Phenotype Standardization for Statin-Induced Myotoxicity

Alfirevic, Ana; Neely, Dermot; Armitage, Jane; Chinoy, Hector; Cooper, Rosemary; Laaksonen, Reijo; Carr, Daniel F.; Bloch, K. M.; Fahy, Jacques; Hanson, Anita; Qy, Yue; Wadelius, Mia; Zee, Anke‐Hilse Maitland‐van der; Voora, Deepak; Psaty, Bruce M.; Palmer, Colin N.A.

doi:10.1038/clpt.2014.121

Cited by 177 publications

(156 citation statements)

References 68 publications

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“…[34][35][36] Definitions of statin intolerance in population-based studies hinge on the elevation of CK and, in some instances, on the resolution of muscle-associated CK elevations on the discontinuation of statin therapy. 19,37,38 The most established threshold for a clinically relevant CK elevation is ≥4× the upper limit of normal (4 × upper limit of the normal) and 10 × upper limit of the normal. 37 However, as this study suggests, these outcomes are less likely to occur among carriers of the CKM variant.…”

Section: Discussionmentioning

confidence: 99%

CKM Glu83Gly Is Associated With Blunted Creatine Kinase Variation, but Not With Myalgia

Siddiqui

Veluchamy

Maroteau

et al. 2017

Circ Cardiovasc Genet

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Background-To test the association of a recently reported variant in the creatine kinase (CK) muscle gene, CKM Glu83Gly (rs11559024) with constitutive creatine phosphokinase (CK) levels, CK variation, and inducibility. Given the diagnostic importance of CK in determining muscle damage, we tested the association of the variant with myalgia. ) and 24% (P value=2×10 −5 ) lower for carriers of the variant, respectively. The variant was not associated with myalgia (odds ratio, 0.84; 95% confidence interval, 0.52-1.38).Conclusions-This study highlights that a genetic factor known to be associated with constitutive CK levels is also associated with CK variability and inducibility. This is discussed in the context of evidence to suggest that the variant has an impact on inducibility of CK by trauma through a previously reported case of a homozygous carrier. However, the lack of association between the variant and myalgia suggests that it cannot reliably be used as a biomarker for muscle symptoms.

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Section: Discussionmentioning

confidence: 99%

CKM Glu83Gly Is Associated With Blunted Creatine Kinase Variation, but Not With Myalgia

Siddiqui

Veluchamy

Maroteau

et al. 2017

Circ Cardiovasc Genet

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“…The former improves with statin discontinuation, whereas in the latter only a few patients improve with drug discontinuation; for the remaining patients, the disease is persistent or progressive despite statin discontinuation. 21,23,24 The autoimmune type is associated with anti-HMGCR antibodies and requires immunosuppressive therapy (steroids and/or intravenous immunoglobulin).…”

Section: Myositismentioning

confidence: 99%

“…8,21,33,34 Attention to these factors may be the best way to minimise the risk of muscle injuries, which are reported with all marketed statins. 33 The highest risk of developing an SaMAE is with 80 mg of simvastatin (18.2%); therefore, this dose is better avoided.…”

Section: Risk Factorsmentioning

confidence: 99%

Statin-Associated Muscle Adverse Events: Update for clinicians

Al-Mohaissen¹,

Ignaszewski²,

Fröhlich³

et al. 2016

SQUMJ

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Statins are potent medications which reduce low-density lipoprotein cholesterol (LDL-C) levels. Their efficacy in cardiovascular risk reduction is well established and indications for their use are expanding. While statins are generally well tolerated and safe, adverse events are relatively common, particularly statinassociated muscle adverse events (SaMAEs), which are the most frequently encountered type of adverse event. Recent guidelines and guideline updates on SaMAEs and statin intolerance have included revised definitions of SaMAEs, incorporating new evidence on their pathogenesis and management. As SaMAEs emerge as a therapeutic challenge, it is important for physicians to be aware of updates on management strategies to ensure better patient outcomes. The majority of patients who are considered statin-intolerant can nevertheless tolerate some forms of statin therapy and successfully achieve optimal LDL-C levels. This review article discusses the recent classification of SaMAEs with emphasis on pathogenesis and management strategies.

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“…1 An estimated 25 million patients worldwide are taking a statin, 1,2 and according to the US National Health and Nutrition Examination Survey (2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012), more than 25% of American adults 40 years of age and older were taking a statin in 2011/12, an increase from about 18% in 2003/04. 3 Statin use is expected to increase further, at least in part because of recently revised guidelines.…”

mentioning

confidence: 99%

“…Most notable are muscle-related effects, varying from tolerable myalgia (estimated incidence of 190 per 100 000 patient-years) to rhabdomyolysis (estimated incidence of 0.1 to 8.4 per 100 000 patient-years). 2 Increased statin concentration, due to higher doses or drug interactions, or both, is a wellknown yet modifiable risk factor for such effects.…”

mentioning

confidence: 99%