Impact of statin withdrawal on perceived and objective muscle function

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).

Fig 1. CONSORT diagram of patients’ recruitment.

* All participants recruited into the pilot study had SAMS and were allocated to the SAMS group; ** The large range here is explained by the fact that the participants in the pilot study did not complete all the measures of the study. Exceptions are presented in the methods section; M: men; SAMS: statin-associated muscle symptoms; W: women.

Fig 2. Pre- and post-statin withdrawal measures of physical performance.

Data are expressed as mean ± standard error; Post value with * is statistically different from pre value with p≤0.01; Post value with † is statistically different from pre value with p<0.05; Eext: endurance in extension (panel A); Efle: endurance in flexion (panel B); Fext: force in extension (panel C); Ffle: force in flexion (panel D); Fhgl: hand grip force left (panel H); Fhgr: hand grip force right (panel G); Pext: power in extension (panel E); Pfle: power in flexion (panel F); SAMS: statin-associated muscle symptoms.

Fig 3. Impact of statin withdrawal on perceived SAMS intensity by SAMS-CI category using a visual analog scale from 0 to 10.

Data are expressed as mean ± standard error; Post value with * is statistically different from pre value; SAMS: statin-associated muscle symptoms; SAMS-CI: SAMS–clinical index.

Fig 4. Impact of statin withdrawal on physical performance by SAMS-CI category.

Data are expressed as mean ± standard error; Post value with * is statistically different from pre value with p≤0.01; Post value with † is statistically different from pre value with p<0.05; Eext: endurance in extension (panel A); Efle: endurance in flexion (panel B); Fext: force in extension (panel C); Ffle: force in flexion (panel D); Fhgl: hand grip force left (panel H); Fhgr: hand grip force right (panel G); Pext: power in extension (panel E); Pfle: power in flexion (panel F); SAMS: statin-associated muscle symptoms; SAMS-CI: SAMS–clinical index.