fenofibrate

Mechanism: Fenofibrate activates peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear transcription factor, upregulating lipoprotein lipase (LPL) expression and enhancing fatty acid oxidation in the liver. This increases clearance of triglyceride-rich lipoproteins (VLDL and chylomicrons) from plasma, lowering triglycerides by 30-50%. It also modestly increases HDL by upregulating apolipoproteins A-I and A-II, and can cause a slight increase or variable effect on LDL (sometimes increasing LDL particle size, making them less atherogenic).

Clinical use: Primarily indicated for severe hypertriglyceridemia (>500 mg/dL) to reduce risk of pancreatitis, and for mixed dyslipidemia. It is less effective than statins for cardiovascular risk reduction and is not first-line for LDL lowering.

Adverse effects: Myopathy/rhabdomyolysis (risk increased when combined with statins, though less than gemfibrozil), hepatotoxicity (monitor LFTs), cholelithiasis (due to increased cholesterol excretion into bile), and increased creatinine (usually reversible). Contraindicated in severe renal or hepatic impairment.

Drug interactions: Increased risk of myopathy when combined with statins; potentiates warfarin's anticoagulant effect (displaces from albumin, requires INR monitoring); can increase risk of gallstones.

Key boards association: Fibrates are the most effective class for lowering triglycerides. Compare with niacin (also lowers TG, raises HDL, but causes flushing) and statins (best for LDL lowering, most evidence for CV risk reduction).