What is the dosing for medications to decrease Low-Density Lipoprotein (LDL) and increase High-Density Lipoprotein (HDL)?

From the Guidelines

To decrease LDL and increase HDL, statins are the first-line medication, with atorvastatin typically prescribed at 10-80 mg daily and rosuvastatin at 5-40 mg daily, as recommended by the most recent guidelines 1. When managing cholesterol levels, it's essential to consider the patient's overall risk profile and medical history.

• For moderate intensity therapy, atorvastatin 10-20 mg or rosuvastatin 5-10 mg daily is recommended, while high-intensity therapy uses atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily.
• If statins are insufficient or not tolerated, ezetimibe 10 mg daily can be added, reducing LDL by an additional 15-20% 1.
• For patients with very high LDL or cardiovascular disease, PCSK9 inhibitors like evolocumab (140 mg every 2 weeks) or alirocumab (75-150 mg every 2 weeks) may be prescribed. To increase HDL, lifestyle modifications are primary, but medications like niacin (extended-release 500-2000 mg daily) can raise HDL by 15-35%, though side effects like flushing are common 1.
• Fibrates such as fenofibrate (48-145 mg daily) or gemfibrozil (600 mg twice daily) can increase HDL by 5-15% while also lowering triglycerides. It's crucial to note that the choice of medication and dosage should be individualized based on the patient's specific needs and medical history, and that regular monitoring of lipid levels and adjustment of therapy as needed is essential to achieve optimal outcomes 1.

From the FDA Drug Label

In a pool of placebo-controlled and active-controlled trials of adult patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks as well as in a separate clinical trial of patients treated with PRALUENT 75 mg every 2 weeks or 300 mg every 4 weeks At month 2, if additional LDL-C lowering was required based on pre-specified LDL-C criteria (LDL-C ≥50 mg/dL), PRALUENT was adjusted to 150 mg every 2 weeks For patients who had their dose adjusted to 150 mg every 2 weeks and who had two consecutive LDL-C values below 25 mg/dL, down-titration from 150 mg every 2 weeks to 75 mg every 2 weeks was performed.

The dosing for alirocumab (PRALUENT) to decrease Low-Density Lipoprotein (LDL) is:

• 75 mg every 2 weeks
• Adjusted to 150 mg every 2 weeks if additional LDL-C lowering is required
• Down-titration from 150 mg every 2 weeks to 75 mg every 2 weeks if two consecutive LDL-C values are below 25 mg/dL There is no information in the provided drug label about increasing High-Density Lipoprotein (HDL). 2

From the Research

Medications to Decrease LDL and Increase HDL

To decrease Low-Density Lipoprotein (LDL) and increase High-Density Lipoprotein (HDL), several medications can be used. The primary goal of these medications is to reduce the risk of atherosclerotic cardiovascular disease (ASCVD).

Statins

• Statins are the most potent drugs for lowering LDL-C and are well tolerated in most patients 3.
• They are recommended as a first-line therapy for the primary and secondary prevention of ASCVD 4.
• Statins may not be sufficient in decreasing LDL cholesterol levels, and additional therapies may be needed 4.

Ezetimibe

• Ezetimibe, a cholesterol absorption inhibitor, can be added to statin therapy to achieve additional LDL cholesterol reduction and reduce ASCVD risk 4, 3.
• Ezetimibe is used in situations of statin-associated adverse effects, such as myalgia, and the combination therapy is relatively safer 4.

PCSK9 Inhibitors

• PCSK9 inhibitors, such as alirocumab and evolocumab, are monoclonal antibodies that can lower LDL cholesterol levels and reduce ASCVD risk when added to maximally tolerated statin therapy 4, 5.
• PCSK9 inhibitors can reduce LDL-C by 50-60% above that achieved by statin therapy alone 5.
• The use of PCSK9 inhibitors is recommended for very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 5.

Fibrates

• Fibrates can modulate lipid metabolism and improve the ratio of high-density to low-density lipoproteins 6.
• Fibrates may be used to increase HDL levels, but their effectiveness in reducing cardiovascular risk is still being studied.

Increasing HDL

• Currently, there are no agents that have shown cardiovascular benefit in increasing HDL levels in patients on background statin therapy 7.
• Future studies targeting low HDL and high triglyceride levels associated with type 2 diabetes could provide additional novel therapies to manage diabetic dyslipidemia 7.