What is the first line treatment for Hyperlipidemia (HLD)?

First-Line Treatment for Hyperlipidemia

Statins are the first-line pharmacological treatment for hyperlipidemia, specifically high-potency statins such as atorvastatin, rosuvastatin, or pitavastatin, combined with lifestyle modifications including dietary changes and regular exercise. 1

Treatment Algorithm

Step 1: Lifestyle Modifications (Always Initiate First)

• Dietary changes: Restrict saturated fat to <7% of total calories and dietary cholesterol to <200 mg/day 1
• Regular physical exercise and weight normalization 1
• Smoking cessation (mandatory counseling for all patients) 1
• Sodium restriction to <2.0 g/day 1
• Consider plant-based diet and avoid red meat 1

Step 2: Risk Stratification and LDL-C Goals

Determine ASCVD risk based on LDL-C, apolipoprotein B, triglycerides, lipoprotein(a) levels, age, and risk enhancers 1:

• No ASCVD or major risk factors: LDL-C goal <100 mg/dL (2.6 mmol/L) 1
• ASCVD on imaging or other major risk factors: LDL-C goal <70 mg/dL (1.8 mmol/L) 1
• Clinical ASCVD present: LDL-C goal <55 mg/dL (1.4 mmol/L) 1
• Recurrent ASCVD event within 2 years: Consider LDL-C goal <40 mg/dL (1.0 mmol/L) 1

Step 3: Pharmacological Therapy

Primary therapy: Initiate maximally tolerated high-potency statin (atorvastatin, rosuvastatin, or pitavastatin) 1

When to start pharmacotherapy:

• If LDL-C exceeds goal by >25 mg/dL, initiate statin therapy simultaneously with lifestyle modifications in high-risk patients 1
• For lower-risk patients, trial lifestyle modifications for 3-6 months before adding pharmacotherapy 1
• In patients with clinical cardiovascular disease or LDL-C >200 mg/dL, start pharmacotherapy immediately with lifestyle changes 1

Step 4: Escalation if Goals Not Met

Add sequentially as needed 1:

1. Ezetimibe (add to statin)
2. Bempedoic acid (if available, add to statin ± ezetimibe)
3. PCSK9-targeted therapy (monoclonal antibodies or inclisiran) if goals still not achieved with maximally tolerated statin, ezetimibe, and bempedoic acid 1

For extremely high-risk patients (post-MI, multivessel coronary disease, polyvascular disease): Consider combination of high-potency statin + ezetimibe + PCSK9 inhibitor as first-line treatment 1

Special Considerations

Hypertriglyceridemia

• Triglycerides ≥1500 mg/dL: Gemfibrozil 600 mg twice daily is first-line to prevent pancreatitis 2
• Triglycerides 500-1500 mg/dL: Gemfibrozil or fenofibrate can be used 2
• Combined hyperlipidemia (elevated LDL-C and triglycerides): High-dose statin is first choice; if combination therapy needed, prefer fenofibrate over gemfibrozil when combining with statins due to lower myopathy risk 1, 2

Monitoring

• Measure fasting lipid profile when making treatment decisions, especially with concomitant hypertriglyceridemia 1
• Monitor hepatic aminotransferases before starting statins and during therapy in high-risk patients 1
• Monitor creatine kinase if musculoskeletal symptoms develop 1
• Monitor glucose/HbA1c if diabetes risk factors present 1

Common Pitfalls

• Do not use nicotinic acid as first-line in diabetic patients due to adverse effects on glycemic control 1
• Avoid gemfibrozil-statin combinations when possible; fenofibrate has lower myopathy risk if combination therapy required 2
• Continue lipid-lowering therapy during acute illness (including COVID-19) unless specifically contraindicated 1

Pediatric Considerations

• Statins can be initiated in children aged >8 years with concerning family history or extremely elevated LDL-C or Lp(a), with informed shared decision-making 1
• Consider pharmacological therapy if LDL-C ≥190 mg/dL without other risk factors, or ≥160 mg/dL with other risk factors present 1