J Atheroscler Thromb"},{"issue":"2","key":"pone.0281178.ref016","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10557-017-6723-4","article-title":"The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI): Revision for Clinical Use, Content Validation, and Inter-rater Reliability","volume":"31","author":"RS Rosenson","year":"2017","journal-title":"Cardiovasc Drugs Ther"},{"key":"pone.0281178.ref017","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.atherosclerosissup.2019.08.026","article-title":"Statin-induced muscular side effects at rest and exercise\u2014An anatomical mapping","volume":"40","author":"T Berent","year":"2019","journal-title":"Atheroscler Suppl"},{"issue":"2","key":"pone.0281178.ref018","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/ageing\/afp203","article-title":"Grip strength and cardiovascular drug use in older people: findings from the Hertfordshire Cohort Study","volume":"39","author":"TA Ashfield","year":"2010","journal-title":"Age Ageing"},{"issue":"4","key":"pone.0281178.ref019","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1097\/MOL.0b013e32833c1edf","article-title":"The effects of statins on skeletal muscle strength and exercise performance","volume":"21","author":"GM Krishnan","year":"2010","journal-title":"Curr Opin Lipidol"},{"issue":"7","key":"pone.0281178.ref020","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1249\/MSS.0000000000001920","article-title":"Aerobic Exercise Performance and Muscle Strength in Statin Users-The LIFESTAT Study","volume":"51","author":"T Morville","year":"2019","journal-title":"Med Sci Sports Exerc"},{"issue":"5","key":"pone.0281178.ref021","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.jacl.2017.07.003","article-title":"The effects of statins on exercise and physical activity","volume":"11","author":"AM Noyes","year":"2017","journal-title":"Journal of Clinical Lipidology"},{"issue":"1","key":"pone.0281178.ref022","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1161\/CIRCULATIONAHA.112.136101","article-title":"Effect of statins on skeletal muscle function","volume":"127","author":"BA Parker","year":"2013","journal-title":"Circulation"},{"issue":"10","key":"pone.0281178.ref023","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/j.mayocp.2015.06.019","article-title":"Effects of Statin Therapy on Exercise Levels in Participants in the National Runners\u2019 and Walkers\u2019 Health Study","volume":"90","author":"PT Williams","year":"2015","journal-title":"Mayo Clin Proc"},{"issue":"4","key":"pone.0281178.ref024","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/ggi.13228","article-title":"Association between statin use and physical function among community-dwelling older Japanese adults","volume":"18","author":"H Kawai","year":"2018","journal-title":"Geriatr Gerontol Int"},{"issue":"5","key":"pone.0281178.ref025","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1113\/jphysiol.2014.285577","article-title":"Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression","volume":"593","author":"JE Mallinson","year":"2015","journal-title":"J Physiol"},{"issue":"3","key":"pone.0281178.ref026","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jacl.2015.01.004","article-title":"Changes in muscle strength in individuals with statin-induced myopathy: A summary of 3 investigations","volume":"9","author":"GA Panza","year":"2015","journal-title":"J Clin Lipidol"},{"issue":"7","key":"pone.0281178.ref027","doi-asserted-by":"crossref","first-page":"581","DOI":"10.7326\/0003-4819-137-7-200210010-00009","article-title":"Statin-Associated Myopathy with Normal Creatine Kinase Levels","volume":"137","author":"PS Phillips","year":"2002","journal-title":"Annals of Internal Medicine"},{"issue":"7","key":"pone.0281178.ref028","doi-asserted-by":"crossref","first-page":"298","DOI":"10.2519\/jospt.1990.11.7.298","article-title":"Test-Retest Reliability of the Biodex lsokinetic Dynamometer","volume":"11","author":"DC Feiring","year":"1990","journal-title":"Journal of Orthopaedic & Sports Physical Therapy"},{"issue":"2","key":"pone.0281178.ref029","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S0363-5023(84)80146-X","article-title":"Reliability and validity of grip and pinch strength evaluations","volume":"9","author":"V Mathiowetz","year":"1984","journal-title":"The Journal of Hand Surgery"},{"key":"pone.0281178.ref030","unstructured":"Add-Ins J. Full Factorial Repeated Measures ANOVA Add-In 2014 [https:\/\/community.jmp.com\/t5\/JMP-Add-Ins\/Full-Factorial-Repeated-Measures-ANOVA-Add-In\/ta-p\/23904?trMode=source."},{"issue":"2","key":"pone.0281178.ref031","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1136\/bjsm.30.2.156","article-title":"Eccentric and concentric isokinetic knee flexion and extension: a reliability study using the Cybex 6000 dynamometer","volume":"30","author":"RC Li","year":"1996","journal-title":"Br J Sports Med"},{"issue":"12","key":"pone.0281178.ref032","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/j.jacc.2021.07.022","article-title":"Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment","volume":"78","author":"JP Howard","year":"2021","journal-title":"J Am Coll Cardiol"},{"issue":"6","key":"pone.0281178.ref033","doi-asserted-by":"crossref","first-page":"e20190672","DOI":"10.1590\/0034-7167-2019-0672","article-title":"Patient-and Family-Centered Care and Patient Safety: reflections upon emerging proximity","volume":"73","author":"AC Cruz","year":"2020","journal-title":"Rev Bras Enferm"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0281178","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T13:33:32Z","timestamp":1686749612000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0281178"}},"subtitle":[],"editor":[{"given":"Yoshihiro","family":"Fukumoto","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,6,14]]},"references-count":33,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0281178","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.01.18.23284717","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,14]]}}}