What is the relationship between HMG-CoA reductase inhibitors (statins) and myopathy (muscle weakness)?

From the Guidelines

Statin-induced muscle weakness should be managed by temporarily stopping the statin, evaluating for other causes of muscle symptoms, and considering alternative statin regimens or nonstatin therapies, as recommended by the 2022 ACC expert consensus decision pathway 1. When experiencing muscle weakness while taking a statin medication, it is essential to contact your healthcare provider rather than stopping the medication abruptly. The approach to managing statin-associated muscle symptoms (SAMS) includes discontinuation of statin therapy until resolution of symptoms and subsequent rechallenge to verify recurrence of muscle-related symptoms 1. Some patients may be able to tolerate a lower statin intensity, an alternative statin, or alternative dosing strategies, such as alternate-day dosing with a long half-life statin or de-escalation dosing 1. Nonstatin therapies, such as ezetimibe or PCSK9 inhibitors, may be considered as first-line therapy in patients with clinical ASCVD and possible SASEs who have failed at least 2 statins, including a trial of 1 attempt at the lowest approved dose or using alternative statin dosing 1. Key considerations in managing statin-induced muscle weakness include:

• Evaluating for other causes of muscle symptoms, such as hypothyroidism, vitamin D deficiency, or recent exercise 1
• Assessing drug-drug interactions that can increase systemic statin exposure 1
• Monitoring creatine kinase levels to assess muscle damage, although routine measurements are not recommended 1
• Considering supplements like coenzyme Q10, although evidence for their effectiveness is mixed 1. It is crucial to balance the cardiovascular benefits of statins against the potential side effects and to work with patients to understand the nature and severity of symptoms, as the nocebo effect may contribute to the perceived side effects 1.

From the FDA Drug Label

Rosuvastatin may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis. The myopathy risk is greater in patients taking rosuvastatin 40 mg daily compared with lower rosuvastatin dosages. Discontinue rosuvastatin if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if rosuvastatin is discontinued.

Statin and Muscle Weakness:

• Myopathy risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher rosuvastatin dosage.
• Symptoms of myopathy include muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK).
• Treatment involves discontinuing rosuvastatin if myopathy is suspected or diagnosed.
• Prevention involves informing patients of the risk of myopathy and rhabdomyolysis when starting or increasing the rosuvastatin dosage, and advising patients to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever 2.

From the Research

Statin and Muscle Weakness

• Statin-associated muscle symptoms are reported by 10% to 29% of patients in clinical practice and are a major determinant of statin nonadherence, discontinuation, and switching 3.
• The prevalence of statin-associated muscle symptoms (SAMS) is estimated to be about 10% (range 5% to 25%), and the prevalence of pharmacological SAMS is estimated to be about 1-2% (range 0.5% to 4%) 4.
• Statin therapy can cause a small excess of mostly mild muscle pain, but most (>90%) of all reports of muscle symptoms by participants allocated statin therapy are not due to the statin 5.
• Individuals with elevated CK levels, with or without muscle discomfort or weakness, may have statin-associated myotoxicity, and rare patients have statin-associated autoimmune myopathy, a disease characterized by proximal muscle weakness, elevated CK levels, and autoantibodies recognizing hydroxy-methyl-glutaryl coenzyme A reductase 6.

Management of Statin-Associated Muscle Symptoms

• Treatment strategies for SAMS include optimizing lifestyle interventions, modulating risk factors that may contribute to muscle symptoms, optimizing statin tolerability by dose reduction, decreased dosing frequency, or use of an alternate statin with more favorable pharmacokinetic properties, and use of non-statins 4.
• Many patients who experience SAMS can tolerate some degree of statin therapy and non-statin medications are available as adjunctive or alternative treatments 7.
• Providers most often suggest switching to another statin, stopping the statin, continuing the statin with further monitoring of muscle symptoms, reducing the statin dose, or getting a blood test for signs of muscle damage for patients with muscle-related symptoms while on a statin 3.

Clinical Perspective

• SAMS need to be addressed in accordance with patients' preferences and experiences, and patient-centered clinical and communication strategies can help mitigate SAMS and improve medication adherence and outcomes among statin users 4.
• The focus of management should be on sustainable lipoprotein goal achievement, which is important for cardiovascular risk reduction 4.
• A thorough clinician-patient discussion and shared decision-making can help identify a treatment plan to achieve therapeutic objectives and reduce the risk of atherosclerotic cardiovascular disease 7.