Impact of statin withdrawal on perceived and objective muscle function

Paul Peyrel; Pascale Mauriège; Jérôme Frenette; Nathalie Laflamme; Karine Greffard; Sébastien S Dufresne; Claire Huth; Jean Bergeron; Denis R Joanisse

doi:10.1371/journal.pone.0281178

Impact of statin withdrawal on perceived and objective muscle function

PLoS One. 2023 Jun 14;18(6):e0281178. doi: 10.1371/journal.pone.0281178. eCollection 2023.

Authors

Paul Peyrel^{1

2}, Pascale Mauriège^{1

2}, Jérôme Frenette^{3

4}, Nathalie Laflamme³, Karine Greffard³, Sébastien S Dufresne⁵, Claire Huth^{1

2}, Jean Bergeron^{3

6}, Denis R Joanisse^{1

2}

Affiliations

¹ Department of Kinesiology, Université Laval, Québec, Québec, Canada.
² Research Center of the University Institute of Cardiology and Pulmonology of Quebec, Québec, Québec, Canada.
³ CHU de Québec - Université Laval Research Center, Québec, Québec, Canada.
⁴ Department of Rehabilitation, Université Laval, Québec, Québec, Canada.
⁵ Department of Health Sciences, Université du Québec à Chicoutimi, Saguenay, Québec, Canada.
⁶ Department of Laboratory Medicine and of Medicine, Université Laval, Québec, Québec, Canada.

Abstract

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) (registered at clinicaltrials.gov, NCT01493648). Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (Fhg) 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 Eext, Efle, Ffle, Pext and Pfle (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). Fhg 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.

Trial registration: This study is registered in clinicaltrials.gov (NCT01493648).

Copyright: © 2023 Peyrel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Clinical Trial

MeSH terms

Antisocial Personality Disorder
Exercise Therapy
Female
Hand Strength
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
Male
Middle Aged
Muscles

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Associated data

ClinicalTrials.gov/NCT01493648

Grants and funding

The study was supported by the Canadian Institutes of Health Research (CIHR grant MOP 114917 to DRJ, JB, and JF [https://cihr-irsc.gc.ca]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.