What adjustments should be made to a patient's lipid-lowering regimen, currently atorvastatin 20mg and fenofibrate 145mg, with hypercholesterolemia, hypoalphalipoproteinemia, and hypertriglyceridemia?

From the Guidelines

For a patient with hypercholesterolemia, hypoalphalipoproteinemia, and hypertriglyceridemia currently on atorvastatin 20mg and fenofibrate 145mg, I recommend increasing the atorvastatin dose to 40mg daily while maintaining the fenofibrate at 145mg daily, as the current regimen does not seem to be adequately controlling the patient's lipid levels, with a total cholesterol of 251 mg/dL, HDL cholesterol of 39 mg/dL, and triglycerides of 513 mg/dL. According to the guidelines from the American Heart Association and American College of Cardiology 1, the goal for LDL-C is 100 mg/dL, and further reduction to 70 mg/dL is reasonable. Given the patient's high triglyceride level, non-HDL-C should be 130 mg/dL, and further reduction to 100 mg/dL is reasonable. The patient's current regimen includes atorvastatin, a statin, which primarily reduces LDL cholesterol, and fenofibrate, a fibrate, which more effectively lowers triglycerides and may further increase HDL cholesterol. Increasing the atorvastatin dose will provide more potent LDL cholesterol reduction, while the fenofibrate addresses the hypertriglyceridemia. Key lifestyle modifications should accompany this regimen, including:

• A Mediterranean or DASH diet
• Regular aerobic exercise (150 minutes weekly)
• Weight management if needed
• Smoking cessation
• Limiting alcohol intake The patient should have liver function tests and creatine kinase levels monitored after 4-6 weeks of the dose increase, then every 3-6 months thereafter. If the patient experiences muscle pain, weakness, or liver enzyme elevations, the regimen should be reassessed immediately. If this adjustment doesn't achieve target lipid levels after 6-8 weeks, consider adding ezetimibe 10mg daily to further reduce LDL cholesterol.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Take orally once daily with or without food ( 2.1). Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating atorvastatin calcium, and adjust dosage if necessary ( 2.1). Adults( 2. 2): Recommended starting dosage is 10 or 20 mg once daily; dosage range is 10 mg to 80 mg once daily. In vitro studies using human liver microsomes indicate that fenofibrate and fenofibric acid are not inhibitors of cytochrome (CYP) P450 isoforms CYP3A4, CYP2D6, CYP2E1 or CYP1A2 Table 2 describes the effects of co-administered drugs on fenofibric acid systemic exposure. Lipid-lowering agents Atorvastatin 20 mg once daily for 10 days Fenofibrate 160 mg1 once daily for 10 days ↓2% ↓4%

The patient is currently on atorvastatin 20mg and fenofibrate 145mg.

• The LDL-C level is not provided, but the patient has hypercholesterolemia, hypoalphalipoproteinemia, and hypertriglyceridemia.
• The dosage of atorvastatin can be adjusted based on the LDL-C level, with a recommended starting dosage of 10 or 20 mg once daily and a dosage range of 10 mg to 80 mg once daily 2.
• The patient is already taking the maximum recommended dose of fenofibrate for adults with normal renal function, which is 145mg once daily.
• Considering the patient's lipid profile, the dosage of atorvastatin may need to be increased, but the exact adjustment cannot be determined without the LDL-C level.
• It is also important to monitor the patient's renal function, as fenofibrate should be avoided in patients with severe renal impairment and dose reduction is required in patients with mild to moderate renal impairment 3.

From the Research

Patient's Current Lipid Profile

• Total Cholesterol: 251 mg/dL (high)
• HDL Cholesterol: 39 mg/dL (low)
• Triglycerides: 513 mg/dL (high)

Current Medication

• Atorvastatin 20mg
• Fenofibrate 145mg

Adjustments to Lipid-Lowering Regimen

• According to the study 4, combination therapy with fenofibrate and a statin is generally safe and effective for the treatment of combined hyperlipidemia.
• The study 5 suggests that atorvastatin and fenofibrate can improve lipoprotein metabolism in type 2 diabetes, but they affect different aspects of lipoprotein metabolism.
• The study 6 found that the combination of atorvastatin and micronised fenofibrate may have a favourable effect on some major coronary artery disease risk factors in patients with severe mixed dyslipidemia.
• Considering the patient's high triglycerides and low HDL cholesterol, increasing the dose of fenofibrate or adding another medication to target these lipid abnormalities may be necessary, as suggested by the study 7.
• However, the study 8 found that fenofibrate and atorvastatin increased circulating PCSK9 in diabetic patients, with no additive effect after 6 weeks of combined therapy, which may need to be taken into account when adjusting the patient's medication regimen.

Potential Adjustments

• Increase the dose of fenofibrate to 200mg or more, as used in the study 4 and 6.
• Consider adding another medication, such as a bile acid sequestrant or a cholesterol absorption inhibitor, to target the patient's high LDL cholesterol and low HDL cholesterol.
• Monitor the patient's lipid profile and adjust the medication regimen as needed to achieve optimal lipid levels.