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| {{CMG}}; {{AE}} [[User:Rim Halaby|Rim Halaby]] | | {{CMG}}; {{AE}} [[User:Rim Halaby|Rim Halaby]] |
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| ==Overview==
| | {{Statin induced myopathy}} |
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| ==Definition== | | ==[[Statin induced myopathy overview|Overview]]== |
| Statin induced myopathy is a spectrum of muscular problems caused by the intake of statin. Myopathy by definition is the any pathology of the muscle. | |
| The spectrum of statin induced myopathy includes:
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| ====Myalgia====
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| * Myalgia is defined as one or combination of symptoms of muscle weakness, tenderness or pain in the context of normal or minimally elevated creatinine kinase.
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| * Patients usually complain of cramping feeling in the muscles.
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| ====Asymptomatic increase in creatine kinase==== | | ==[[Statin induced myopathy classification|Classification]]== |
| ====Myositis====
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| * Myositis is the inflammation of the muscle.
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| * Myosisitis is defines as the presence of symptoms of muscle weakness, tenderness or pain in the setting of an elevated creatine kinase up to ten folds.
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| ====Rhabdomyositis==== | | ==[[Statin induced myopathy pathophysiology|Pathophysiology]]== |
| * Rhabdomyositis is the acute degeneration of the skeletal muscle.
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| * It is a potentially lethal condition due to its associated nephrotoxicity caused by myoglobinuria and myoglobinemia.
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| * Creatine kinase is elevated in rhabdomyosistis more than ten folds the upper normal limits.
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| * The complications of rhabdomyositis are acute tubular necrosis, hypocalcemia, hyperkalemia, metabolic acidosis, hyperuricemia, DIC and cardiomyopathy.<ref name="baker">Baker, S.K. & Tarnopolsky, M.A. (2001). Statin myopathies: pathophysiologic and clinical perspectives. Clin. Invest. Med., 24(5): 258-272.</ref>
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| ====Other Statin Induced Myopathies==== | | ==[[Statin induced myopathy epidemiology and demographics|Epidemiology & Demographics]]== |
| * Elevated creatine kinase after statin withdrawal<ref name="pmid12672737">{{cite journal| author=Thompson PD, Clarkson P, Karas RH| title=Statin-associated myopathy. | journal=JAMA | year= 2003 | volume= 289 | issue= 13 | pages= 1681-90 | pmid=12672737 | doi=10.1001/jama.289.13.1681 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12672737 }} </ref>
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| * Autoimmune myopathy requiring immunosuppressive therapy<ref name="pmid18367041">{{cite journal| author=Radcliffe KA, Campbell WW| title=Statin myopathy. | journal=Curr Neurol Neurosci Rep | year= 2008 | volume= 8 | issue= 1 | pages= 66-72 | pmid=18367041 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18367041 }} </ref>
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| ==Prevalence== | | ==[[Statin induced myopathy epidemiology and demographics|Risk Factors]]== |
| The prevalence of statin induced myopathy, described as a spectrum of clinical conditions ranging from myalgia to myositis and rhabdomyolysis, is almost 10-15%<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref>
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| ==Risk Factors== | | ==[[Statin induced myopathy screening|Screening]]== |
| * Age more than 80<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515 }} </ref>
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| * Genetics (single nucleotide polymorphism of the gene SLCO1B1)<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref>*High dose of statin<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref>
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| * Concurrent use of hepatic [[cytochrome P450 inhibitors]]
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| * Concurrent use of [[fibrates]]
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| * Cerivastatin use especially in combination with [[gemfibrosil]]<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9| pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079 }} </ref>* Major trauma<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9 | pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079 }} </ref>
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| *Polypharmacy<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref>
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| * Small body size<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515 }} </ref>
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| * [[Surgery]]<ref name="pmid11758079">{{cite journal| author=Hamilton-Craig I| title=Statin-associated myopathy. | journal=Med J Aust | year= 2001 | volume= 175 | issue= 9 | pages= 486-9 | pmid=11758079 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11758079 }} </ref>
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| * Systemic disease
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| **[[Liver]] disease
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| **[[Kidney]] disease
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| **[[Diabetes]]
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| **[[Hypothyroidism]]<ref name="pmid19217515">{{cite journal| author=Venero CV, Thompson PD| title=Managing statin myopathy. | journal=Endocrinol Metab Clin North Am | year= 2009 | volume= 38 | issue= 1 | pages= 121-36 | pmid=19217515 | doi=10.1016/j.ecl.2008.11.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19217515 }} </ref>
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| ==Pathophysiology== | | ==[[Statin induced myopathy differential diagnosis|Differentiating Statin induced myopathy from other Diseases]]== |
| [[Statin induced myopathy]] has a complex poorly understood multifactorial pathophysiology. It is postulated that [[statin induced myopathy]] is caused by [[apoptosis]] of the skeletal muscle cells because of disrupted intracellular calcium signaling and mitochondrial dysfunction due to depletion of mevalonate metabolism products, notably isoprenoids.<ref name="pmid16885396">{{cite journal| author=Dirks AJ, Jones KM| title=Statin-induced apoptosis and skeletal myopathy. | journal=Am J Physiol Cell Physiol | year= 2006 | volume= 291 | issue= 6 | pages= C1208-12 | pmid=16885396 | doi=10.1152/ajpcell.00226.2006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16885396 }} </ref> | |
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| The following changes are caused by [[statin]]:
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| * Changes in [[cholesterol]] content and alteration of the membrane fluidity of [[skeletal muscle]] cells which disrupts their normal function
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| * Changes in skeletal muscle cells membrane electrical properties
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| * Changes in Na+/K+ pump density resulting in decreased production of ATP
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| * Changes in the excitation-contraction coupling
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| * Changes in the cell surface receptor transduction cascades
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| * Decreased synthesis of ubiquinone (Q10), a component of the mitochondrial electron transport chain, leading to decreased ATP production and decreased free radical scavenging
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| * Increased intracellular calcium causing apoptosis of the skeletal muscle cells<ref name="baker">Baker, S.K. & Tarnopolsky, M.A. (2001). Statin myopathies: pathophysiologic and clinical perspectives. Clin. Invest. Med., 24(5): 258-272.</ref>
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| * Decreased mevalonate metabolism products, particularly isoprenoids, leading to a chain of events that culminate in the [[apoptosis]] of skeletal muscle cells<ref name="pmid16885396">{{cite journal| author=Dirks AJ, Jones KM| title=Statin-induced apoptosis and skeletal myopathy. | journal=Am J Physiol Cell Physiol | year= 2006 | volume= 291 | issue= 6 | pages= C1208-12 | pmid=16885396 | doi=10.1152/ajpcell.00226.2006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16885396 }} </ref>
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| In addition, muscle biopsies of patients suffering from statin induced rhabdomyolysis show a ragged red fibers appearance.Mohaupt MG, Karas RH, Babiychuk EB, et al.: Association between statin-associated myopathy and skeletal muscle damage. CMAJ Can Med Assoc J 2009, 181:E11–E18
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| ;Shown below is an image depicting the mechanism of statin induced myopathy through increasing the intracellular calcium concentration.
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| [[Image:Statin_induced_myopathy.png|center|Statin induced myopathy through increased intracellular calcium]]
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| | ==Diagnosis== |
| | [[Statin induced myopathy history and symptoms|History & Symptoms]] | [[Statin induced myopathy laboratory tests|Lab Tests]] |
| ==Treatment== | | ==Treatment== |
| When symptoms of myopathy or elevation of creatine kinase occur in the setting of a patient taking statin, the majority of patients can safely continue the treatment with statin.
| | [[Statin induced myopathy medical therapy|Medical Therapy]] |
| * Patients with asymptomatic elevation of creatine kinase level less than 3-5 times the upper normal level:
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| **Statin treatment can be safely continued<ref name="pmid21414023">{{cite journal| author=Blaier O, Lishner M, Elis A| title=Managing statin-induced muscle toxicity in a lipid clinic. | journal=J Clin Pharm Ther | year= 2011 | volume= 36 | issue= 3 | pages= 336-41 | pmid=21414023 | doi=10.1111/j.1365-2710.2011.01254.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21414023 }} </ref>
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| * Patients with elevation of creatine kinase more than 3-5 times the upper normal level:
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| **Administration of a lower dose statin
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| **Alternation in the dosing
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| **Using twice weekly dosing with longer half lives statins<ref name="pmid20628837">{{cite journal| author=Harper CR, Jacobson TA| title=Evidence-based management of statin myopathy. | journal=Curr Atheroscler Rep | year= 2010 | volume= 12 | issue= 5 | pages= 322-30 | pmid=20628837 | doi=10.1007/s11883-010-0120-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20628837 }} </ref>
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| * Discontinue statin
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| Monitor creatinine kinase levels.
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| ==References== | | ==References== |
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| [[Category:Cardiology]] | | [[Category:Cardiology]] |
| [[Category:Drugs]] | | [[Category:Drugs]] |
| | [[Category:Disease]] |
| | [[Category:Up-To-Date cardiology]] |
| | [[Category:Up-To-Date]] |