Six classes side by side: how each works, what it does to low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides, and what to warn about.
| Class and examples | How it works | Effect on low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides | Signature adverse effect | Do not use / cautions | Patient education | Source |
|---|---|---|---|---|---|---|
| Statins atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin | Block cholesterol synthesis in the liver, so the liver makes more low-density lipoprotein (LDL) cholesterol receptors and removes more LDL from the blood | LDL ↓ 18-55% (largest fall of the single oral agents) high-density lipoprotein (HDL) cholesterol ↑ 5-15% Triglycerides ↓ 7-30% | Muscle toxicity (myalgia, myopathy, rare rhabdomyolysis); liver enzyme rise | Contraindicated in active hepatic disease and pregnancy. CYP3A4 (cytochrome P450 3A4) interactions: verapamil, amiodarone, grapefruit juice. Niacin and fibrates also raise the risk of muscle toxicity | Report muscle symptoms; avoid grapefruit juice (mainly with atorvastatin, lovastatin and simvastatin); not for use in pregnancy, stop if pregnancy occurs | L7 slide 61 slide 18 slide 22 slide 21 slide 23 slide 24 |
| Ezetimibe Zetia | Blocks cholesterol absorption in the intestine, so less cholesterol reaches the liver and liver low-density lipoprotein (LDL) cholesterol receptors increase | LDL ↓ 18% high-density lipoprotein (HDL) cholesterol insignificant Triglycerides ↓ 8% (adds 15%-20% more LDL lowering to a statin) | Gastrointestinal effects; raised liver transaminases with a statin | No contraindication stated. Fibrates raise gallstone and muscle risk; bile acid sequestrants and antacids lower levels; cyclosporine raises them | Take with or without meals; tell the prescriber about antacids and bile acid sequestrants, which lower its levels | L7 slide 61 slide 28 slide 29 slide 30 slide 31 |
| Bile acid sequestrants cholestyramine, colestipol, colesevelam | Bind bile acids in the gut so they are lost in the feces; the liver makes more bile acids and more low-density lipoprotein (LDL) cholesterol receptors | LDL ↓ 15-50% high-density lipoprotein (HDL) cholesterol ↑ 3-5% Triglycerides no change or ↑ | Bloating, flatulence, constipation; malabsorption of vitamins A, D, E, K and folic acid; may raise triglycerides | Absolute: triglycerides above 400 mg/dL, familial dysbetalipoproteinemia. Relative: triglycerides above 200 mg/dL. Binds other drugs (digoxin, warfarin, thyroxine, beta blockers, thiazides) | Mix powder in water or pulpy juice; take within 1 hour of a meal; other drugs 1 hour before or 4 hours after. Approved in children and pregnancy | L7 slide 61 slide 42 slide 46 slide 48 slide 47 slide 45 |
| Fibrates gemfibrozil, fenofibrate, bezafibrate | Activate peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear transcription factor: less secretion of triglyceride-rich very low-density lipoprotein (VLDL), and more apoprotein A-1, which raises high-density lipoprotein (HDL) cholesterol | low-density lipoprotein (LDL) cholesterol ↓ 5-20% HDL ↑ 10-35% Triglycerides ↓ 20-50% | Gastrointestinal effects; cholelithiasis; myopathy | Contraindicated in pregnancy, severe hepatic or renal dysfunction, existing gallbladder disease. Increases the anticoagulant effect of warfarin | Primary use: triglycerides above 1000 mg/dL or low HDL; watch for bruising or bleeding on warfarin; report muscle symptoms | L7 slide 61 slide 34 slide 36 slide 37 slide 38 slide 39 |
| Niacin nicotinic acid, vitamin B3; Niaspan (extended release), Niacor (immediate release) | Reduces free fatty acid mobilization and liver production of very low-density lipoprotein (VLDL) and apoprotein B, so less low-density lipoprotein (LDL) cholesterol forms | LDL ↓ 5-25% high-density lipoprotein (HDL) cholesterol ↑ 15-35% (with fibrates, the largest rise) Triglycerides ↓ 20-50% | Cutaneous flushing (prostaglandin mediated); nausea; raised liver enzymes, glucose and uric acid at larger doses | Absolute: chronic liver disease. Relative: peptic ulcer disease, symptomatic gout, significant hyperuricemia, diabetes. Interacts with statins, bile acid sequestrants, alcohol | Premedicate with aspirin to minimize flushing; use niacin, not niacinamide, which is not effective | L7 slide 61 slide 53 slide 55 slide 56 slide 57 slide 50 |
| PCSK9 inhibitors alirocumab (Praluent), evolocumab (Repatha) | Monoclonal antibodies that bind and block proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that marks liver low-density lipoprotein (LDL) cholesterol receptors for breakdown, so the receptors stay active longer | LDL ↓ 43-58% high-density lipoprotein (HDL) cholesterol and triglyceride effects not given | Hypersensitivity reactions (the most serious adverse reaction) | No contraindication listed; prior serious allergic reaction to the drug rules out further use; expensive | Injectable only; report allergic reactions | L7 slide 60 slide 60 |
| Lovastatin plus niacin Advicor (combination product) | Combines a statin with extended release niacin | low-density lipoprotein (LDL) cholesterol ↓ ~50% high-density lipoprotein (HDL) cholesterol ↑ ~30% Triglycerides ↓ ~40% | Hepatotoxicity, myopathy and flushing | Carries the cautions of both drugs (see the statin and niacin rows) | Report muscle symptoms; expect flushing | L7 slide 59 slide 59 |