When to initiate antihyperlipidemia medications, specifically lipid-lowering (LL) therapy, for the treatment of hyperlipidemia?

From the Guidelines

Antihyperlipidemia medications should be initiated in patients with established atherosclerotic cardiovascular disease (ASCVD), LDL cholesterol ≥190 mg/dL, diabetes mellitus with age 40-75 years, or those with a calculated 10-year ASCVD risk ≥7.5%. Treatment is generally recommended based on cardiovascular risk assessment rather than lipid levels alone 1. Statins are the first-line therapy, with high-intensity options like atorvastatin 40-80mg or rosuvastatin 20-40mg daily for highest risk patients, and moderate-intensity options like atorvastatin 10-20mg, rosuvastatin 5-10mg, or simvastatin 20-40mg daily for moderate risk patients. Some key points to consider when initiating antihyperlipidemia medications include:

• High-intensity statin therapy should be initiated or continued as first-line therapy in women and men 75 years of age who have clinical ASCVD, unless contraindicated 1.
• In individuals with clinical ASCVD in whom high-intensity statin therapy would otherwise be used, when high-intensity statin therapy is contraindicated or when characteristics predisposing to statin-associated adverse effects are present, moderate-intensity statin should be used as the second option if tolerated 1.
• For primary prevention in individuals with LDL-C ≥190 mg/dL, statin therapy should be initiated, with high-intensity statin therapy used unless contraindicated 1. If statins are insufficient or not tolerated, other options can be considered, such as:
• Ezetimibe 10mg daily, which has been shown to reduce LDL-C and improve cardiovascular outcomes in patients with ASCVD 1.
• PCSK9 inhibitors, such as evolocumab 140mg every 2 weeks or alirocumab 75-150mg every 2 weeks, which have been shown to significantly reduce LDL-C and improve cardiovascular outcomes in patients with ASCVD 1. Treatment goals typically aim for a 50% reduction in LDL for high-risk patients or LDL <70 mg/dL for very high-risk patients. Lifestyle modifications, including diet changes, exercise, weight management, and smoking cessation, should be implemented alongside medication. Regular monitoring of lipid levels and liver function tests is essential, with follow-up lipid panels recommended 4-12 weeks after initiation and then every 3-12 months based on response and risk.

From the FDA Drug Label

To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease As an adjunct to diet, alone or in combination with other low density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C.

The decision to initiate antihyperlipidemia medications, such as alirocumab, should be based on the presence of established cardiovascular disease or primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH).

• Key considerations for initiating antihyperlipidemia meds include:
  • Presence of established cardiovascular disease
  • Presence of primary hyperlipidemia, including HeFH
  • Need to reduce LDL-C levels
  • Use as an adjunct to diet and other LDL-C-lowering therapies 2 2

From the Research

Initiation of Antihyperlipidemia Medications

The decision to initiate antihyperlipidemia medications depends on various factors, including the patient's risk of atherosclerotic cardiovascular disease (ASCVD) and baseline low-density lipoprotein cholesterol (LDL-C) levels.

• According to the American College of Cardiology and the American Heart Association guidelines updated in 2018, a more aggressive approach to hyperlipidemia is recommended 3.
• Statins are recommended as first-line therapy for LDL-C reduction, with the addition of nonstatin lipid-lowering therapy for patients at very high risk of ASCVD events 4.
• The percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels, and is even greater for PCSK9 inhibition 5.
• Combination therapies comprising statin and nonstatin agents may be considered for patients at high risk of ASCVD events who require significant LDL-C lowering 4.

Patient Risk Assessment

Patient risk assessment is crucial in determining the need for antihyperlipidemia medications.

• Patients with a history of cardiovascular events, adult diabetic patients, individuals with LDL-C levels ≥190 mg/dL, and those with an estimated 10-year cardiovascular risk ≥7.5% are considered high-risk and may benefit from cholesterol-lowering treatment 6.
• However, recommending cholesterol-lowering treatment based on estimated cardiovascular risk may not identify all high-risk patients and may lead to unnecessary treatment of low-risk individuals 6.

Treatment Options

Various treatment options are available for antihyperlipidemia, including:

• Statins, which inhibit 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) to reduce LDL-C by about 20% to 45% 7.
• Ezetimibe, which inhibits cholesterol absorption by targeting the Niemann-Pick C1-like 1 protein (NPC1L1) and lowers LDL-C by about 18% when used alone and by an additional 25% when combined with statin therapy 7.
• PCSK9 inhibitors, such as evolocumab, which can reduce LDL-C from baseline by 53% to 56% 7.