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==Overview== | ==Overview== | ||
[[Statin induced myopathy]] is a common entity that presents as a spectrum of symptoms ranging from complete absence of symptoms to [[ | [[Statin induced myopathy]] is a common entity that presents as a spectrum of symptoms ranging from complete absence of symptoms to [[myalgia]], [[myositis]] and [[rhabdomyolysis]]. [[Myopathy]], which is a general term that describes any pathology of the muscle, occurs in around 10 to 15% of patients taking [[statins]]. The pathophysiology of [[statin induced myopathy]] is complex. As for the treatment, it is guided by the severity of the symptoms and the degree of increase in [[creatine kinase]] levels. | ||
[[Randomized_controlled_trial#-of-1|N-of-1 trial]]s have examined this: | |||
* StatinWISE<ref name="pmid33627334">{{cite journal| author=Herrett E, Williamson E, Brack K, Beaumont D, Perkins A, Thayne A | display-authors=etal| title=Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials. | journal=BMJ | year= 2021 | volume= 372 | issue= | pages= n135 | pmid=33627334 | doi=10.1136/bmj.n135 | pmc=7903384 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33627334 }} </ref><ref name="pmid33709907">{{cite journal| author=Herrett E, Williamson E, Brack K, Perkins A, Thayne A, Shakur-Still H | display-authors=etal| title=The effect of statins on muscle symptoms in primary care: the StatinWISE series of 200 N-of-1 RCTs. | journal=Health Technol Assess | year= 2021 | volume= 25 | issue= 16 | pages= 1-62 | pmid=33709907 | doi=10.3310/hta25160 | pmc=8020196 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33709907 }} </ref> | |||
* TaSINI<ref name="pmid32051312">{{cite journal| author=Tudor K, Brooks J, Howick J, Fox R, Aveyard P| title=Tackling statin intolerance with n-of-1 trials (TaSINI) in primary care: protocol for a feasibility randomised trial to increase statin adherence. | journal=BMJ Open | year= 2020 | volume= 10 | issue= 2 | pages= e033070 | pmid=32051312 | doi=10.1136/bmjopen-2019-033070 | pmc=7044821 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32051312 }} </ref> | |||
* Wood<ref name="pmid33196154">{{cite journal| author=Wood FA, Howard JP, Finegold JA, Nowbar AN, Thompson DM, Arnold AD | display-authors=etal| title=N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects. | journal=N Engl J Med | year= 2020 | volume= 383 | issue= 22 | pages= 2182-2184 | pmid=33196154 | doi=10.1056/NEJMc2031173 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33196154 }} </ref> | |||
==Classification== | ==Classification== | ||
[[Statin induced myopathy]] is a spectrum of muscular problems caused by the intake of [[statins]]. [[Myopathy]] by definition | [[Statin induced myopathy]] is a spectrum of muscular problems caused by the intake of [[statins]]. [[Myopathy]] is, by definition, any pathology of the [[muscle]]. The spectrum of [[statin induced myopathy]] can be classified into: [[myalgia]], asymptomatic increase in [[creatine kinase]], [[myositis]] and [[rhabdomyolysis]]. [[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]]. [[Myositis]] is defined as the presence of symptoms of muscle weakness, tenderness or pain in the setting of an [[elevated creatine kinase]] up to ten folds the normal level. [[Rhabdomyolysis]] is a potentially lethal acute degeneration of the [[skeletal muscle]].<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><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> | ||
==Pathophysiology== | ==Pathophysiology== | ||
[[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 | [[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 due to disrupted intracellular calcium signaling and mitochondrial dysfunction secondary to the depletion of mevalonate metabolism products, particularly coenzyme Q10.<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> | ||
[[Image:Statin_induced_myopathy.png|center|Statin induced myopathy through increased intracellular calcium]] | [[Image:Statin_induced_myopathy.png|center|Statin induced myopathy through increased intracellular calcium]] | ||
==Epidemiology== | ==Epidemiology== | ||
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> | 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> | ||
==Risk Factors== | ==Risk Factors== | ||
Several risk factors predispose to [[statin induced myopathy]]. Some of the intrinsic risk factors are advanced age, genetic predisposition, [[diabetes]], [[hypertension]], [[hypothyroidism]] and renal | Several risk factors predispose to [[statin induced myopathy]]. Some of the intrinsic risk factors are advanced age, genetic predisposition, [[diabetes]], [[hypertension]], [[hypothyroidism]] and renal diseases. Other extrinsic factors play a role in [[statin induced myopathy]], including [[alcohol]] consumption, [[vitamin D deficiency]], excessive exercise, trauma or concomitant use of other drugs like [[fibrates]], mainly [[gemfibrosil]], [[protease inhibitors]] and [[macrolide|macrolide antibiotics]].<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><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><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> | ||
==Screening== | ==Screening== | ||
Screening by | Screening by measuring the [[creatine kinase]] level is not recommended by the national lipid association for [[statin induced myopathy]] unless the patient has significant predisposing factors like renal diseases, [[thyroid]] problems, [[metabolic diseases]] or pre-existing muscular diseases.<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> | ||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
[[Myalgia]] is a common complaint and should not be attributed directly to the use of [[statins]]. The patient should | [[Myalgia]] is a common complaint and should not be attributed directly to the use of [[statins]]. The patient should be evaluated for any [[thyroid]] problems, inflammatory processes, [[alcohol]] use, excessive exercise, [[electrolyte]] disturbances, side effects of other medications or [[vitamin]] deficiencies.<ref name="pmid21632911">{{cite journal| author=Fernandez G, Spatz ES, Jablecki C, Phillips PS| title=Statin myopathy: a common dilemma not reflected in clinical trials. | journal=Cleve Clin J Med | year= 2011 | volume= 78 | issue= 6 | pages= 393-403 | pmid=21632911 | doi=10.3949/ccjm.78a.10073 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21632911 }} </ref> | ||
==Diagnosis== | ==Diagnosis== | ||
==History and Symptoms== | ==History and Symptoms== | ||
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>The history of the patient | 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 time 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>The history of the patient should provide a description of the characteristics of the muscle pain as well as details about medications, history of trauma, exercise or excessive [[alcohol]] use. | ||
==Laboratory Tests== | ==Laboratory Tests== | ||
When a patient presents with symptoms suggestive of [[statin induced myopathy]], the diagnostic evaluation should include measuring the level of [[creatine kinase]]. It is useful to obtain the levels of [[TSH]], [[ESR]] and [[vitamin D]] levels as well in order to rule out other diseases that can cause [[myalgia]]. | When a patient presents with symptoms suggestive of [[statin induced myopathy]], the diagnostic evaluation should include measuring the level of [[creatine kinase]]. It is useful to obtain the levels of [[TSH]], [[ESR]] and [[vitamin D]] levels as well in order to rule out other diseases that can cause [[myalgia]].<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><ref name="pmid21632911">{{cite journal| author=Fernandez G, Spatz ES, Jablecki C, Phillips PS| title=Statin myopathy: a common dilemma not reflected in clinical trials. | journal=Cleve Clin J Med | year= 2011 | volume= 78 | issue= 6 | pages= 393-403 | pmid=21632911 | doi=10.3949/ccjm.78a.10073 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21632911 }} </ref> | ||
==Treatment== | ==Treatment== | ||
When symptoms of [[myopathy]] or elevation of [[creatine kinase]] occur in the setting of a patient taking [[statins]], the majority of patients may safely continue the treatment with [[ | When symptoms of [[myopathy]] or elevation of [[creatine kinase]] occur in the setting of a patient taking [[statins]], the majority of patients may safely continue the treatment with [[statins]]. The decision on whether the patient can discontinue or continue [[statins]] depends on two factors: the severity of the symptoms and the severity of the increase in the [[creatine kinase]] level. [[Statins]] can be safely continued when the symptoms are tolerable and the [[creatine kinase]] is elevated less than 5 times the upper limits of normal. Otherwise, if the [[creatine kinase]] level is higher than five times the upper limit of normal or if the symptoms are intolerable regardless of the level of [[creatine kinase]], statins should be stopped for a certain period of time and restarted again with lower doses or with different types of statins. The role of [[vitamin D]] and [[coenzyme Q10]] is still controversial in the management of [[statin induced myopathy]] as no studies support their use yet.<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><ref name="pmid20601617">{{cite journal| author=Wyman M, Leonard M, Morledge T| title=Coenzyme Q10: a therapy for hypertension and statin-induced myalgia? | journal=Cleve Clin J Med | year= 2010 | volume= 77 | issue= 7 | pages= 435-42 | pmid=20601617 | doi=10.3949/ccjm.77a.09078 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20601617 }} </ref><ref name="pmid21547103">{{cite journal| author=Linde R, Peng L, Desai M, Feldman D| title=The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias. | journal=Dermatoendocrinol | year= 2010 | volume= 2 | issue= 2 | pages= 77-84 | pmid=21547103 | doi=10.4161/derm.2.2.13509 | pmc=PMC3081682 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21547103 }} </ref> | ||
==References== | ==References== | ||
Latest revision as of 16:49, 11 March 2022
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby
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Overview
Statin induced myopathy is a common entity that presents as a spectrum of symptoms ranging from complete absence of symptoms to myalgia, myositis and rhabdomyolysis. Myopathy, which is a general term that describes any pathology of the muscle, occurs in around 10 to 15% of patients taking statins. The pathophysiology of statin induced myopathy is complex. As for the treatment, it is guided by the severity of the symptoms and the degree of increase in creatine kinase levels.
N-of-1 trials have examined this:
Classification
Statin induced myopathy is a spectrum of muscular problems caused by the intake of statins. Myopathy is, by definition, any pathology of the muscle. The spectrum of statin induced myopathy can be classified into: myalgia, asymptomatic increase in creatine kinase, myositis and rhabdomyolysis. 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. Myositis is defined as the presence of symptoms of muscle weakness, tenderness or pain in the setting of an elevated creatine kinase up to ten folds the normal level. Rhabdomyolysis is a potentially lethal acute degeneration of the skeletal muscle.[5][6]
Pathophysiology
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 due to disrupted intracellular calcium signaling and mitochondrial dysfunction secondary to the depletion of mevalonate metabolism products, particularly coenzyme Q10.[7]
Epidemiology
The prevalence of statin induced myopathy, described as a spectrum of clinical conditions ranging from myalgia to myositis and rhabdomyolysis, is almost 10-15%.[8]
Risk Factors
Several risk factors predispose to statin induced myopathy. Some of the intrinsic risk factors are advanced age, genetic predisposition, diabetes, hypertension, hypothyroidism and renal diseases. Other extrinsic factors play a role in statin induced myopathy, including alcohol consumption, vitamin D deficiency, excessive exercise, trauma or concomitant use of other drugs like fibrates, mainly gemfibrosil, protease inhibitors and macrolide antibiotics.[9][8][10]
Screening
Screening by measuring the creatine kinase level is not recommended by the national lipid association for statin induced myopathy unless the patient has significant predisposing factors like renal diseases, thyroid problems, metabolic diseases or pre-existing muscular diseases.[8]
Differential Diagnosis
Myalgia is a common complaint and should not be attributed directly to the use of statins. The patient should be evaluated for any thyroid problems, inflammatory processes, alcohol use, excessive exercise, electrolyte disturbances, side effects of other medications or vitamin deficiencies.[11]
Diagnosis
History and Symptoms
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 time 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.[12]The history of the patient should provide a description of the characteristics of the muscle pain as well as details about medications, history of trauma, exercise or excessive alcohol use.
Laboratory Tests
When a patient presents with symptoms suggestive of statin induced myopathy, the diagnostic evaluation should include measuring the level of creatine kinase. It is useful to obtain the levels of TSH, ESR and vitamin D levels as well in order to rule out other diseases that can cause myalgia.[8][11]
Treatment
When symptoms of myopathy or elevation of creatine kinase occur in the setting of a patient taking statins, the majority of patients may safely continue the treatment with statins. The decision on whether the patient can discontinue or continue statins depends on two factors: the severity of the symptoms and the severity of the increase in the creatine kinase level. Statins can be safely continued when the symptoms are tolerable and the creatine kinase is elevated less than 5 times the upper limits of normal. Otherwise, if the creatine kinase level is higher than five times the upper limit of normal or if the symptoms are intolerable regardless of the level of creatine kinase, statins should be stopped for a certain period of time and restarted again with lower doses or with different types of statins. The role of vitamin D and coenzyme Q10 is still controversial in the management of statin induced myopathy as no studies support their use yet.[8][13][14]
References
- ↑ Herrett E, Williamson E, Brack K, Beaumont D, Perkins A, Thayne A; et al. (2021). "Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials". BMJ. 372: n135. doi:10.1136/bmj.n135. PMC 7903384 Check
|pmc=value (help). PMID 33627334 Check|pmid=value (help). - ↑ Herrett E, Williamson E, Brack K, Perkins A, Thayne A, Shakur-Still H; et al. (2021). "The effect of statins on muscle symptoms in primary care: the StatinWISE series of 200 N-of-1 RCTs". Health Technol Assess. 25 (16): 1–62. doi:10.3310/hta25160. PMC 8020196 Check
|pmc=value (help). PMID 33709907 Check|pmid=value (help). - ↑ Tudor K, Brooks J, Howick J, Fox R, Aveyard P (2020). "Tackling statin intolerance with n-of-1 trials (TaSINI) in primary care: protocol for a feasibility randomised trial to increase statin adherence". BMJ Open. 10 (2): e033070. doi:10.1136/bmjopen-2019-033070. PMC 7044821 Check
|pmc=value (help). PMID 32051312 Check|pmid=value (help). - ↑ Wood FA, Howard JP, Finegold JA, Nowbar AN, Thompson DM, Arnold AD; et al. (2020). "N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects". N Engl J Med. 383 (22): 2182–2184. doi:10.1056/NEJMc2031173. PMID 33196154 Check
|pmid=value (help). - ↑ Thompson PD, Clarkson P, Karas RH (2003). "Statin-associated myopathy". JAMA. 289 (13): 1681–90. doi:10.1001/jama.289.13.1681. PMID 12672737.
- ↑ Radcliffe KA, Campbell WW (2008). "Statin myopathy". Curr Neurol Neurosci Rep. 8 (1): 66–72. PMID 18367041.
- ↑ Dirks AJ, Jones KM (2006). "Statin-induced apoptosis and skeletal myopathy". Am J Physiol Cell Physiol. 291 (6): C1208–12. doi:10.1152/ajpcell.00226.2006. PMID 16885396.
- ↑ 8.0 8.1 8.2 8.3 8.4 Harper CR, Jacobson TA (2010). "Evidence-based management of statin myopathy". Curr Atheroscler Rep. 12 (5): 322–30. doi:10.1007/s11883-010-0120-9. PMID 20628837.
- ↑ Venero CV, Thompson PD (2009). "Managing statin myopathy". Endocrinol Metab Clin North Am. 38 (1): 121–36. doi:10.1016/j.ecl.2008.11.002. PMID 19217515.
- ↑ Toth PP, Harper CR, Jacobson TA: Clinical characterization and molecular mechanisms of statin myopathy. Expert Rev Cardiovasc Ther 2008, 6:955–969
- ↑ 11.0 11.1 Fernandez G, Spatz ES, Jablecki C, Phillips PS (2011). "Statin myopathy: a common dilemma not reflected in clinical trials". Cleve Clin J Med. 78 (6): 393–403. doi:10.3949/ccjm.78a.10073. PMID 21632911.
- ↑ 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.
- ↑ Wyman M, Leonard M, Morledge T (2010). "Coenzyme Q10: a therapy for hypertension and statin-induced myalgia?". Cleve Clin J Med. 77 (7): 435–42. doi:10.3949/ccjm.77a.09078. PMID 20601617.
- ↑ Linde R, Peng L, Desai M, Feldman D (2010). "The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias". Dermatoendocrinol. 2 (2): 77–84. doi:10.4161/derm.2.2.13509. PMC 3081682. PMID 21547103.