What's the next step for a patient with a family history of atherosclerosis before 50 years, currently on rosuvastatin (rosuvastatin) 40 mg and ezetimibe (ezetimibe) 10 mg, experiencing muscle fatigue after intense workouts with an LDL (low-density lipoprotein) level of 90 mg/dl?

Management of Muscle Fatigue in a Patient on High-Intensity Statin Therapy

For a patient with family history of atherosclerosis before 50 years, currently on rosuvastatin 40 mg and ezetimibe 10 mg who is experiencing muscle fatigue after intense workouts with an LDL of 90 mg/dl, the next step should be to temporarily discontinue rosuvastatin to establish if there is a causal relationship between the statin and muscle symptoms.

Evaluation of Muscle Symptoms

• First, evaluate the patient for other conditions that might increase risk for muscle symptoms, including hypothyroidism, reduced renal or hepatic function, rheumatologic disorders, steroid myopathy, vitamin D deficiency, or primary muscle diseases 1
• Measure creatine kinase (CK) levels to assess for muscle damage 1
• Consider timing of symptoms in relation to exercise - statin-related myopathy typically persists beyond normal post-exercise recovery period 1

Management Algorithm

1. Temporarily discontinue rosuvastatin to determine if there is a causal relationship between the statin and muscle symptoms 1
2. If muscle symptoms resolve after discontinuation:
   • Restart with a lower dose of rosuvastatin (e.g., 20 mg) or switch to a different statin at a low dose 1
   • Gradually increase the dose as tolerated 1
3. If symptoms persist after 2 months without statin treatment:
   • Consider other causes of muscle symptoms 1
   • If symptoms are determined to arise from a condition unrelated to statin therapy, resume original statin therapy 1

Considerations for This Patient

• Current LDL-C level of 90 mg/dl is already below the target of <100 mg/dl for high-risk patients 1
• The combination of rosuvastatin and ezetimibe is highly effective for LDL-C reduction 2, 3
• Family history of premature atherosclerosis suggests possible familial hypercholesterolemia, requiring aggressive lipid management 1

Alternative Treatment Options

If statin intolerance is confirmed:

• Consider a lower dose of rosuvastatin (10-20 mg) plus ezetimibe, which may provide similar LDL-C reduction with fewer side effects 4, 5
• For patients with statin intolerance, bempedoic acid may be considered in addition to ezetimibe 1
• If LDL-C goals cannot be achieved with these combinations, consider adding a PCSK9 inhibitor, especially for very high-risk patients 1

Important Considerations

• Muscle symptoms are the most common adverse effect of statins, occurring in 5-10% of patients 1
• Rosuvastatin at 40 mg is the highest approved dose and carries increased risk of myopathy 6
• Drug interactions may increase risk of myopathy - check for medications that might interact with rosuvastatin 6
• Patients with family history of premature atherosclerosis often require combination therapy to achieve optimal LDL-C levels 1, 5

Common Pitfalls to Avoid

• Don't permanently discontinue statin therapy without establishing causality - many patients with initial muscle symptoms can tolerate a lower dose or different statin 1
• Don't ignore the importance of achieving LDL-C goals in patients with family history of premature atherosclerosis 1
• Don't overlook the possibility of vitamin D deficiency, which can exacerbate statin-associated muscle symptoms 1
• Don't miss potential drug interactions that could increase statin concentration and risk of myopathy 6