Impact of statin withdrawal on perceived and objective muscle function

Background and Aims 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. Methods Patients (59 men, 33 women, 50.3±9.6 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). Force (FO), endurance (EN) and power (PO) of the leg extensors (EXT) and flexors (FLE) and handgrip strength (FOHG) 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. Results Following withdrawal, repeated-measures analyses show improvements for the entire cohort in ENEXT, ENFLE, FOFLE, POEXT and POFLE (range +7.2 to +13.3%, all p≤0.02). 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). FOHG was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (−1.7 to -4.2%) (all p=0.02). Conclusions Whether suffering from “true” 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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial [clinicaltrials.gov][1] [NCT01493648][2] ### Funding Statement The study was supported by the Canadian Institutes of Health Research (CIHR grant MOP 114917 to DRJ, JB, and JF []). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The protocol was approved by the CHU de Québec – Université Laval ethics committee, and all participants provided informed written consent. The study design complied with the principles of the Declaration of Helsinki and was registered in [clinicaltrials.gov][1] ([NCT01493648][2]). Recruitment and data acquisition were conducted from October 2011 to October 2015. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All XXX files are available from the XXX database (accession number(s) XXX, XXX.) [1]: https://clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01493648&atom=%2Fmedrxiv%2Fearly%2F2023%2F01%2F19%2F2023.01.18.23284717.atom