title: Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.
abstract: Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7-29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands e.s.stroes@amc.uva.nl.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Stroes
authors.affiliation: Hartford Hospital, Hartford, CT, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
authors.affiliation: University of Milan and Multimedica IRCSS Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Corsini
authors.affiliation: School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Georgirene D
authors.initials: GD
authors.lastname: Vladutiu
authors.affiliation: University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Raal
authors.affiliation: St. Georges's University of London, UK.
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.affiliation: Department of Endocrinology and Diabetology, University Hospital Düsseldorf Heinrich-Heine University, and Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Metabolic and Atherosclerosis Research Centre, Cincinnati, OH, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Stein
authors.affiliation: Hacettepe University, Ankara, Turkey.
authors.forename: Lale
authors.initials: L
authors.lastname: Tokgözoğlu
authors.affiliation: Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Pitié-Salpetriere University Hospital, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.affiliation: Ghent University, Ghent, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: De Backer
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
authors.affiliation: Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.affiliation: University of Sao Paulo, Brazil.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.affiliation: Western University, London, ON, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.affiliation: Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Canada.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Cardiology Service, HUG, Geneva, Switzerland.
authors.forename: Francois
authors.initials: F
authors.lastname: Mach
authors.affiliation: Synlab Center of Laboratory Diagnostics Heidelberg, Heidelberg, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Connie B
authors.initials: CB
authors.lastname: Newman
authors.affiliation: Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Olov
authors.initials: O
authors.lastname: Wiklund
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Terry A
authors.initials: TA
authors.lastname: Jacobson
authors.affiliation: University of Milan and Multimedica IRCSS Milano, Italy.
authors.forename: Alberico L
authors.initials: AL
authors.lastname: Catapano
authors.affiliation: INSERM, Pitié-Salpetriere University Hospital, Paris, France.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
mesh_terms: D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D000529:Complementary Therapies; D032921:Consensus; D003402:Creatine Kinase / Q000378:metabolism; D004032:Diet; D020022:Genetic Predisposition to Disease / Q000209:etiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008931:Mitochondria, Muscle; D028361:Mitochondrial Diseases / Q000150:complications; D009135:Muscular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000628:therapy; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors; D012307:Risk Factors; D012697:Serine Endopeptidases
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D003402:Creatine Kinase; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Cholesterol; Consensus statement; Lipids; Mitochondrial; Muscle symptoms; Myalgia; Myopathy; Statin; Statin intolerance