fibrates + niacin

**Fibrates + niacin** refers to the combination therapy of a **fibrate** (such as fenofibrate or gemfibrozil) and **niacin** (nicotinic acid or vitamin B3) for the management of dyslipidemia and associated cardiovascular risk. **Fibrates** act as agonists at the peroxisome proliferator-activated receptor alpha (PPARα), increasing the activity of lipoprotein lipase and thus enhancing the catabolism of triglyceride-rich particles, reducing triglycerides, and modestly increasing HDL cholesterol. **Niacin** reduces hepatic synthesis of VLDL and LDL cholesterol, lowers triglycerides, and increases HDL cholesterol, possibly by inhibiting the lipolysis of adipose tissue and reducing the hepatic synthesis of VLDL. The combination has been used historically to obtain synergistic effects on lipid profiles, particularly for patients with mixed dyslipidemia, hypertriglyceridemia, or low HDL cholesterol. However, the cardiovascular outcome evidence for this combination as add-on therapy to statins is lacking, and major regulatory agencies no longer recommend it due to insufficient added benefit and increased risk of adverse effects. Clinical trials (e.g., AIM-HIGH, HPS2-THRIVE, ACCORD) failed to demonstrate additional cardiovascular benefit compared to statin monotherapy, and there were concerns about increased risks (myopathy, liver dysfunction, etc.)[2][3][4].