Is Ezetimibe (Zetia) a Statin?
No, ezetimibe (Zetia) is not a statin but rather a non-statin cholesterol-lowering medication that works by inhibiting intestinal cholesterol absorption through a different mechanism than statins. 1, 2
Mechanism of Action and Classification
- Ezetimibe belongs to a class of medications called cholesterol absorption inhibitors that work by reducing cholesterol absorption in the small intestine 3
- Unlike statins, which inhibit HMG-CoA reductase enzyme in the liver to reduce cholesterol synthesis, ezetimibe binds to the Niemann-Pick C1 Like 1 (NPC1L1) protein in the intestinal wall to prevent cholesterol absorption 3, 4
- Ezetimibe undergoes glucuronidation to form its active metabolite (ezetimibe-glucuronide), which has higher affinity for NPC1L1 than the parent compound 3
Efficacy as Monotherapy vs. Combination Therapy
- As monotherapy, ezetimibe reduces LDL cholesterol by approximately 18% 5, 3
- When added to statin therapy, ezetimibe provides an additional 25% reduction in LDL-C beyond what statins alone achieve 1, 5
- The complementary mechanisms of action (intestinal cholesterol absorption inhibition by ezetimibe and hepatic cholesterol synthesis inhibition by statins) make this combination particularly effective 6
Clinical Use and Indications
- Ezetimibe is FDA-approved as an adjunct to diet for reducing LDL-C in adults with primary hyperlipidemia, either alone or in combination with statin therapy 2
- It is particularly useful for patients who:
- Cannot achieve adequate LDL-C reduction with maximally tolerated statin therapy 1, 5
- Experience statin-induced myalgias or are intolerant to statins (defined as intolerant to 2 or more statins and failed alternate dosing therapy) 1, 7
- Require additional LDL-C lowering beyond what can be achieved with maximum-tolerated statin therapy 2, 6
Safety Profile
- Ezetimibe has a favorable safety profile compared to some other lipid-lowering medications 7
- It has minimal systemic absorption and undergoes enterohepatic recirculation, which limits peripheral exposure 3, 4
- Unlike statins, ezetimibe does not significantly affect the activity of major drug metabolizing enzymes (CYP450), reducing potential drug-drug interactions 3
- The most common side effects include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities 5
Important Clinical Considerations
- Ezetimibe should be administered once daily with or without food 2
- When used with bile acid sequestrants (another class of non-statin cholesterol-lowering drugs), ezetimibe should be taken either ≥2 hours before or ≥4 hours after the bile acid sequestrant to avoid reduced absorption 5, 4
- Ezetimibe is contraindicated during pregnancy and should be discontinued 1-2 months before attempting pregnancy 1
In summary, while both ezetimibe and statins lower cholesterol and reduce cardiovascular risk, they belong to different medication classes with distinct mechanisms of action. Ezetimibe is a cholesterol absorption inhibitor that targets intestinal cholesterol uptake, while statins inhibit cholesterol synthesis in the liver.