What is the management of Low-Density Lipoprotein (LDL) in a patient with elevated Creatine Phosphokinase (CPK) levels while on statins (HMG-CoA reductase inhibitors)?

From the Guidelines

For patients with elevated CPK while on statins, consider switching to a hydrophilic statin like rosuvastatin (5-10 mg) or pravastatin (20-40 mg) at a lower dose with alternate-day dosing, as this approach has been shown to reduce muscle toxicity 1. If muscle symptoms persist, discontinue the statin and try ezetimibe 10 mg daily as monotherapy or add bempedoic acid 180 mg daily. For high-risk patients requiring more aggressive LDL lowering, consider PCSK9 inhibitors like evolocumab (140 mg every 2 weeks) or alirocumab (75-150 mg every 2 weeks), as they have been demonstrated to provide significant cardiovascular risk reduction benefits in patients with atherosclerotic cardiovascular disease (ASCVD) 1. Before making changes, confirm that the CPK elevation is statin-related by checking if levels normalize after a 2-4 week washout period. Hydrophilic statins cause less muscle toxicity because they have reduced penetration into muscle tissue. Coenzyme Q10 supplementation (100-200 mg daily) may help some patients tolerate statins, though evidence is mixed. Always monitor CPK levels and symptoms after any medication change, and consider underlying conditions like hypothyroidism or vitamin D deficiency that might contribute to statin intolerance. Key considerations in managing these patients include:

• Identifying the underlying cause of CPK elevation and confirming statin-related muscle symptoms
• Selecting alternative lipid-lowering therapies that balance efficacy with tolerability
• Monitoring for adverse effects and adjusting treatment as needed to optimize patient outcomes
• Prioritizing patient-centered care and shared decision-making in the management of ASCVD risk.

From the FDA Drug Label

Rosuvastatin may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis. Discontinue rosuvastatin if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected.

LDL management for the patient with elevated CPK with statins:

• Discontinue statin use if markedly elevated CPK levels occur or if myopathy is either diagnosed or suspected.
• Monitor CPK levels and muscle symptoms in patients taking statins, especially those with risk factors for myopathy.
• Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the statin dosage, and instruct them to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever 2 2.

From the Research

LDL Management for Patients with Elevated CPK on Statins

• Patients with elevated creatine phosphokinase (CPK) levels often experience statin intolerance, which can lead to the discontinuation of statin therapy 3.
• In such cases, alternative treatment options like proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe can be considered for low-density lipoprotein cholesterol (LDL-C) reduction.

Efficacy of PCSK9 Inhibitors in Patients with Elevated CPK

• A study found that PCSK9 inhibitors can be a safe and effective treatment for hyperlipidemia in patients with markedly elevated CPK levels, with 92% of patients demonstrating a reduction in CPK of >50% 3.
• Another study compared the efficacy of ezetimibe and PCSK9 inhibitors in patients not receiving statins and found that PCSK9 inhibitors lowered LDL-C levels significantly more than ezetimibe 4.

Comparison of Ezetimibe and PCSK9 Inhibitors

• A meta-analysis found that PCSK9 inhibitors showed significantly greater reduction in LDL-C levels compared to ezetimibe in statin-intolerant patients 4.
• A systematic review and network meta-analysis found that adding PCSK9 inhibitors to statins reduced non-fatal myocardial infarction (MI) and stroke, but not all-cause mortality or cardiovascular mortality 5.

Considerations for Re-Challenging Statins in Patients with Statin-Induced Myopathy

• A case report highlighted the importance of careful consideration before re-challenging statins in patients with statin-induced myopathy, as it can lead to severe myalgia and elevated CPK levels 6.
• The study suggests that alternative treatment options like PCSK9 inhibitors and ezetimibe should be considered in patients who are statin intolerant or have a history of statin-induced myopathy.

Treatment Strategies for Patients with Elevated CPK on Statins

• Current guidelines recommend the use of ezetimibe and PCSK9 inhibitors as alternative treatment options for patients who are statin intolerant or have a history of statin-induced myopathy 7.
• A treatment strategy that involves the use of PCSK9 inhibitors and ezetimibe, with or without statin therapy, can be effective in reducing LDL-C levels and cardiovascular risk in patients with elevated CPK levels 5.