Abstract
Background
Statins are the treatment of choice for dyslipidemia, primarily lowering elevated
LDL-C levels and reducing the occurrence of major cardiovascular events. In June 2011,
the Food and Drug Administration issued a warning regarding the use of high-dose simvastatin
80 mg and its risk of myopathy.
Objective
The incidence of myalgia, myopathy, and rhabdomyolysis was analyzed in a veteran population
prescribed simvastatin 80 mg. Risk factors for myalgia were examined and compared
with the results of recently published studies.
Methods
This was a retrospective medical record review of 450 patients who were prescribed
simvastatin 80 mg at the Veterans Affairs Western New York Healthcare System between
August 1, 2006, and July 31, 2011. Records were examined for evidence of myalgia,
myopathy (incipient or definite), and rhabdomyolysis. Variables that may have contributed
to the development of myalgia were also collected and analyzed.
Results
Myalgia was reported by 50 patients (11.1%), whereas rhabdomyolysis developed in 1
patient (0.22%). No patient fit the criteria for myopathy (incipient or definite).
Myalgia was statistically more likely to occur in younger patients, patients with
a history of myalgia, and patients with low vitamin D levels. The mean (SD) vitamin
D level in patients experiencing myalgia was 26.2 (12.9) versus 36.3 (11.8) ng/mL.
The 25-hydroxyvitamin D level in those who reported myalgia was approximately 10 ng/mL
lower compared with those who tolerated simvastatin 80 mg (P = 0.0003). There was no statistically significant association between length of therapy
and development of myalgia.
Conclusion
A lower incidence of adverse muscle events with high-dose simvastatin 80 mg was found
in patients with higher vitamin D levels, suggesting that correction of 25-hydroxyvitamin
D levels before statin therapy initiation may mitigate one risk factor in the development
of statin-related myalgia. Vitamin D insufficiency appears to be a risk factor for
the development of myalgia.
Key words
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References
The Use of Medicines in the United States: Review of 2010. http://www.imshealth.com/imshealth/Global/Content/IMSInstitute/Documents/IHII_UseOfMed_report .pdf. 2011; http://www.imshealth.com/imshealth/Global/Content/IMS/Institute/Documents/IHII_UseOfMed_report .pdf. Accessed August 1, 2011.
FDA: Limit Use of 80 mg Simvastatin. United States Food and Drug Administration. Consumer Updates. 2011. http://www.fda.gov/forconsumers/consumerupdates/ucm257884.htm. Accessed June 8, 2011.
- Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial.Lancet. 2010; 376: 1658-1669
Simvastatin. Hudson, OH: Lexi-Comp Inc; 2012.
- ACC/AHA/NHLBI clinical advisory on the use and safety of statins.Stroke. 2002; 33: 2337-2341
- Selection of variables in multiple regression, part I: a review and evaluation.Int Stat Rev. 1978; 46: 1-19
- Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.PLoS One. 2011; 6: e28124
FDA Drug Safety Communication: new restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. http://www.fda.gov/drugs/drugsafety/ucm256581.htm. Accessed January 26, 2014.
- Statin myopathy: incidence, risk factors, and pathophysiology.Curr Atheroscler Rep. 2007; 9: 389-396
- The relationship of vitamin D deficiency to statin myopathy.Atherosclerosis. 2011; 215: 23-29
- Symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent vitamin D deficiency leading to statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle.Med Hypotheses. 2011; 77: 658-661
- Low serum 25 (OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients.Transl Res. 2009; 153: 11-16
- Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor?.J Am Coll Cardiol. 2008; 52: 1949-1956
- Myopathy during statin therapy in the daily practice of an outpatient cardiology clinic: prevalence, predictors and relation with vitamin D.Curr Med Res Opin. 2012; 28: 1247-1252
- Statin myopathy: a common dilemma not reflected in clinical trials.Cleve Clin J Med. 2011; 78: 393-403
- Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force.Am J Cardiol. 2006; 97: 89C-94C
Article info
Publication history
Published online: April 14, 2014
Accepted:
February 27,
2014
Identification
Copyright
Published by Elsevier Inc.
