What is the treatment for high Low-Density Lipoprotein (LDL) cholesterol?

Management of High LDL Cholesterol

For patients with high LDL cholesterol, treatment should begin with therapeutic lifestyle changes (TLC) followed by statin therapy if goals are not achieved, with treatment intensity based on individual cardiovascular risk assessment. 1

Risk Assessment and Treatment Goals

• LDL cholesterol is the primary target for cholesterol-lowering therapy, with goals based on individual cardiovascular risk assessment 1, 2
• For high-risk patients (those with coronary heart disease or CHD risk equivalents with 10-year risk >20%), the LDL goal is <100 mg/dL 3, 2
• For very high-risk patients, an optional goal of <70 mg/dL is reasonable 1, 2
• For moderately high-risk persons (10-year risk 10-20%), the LDL goal is <130 mg/dL, with an optional goal of <100 mg/dL 3, 1
• For patients with 0-1 risk factor (low-risk), the LDL goal is <160 mg/dL 3, 2
• For patients with diabetes, the LDL goal is <100 mg/dL regardless of the presence of overt cardiovascular disease 3

First-Line Approach: Therapeutic Lifestyle Changes (TLC)

• TLC should be initiated first for all patients with elevated LDL cholesterol 3, 1
• Dietary recommendations include:
  • Limiting saturated fat to 7-10% of total calories 1, 2
  • Limiting dietary cholesterol to 200-300 mg/day 1
  • Reducing trans-fatty acid intake 2
  • Adding plant stanols/sterols (2 g/day) 1, 2
  • Increasing viscous (soluble) fiber (10-25 g/day) 2
• Regular physical activity (30-60 minutes most days) should be encouraged 1, 4
• Weight loss for overweight/obese patients can reduce triglycerides and modestly lower LDL 2, 5
• TLC should be attempted for 12 weeks before considering pharmacological therapy 3

Pharmacological Therapy

Statin Therapy (First-Line Medication)

• Statins are the preferred first-line agents for LDL reduction 3, 1, 2
• For high-risk patients, statin therapy should be initiated if LDL remains ≥100 mg/dL after TLC 3
• For moderately high-risk patients, statin therapy should be considered if LDL remains ≥130 mg/dL after TLC 3
• For low-risk patients, statin therapy should be considered if LDL remains ≥190 mg/dL after TLC (optional at 160-189 mg/dL) 3
• When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, intensity should be sufficient to achieve at least a 30-40% reduction in LDL levels 3, 1
• Atorvastatin has been shown to significantly reduce cardiovascular events in patients with multiple risk factors 6

Second-Line/Combination Therapy

• For patients not achieving LDL goals on statins alone, consider adding ezetimibe 1
• For patients with combined hyperlipidemia (elevated LDL and triglycerides), consider:
  • Improved glycemic control plus high-dose statin (if diabetic) 3
  • Statin plus fibrate (fenofibrate preferred over gemfibrozil due to lower myopathy risk) 3, 2
  • Statin plus nicotinic acid (with careful monitoring of glycemic control in diabetic patients) 3, 2
• For very high-risk patients whose LDL remains ≥70 mg/dL despite statin and ezetimibe therapy, adding a PCSK9 inhibitor is reasonable 1, 7

Special Considerations

• For patients with diabetes, statins are the preferred agents, with an LDL goal of <100 mg/dL 3
• Combination therapy with statins and fibrates (especially gemfibrozil) increases risk of myositis; monitor closely 3, 2
• Nicotinic acid should be used with caution in patients with diabetes due to potential effects on glycemic control 3, 4
• For patients with severe hypertriglyceridemia (>400 mg/dL), focus on triglyceride lowering first through glycemic control, fibrates, or high-dose statins 3, 5

Monitoring

• Check lipid levels every year in adults; if at low-risk levels, assessment may be repeated every 2 years 3
• After initiating therapy, laboratory follow-up between 4-12 weeks is recommended 2
• Once goals are achieved, monitor every 6-12 months 1, 2