Hyperlipidemia involves elevated levels of lipids in the blood, increasing the risk of atherosclerosis, coronary artery disease, and stroke.
Anti-hyperlipidemic drugs aim to lower lipid levels, particularly low-density lipoprotein (LDL) cholesterol, and raise high-density lipoprotein (HDL) cholesterol.
Major Classes of Anti-Hyperlipidemic Drugs
1) Statins (HMG-CoA Reductase Inhibitors)
Examples: Atorvastatin, Simvastatin, Rosuvastatin
MOA: Inhibit HMG-CoA reductase, reducing cholesterol synthesis and upregulating LDL receptors for clearance.
Benefits: Lower LDL, reduce cardiovascular risks, and stabilize plaques.
Side Effects: Myopathy, rhabdomyolysis, elevated liver enzymes, GI disturbances.
Considerations: Monitor liver enzymes and use cautiously in liver disease.
2) Ezetimibe
Example: Ezetimibe (Zetia)
MOA: Blocks cholesterol absorption in the intestine by inhibiting NPC1L1 protein.
Benefits: Lowers LDL; effective alone or with statins.
Side Effects: Diarrhea, abdominal pain, elevated liver enzymes.
Considerations: Often combined with statins for enhanced LDL reduction.
3) Bile Acid Sequestrants
Examples: Cholestyramine, Colestipol, Colesevelam
MOA: Bind bile acids, promoting cholesterol conversion to bile acids and reducing LDL.
Benefits: Lower LDL; may increase HDL slightly.
Side Effects: GI issues (constipation, bloating), increased triglycerides, impaired vitamin absorption.
Considerations: Separate dosing from other medications and supplement fat-soluble vitamins if needed.
4) Fibrates
Examples: Gemfibrozil, Fenofibrate
MOA: Activate PPAR-α, enhancing fatty acid oxidation and lipase activity to lower triglycerides and increase HDL.
Benefits: Reduce triglycerides and raise HDL.
Side Effects: Myopathy (especially with statins), gallstones, elevated liver enzymes.
Considerations: Monitor liver and kidney function; caution with statin combinations.
5) Niacin (Vitamin B3)
Example: Niacin (Nicotinic Acid)
MOA: Reduces VLDL synthesis, lowering LDL and triglycerides while raising HDL.
Benefits: Improves overall lipid profile.
Side Effects: Flushing, hyperglycemia, hyperuricemia, hepatotoxicity.
Considerations: Aspirin can reduce flushing; monitor liver function at high doses.
6) PCSK9 Inhibitors
Examples: Alirocumab, Evolocumab
MOA: Monoclonal antibodies inhibiting PCSK9, promoting LDL receptor recycling and LDL clearance.
Benefits: Marked LDL reduction; effective in familial hypercholesterolemia or statin intolerance.
Side Effects: Injection site reactions, nasopharyngitis, neurocognitive effects.
Considerations: Given via subcutaneous injection, often combined with other therapies.
7) Omega-3 Fatty Acid Derivatives
Examples: Icosapent Ethyl (Vascepa)
MOA: Decrease triglyceride synthesis and VLDL production while promoting fatty acid oxidation.
Benefits: Lower triglycerides and reduce cardiovascular risk.
Side Effects: GI issues, elevated liver enzymes.
Considerations: May complement statin therapy for comprehensive lipid management.
Clinical Considerations:
Risk Assessment: Based on factors like LDL levels, cardiovascular risk, and presence of diabetes or existing atherosclerosis.
Combination Therapy: May be necessary for optimal lipid control.
Monitoring: Regular lipid panels, liver function tests, and assessment for muscle symptoms.
Lifestyle Modifications: Diet, exercise, and smoking cessation are fundamental alongside pharmacotherapy.