What is the next best step in managing a patient with hypercholesterolemia (high cholesterol) and hypertriglyceridemia (elevated triglycerides) who developed muscle pain and elevated creatine kinase (CK) levels while on atorvastatin (a statin), which resolved after discontinuation of the medication?

From the Guidelines

The correct option is C. Pravastatin. This patient experienced statin-induced myopathy with elevated CK levels while on atorvastatin, which resolved after discontinuation, as described in the 2019 guideline on the management of blood cholesterol 1. However, the patient still needs lipid management as evidenced by increased cholesterol and triglycerides. Pravastatin is the best choice because it is less likely to cause myopathy compared to other statins due to its hydrophilic properties and minimal metabolism through the cytochrome P450 system.

• Option A (gemfibrozil) would be inappropriate as fibrates can independently cause myopathy and increase the risk when combined with any statin.
• Option B (ezetimibe) alone would provide insufficient lipid lowering for most patients requiring statin therapy, as noted in the 2022 acc expert consensus decision pathway on the role of nonstatin therapies for ldl-cholesterol lowering 1.
• Option D (restarting atorvastatin) would likely cause recurrence of the same adverse effects. Pravastatin provides a reasonable alternative that balances the need for lipid management while minimizing the risk of recurrent myopathy. According to the 2019 guideline, a thorough assessment of symptoms is recommended, in addition to evaluation for nonstatin etiologies, assessment of predisposing factors, and a physical exam 1. The 2022 acc expert consensus decision pathway also supports the use of alternative statin therapies, such as pravastatin, in patients who experience statin-associated side effects 1.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Concomitant use of cyclosporine, gemfibrozil, tipranavir plus ritonavir, or glecaprevir plus pibrentasvir with atorvastatin is not recommended Cases of myopathy/rhabdomyolysis have been reported with atorvastatin co-administered with lipid modifying doses (>1 gram/day) of niacin, fibrates, colchicine, and ledipasvir plus sofosbuvir

The patient had myopathy and elevated CK while on atorvastatin, which resolved when the medication was stopped. Considering the risk of myopathy and rhabdomyolysis with concomitant use of certain medications, including fibrates like gemfibrozil, the best option would be to avoid medications that increase this risk.

• Restarting atorvastatin may pose a risk of myopathy recurrence.
• Adding gemfibrozil is not recommended due to the increased risk of myopathy and rhabdomyolysis.
• Adding ezetimibe is a viable option as it does not increase the risk of myopathy and rhabdomyolysis.
• Pravastatin is another statin, and while it may be considered, the patient's initial reaction to atorvastatin suggests caution with statins in general. The most appropriate choice is ezetimibe as it is a non-statin lipid-lowering medication that can help manage cholesterol levels without increasing the risk of myopathy and rhabdomyolysis 2.

From the Research

Statin Intolerance and Alternative Therapies

The patient presented with muscular pain while on atorvastatin, which resolved after discontinuation, but led to increased cholesterol and triglycerides. Considering the evidence:

• Statin intolerance is a significant issue, with up to 10% of patients experiencing myopathies 3.
• Intermittent statin dosing regimens have been shown to be effective in reducing adverse effects while maintaining efficacy in patients with previous statin-induced myopathy 3.
• Ezetimibe has been found to be safe and not associated with an increased risk of myopathy, even in combination with statins 4.
• Alternative therapies such as fibrates, ezetimibe, nutraceuticals, and anti-PCSK9 antibodies can be used in patients who are intolerant to statins 5.

Management of Statin Intolerance

Given the patient's history of statin intolerance, the following options can be considered:

• Restarting atorvastatin may not be the best option, as the patient has already experienced muscular pain while on this medication.
• Adding gemfibrozil (a fibrate) may be an option, but it is not the most suitable choice based on the evidence.
• Adding ezetimibe is a viable option, as it has been shown to be safe and effective in reducing LDL-C levels 4.
• Pravastatin is another option, but the evidence suggests that intermittent dosing regimens may be more effective in reducing adverse effects 3.

Best Course of Action

Based on the evidence, the best course of action would be to:

• Consider alternative therapies such as ezetimibe, which has been shown to be safe and effective in reducing LDL-C levels 4.
• If statin therapy is still desired, consider intermittent dosing regimens, which have been shown to be effective in reducing adverse effects while maintaining efficacy 3.

The correct answer is: b. Add ezetimibe