What drugs affect lipid profiles?

Drugs That Affect Lipid Profiles

Statins are the first-line therapy for lipid management, with additional agents such as ezetimibe, PCSK9 inhibitors, and bempedoic acid recommended for patients who don't achieve LDL-C goals or are statin-intolerant. 1

Primary Lipid-Modifying Medications

Statins

• First-line therapy for lipid management
• Mechanism: Inhibit HMG-CoA reductase, reducing cholesterol synthesis
• Efficacy:
  • High-intensity statins (atorvastatin 40-80mg, rosuvastatin 20-40mg) reduce LDL-C by ≥50% 1
  • Atorvastatin is the most effective statin tested in lowering cholesterol in LDL, non-HDL, and remnant lipoproteins 2
• Relative potency: Atorvastatin > simvastatin (85% of atorvastatin efficacy) > lovastatin (60%) > pravastatin (50%) > fluvastatin (33%) 2

Ezetimibe

• Add-on therapy to statins for additional LDL-C lowering
• Mechanism: Inhibits intestinal cholesterol absorption by blocking NPC1L1 protein
• Efficacy: Reduces LDL-C by an additional 20-25% when added to statins 1

PCSK9 Inhibitors

• Indicated for: Very high-risk patients not reaching goals with statins
• Examples: Alirocumab, evolocumab
• Mechanism: Block PCSK9 protein, increasing LDL receptor availability
• Efficacy: Reduce LDL-C by an additional 60% when added to statin therapy
• Administration: Subcutaneous injection every 2-4 weeks 1

Bempedoic Acid

• Indicated for: Statin-intolerant patients
• Mechanism: Inhibits ATP citrate lyase, reducing cholesterol synthesis
• Efficacy: Moderate LDL-C reduction 1

Additional Lipid-Modifying Medications

Fibrates (e.g., Fenofibrate)

• Primary indication: Hypertriglyceridemia 1, 3
• FDA-approved indications: Primary hypercholesterolemia, mixed dyslipidemia, severe hypertriglyceridemia 3
• Mechanism: PPAR-α agonists, increase lipoprotein lipase activity
• Effects on lipid profile:
  • Reduce triglycerides
  • Modestly increase HDL-C
  • Variable effects on LDL-C 1

Niacin

• Indicated for: Hypertriglyceridemia
• Effects on lipid profile:
  • Reduces triglycerides
  • Increases HDL-C
  • Modestly reduces LDL-C 1

Bile Acid Sequestrants

• Mechanism: Bind bile acids in intestine, increasing cholesterol conversion to bile acids
• Efficacy: Effective for decreasing LDL-C
• Safety: Generally safe option for statin-intolerant patients 4
• Caution: Should be avoided in patients with triglycerides >300 mg/dL 1

Omega-3 Fatty Acids

• Primary indication: Hypertriglyceridemia
• Efficacy: Effective for decreasing triglycerides
• Safety: Safe option for triglyceride management 4

Monitoring and Safety Considerations

Monitoring

• Check lipid profile 4-6 weeks after initiating therapy or changing doses
• Monitor liver function tests with statin therapy
• Once LDL-C goals achieved, monitor lipid profile every 6-12 months 1

Safety Concerns

1. Statins:

   • Myopathy and rhabdomyolysis (dose-related)
   • Increased risk with high-dose simvastatin (80mg should be avoided)
   • Drug interactions with cyclosporin, macrolides, azole antifungals 1, 4

2. Combination therapy:

   • Statin + fibrate: Increased myopathy risk, especially with gemfibrozil
   • Careful monitoring needed with multiple agents 1, 4

3. Fenofibrate-specific warnings:

   • Mortality and coronary heart disease morbidity
   • Hepatotoxicity
   • Myopathy and rhabdomyolysis
   • Serum creatinine elevation
   • Cholelithiasis
   • Interactions with coumarin anticoagulants
   • Pancreatitis 3

Special Patient Populations

Familial Hypercholesterolemia

• Combination therapy recommended: High-intensity statin + ezetimibe and/or PCSK9 inhibitor 1

Diabetes with Dyslipidemia

• Statins recommended as first-line therapy 1

Statin Intolerance

• Consider bempedoic acid, bile acid sequestrants, or omega-3 fatty acids 1, 4

Clinical Impact

• For each 1% reduction in LDL-C, there is approximately a 1% reduction in ASCVD risk
• Combination therapy valuable for high-risk patients 1
• Despite aggressive lipid lowering, residual cardiovascular risk remains in some patients 4