What are the indications for treating hyperlipidemia?

From the Guidelines

Hyperlipidemia should be treated when a patient has elevated lipid levels that increase their risk of cardiovascular disease, particularly in individuals with established atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus, or those with a calculated 10-year ASCVD risk ≥7.5%. The primary goal of therapy is to lower LDL cholesterol to <100 mg/dl (2.6 mmol/l) as the primary goal of therapy for adults, as stated in the standards of medical care in diabetes 1.

Key Considerations

• Treatment is indicated for individuals with established ASCVD, severely elevated LDL cholesterol (≥190 mg/dL), diabetes mellitus in adults aged 40-75 years, or those with a calculated 10-year ASCVD risk ≥7.5% 1.
• First-line pharmacological treatment typically involves statins such as atorvastatin or rosuvastatin, with intensity selected based on risk level.
• High-intensity statins are recommended for secondary prevention in patients with established ASCVD.
• For patients who cannot tolerate statins or who don't achieve target LDL levels, additional options include ezetimibe, PCSK9 inhibitors, or bempedoic acid.
• Treatment should always be accompanied by lifestyle modifications including a heart-healthy diet low in saturated fats, regular physical activity, weight management, smoking cessation, and limited alcohol consumption.

Lifestyle Modifications

• All patients, regardless of lipid levels, should be offered counseling about the benefits of a diet low in saturated fat and high in fruits and vegetables, regular physical activity, avoiding tobacco use, and maintaining a healthy weight 1.
• Long-term adherence to therapies should be emphasized, and interventions that address all modifiable risk factors for heart disease should be implemented.

Pharmacological Treatment

• Statins are the drugs of choice for lowering LDL cholesterol, and severe hypertriglyceridemia may warrant immediate therapy with lifestyle and usually pharmacologic therapy (fibric acid derivative or niacin) to reduce the risk of acute pancreatitis 1.
• Combination therapy employing statins and fibrates or niacin may be necessary to achieve lipid targets, but have not been evaluated in outcomes studies for either event reduction or safety 1.

From the FDA Drug Label

Ezetimibe Tablets is indicated: In combination with a statin, or alone when additional low-density lipoprotein cholesterol (LDL-C) lowering therapy is not possible, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH)

• Indication: Ezetimibe is indicated to treat hyperlipidemia in adults, specifically to reduce elevated LDL-C levels, as an adjunct to diet.
• Usage: It can be used alone or in combination with a statin when additional LDL-C lowering therapy is not possible. 2

From the Research

Indications for Treating Hyperlipidemia

• Hyperlipidemia is a prevalent condition that contributes to atherosclerotic cardiovascular disease (ASCVD), a primary cause of morbidity and mortality in the United States 3.
• Low-density lipoprotein cholesterol (LDL-C) is a causal factor for the development of ASCVD, and reductions in LDL-C produce a corresponding decrease in ASCVD risk for cardiovascular events 3, 4.
• The primary pharmacologic intervention for ASCVD risk reduction is statins, which have proven efficacy and safety in reducing cardiovascular events and total mortality in patients with and without clinically evident ASCVD 5.

Treatment Guidelines

• Clinical guidelines recommend add-on therapy with ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors when maximally tolerated statin therapy results in suboptimal LDL-C reduction 3, 6.
• The 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias include the use of PCSK9 inhibitors to very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 6.
• The use of statins to treat hyperlipidemia has been widely accepted and recommended in adults aged 40-75 years old with at least one risk factor and a calculated 10-year cardiovascular disease risk of 10% 7.

Special Considerations

• High-risk patients with established ASCVD or familial hypercholesterolemia (FH) may require more aggressive LDL-C reduction, and PCSK9 inhibitors may be necessary to achieve treatment goals 3, 4.
• Patients with very high cardiovascular risk may benefit from an aggressive LDL-C-lowering approach, aiming for the lowest LDL-C level, independently of recommended goals, with all available pharmacological approaches 4.
• The cost-effectiveness of PCSK9 inhibitor therapy is limited to secondary prevention in high-risk patients 6.