AB0978 Effect of atorvastatin on skeletal muscles of patients with knee osteoarthritis: post-hoc analysis of a randomised controlled trial

Abstract

BackgroundStatins are often discontinued due to muscle-related side effects. The effect of statin on skeletal muscles in populations with osteoarthritis is unknown.ObjectivesThis study aims to examine the effect of atorvastatin on skeletal muscle biochemistry, strength, size and symptoms in patients with symptomatic knee osteoarthritis.MethodsThis is a post-hoc analysis of a multicentre randomised, double-blind, placebo-controlled trial over 2 years in which participants with knee osteoarthritis who met the American College of Rheumatology clinical criteria received atorvastatin 40mg daily (n=151) or placebo (n=153). Outcomes included levels of creatinine kinase (CK), aspartate transaminases (AST) and alanine transaminases (ALT) at baseline, 4 weeks, 6, 12 and 24 months; muscle strength measured by dynamometry at baseline, 12 and 24 months; vastus medialis cross-sectional area (CSA) on magnetic resonance imaging at baseline and 24 months; and self-reported myalgia during the trial.Results304 participants [mean age 55.7 (SD 7.6) years, 55.6% female] were randomised. There were no significant differences in CK and AST levels between atorvastatin and placebo groups at 4 weeks (CK median 107 vs 110, p=0.76; AST 22 vs 21, p=0.14), 6 (CK 109 vs 101.5, p=0.37; AST 21 vs 20, p=0.45), 12 (CK 103 vs 103, p=0.93; AST 22 vs 21, p=0.99), and 24 (CK 103 vs 93.5, p=0.17; AST 22 vs 21, p=0.34) months. The atorvastatin group had higher ALT levels than the placebo group at 4 weeks [26 vs 21, p=0.0004] and 6 months [25 vs 22, p=0.007] but no between-group differences at 12 [24 vs 21, p=0.08] and 24 [24 vs 21, p=0.053] months. Muscle strength significantly increased in the atorvastatin group but not the placebo group over 24 months with no between-group differences [mean 8.5 (95% CI 2.6,14.4) vs 5.6 (-0.3,11.5), p=0.50]. Change in vastus medialis CSA over 24 months showed between-group differences favouring the atorvastatin group [+0.12 (-0.09,0.34) vs -0.24 (-0.48,0.01), p=0.03] but of uncertain clinical significance. There was a trend for more myalgia in the atorvastatin group over 2 years (8/151 vs 2/153, p=0.06), mostly occurring within 6 months (7/151 vs 1/153, p=0.04). Of the 10 participants with myalgia, there was no relationship between the incidence of myalgia and CK levels.ConclusionIn those with symptomatic knee osteoarthritis, despite a trend for more myalgia, there was no clear evidence of an adverse effect of atorvastatin on skeletal muscles, including those most relevant to knee joint health.Disclosure of InterestsYuan Lim: None declared, Flavia Cicuttini: None declared, Anita Wluka: None declared, Graeme Jones Speakers bureau: GJ received honoraria for talks from BMS, Roche, AbbVie, Amgen, Lilly, Novartis, and Janssen, Grant/research support from: GJ received grant for a clinical trial from Covance, Catherine Hill: None declared, Andrew Forbes: None declared, Andrew Tonkin Speakers bureau: AT received honoraria for lectures from Pfizer; honoraria for lectures and advisory board participation from Amgen, Consultant of: AT received honoraria for lectures and advisory board participation from Amgen, honoraria for data and safety monitoring board participation from Merck, and honoraria for data and safety monitoring board participation from Novartis, Sofia Berezovskaya: None declared, Lynn Tan: None declared, Changhai Ding: None declared, Yuanyuan Wang: None declared