What drugs affect lipid profiles?

Drugs that Affect Lipid Profile

Statins are the cornerstone of lipid-lowering therapy, with high-intensity statins (atorvastatin 40-80 mg and rosuvastatin 20-40 mg) being most effective at reducing LDL-C by ≥50% from baseline. 1 Other classes of medications that affect lipid profiles include ezetimibe, bile acid sequestrants, PCSK9 inhibitors, fibrates, and niacin, each with distinct effects on different lipid parameters.

Major Drug Classes and Their Effects on Lipid Parameters

Statins

• Mechanism: Inhibit HMG-CoA reductase, reducing cholesterol synthesis
• LDL-C reduction: 35-55% (high-intensity)
• HDL-C effect: Modest increase (5-15%)
• Triglyceride effect: Moderate reduction (7-30%)
• Examples: Atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, pitavastatin 2
• Comparative efficacy: At equivalent doses, atorvastatin has approximately 85% greater efficacy than simvastatin, with fluvastatin, pravastatin, and lovastatin having about 33%, 50%, and 60% of atorvastatin's efficacy, respectively 3

Ezetimibe

• Mechanism: Inhibits intestinal cholesterol absorption
• LDL-C reduction: 18-25%
• HDL-C effect: Minimal effect
• Triglyceride effect: Minimal effect
• Use: Often added to statins for additional LDL-C lowering 2

Bile Acid Sequestrants

• Mechanism: Bind bile acids in intestine, preventing reabsorption
• LDL-C reduction: 15-30%
• HDL-C effect: Minimal increase
• Triglyceride effect: May increase triglycerides
• Examples: Cholestyramine, colestipol, colesevelam
• Caution: Contraindicated in patients with triglycerides >300 mg/dL 2

PCSK9 Inhibitors

• Mechanism: Monoclonal antibodies that increase LDL receptor availability
• LDL-C reduction: 40-65%
• HDL-C effect: Slight increase
• Triglyceride effect: Modest reduction
• Examples: Evolocumab, alirocumab
• Administration: Subcutaneous injection every 2-4 weeks 2, 1

Fibrates

• Mechanism: Activate peroxisome proliferator-activated receptors (PPARs)
• LDL-C reduction: 5-15% (variable)
• HDL-C effect: Significant increase (15-25%)
• Triglyceride effect: Substantial reduction (30-50%)
• Examples: Gemfibrozil, fenofibrate, bezafibrate
• Primary indication: Severe hypertriglyceridemia 2, 4

Niacin (Nicotinic Acid)

• Mechanism: Multiple effects on lipid metabolism
• LDL-C reduction: 15-25%
• HDL-C effect: Substantial increase (15-35%)
• Triglyceride effect: Significant reduction (20-50%)
• Formulations: Immediate-release, extended-release, sustained-release
• Limitations: Side effects (flushing, hyperglycemia) limit use 2

Emerging Therapies

Bempedoic Acid

• Mechanism: ATP citrate lyase inhibitor
• LDL-C reduction: 20-28%
• Advantage: Alternative for statin-intolerant patients 2, 1

CETP Inhibitors

• Mechanism: Inhibit cholesterol ester transfer protein
• LDL-C reduction: 20-30%
• HDL-C effect: Substantial increase (80-100%)
• Examples: Anacetrapib, evacetrapib 2

Clinical Considerations

Drug Selection Algorithm

1. First-line therapy: Statins (intensity based on ASCVD risk)
2. If LDL-C goal not achieved: Add ezetimibe
3. If still not at goal: Consider PCSK9 inhibitor (for very high-risk patients) or bempedoic acid (for statin-intolerant patients)
4. For hypertriglyceridemia: Consider fibrates or niacin 2

Special Populations

• Familial hypercholesterolemia: May require combination therapy with high-intensity statin plus ezetimibe and/or PCSK9 inhibitor 2
• Diabetes with dyslipidemia: Statins are first-line; atorvastatin has shown benefits in shifting LDL particle size from small, dense to larger, less atherogenic particles 5
• Statin intolerance: Consider ezetimibe, bempedoic acid, or PCSK9 inhibitors 1

Important Cautions

• Drug interactions: Statins may interact with certain medications (e.g., cyclosporin, macrolides, azole antifungals) increasing myopathy risk 2
• Simvastatin 80 mg: Not recommended due to increased risk of myopathy and rhabdomyolysis 2, 1
• Fibrates with statins: Increased risk of myopathy, especially with gemfibrozil 2
• Bile acid sequestrants: Can increase triglycerides; avoid in patients with triglycerides >300 mg/dL 2

Monitoring Recommendations

• Check lipid profile 4-6 weeks after initiating therapy or changing doses
• Monitor liver function tests with statin therapy
• For patients on combination therapy, monitor for drug-specific adverse effects
• Once LDL-C goals are achieved, monitor lipid profile every 6-12 months 2

Understanding the distinct effects of each drug class on different lipid parameters allows for targeted therapy based on the specific lipid abnormalities present in individual patients.