What is the next step for a patient with Coronary Artery Disease (CAD) who requires a Low-Density Lipoprotein (LDL) level < 70 and has developed statin-induced myalgia with elevated Creatine Kinase (CK) while taking atorvastatin (Lipitor) 80 mg/day?

From the Guidelines

For a patient with CAD requiring LDL < 70 mg/dL who has developed statin-induced myalgia with elevated CK on atorvastatin 80 mg/day, the next step should be to discontinue the atorvastatin temporarily until symptoms resolve and CK levels normalize, as suggested by the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1. Once this occurs, consider restarting with a lower-intensity statin such as rosuvastatin 5-10 mg or pravastatin 20-40 mg, which are less likely to cause myopathy. Alternative dosing strategies include every-other-day or twice-weekly dosing of a long-acting statin like rosuvastatin. If statins remain problematic, add or switch to ezetimibe 10 mg daily, which lowers LDL by inhibiting intestinal cholesterol absorption without causing muscle symptoms, as recommended by the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk 1. For patients still not reaching goals, consider adding a PCSK9 inhibitor such as evolocumab 140 mg subcutaneously every 2 weeks or alirocumab 75-150 mg every 2 weeks. Bempedoic acid 180 mg daily is another non-statin option that works upstream of statins in the cholesterol synthesis pathway and has lower rates of muscle symptoms. Throughout this process, maintain lifestyle modifications including a Mediterranean or DASH diet, regular exercise as tolerated, and weight management. The goal is to find the maximum tolerated statin dose (if any) and supplement with non-statin therapies to achieve the target LDL < 70 mg/dL for secondary prevention in CAD. Some key considerations in managing these patients include:

• The potential for statin dose reduction or switching to a different statin to minimize muscle symptoms, as seen in trials such as IDEAL and PROVE-IT 1.
• The use of non-statin therapies like ezetimibe, PCSK9 inhibitors, and bempedoic acid to achieve additional LDL lowering, as recommended by the 2022 ACC expert consensus decision pathway 1.
• The importance of lifestyle modifications, including diet and exercise, in managing CAD and reducing cardiovascular risk. It is also important to note that the 2022 ACC expert consensus decision pathway recommends considering the simultaneous addition of 2 agents to more rapidly reduce the risk of recurrent events in patients with clinical ASCVD and LDL-C ≥190 mg/dL who require greater LDL-C reduction than any additional agent alone can expect to achieve 1. Ultimately, the management of patients with CAD and statin-induced myalgia requires a personalized approach, taking into account the individual patient's needs, preferences, and response to different therapies.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Discontinue atorvastatin calcium tablets if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if atorvastatin calcium tablets are discontinued

The patient has developed statin-induced myalgia with elevated CK on atorvastatin 80 mg/d, so discontinue atorvastatin. Consider alternative treatments to achieve the goal of LDL < 70 due to CAD, such as:

• Ezetimibe
• PCSK9 inhibitors
• Bile acid sequestrants
• Fibrates (with caution due to increased risk of myopathy) Consult with a healthcare professional to determine the best course of action 2 2.

From the Research

Patient Management

For a patient with coronary artery disease (CAD) who needs to achieve a low-density lipoprotein (LDL) level of < 70 mg/dL and has developed statin-induced myalgia with elevated creatine kinase (CK) on atorvastatin 80 mg/d, the next steps in management can be considered based on available evidence:

• The patient's condition and the need for LDL reduction are critical, as high LDL levels are a major risk factor for CAD 3, 4.
• Given the patient's statin-induced myalgia, alternative statins or doses may be considered to minimize side effects while still achieving the desired LDL reduction 5, 6.
• The goal of achieving an LDL level of < 70 mg/dL is supported by guidelines for patients at high or very high risk of cardiovascular events, as it is associated with a reduced risk of atherosclerotic heart disease 4, 6.
• Other lipid parameters and risk factors should also be considered in the patient's management plan, as they can influence CAD risk 7.

Treatment Options

Treatment options for the patient could include:

• Switching to a different statin that may have a lower risk of myalgia, such as rosuvastatin or pitavastatin.
• Reducing the dose of atorvastatin to minimize side effects while still achieving some degree of LDL reduction.
• Adding other lipid-lowering therapies, such as ezetimibe or a PCSK9 inhibitor, to help achieve the desired LDL level.
• Considering non-statin therapies, such as fibrates or niacin, although these may have their own set of side effects and limitations.

Monitoring and Follow-up

Regular monitoring of the patient's LDL levels, CK, and other relevant parameters will be necessary to assess the effectiveness of the chosen treatment strategy and to minimize the risk of adverse effects 5, 6.