What to do about a patient with hyperckemia who is taking Crestor (rosuvastatin)?

From the Guidelines

For a patient with hyperCKemia who is taking Crestor (rosuvastatin), the first step is to temporarily discontinue the statin medication while evaluating the clinical situation, as recommended by the 2016 ESC/EAS guidelines for the management of dyslipidaemias 1. If the patient is experiencing muscle symptoms like pain, weakness, or tenderness along with the elevated CK, this suggests statin-induced myopathy. After stopping the medication, monitor CK levels until they normalize, which typically occurs within 2-6 weeks. Some key points to consider in managing such patients include:

• Re-evaluating the indication for statin treatment if CK levels become elevated, especially if ≥4 x ULN 1.
• Considering the possibility of transient CK elevation due to other reasons such as exertion, and evaluating for myopathy if CK remains elevated 1.
• If CK <10x ULN and no symptoms are present, continuing lipid-lowering therapy while monitoring CK, but if symptoms are present, stopping the statin and monitoring until CK normalizes before potentially re-challenging with a lower dose 1.
• Considering alternative lipid-lowering strategies for patients who cannot tolerate statins, such as ezetimibe or PCSK9 inhibitors, as suggested by various guidelines including the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1. Once levels normalize, consider either restarting rosuvastatin at a lower dose, switching to a different statin with lower myopathy risk, or trying an alternate-day dosing regimen. The mechanism behind statin-induced hyperCKemia involves inhibition of HMG-CoA reductase, which can affect muscle cell metabolism and membrane integrity, particularly in genetically predisposed individuals or those with risk factors like advanced age, renal impairment, hypothyroidism, or concurrent use of medications that interact with statins. It's also important to be aware of the patient's overall clinical context, including the presence of any comorbidities or concomitant medications that could influence the risk of statin-induced myopathy or the choice of alternative therapies. Given the potential for statin therapy to significantly reduce the risk of atherosclerotic cardiovascular disease, careful consideration should be given to the balance between the benefits and risks of statin use in each individual patient, as emphasized in guidelines such as those from the ACC/AHA 1.

From the FDA Drug Label

Rosuvastatin tablets may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis. Discontinue rosuvastatin tablets if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Temporarily discontinue rosuvastatin tablets in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).

The patient has hyperckemia (elevated creatine kinase) while taking Crestor (rosuvastatin).

• The main risk is myopathy and rhabdomyolysis.
• Discontinue rosuvastatin tablets if markedly elevated CK levels occur or if myopathy is diagnosed or suspected 2.
• Temporarily discontinue rosuvastatin tablets in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis 2.

From the Research

Patient with Hyperckemia Taking Crestor (Rosuvastatin)

• The patient is taking Crestor (rosuvastatin) and has hyperckemia, which is a common side effect of statin therapy 3, 4.
• According to the study by 3, myopathy occurs in approximately 10% of statin-treated patients and is most commonly manifested by myalgias with or without plasma creatine kinase (CK) elevations.
• The study by 4 suggests that the risk of statin-associated myopathy can be minimized by identifying vulnerable patients and/or by eliminating-avoiding statin interactions with specific drugs.
• If the patient has moderate to severe symptoms and CK elevated to more than 5-fold the upper limit of normal, the statin should be stopped 3.
• In patients with CK elevations, CK should be monitored, and the existing statin should be titrated to achieve cholesterol goals and the CK repeated when symptoms appear or worsen 3.
• Alternative strategies for managing hypercholesterolemia in patients with hyperckemia include using a different statin, such as fluvastatin or pravastatin, or combining a low-dose statin with a cholesterol absorption inhibitor (ezetimibe) and/or bile acid sequestrant 3, 4.
• The study by 5 suggests that high pretreatment CK, particularly 1 to 5 times the upper limit of normal, should not be an impediment to start or continue statins to lower low-density lipoprotein cholesterol (LDLC).

Management of Statin-Associated Myopathy

• The study by 4 suggests that potential strategies for managing statin-associated myopathy include using the same statin at a lower dose, initiating fluvastatin XL 80 mg daily or rosuvastatin intermittently in low dose (5-10mg), combined usually with ezetimibe 10mg daily.
• In patients who fail these approaches, non-statin lipid-lowering drugs, such as ezetimibe or colesevelam, may be necessary 4.
• The study by 6 highlights the importance of monitoring CK levels and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody in patients with suspected statin-associated immune-mediated necrotizing myopathy (IMNM).

Monitoring and Follow-up

• The study by 7 suggests that CK values show great variability among individuals, and some athletes are low responders to physical training, with chronically low CK serum levels.
• In patients with hyperckemia, CK levels should be monitored regularly, and the patient should be followed up clinically to assess for any changes in symptoms or CK levels 3, 4.