What is the management of hypercholesterolemia (elevated low-density lipoprotein cholesterol)?

From the Guidelines

Management of hypercholesterolemia requires a combination of lifestyle modifications and pharmacological interventions, with the goal of lowering LDL-C to <1.4 mmol/L (<55 mg/dL) and reducing it by at least 50% if the baseline LDL-C level is 1.8-3.5 mmol/L (70-135 mg/dL), as recommended by the 2020 ESC guidelines 1.

Lifestyle Modifications

• Adopting a heart-healthy diet low in saturated fats and trans fats
• Regular physical activity (at least 150 minutes of moderate-intensity exercise weekly)
• Weight management
• Smoking cessation
• Limiting alcohol consumption

Pharmacological Management

• Statins are the cornerstone therapy, with options including atorvastatin, rosuvastatin, simvastatin, and pravastatin
• For patients who cannot tolerate statins or need additional lipid lowering, second-line agents include ezetimibe, PCSK9 inhibitors like evolocumab or alirocumab, bile acid sequestrants, and fibrates
• Treatment goals should be individualized based on cardiovascular risk, with more aggressive targets (LDL-C <70 mg/dL) for those with established cardiovascular disease or high-risk conditions

Monitoring and Education

• Regular monitoring of lipid levels and liver function tests is essential, typically 4-12 weeks after starting therapy and then periodically thereafter
• Patients should be educated about potential side effects, particularly muscle pain with statins, and encouraged to maintain adherence to both medications and lifestyle modifications for optimal outcomes. Some key points to consider in the management of hypercholesterolemia include:
• The importance of therapeutic lifestyle changes (TLC) in achieving risk reduction through both LDL-C lowering and metabolic syndrome management 1
• The use of statins as the primary pharmacological treatment for hypercholesterolemia, with the goal of lowering LDL-C to <1.4 mmol/L (<55 mg/dL) and reducing it by at least 50% if the baseline LDL-C level is 1.8-3.5 mmol/L (70-135 mg/dL) 1
• The consideration of other lipid-lowering agents, such as ezetimibe and PCSK9 inhibitors, for patients who cannot tolerate statins or need additional lipid lowering 1

From the FDA Drug Label

EZETIMIBE Tablets is indicated (1): • 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) • In combination with a statin as an adjunct to diet to reduce elevated LDL-C in pediatric patients 10 years of age and older with HeFH. • In combination with fenofibrate as an adjunct to diet to reduce elevated LDL-C in adults with mixed hyperlipidemia • In combination with a statin, and other LDL-C lowering therapies, to reduce elevated LDL-C levels in adults and in pediatric patients 10 years of age and older with homozygous familial hypercholesterolemia (HoFH) • As an adjunct to diet for the reduction of elevated sitosterol and campesterol levels in adults and in pediatric patients 9 years of age and older with homozygous familial sitosterolemia

The management of hypercholesterolemia with ezetimibe involves:

• Dietary adjustments: as an adjunct to diet to reduce elevated LDL-C
• Combination therapy: with a statin, or alone when additional LDL-C lowering therapy is not possible
• Specific patient populations:
  • Adults with primary hyperlipidemia, including HeFH
  • Pediatric patients 10 years of age and older with HeFH
  • Adults with mixed hyperlipidemia
  • Adults and pediatric patients 10 years of age and older with HoFH
  • Adults and pediatric patients 9 years of age and older with homozygous familial sitosterolemia 2

From the Research

Management of Hypercholesterolemia

• The management of hypercholesterolemia involves lifestyle modifications and pharmacological interventions 3, 4, 5.
• Lifestyle modifications include dietary changes, weight reduction, and increased physical activity, with the goal of reducing total cholesterol to <200 mg/dL and LDL-C <100 mg/dL 3.
• Dietary constituents such as green tea, plant sterols, and soy protein have been shown to have important influences on total cholesterol levels 3.
• Physical activity is a critical component of first-line treatment for elevated blood pressure or cholesterol, and has extensive benefits, including improving both blood pressure and blood cholesterol 5.
• Pharmacological interventions, such as statins, ezetimibe, and PCSK9 inhibitors, can be used to lower LDL-C levels, especially in patients who have not reached their target cholesterol levels through lifestyle modifications alone 6, 7.

Lifestyle Modifications

• The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines recommend therapeutic lifestyle changes (TLC) for the treatment of patients with dyslipidemias, including dietary modifications, weight reduction, and increased physical activity 4.
• Dietary modifications should focus on limiting saturated fat intake to less than 7% of total caloric intake and trans-fatty acid intake to low levels 4.
• Persons who are overweight or obese with dyslipidemias should reduce body weight through a combination of physical activity, total calorie reduction, and behavior therapy modifications 4.

Pharmacological Interventions

• Statins, ezetimibe, and PCSK9 inhibitors can be used to lower LDL-C levels, especially in patients who have not reached their target cholesterol levels through lifestyle modifications alone 6, 7.
• 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 6.6% greater for PCSK9 inhibition 7.
• The use of intensive LDL-C-lowering therapy, even for patients with lower LDL-C levels, is encouraged, as it has been shown to have significant benefits in reducing cardiovascular risk 7.