What is the relationship between statin (HMG-CoA reductase inhibitor) use and the development of polyneuropathy?

From the Guidelines

Statin-induced polyneuropathy is a rare but recognized adverse effect of statin medications used to lower cholesterol, and if a patient develops symptoms of polyneuropathy while on statin therapy, the medication should be discontinued immediately to prevent further nerve damage, as suggested by the most recent evidence 1.

Key Points

• The relationship between statin use and the development of polyneuropathy is rare, but it has been suggested by some observational studies 1.
• The mechanism behind statin-induced neuropathy likely involves inhibition of cholesterol synthesis in nerve cell membranes and mitochondrial dysfunction.
• Symptoms of statin-induced polyneuropathy typically include numbness, tingling, burning pain, muscle weakness, and reduced reflexes, usually beginning in the feet and hands with a "stocking-glove" distribution pattern.
• Diagnosis involves clinical evaluation, nerve conduction studies, and ruling out other causes of neuropathy such as diabetes.
• After discontinuing the statin, symptoms may improve over weeks to months, though complete recovery is not guaranteed.
• Alternative cholesterol management strategies should be considered, including other lipid-lowering medications like ezetimibe (Zetia), PCSK9 inhibitors, or bile acid sequestrants.
• Patients with pre-existing neuropathy, diabetes, or vitamin deficiencies may be at higher risk for developing this complication.

Management

• If a patient develops symptoms of polyneuropathy while on statin therapy, the medication should be discontinued immediately to prevent further nerve damage.
• A thorough evaluation of musculoskeletal symptoms and predisposing factors for statin-associated side effects should be performed before initiating statin therapy.
• CK and transaminase levels should not be routinely measured, given the unlikely impact on clinical outcomes and the lack of established cost-effectiveness 1.
• In patients at increased ASCVD risk with severe statin-associated side effects or recurrent SAMS, nonstatin therapy should be considered when there is net clinical benefit 1.

From the Research

Relationship Between Statin Use and Polyneuropathy

• The relationship between statin use and the development of polyneuropathy has been investigated in several studies 2, 3, 4, 5, 6.
• Some studies have reported cases of peripheral polyneuropathy attributed to statin use, with symptoms including sensory impairment, decreased muscle strength, and suppression of osteotendinous reflexes 2, 6.
• Epidemiological studies and clinical trials have shown that the risk of polyneuropathy associated with statin use is rare, affecting approximately one patient in 10,000 treated for one year 2.
• A study found that 66% of patients taking atorvastatin or rosuvastatin for hypercholesterolemia developed polyneuropathy, with the severity increasing with the duration of treatment 3.
• However, a meta-analysis of observational studies found no significant association between statin exposure and peripheral neuropathy risk (RR 1.26,95% CI 0.92-1.74) 4.
• Another study found that statin use does not increase the risk of chronic polyneuropathy, and may even decrease the odds of polyneuropathy with increased exposure duration 5.

Risk Factors and Clinical Implications

• Renal failure and diabetes may increase the risk of polyneuropathy associated with statin use 2.
• Early detection of peripheral neuropathy and changing hypercholesterolemia treatment may prevent permanent nerve damage 3.
• The assessment of neurological symptoms, such as tingling, numbness, and pain, may be useful in the follow-up of patients on long-term statin treatment 3.
• Statin withdrawal often leads to clinical improvement in patients with polyneuropathy 2.