LETTER TO EDITOR
Year : 2015 | Volume
: 7 | Issue : 7 | Page : 337--338
Statin intolerance and vitamin D supplementation: Sunny, but a few clouds remain...
James M Backes1, Janelle F Ruisinger1, Brian J Barnes2, Patrick M Moriarty3,
1 Department of Pharmacy Practice and Medicine, Kansas University Medical Center and the University of Kansas School of Pharmacy, Kansas, USA
2 Department of Pharmacy Practice, University of Kansas School of Pharmacy, Kansas, USA
3 Department of Medicine, Kansas University Medical Center and the University of Kansas School of Pharmacy, Kansas, USA
James M Backes
Department of Pharmacy Practice and Medicine, Kansas University Medical Center and the University of Kansas School of Pharmacy, Kansas
|How to cite this article:|
Backes JM, Ruisinger JF, Barnes BJ, Moriarty PM. Statin intolerance and vitamin D supplementation: Sunny, but a few clouds remain... North Am J Med Sci 2015;7:337-338
|How to cite this URL:|
Backes JM, Ruisinger JF, Barnes BJ, Moriarty PM. Statin intolerance and vitamin D supplementation: Sunny, but a few clouds remain... North Am J Med Sci [serial online] 2015 [cited 2021 Oct 25 ];7:337-338
Available from: https://www.najms.org/text.asp?2015/7/7/337/161255
We read with interest the article by Khayznikov et al., regarding the resolution of statin intolerance with vitamin D repletion.  We too have tried this strategy among a similarly statin intolerant population (median - three previous statins) and believe vitamin D supplementation plays a role in treating certain individuals. Our results demonstrated that vitamin D repletion to >30 ng/ml, allowed 53% (18/34) of the intolerant patients to utilize some form of alternative or daily statin dosing or a higher dose among those receiving a statin but experiencing tolerable symptoms, for at least four months (mean follow up 8.5 + 4.4 months). Our findings are encouraging but well below the 88-95% statin tolerability rates reported in the present study.
Directly comparing study populations and results is not feasible; however, one potential explanation for response differences may be the vitamin D level achieved. For instance, the vitamin D levels among those tolerating the statin rechallenge in our group was 44 ng/ml compared to 53-55 ng/ml in the current report, suggesting that perhaps our vitamin D repletion was incomplete, despite each group falling within the range suggested by the Endocrine Society. 
Another factor that we believe played a prominent role in the resolution of myalgic symptoms in the current study was the predominant utilization of rosuvastatin. The authors recognize that rosuvastatin is less frequently associated with myotoxicity; however, this should not be minimized. In fact, the same research center performed a similar study, and determined that the vast majority of previously statin intolerant subjects reported no adverse effects when rechallenged with rosuvastatin 5-10 mg daily. 
Lastly, we agree with the authors that an optimal study evaluating statin intolerance would be blinded and placebo-controlled, given the subjective nature of most myotoxicity. In fact, this design was recently utilized to assess various lipid-altering agents, including the investigational proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, among subjects unable to tolerate two or more different statins because of unexplained muscle-related symptoms.  After successful completion of a four-week single-blind placebo run-in period, subjects were randomized in a double-blind manner to a PCSK9 injection Q two weeks + oral placebo daily, ezetimibe 10 mg daily + placebo injection Q two weeks, or atorvastatin 20 mg daily + placebo injection Q two weeks, for 24 weeks. Such a study design provided novel, insightful, and revealing findings with regard to statin intolerance. For example, the trial demonstrated that 6.9% of subjects were excluded from randomization due to muscle-related adverse events during the placebo run-in period. Further, 75% of the previously intolerant patients tolerated the atorvastatin 20 mg daily for the duration of the 24-week study period. Such results strongly highlight the subjectivity of statin intolerance and the major influence of a placebo effect in many patients.
Statin intolerance, especially among patients with previous sensitivity to multiple agents, is a complex and poorly understood issue that remains a clinical challenge. In the present study, vitamin D repletion likely improved muscle function and resolved symptoms in some patients. However, the vitamin D supplementation may have also provided a placebo effect, while the utilization of rosuvastatin further enhanced response.
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Conflicts of interest
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|1||Khayznikov M, Hemachrandra K, Pandit R, Kumar A, Wang P, Glueck CJ. Statin Intolerance Because of Myalgia, Myositis, Myopathy, or Myonecrosis Can in Most Cases be Safely Resolved by Vitamin D Supplementation. N Am J Med Sci 2015;7:86-93.|
|2||Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality - A review of recent evidence. Autoimmun Rev 2013;12:976-89.|
|3||Glueck CJ, Aregawi D, Agloria M, Khalil Q, Winiarska M, Munjal J, et al. Rosuvastatin 5 and 10 mg/d: A pilot study of the effects in hypercholesterolemic adults unable to tolerate other statins and reach LDL cholesterol goals with nonstatin lipid-lowering therapies. Clin Ther 2006;28:933-42.|
|4||Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron J, Zieve FJ, et al. ODYSSEY ALTERNATIVE: Efficacy and Safety of the Proprotein Convertase Subtilisin/kexin Type 9 Monoclonal Antibody, Alirocumab, versus Ezetimibe, in Patients with Statin Intolerance as Defined by a Placebo Run-in and Statin Rechallenge Arm. American Heart Association Scientific Sessions 2014; 2014 November 17 th , 2014.|