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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]]== |
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| ====Myositis==== | | ==[[Statin induced myopathy pathophysiology|Pathophysiology]]== |
| * 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 epidemiology and demographics|Epidemiology & Demographics]]== |
| * 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|Risk Factors]]== |
| * 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==
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| 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==
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| ===Intrinsic Risk Factors===
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| *Advanced age (> 80 years)<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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| *Hypertension
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| *Diabetes mellitus
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| *Small body mass index<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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| *Renal disease
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| *Hepatic disease
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| *Hypothyroidism
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| *Genetic polymorphisms of CYP450 isoenzymess (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>
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| *Metabolic muscle disease
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| *McArdle disease
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| *Carnitine palmityl transferase II deficiency
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| *Myadenylate deaminase deficiency<ref name="toth">Toth PP, Harper CR, Jacobson TA: Clinical characterization and molecular mechanisms of statin myopathy. Expert Rev Cardiovasc Ther 2008, 6:955–969</ref>
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| ===Extrinsic Risk Factors===
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| *Alcohol consumption
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| *Heavy exercise
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| *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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| *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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| *Fibrates particularly gemfibrozil (Cerivastatin 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>
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| *Warfarin
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| *Cyclosporine
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| *Grapefruit juice (> 1quart/day)
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| *Amiodarone
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| *Azole antifungals
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| *Macrolide antibiotics
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| *Protease inhibitors<ref name="toth">Toth PP, Harper CR, Jacobson TA: Clinical characterization and molecular mechanisms of statin myopathy. Expert Rev Cardiovasc Ther 2008, 6:955–969</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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| *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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| ==Pathophysiology==
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| [[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.<ref>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</ref>
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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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| ==Symptoms==
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| The symptoms of statin induced myopathy belong to a spectrum ranging from being mild and asymptomatic to severe and lethal. The time of onset of symptoms varies among people, but the median of onset of symptoms is four weeks since the beginning of the treatment. Similarly, the time for the resolution of symptoms after appropriate management also varies among individuals.<ref>Bruckert E, Hayem G, Dejager S, et al.: Mild to moderate muscular symptoms with high-dosage statin therapy in hyper- lipidemic patients–the PRIMO study [see comment]. Cardiovasc Drugs Ther 2005, 19:403–414.</ref>
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| The list of symptoms is the following:
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| *Fatigue
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| *Generalized aching
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| *Low back or proximal muscle pain
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| *Myalgia
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| *Nocturnal muscle cramps
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| *Tendon pain
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| *Weakness<ref>Toth PP, Harper CR, Jacobson TA: Clinical characterization and molecular mechanisms of statin myopathy. Expert Rev Cardiovasc
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| Ther 2008, 6:955–969.</ref>
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| | ==[[Statin induced myopathy screening|Screening]]== |
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| | ==[[Statin induced myopathy differential diagnosis|Differentiating Statin induced myopathy from other Diseases]]== |
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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]] |