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

Objective Populations with knee osteoarthritis (KOA) are at increased risk of cardiovascular disease, due to higher prevalence of risk factors including dyslipidaemia, where statins are commonly prescribed. However, the effect of statins on muscles and symptoms in this population is unknown. Thus, this study examined the effect of atorvastatin on muscle properties in patients with symptomatic KOA. Design Post-hoc analysis of a 2-year multicentre randomised, double-blind, placebo-controlled trial. Setting Australian community. Participants Participants aged 40–70 years (mean age 55.7 years, 55.6% female) with KOA who met the American College of Rheumatology clinical criteria received atorvastatin 40 mg daily (n = 151) or placebo (n = 153). Main outcome measures Levels of creatinine kinase (CK), aspartate transaminase (AST), and alanine transaminase (ALT) at 1, 6, 12, and 24 months; muscle strength (by dynamometry) at 12 and 24 months; vastus medialis cross-sectional area (CSA) on magnetic resonance imaging at 24 months; and self-reported myalgia. Results There were no significant between-group differences in CK and AST at all timespoints. The atorvastatin group had higher ALT than placebo group at 1 (median 26 vs. 21, p = 0.004) and 6 (25 vs. 22, p = 0.007) months without significant between-group differences at 12 and 24 months. Muscle strength increased in both groups at 24 months without between-group differences [mean 8.2 (95% CI 3.5, 12.9) vs. 5.9 (1.3, 10.4), p = 0.49]. Change in vastus medialis CSA at 24 months favoured the atorvastatin group [0.11 (−0.10, 0.31) vs. −0.23 (−0.43, −0.03), p = 0.02] but of uncertain clinical significance. There was a trend for more myalgia in the atorvastatin group (8/151 vs. 2/153, p = 0.06) over 2 years, mostly occurring within 6 months (7/151 vs. 1/153, p = 0.04). Conclusions In those with symptomatic KOA, despite a trend for more myalgia, there was no clear evidence of an adverse effect of atorvastatin on muscles, including those most relevant to knee joint health.

[1]  F. Cicuttini,et al.  Effect of Atorvastatin on Knee Cartilage Volume in Patients With Symptomatic Knee Osteoarthritis: Results From a Randomized Placebo‐Controlled Trial , 2021, Arthritis & rheumatology.

[2]  D. Francis,et al.  N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects. , 2020, The New England journal of medicine.

[3]  S. Virani,et al.  Popular Media and Cardiovascular Medicine: “with Great Power There Must Also Come Great Responsibility” , 2019, Current Atherosclerosis Reports.

[4]  S. Mathieu,et al.  Cardiovascular profile in osteoarthritis: A meta-analysis of cardiovascular events and risk factors. , 2019, Joint, bone, spine : revue du rhumatisme.

[5]  R. Eckel,et al.  Statin Toxicity: Mechanistic Insights and Clinical Implications , 2019, Circulation research.

[6]  M. Delgado-Rodríguez,et al.  Systematic review and meta-analysis. , 2017, Medicina intensiva.

[7]  Thomas R Hustead,et al.  Mildly Elevated Liver Transaminase Levels: Causes and Evaluation. , 2017, American family physician.

[8]  G. Hawker,et al.  The longitudinal relationship between hand, hip and knee osteoarthritis and cardiovascular events: a population-based cohort study. , 2017, Osteoarthritis and cartilage.

[9]  F. Eckstein,et al.  Knee Extensor Strength and Risk of Structural, Symptomatic, and Functional Decline in Knee Osteoarthritis: A Systematic Review and Meta‐Analysis , 2017, Arthritis care & research.

[10]  Xinrong Hu,et al.  Osteoarthritis and the risk of cardiovascular disease: a meta-analysis of observational studies , 2016, Scientific Reports.

[11]  Peter Sandercock,et al.  Interpretation of the evidence for the efficacy and safety of statin therapy , 2016, The Lancet.

[12]  Brian A Ference,et al.  Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. , 2016, JAMA.

[13]  F. Cicuttini,et al.  Does statin use have a disease modifying effect in symptomatic knee osteoarthritis? Study protocol for a randomised controlled trial , 2015, Trials.

[14]  C. Juhl,et al.  Knee extensor muscle weakness is a risk factor for development of knee osteoarthritis. A systematic review and meta-analysis. , 2015, Osteoarthritis and cartilage.

[15]  Cheng-Li Lin,et al.  A population-based cohort study. , 2015 .

[16]  Seth S Martin,et al.  Non-cardiovascular effects associated with statins , 2014, BMJ : British Medical Journal.

[17]  R. Rosenson,et al.  An assessment by the Statin Muscle Safety Task Force: 2014 update. , 2014, Journal of clinical lipidology.

[18]  P. Thompson,et al.  Effect of Statins on Skeletal Muscle Function , 2012, Circulation.

[19]  Emma Svärd.  "...with great power there must also come --great responsibility!" : An ethical power-analysis of the institutional justice of the European Union’s approach to Food Security in , 2013 .

[20]  David G Lloyd,et al.  Increase in vastus medialis cross-sectional area is associated with reduced pain, cartilage loss, and joint replacement risk in knee osteoarthritis. , 2012, Arthritis and rheumatism.

[21]  R. Collins,et al.  The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials , 2012, The Lancet.

[22]  Matthew K Ito,et al.  Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users. , 2012, Journal of clinical lipidology.

[23]  Cholesterol Treatment Trialists' Collaborato.  The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials , 2012 .

[24]  D. Greenwood,et al.  Meta-analysis of Observational Studies , 2012 .

[25]  S. Reichenbach,et al.  All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study , 2011, BMJ : British Medical Journal.

[26]  R. Collins,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010, The Lancet.

[27]  R. Collins,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010, The Lancet.

[28]  R. Collins,et al.  Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial , 2010, The Lancet.

[29]  T. Bader.  The Myth of Statin-Induced Hepatotoxicity , 2010, The American Journal of Gastroenterology.

[30]  L. Blizzard,et al.  Statin therapy, muscle function and falls risk in community-dwelling older adults. , 2009, QJM : monthly journal of the Association of Physicians.

[31]  D. English,et al.  Vastus medialis cross-sectional area is positively associated with patella cartilage and bone volumes in a pain-free community-based population , 2008, Arthritis research & therapy.

[32]  G. Zhai,et al.  Correlates of knee pain in older adults: Tasmanian Older Adult Cohort Study. , 2006, Arthritis and rheumatism.

[33]  F. Cicuttini,et al.  Sex and site differences in cartilage development: a possible explanation for variations in knee osteoarthritis in later life. , 2000, Arthritis and rheumatism.

[34]  M Lequesne,et al.  Atlas of individual radiographic features in osteoarthritis. , 1995, Osteoarthritis and cartilage.

[35]  R. Moskowitz,et al.  Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. , 1986, Arthritis and rheumatism.