What medications are indicated for a patient with elevated Low-Density Lipoprotein (LDL) cholesterol and hypercholesterolemia, with total cholesterol levels of 238 mg/dL?

From the Guidelines

The patient should be started on a moderate-intensity statin, such as atorvastatin 10-20 mg daily or rosuvastatin 5-10 mg daily, as first-line therapy to reduce LDL levels and cardiovascular risk. This recommendation is based on the 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline, which suggests that statin therapy is indicated for patients with elevated LDL levels, such as this patient with an LDL of 143 mg/dL and total cholesterol of 238 mg/dL 1.

Before initiating medication, lifestyle modifications should be implemented concurrently, including:

• A heart-healthy diet low in saturated fats
• Regular physical activity (150 minutes of moderate-intensity exercise weekly)
• Weight management if needed
• Smoking cessation if applicable

The decision to start statin therapy should consider the patient's overall cardiovascular risk, including factors such as age, gender, blood pressure, diabetes status, and smoking history. Statins work by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, thereby reducing LDL production and increasing LDL receptor expression on hepatocytes, which enhances LDL clearance from circulation.

Treatment should be monitored with follow-up lipid panels in 4-12 weeks after initiation, with a goal of at least 30-50% reduction in LDL, as recommended by the guideline 1. Potential side effects include muscle pain, liver enzyme elevations, and rarely rhabdomyolysis, so baseline liver function tests should be obtained before starting therapy.

It is also important to note that the patient's LDL level is not considered very high risk, as defined by the guideline, which is an LDL-C level of 190 mg/dL or higher 1. Therefore, the addition of nonstatin medications, such as ezetimibe or PCSK9 inhibitors, is not indicated at this time. However, if the patient's LDL level remains elevated despite statin therapy, the addition of these medications may be considered in the future.

From the FDA Drug Label

INDICATIONS AND USAGE EZETIMIBE Tablets is indicated (1): • In combination with a statin, or alone when additional low density lipoprotein cholesterol (LDL-C) lowering therapy is not possible, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH)

2.1 Important Dosage and Administration Information Take simvastatin tablets USP orally once daily in the evening. The maximum recommended dosage is simvastatin tablets USP 40 mg once daily [see DOSAGE AND ADMINISTRATION(2.2, 2.3)].

The patient's LDL is 143 and total cholesterol is 238, which are elevated. Ezetimibe and simvastatin are indicated for the reduction of elevated LDL-C.

• Ezetimibe can be used alone or in combination with a statin, such as simvastatin, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia.
• Simvastatin can be used to reduce elevated LDL-C in adults, with a recommended dosage range of 20 mg to 40 mg once daily. The patient should be started on a statin, such as simvastatin, and/or ezetimibe, in addition to diet and lifestyle modifications, to reduce their LDL-C levels 2, 3.

From the Research

Indicated Medications for High LDL and Total Cholesterol

The patient's LDL level is 143 and total cholesterol is 238, indicating a need for lipid-lowering therapy. Based on the provided studies, the following medications are indicated:

• Statins: as a first-line agent for primary and secondary prevention of cardiovascular disease, especially in patients at high or very high risk for ASCVD events 4
• Ezetimibe: as an add-on therapy to statins for additional LDL cholesterol reduction and decreased ASCVD risk 5, 6, 7, 8
• PCSK9 inhibitors (e.g. evolocumab): for patients who require further LDL cholesterol reduction, especially those at very high cardiovascular risk 5, 7

Treatment Approach

The treatment approach should be tailored to the individual's cardiovascular risk and tolerance to potential adverse effects. The goal is to achieve guidelines-directed LDL goals, which may involve:

• Initiating high-intensity statin therapy or a combination of statin and ezetimibe, depending on initial LDL-C levels and patient history 8
• Adjusting the potency and dose of statins and other lipid-lowering agents to achieve optimal LDL cholesterol reduction 4, 7
• Considering combination therapy with statins, ezetimibe, and PCSK9 inhibitors for patients who require more aggressive LDL cholesterol reduction 7

Key Considerations

When selecting medications, consider the following:

• The patient's cardiovascular risk profile and history of ASCVD events 4, 8
• The potential for adverse effects, such as myalgia with statin therapy, and the need for alternative or combination therapies 5, 6
• The importance of achieving guidelines-directed LDL goals to reduce cardiovascular risk 4, 8