Is there an association between peripheral neuropathy and the use of statins (HMG-CoA reductase inhibitors)?

From the Guidelines

Peripheral neuropathy is an uncommon but recognized side effect of statin medications, and if a patient develops symptoms, the medication should be temporarily discontinued to determine if symptoms improve. This recommendation is based on the available evidence, including a study published in the Journal of the American College of Cardiology 1, which suggests a rare association of statin use with polyneuropathy, although this has not been found in large blinded randomized controlled trials.

For patients who experience statin-induced peripheral neuropathy, options include:

• Trying a lower dose of the same statin
• Switching to a different statin, particularly pravastatin or fluvastatin, which are more hydrophilic and less likely to cross the blood-nerve barrier
• Considering non-statin alternatives like ezetimibe or PCSK9 inhibitors The mechanism behind statin-induced neuropathy likely involves inhibition of cholesterol synthesis in nerve cells, disrupting myelin formation and nerve function, as suggested by studies on the use and safety of statins 1.

Coenzyme Q10 supplementation (100-200 mg daily) may help mitigate neuropathic symptoms in some patients continuing statin therapy, as statins reduce CoQ10 levels which are important for mitochondrial function in nerve cells. Regular monitoring for neuropathic symptoms is recommended for all patients on statins, especially those with pre-existing risk factors like diabetes, vitamin B12 deficiency, or alcohol use disorder, as highlighted in a study on painful diabetic peripheral neuropathy 1. Most cases of statin-induced neuropathy resolve within weeks to months after discontinuation, though some may persist longer.

From the FDA Drug Label

Nervous System Disorders: peripheral neuropathy, rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, and confusion) associated with the use of all statins. Nervous System: dysfunction of certain cranial nerves (including alteration of taste, impairment of extraocular movement, facial paresis), peripheral nerve palsy. Rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use.

Peripheral Neuropathy and Statins:

• Peripheral neuropathy has been reported as a rare postmarketing adverse reaction in patients taking statins, including rosuvastatin 2 and pravastatin 3.
• The exact mechanism of statin-induced peripheral neuropathy is not well understood, and the evidence is largely based on case reports and postmarketing surveillance.
• Key Points:
  • Peripheral neuropathy is a rare adverse reaction associated with statin use.
  • The risk of peripheral neuropathy with statins is not well established, and more research is needed to fully understand this potential association.
  • Patients taking statins should be monitored for signs and symptoms of peripheral neuropathy, such as numbness, tingling, or weakness in the hands and feet.

From the Research

Peripheral Neuropathy and Statins

• The relationship between statin use and peripheral neuropathy has been investigated in several studies, with conflicting results 4, 5, 6, 7.
• A study published in 2020 found that statins combined with niacin may reduce the risk of peripheral neuropathy, suggesting that the controversial association of statins with neuropathy may be due to the fact that previous studies have not included the use of niacin and its potential neuroprotective effects 4.
• A meta-analysis published in 2021 found no significant association between statin exposure and peripheral neuropathy risk, although the quality of the evidence included in the study was low 5.
• Another study published in 2013 found a modest association between peripheral neuropathy and statin use, with the prevalence of peripheral neuropathy being significantly higher among those who used statins compared to those who did not 6.
• A study published in 2019 found an increased risk of peripheral neuropathy with long-term statin use, with the severity of the polyneuropathy increasing with the duration of the treatment 7.

Statin Types and Peripheral Neuropathy

• The association between statins and peripheral neuropathy may vary depending on the type of statin used, with lipophilic statins such as atorvastatin and fluvastatin having a stronger association with neuropathy than hydrophilic statins such as rosuvastatin and pravastatin 4.
• Pitavastatin was found to be the only exception, with no reports of an association with neuropathy 4.

Prevention and Treatment of Peripheral Neuropathy

• While statins may be associated with an increased risk of peripheral neuropathy, other factors such as poor glycemic control, vitamin B12 deficiency, elevated blood pressure, and obesity also play a role in the development of neuropathy 8.
• Treatment options for peripheral neuropathy include medications such as duloxetine, gabapentin, and pregabalin, as well as nondrug therapies such as exercise and neuromodulation 8.