How to lower Low-Density Lipoprotein (LDL) levels?

From the Guidelines

To lower LDL cholesterol levels, it is recommended to focus on both lifestyle modifications and medication if needed, with the goal of reducing LDL cholesterol to <55 mg/dL and achieving at least a 50% reduction in LDL cholesterol levels, as suggested by the 2020 ESC guidelines for the management of acute coronary syndromes 1.

Lifestyle Modifications

• Adopt a heart-healthy diet low in saturated fats, trans fats, and cholesterol while increasing fiber intake through fruits, vegetables, whole grains, and legumes.
• Regular physical activity, aiming for at least 150 minutes of moderate exercise weekly, can help reduce LDL levels.
• Weight loss if overweight and limiting alcohol consumption are also beneficial.
• Avoid smoking as it damages blood vessels and lowers HDL (good) cholesterol.

Medication

• Statins are typically the first-line treatment, including atorvastatin (10-80mg daily), rosuvastatin (5-40mg daily), or simvastatin (10-40mg daily).
• Other options include ezetimibe (10mg daily), PCSK9 inhibitors (evolocumab or alirocumab), bile acid sequestrants, or bempedoic acid.
• These medications work by either reducing cholesterol production in the liver, increasing cholesterol removal from the bloodstream, or blocking intestinal absorption.

Monitoring and Maintenance

• Regular monitoring of cholesterol levels every 3-6 months is important to assess treatment effectiveness.
• Lifestyle changes should be maintained even when taking medication for optimal results.
• The addition of ezetimibe has been demonstrated to decrease cholesterol and cardiovascular events in post-ACS patients, and in patients with diabetes 1.
• It is also recommended to limit saturated and trans fatty acids to <10% and preferably to <7% of energy intake, and to limit cholesterol intake to <200 mg/day 1.

From the FDA Drug Label

Inhibition of HMG-CoA reductase by simvastatin acid accelerates the expression of LDL-receptors, followed by the uptake of LDL-C from blood to the liver, leading to a decrease in plasma LDL-C and total cholesterol. To lower Low-Density Lipoprotein (LDL) levels, one option is to use a medication such as simvastatin 2, which works by inhibiting the enzyme HMG-CoA reductase, leading to a decrease in plasma LDL-C and total cholesterol. Another option is to use ezetimibe 3 3, which can be used alone or in combination with a statin to reduce elevated LDL-C levels. Key points to consider when using these medications include:

• Dosage: Simvastatin and ezetimibe have specific dosage recommendations, and patients should follow the prescribed dosage regimen.
• Contraindications: Patients should be aware of the contraindications for these medications, such as hypersensitivity to the medication or certain medical conditions.
• Monitoring: Patients should have their LDL-C levels monitored regularly to assess the effectiveness of the medication.

From the Research

Lowering LDL Levels

To lower Low-Density Lipoprotein (LDL) levels, several approaches can be considered:

• Medications: Statins are the most-effective therapy currently available for lowering LDL-cholesterol (LDL-C) levels and preventing cardiovascular events 4. Additional therapies such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can be used in combination with statins to produce an additional 50-60% decrease in LDL-C levels 4, 5.
• Lifestyle Modifications: Dietary composition is crucial in controlling dyslipidemias. Replacing saturated fat with monounsaturated fatty acids (MUFAs) or n-6 polyunsaturated fatty acids (PUFAs) can lower plasma LDL cholesterol and ameliorate the LDL/HDL ratio 6. Increasing physical activity and achieving weight reduction can also help lower LDL levels.
• Combination Therapy: Using a combination of high-intensity statins and ezetimibe can help achieve target LDL-C levels 7. PCSK9 inhibitors can be added to the treatment regimen if the patient does not reach LDL-C levels below 55 mg/dL despite maximal tolerated dose statin and ezetimibe.

Treatment Strategies

The following treatment strategies can be employed to lower LDL levels:

• Early Use of High-Intensity Statins: High-intensity statins such as atorvastatin or rosuvastatin can be used in combination with ezetimibe to rapidly decrease LDL-C levels 7.
• Addition of PCSK9 Inhibitors: PCSK9 inhibitors can be added to the treatment regimen if the patient does not reach LDL-C levels below 55 mg/dL despite maximal tolerated dose statin and ezetimibe 7.
• Use of Alternative Treatments: Alternative treatments such as ezetimibe, PCSK9 inhibitors, and bempedoic acid can be used in patients who are unable to tolerate statins or require additional LDL-C lowering 8.

Safety Evaluation

The safety of statin alternatives has been evaluated, and most have shown an excellent safety profile 8. However, injectable PCSK9 inhibitors are associated with a small increase in injection site reactions, and bempedoic acid is associated with a small increase in plasma uric acid and slightly increased frequency of episodes of gout in susceptible subjects.