What medication should be initiated for a patient with elevated Low-Density Lipoprotein (LDL) and hypercholesterolemia, with a family history of cardiovascular disease, hyperlipidemia, and hypertension?

From the Guidelines

For a patient with an LDL of 190 mg/dL, total cholesterol of 255 mg/dL, and family history of heart disease, hyperlipidemia, and hypertension, high-intensity statin therapy is recommended as first-line treatment. Specifically, atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily would be appropriate initial choices, as recommended by the 2013 American College of Cardiology/American Heart Association cholesterol guideline 1. These medications should be taken at the same time each day, preferably in the evening for simvastatin, but atorvastatin and rosuvastatin can be taken any time. The patient should be monitored with a lipid panel after 4-12 weeks of therapy to assess response, with a goal of at least 50% reduction in LDL levels. Liver function tests should be checked at baseline and as clinically indicated. Common side effects include muscle pain, which should be reported promptly. Lifestyle modifications are also essential, including a heart-healthy diet low in saturated fats, regular exercise, weight management, and smoking cessation if applicable. High-intensity statins are recommended because the LDL level exceeds 190 mg/dL, which is considered severe hypercholesterolemia, and the family history significantly increases cardiovascular risk, making aggressive lipid-lowering therapy necessary to reduce the risk of atherosclerotic cardiovascular disease.

Some key points to consider when initiating statin therapy include:

• Assessing and providing feedback to promote adherence to healthy lifestyle behaviors and statin therapy 1
• Monitoring safety measurements as clinically indicated 1
• Considering nonstatin LDL-C–lowering drugs, such as ezetimibe or PCSK9 inhibitors, in higher-risk adults if the potential for additional ASCVD risk reduction outweighs the potential for adverse effects 1
• Referring patients to a lipid specialist or registered dietitian if necessary, especially if they have ASCVD and/or baseline LDL-C ≥190 mg/dL 1

It's also important to note that 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 recommends considering nonstatin agents, such as ezetimibe or PCSK9 inhibitors, in patients with ASCVD and/or baseline LDL-C ≥190 mg/dL who do not achieve adequate LDL-C reduction with statin therapy alone 1. However, high-intensity statin therapy remains the first-line treatment for patients with severe hypercholesterolemia and high cardiovascular risk.

From the FDA Drug Label

The mean baseline LDL-C value was 219 mg/dL (range: 139 to 385 mg/dL) in the atorvastatin calcium group compared to 230 mg/dL (range: 160 to 325 mg/dL) in the placebo group Inclusion in the trial required 1) a baseline LDL-C level ≥190 mg/dL or 2) a baseline LDL-C level ≥160 mg/dL and positive family history of FH or documented premature cardiovascular disease in a first or second-degree relative. Atorvastatin calcium significantly decreased plasma levels of total-C, LDL-C, TG, and apolipoprotein B during the 26-week double-blind phase

The patient has an LDL of 190 and a family history of heart disease, hyperlipidemia, and hypertension. Atorvastatin should be started for this patient, as it has been shown to significantly decrease LDL-C levels in patients with similar characteristics 2.

• The dosage of atorvastatin calcium (once daily) was 10 mg for the first 4 weeks and uptitrated to 20 mg if the LDL-C level was >130 mg/dL.
• The patient's LDL level and family history meet the inclusion criteria for the trial.
• Atorvastatin has been shown to be effective in reducing LDL-C levels in patients with heterozygous familial hypercholesterolemia (HeFH) 2.

From the Research

Medication Recommendations for High LDL and Cholesterol Levels

Given the patient's LDL level of 190 and cholesterol level of 255, along with a family history of heart disease, hyperlipidemia, and hypertension, the following considerations are important:

• The patient's high LDL level puts them at significant risk for cardiovascular disease, as indicated by studies such as 3 and 4.
• Statins are recommended as a first-line therapy for reducing LDL cholesterol levels and the risk of atherosclerotic cardiovascular disease (ASCVD), as stated in 3.
• For patients with severely elevated LDL levels (≥190 mg/dL), such as the one in question, additional therapies beyond statins may be necessary to achieve adequate LDL reduction, as discussed in 3 and 5.
• Ezetimibe, a cholesterol absorption inhibitor, can be added to statin therapy to further reduce LDL cholesterol levels and decrease ASCVD risk, as shown in 3 and 6.
• Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab and evolocumab, are also effective in lowering LDL cholesterol levels and can be considered for patients who require more intensive therapy, as mentioned in 3 and 7.

Considerations for Treatment

• The choice of medication should be based on the patient's individual risk factors, including their family history of heart disease, hyperlipidemia, and hypertension.
• The goal of treatment should be to reduce the patient's LDL level to a target range, which may vary depending on their individual risk factors, as discussed in 5 and 7.
• Regular monitoring of the patient's LDL levels and other cardiovascular risk factors will be necessary to adjust their treatment plan as needed, as indicated by 4.