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Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management
Consensus Statement of the European Atherosclerosis Society
Publication in full
Erik S. Stroes*, Paul D. Thompson, Alberto Corsini, Georgirene D. Vladutiu, Frederick J. Raal, Kausik K. Ray, Michael Roden, Evan Stein, Lale Tokgözoğlu, Børge G. Nordestgaard, Eric Bruckert, Guy De Backer, Ronald M. Krauss, Ulrich Laufs, Raul D. Santos, Robert A. Hegele, G. Kees Hoving7, Lawrence A. Leiter, Francois Mach, Winfried März, Connie B. Newman, Olov Wiklund, Terry A. Jacobson, Alberico L. Catapano, M. John Chapman and Henry N. Ginsberg, European Atherosclerosis Society Consensus Panel
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.
Lowering LDL-C with statin therapy reduces CVD risk by up to 40% in a wide range of patients. Given that the main reason for statin non-adherence/discontinuation relates to the onset of (perceived) side effects, it follows that the high prevalence of SAMS reported from observational studies is likely to adversely affect the CVD benefits of statins.119 Strategies to prevent the loss of effective statin therapy because of SAMS are still lacking. In the absence of a gold standard definition, this EAS Consensus Panel proposes to base the probability of SAMS being caused by statins on the nature of symptoms and their temporal relationship with statin initiation, statin discontinuation (or dechallenge), and repetitive re-challenge (Figure 2). Optimal therapy should combine a maximally tolerated, or even non-daily statin dose, together with non-statin-based lipid-lowering therapies in order to achieve LDL-C targets.
This Consensus Panel also highlights the need for further research into the pathophysiology of SAMS. Accumulating preclinical data show that statins decrease mitochondrial function, and alter muscle protein degradation, providing a possible pathophysiological link between statins and muscle symptoms. Studies in the clinical setting are a priority to further understanding of these mechanisms, and may offer therapeutic potential. In the absence of therapies to prevent these symptoms, this Consensus Panel recommends that the response of patients with SAMS to three or more statins should be considered for referral to specialized settings. By recognizing SAMS and adhering to a structured work-up, the Panel anticipates that individuals with clinically relevant SAMS will be offered alternative and/or novel therapeutic regimens that can satisfactorily address their CVD risk.
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