Journal of Clinical Pharmacy and Therapeutics

Volume 46, Issue 4 pp. 1046-1054

ORIGINAL ARTICLE

The association between statins exposure and peripheral neuropathy risk: A meta-analysis

Miao Wang MS,

Miao Wang MS

orcid.org/0000-0002-5994-1978

Department of Endocrinology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

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Muqin Li MS,

Muqin Li MS

Department of Endocrinology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

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Ying Xie MD,

Corresponding Author

Ying Xie MD

[email protected]

Department of Endocrinology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

Correspondence

Ying Xie, Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.

Email: [email protected]

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Miao Wang MS,

Miao Wang MS

orcid.org/0000-0002-5994-1978

Department of Endocrinology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

Search for more papers by this author

Muqin Li MS,

Muqin Li MS

Department of Endocrinology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

Search for more papers by this author

Ying Xie MD,

Corresponding Author

Ying Xie MD

[email protected]

Department of Endocrinology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

Correspondence

Ying Xie, Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.

Email: [email protected]

Search for more papers by this author

First published: 25 February 2021

https://doi.org/10.1111/jcpt.13393

Citations: 6

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Abstract

What is known and objective

Statins are widely used lipid-lowering drugs and play an important role in the treatment of many cardiovascular diseases. With the increase in the scope of use and the number of users, peripheral neuropathy caused by statins has been frequently reported. There are no randomized controlled trials comparing the relationship between statins and the risk of peripheral neuropathy. Therefore, we systematically reviewed and meta-analysed observational studies evaluating the impact of statins on the risk of peripheral neuropathy.

Methods

PubMed, Embase, the Cochrane Library databases and Web of Science were used to search the effects of statins on polyneuropathy from inception to 3 December 2020. We included studies that met the following criteria: (i) A randomized controlled trial, prospective or retrospective cohort study examining the relationship between statins and peripheral neuropathy (PN). Exclusion criteria included the following: Reviews and research related to other diseases or subjects; and studies without data on the prevalence of PN were excluded. Newcastle-Ottawa scale (NOS) was used for quality assessment of included studies. Meta-analysis was used to estimate the risk of disease. We conducted a subgroup analysis of duration of follow-up, adjusted (adjusted RR vs. unadjusted RR), sample size, study design and region.

Results and discussion

A total of 9 independent studies assessing 150 556 patients were included in this analysis. In this meta-analysis, we found that there was a nonsignificant increase of PN with statins exposure (RR 1.26, 95% CI (0.92-1.74)). Our results revealed that there was no significant association between statins exposure and peripheral neuropathy risk.

What is new and conclusion

Statins exposure does not influence the risk of developing peripheral neuropathy. The quality of the evidence included in this study is low, but it can provide useful information for clinicians.

CONFLICT OF INTEREST

The authors declare no competing or financial interests in this work.

Open Research

DATA AVAILABILITY STATEMENT

Data supporting the results of this study are available upon reasonable request of the corresponding author.

REFERENCES

1Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017; 3: 17002.
10.1038/nrdp.2017.2
PubMed Web of Science® Google Scholar
2Hanewinckel R, van Oijen M, Ikram MA, van Doorn PA. The epidemiology and risk factors of chronic polyneuropathy. Eur J Epidemiol. 2016; 31: 5-20.
10.1007/s10654-015-0094-6
PubMed Web of Science® Google Scholar
3Mathis S, Soulages A, Vallat J-M, Le Masson G. Epidemics and outbreaks of peripheral nervous system disorders: II. Toxic and nutritional causes. J Neurol. 2020;https://doi.org/10.1007/s00415-020-10216-8
Web of Science® Google Scholar
4Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003; 349(16): 1543-1554.
10.1056/NEJMra023009
CAS PubMed Web of Science® Google Scholar
5Bennett BK, Park SB, Lin C-Y, et al. Impact of oxaliplatin-induced neuropathy: a patient perspective. Support Care Cancer. 2012; 20: 2959-2967.
10.1007/s00520-012-1428-5
PubMed Web of Science® Google Scholar
6Cocito D, Paolasso I, Pazzaglia C, et al. Pain affects the quality of life of neuropathic patients. Neurol Sci. 2006; 27: 155-160.
10.1007/s10072-006-0660-5
CAS PubMed Web of Science® Google Scholar
7Chronic symmetric symptomatic polyneuropathy in the elderly: a field screening investigation in two Italian regions. I. Prevalence and general characteristics of the sample. Italian General Practitioner Study Group (IGPSG). Neurology. 1995; 45: 1832-1836.
10.1212/WNL.45.10.1832
CAS PubMed Web of Science® Google Scholar
8Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet. 2007; 370: 1829-1839.
10.1016/S0140-6736(07)61778-4
CAS PubMed Web of Science® Google Scholar
9De Langen JJ, Van Puijenbroek EP. HMG-CoA-reductase inhibitors and neuropathy: reports to the Netherlands Pharmacovigilance Centre. Neth J Med. 2006; 64(9): 334-338.
CAS PubMed Web of Science® Google Scholar
10Ahmad S. Lovastatin and peripheral neuropathy. Am Heart J. 1995; 130: 1321.
10.1016/0002-8703(95)90185-X
CAS PubMed Web of Science® Google Scholar
11Jacobs MB. HMG-CoA reductase inhibitor therapy and peripheral neuropathy. Ann Intern Med. 1994; 120: 970.
10.7326/0003-4819-120-11-199406010-00013
CAS PubMed Web of Science® Google Scholar
12Jeppesen U, Gaist D, Smith T, Sindrup SH. Statins and peripheral neuropathy. Eur J Clin Pharmacol. 1999; 54: 835-838.
10.1007/s002280050562
CAS PubMed Web of Science® Google Scholar
13Lo YL, Leoh TH, Loh LM, Tan CE. Statin therapy and small fibre neuropathy: a serial electrophysiological study. J Neurol Sci. 2003; 208: 105-108.
10.1016/S0022-510X(02)00396-9
CAS PubMed Web of Science® Google Scholar
14Phan T, McLeod JG, Pollard JD, et al. Peripheral neuropathy associated with simvastatin. J Neurol Neurosurg Psychiatr. 1995; 58(5): 625-628.
10.1136/jnnp.58.5.625
CAS PubMed Web of Science® Google Scholar
15 Ahn. Neuromuscular complications of statins. Phys Med Rehabil Clin N Am. 2008; 19.
10.1016/j.pmr.2007.10.002
PubMed Web of Science® Google Scholar
16Bays H. Statin safety: an overview and assessment of the data–2005. Am J Cardiol. 2006; 97: S6-S26.
10.1016/j.amjcard.2005.12.006
CAS PubMed Web of Science® Google Scholar
17Davidson MH, Clark JA, Glass LM, Kanumalla A. Statin safety: an appraisal from the adverse event reporting system. Am J Cardiol. 2006; 97(8): S32-S43.
10.1016/j.amjcard.2005.12.008
Web of Science® Google Scholar
18Edwards IR, Star K, Kiuru A. Statins, neuromuscular degenerative disease and an amyotrophic lateral sclerosis-like syndrome: an analysis of individual case safety reports from vigibase. Drug Saf. 2007; 30: 515-525.
10.2165/00002018-200730060-00005
PubMed Web of Science® Google Scholar
19Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006; 97(8): S52-S60.
10.1016/j.amjcard.2005.12.010
Web of Science® Google Scholar
20Backes JM, Howard PA. Association of HMG-CoA reductase inhibitors with neuropathy. Ann Pharmacother. 2003; 37(2): 274-278.
10.1177/106002800303700220
CAS PubMed Web of Science® Google Scholar
21Corrao Z, Bertù B. Lipid lowering drugs prescription and the risk of peripheral neuropathy: an exploratory case-control study using automated databases. J Epidemiol Community Health. 2004; 58: 1047-1051.
10.1136/jech.2003.013409
PubMed Web of Science® Google Scholar
22Gaist D, Jeppesen U, Andersen M, Rodriguez LG, Hallas J, Sindrup SH. Statins and risk of polyneuropathy: a case-control study. Neurology. 2002; 58(9): 1333-1337.
10.1212/WNL.58.9.1333
CAS PubMed Web of Science® Google Scholar
23Gaist D, Rodríguez LA, Huerta C, Hallas J, Sindrup SH. Are users of lipid-lowering drugs at increased risk of peripheral neuropathy?. European J Clin Pharmacol. 2001; 56(12): 931-933.
10.1007/s002280000248
CAS PubMed Web of Science® Google Scholar
24Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015; 36: 1012-1022.
10.1093/eurheartj/ehv043
CAS PubMed Web of Science® Google Scholar
25Gurha N, Rehan HS, Yadav M, Gupta LK. Association of statin induced reduction in serum coenzyme Q10 level and conduction deficits in motor and sensory nerves: An observational cross-sectional study. Clin Neurol Neurosurg. 2020; 196: 106046.
10.1016/j.clineuro.2020.106046
PubMed Web of Science® Google Scholar
26Michikawa M, Yanagisawa K. Inhibition of cholesterol production but not of nonsterol isoprenoid products induces neuronal cell death. J Neurochem. 1999; 72: 2278-2285.
10.1046/j.1471-4159.1999.0722278.x
CAS PubMed Web of Science® Google Scholar
27Chu LW, Chen JY, Yu KL, et al. Neuroprotective and anti-inflammatory activities of atorvastatin in a rat chronic constriction injury model. Int J Immunopathol Pharmacol. 2012; 25: 219-230.
10.1177/039463201202500124
CAS PubMed Web of Science® Google Scholar
28Xavier AM, Serafim K, Higashi DT, et al. Simvastatin improves morphological and functional recovery of sciatic nerve injury in Wistar rats. Injury. 2012; 43: 284-289.
10.1016/j.injury.2011.05.036
CAS PubMed Web of Science® Google Scholar
29Lo CK, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol. 2014; 14(1): 1-5.
10.1186/1471-2288-14-45
PubMed Web of Science® Google Scholar
30Holmberg E, Nordstrom T, Gross M, et al. Simvastatin promotes neurite outgrowth in the presence of inhibitory molecules found in central nervous system injury. J Neurotrauma. 2006; 23: 1366-1378.
10.1089/neu.2006.23.1366
PubMed Web of Science® Google Scholar
31Klopfleisch S, Merkler D, Schmitz M, et al. Negative impact of statins on oligodendrocytes and myelin formation in vitro and in vivo. J Neurosci. 2008; 28: 13609-13614.
10.1523/JNEUROSCI.2765-08.2008
CAS PubMed Web of Science® Google Scholar
32Park D-S, So H-S, Lee J-H, et al. Simvastatin treatment induces morphology alterations and apoptosis in murine cochlear neuronal cells. Acta Oto-Laryngol. 2009; 129: 166-174.
10.1080/00016480802163358
CAS PubMed Web of Science® Google Scholar
33Tierney T, Beckles C. (2013) Association of statin use with peripheral neuropathy in the U.S. population 40 years of age or older. 5: 207-215.
Google Scholar
34Corrao G. Lipid lowering drugs prescription and the risk of peripheral neuropathy: an exploratory case-control study using automated databases. J Epidemiol Commun Health. 2004; 58(12): 1047-1051.
10.1136/jech.2003.013409
PubMed Web of Science® Google Scholar
35Jacobs MB. HMG-CoA reductase inhibitor therapy and peripheral neuropathy. Ann Int Med. 1994; 120(11): 970.
Google Scholar
36Chong PH, Boskovich A, Stevkovic N, Bartt RE. Statin-associated peripheral neuropathy: review of the literature. Pharmacotherapy. 2004; 24: 1194-1203.
10.1592/phco.24.13.1194.38084
CAS PubMed Web of Science® Google Scholar
37Özdemir C, Tıkız T. Peripheral polyneuropathy in patients receiving long-term statin therapy. Turk Kardiyol Dern Ars. 2019; 47: 554-563.
PubMed Web of Science® Google Scholar
38Emad M, Arjmand H, Farpour HR, Kardeh B. Lipid-lowering drugs (statins) and peripheral neuropathy. Electronic Physician. 2018; 10(3): 6527-6533.
10.19082/6527
PubMed Google Scholar

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The association between statins exposure and peripheral neuropathy risk: A meta-analysis

Abstract

What is known and objective

Methods

Results and discussion

What is new and conclusion

CONFLICT OF INTEREST

Open Research

DATA AVAILABILITY STATEMENT

REFERENCES

Citing Literature

References

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The association between statins exposure and peripheral neuropathy risk: A meta-analysis

Abstract

What is known and objective

Methods

Results and discussion

What is new and conclusion

CONFLICT OF INTEREST

Open Research

DATA AVAILABILITY STATEMENT

REFERENCES

Citing Literature

References

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