What is the incidence of myalgia associated with HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor, also known as statin, medications?

From the Guidelines

Statin medications are associated with myalgia in approximately 5-10% of patients, and a thorough assessment of symptoms is recommended to determine the likelihood of statin-associated muscle symptoms (SAMS) 1. When considering the incidence of myalgia in patients taking statin medications, it is essential to evaluate the symptoms carefully and consider alternative causes.

• The frequency of myalgias (CK Normal) is reported to be infrequent (1% to 5%) in RCTs, but more frequent (5% to 10%) in observational studies and clinical settings 1.
• Predisposing factors for SAMS include age, female sex, low body mass index, high-risk medications, comorbidities, Asian ancestry, excess alcohol, high levels of physical activity, and trauma 1.
• A systematic approach to evaluating SASEs is crucial to encourage adherence to evidence-based statin treatment, and avoiding complete discontinuation of statin treatment is strongly recommended unless absolutely necessary 1.
• The approach to SASEs should include discontinuation of statin therapy until resolution of symptoms and subsequent rechallenge to verify recurrence of muscle-related symptoms, and most patients who experience SASEs are able to tolerate statin rechallenge with an alternative statin or dose reduction with the same statin 1. Key considerations for managing myalgia in patients taking statins include:
• Temporary discontinuation of the statin for 2-4 weeks to confirm the association
• Restarting the same statin at a lower dose or switching to a different statin
• Using an alternate-day dosing regimen
• Adding CoQ10 supplementation (100-200 mg daily) may help some patients, though evidence is mixed 1. It is crucial to advise patients to report muscle pain promptly, especially if severe or accompanied by weakness or dark urine, as these could indicate more serious muscle damage (rhabdomyolysis) 1.

From the FDA Drug Label

The most common adverse reactions that led to discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0. 1%). Myglia 3.2 3.7 The incidence of myopathy (defined as unexplained muscle weakness, pain, or tenderness accompanied by CK increases greater than 10xULN) was approximately 0.03%, 0.08%, and 0. 61% for the simvastatin 20 mg, 40 mg, and 80 mg daily groups, respectively. Myalgia Incidence:

• The incidence of myalgia in patients taking simvastatin was 3.7% in the simvastatin group, as shown in Table 1.
• Myalgia was also one of the most common adverse reactions that led to discontinuation of simvastatin, occurring in 0.1% of patients. 2

From the Research

Statin Medications and Myalgia Incidence

• Statin-associated myalgia is a common adverse effect of statin therapy, occurring in up to 10% of patients prescribed statin therapy 3.
• The prevalence of myalgia among statin users can be a significant barrier to effective treatment of hyperlipidemia, with conventional clinical risk factors for myositis not appearing to be predictive of statin-associated myalgia 3.
• Strategies to preserve the use of statins in patients with previous muscular adverse effects include alternative statin dosing, co-enzyme Q10 supplementation, vitamin D supplementation, conversion to red yeast rice therapy, and conversion to a different statin 4.

Risk Factors and Mechanisms

• The mechanisms underlying statin myalgia are not clearly understood, but may involve cellular stress, apoptosis, cell senescence, and DNA repair, as well as activation of pro-inflammatory immune response and protein catabolism 5.
• Vitamin D deficiency may also play a role in statin-induced myalgia, with supplementation resulting in improved statin tolerance and reduced myositis-myalgia in some patients 6.
• Genetic predisposition may also contribute to the development of statin myalgia, with certain single nucleotide polymorphisms associated with increased risk of statin-induced myopathies 5.

Treatment and Management

• Coenzyme Q10 supplementation has been studied as a potential treatment for statin-associated myalgia, but a systematic review and meta-analysis found no significant benefit in improving myalgia symptoms or adherence to statin therapy 7.
• Vitamin D supplementation, on the other hand, has been shown to improve statin tolerance and reduce myositis-myalgia in patients with vitamin D deficiency 6.
• Alternative statin dosing and conversion to a different statin may also be effective strategies for managing statin-associated myalgia, with some patients able to tolerate alternative statins or dosing regimens 3, 4.