Statin-associated Muscle Symptoms: Impact on Statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management

Eur Heart J. 2015 May 1;36(17):1012-22. doi: 10.1093/eurheartj/ehv043. Epub 2015 Feb 18.

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.

Keywords: Cholesterol; Consensus statement; Lipids; Mitochondrial; Muscle symptoms; Myalgia; Myopathy; Statin; Statin intolerance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors
  • Complementary Therapies
  • Consensus
  • Creatine Kinase / metabolism
  • Diet
  • Genetic Predisposition to Disease / etiology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Hypolipidemic Agents / therapeutic use
  • Mitochondria, Muscle
  • Mitochondrial Diseases / complications
  • Muscular Diseases / chemically induced*
  • Muscular Diseases / diagnosis
  • Muscular Diseases / therapy
  • Proprotein Convertase 9
  • Proprotein Convertases / antagonists & inhibitors
  • Risk Factors
  • Serine Endopeptidases

Substances

  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Creatine Kinase
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases