Can ezetimibe and atorvastatin (HMG-CoA reductase inhibitor) be taken together?

Ezetimibe and Atorvastatin Combination Therapy for Lipid Management

Ezetimibe and atorvastatin can be safely and effectively taken together as a combination therapy for enhanced lipid-lowering effects in patients requiring additional LDL-cholesterol reduction.

Mechanism and Indications

• Ezetimibe inhibits the NPC1L1 protein, reducing cholesterol absorption in the small intestine, while atorvastatin (an HMG-CoA reductase inhibitor) decreases cholesterol production in the liver, providing complementary mechanisms for LDL-C reduction 1
• Ezetimibe is FDA-approved for use in combination with statins (including atorvastatin) as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia 2
• The combination of ezetimibe with atorvastatin is particularly beneficial for patients who cannot achieve adequate LDL-C reduction with maximally tolerated statin therapy alone 1, 3

Efficacy of Combination Therapy

• Adding ezetimibe 10 mg to atorvastatin provides an additional 15-25% reduction in LDL-C beyond statin monotherapy alone 3, 4
• The combination therapy results in significantly greater reductions in total cholesterol, triglycerides, non-HDL cholesterol, and apolipoprotein B compared to atorvastatin monotherapy 5
• Studies comparing the lipid-lowering efficacy of atorvastatin-ezetimibe combination with statin dose titration consistently show that combination therapy provides greater LDL-C reduction and helps more patients achieve their lipid goals 6, 5

Clinical Guidelines Supporting Combination Use

• The 2022 ACC Expert Consensus recommends adding ezetimibe to maximally tolerated statin therapy when LDL-C targets are not achieved with statin monotherapy 1
• The International Stroke Organization recommends that in patients with ischemic stroke/TIA and atherosclerotic disease, ezetimibe can be added to atorvastatin to reach the target LDL-C goal of <1.8 mmol/L (70 mg/dL) 1
• The International Lipid Expert Panel (ILEP) recommends upfront lipid-lowering combination therapy with a high-intensity statin (if tolerated) and ezetimibe for high-risk patients 1

Safety Profile

• Ezetimibe and atorvastatin combination is generally well tolerated with a safety profile comparable to statin monotherapy 4, 6
• Common adverse effects when ezetimibe is used with statins include nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, diarrhea, back pain, influenza, pain in extremity, and fatigue 2
• When taking ezetimibe with atorvastatin, monitoring of hepatic transaminases is recommended before and during treatment based on monitoring recommendations for statin therapy 1, 2
• Cases of myopathy and rhabdomyolysis have been reported with ezetimibe alone or in combination with statin therapy, though these are relatively rare 1, 2

Administration Considerations

• Ezetimibe 10 mg can be taken orally once daily, with or without food, alongside any dose of atorvastatin 2
• If also taking bile acid sequestrants, administer ezetimibe either ≥2 hours before or ≥4 hours after the bile acid sequestrant 2
• Fixed-dose combinations of ezetimibe and atorvastatin are available in some countries and may improve medication adherence 4, 6

Special Populations

• In patients ≥65 years of age, adding ezetimibe to atorvastatin 10 mg produces significantly greater favorable changes in lipid parameters compared to doubling or quadrupling the atorvastatin dose 5
• For patients with type 2 diabetes and acute coronary syndrome, the combination of ezetimibe and atorvastatin has shown superior efficacy in lipid control compared to atorvastatin alone 7
• The combination therapy is particularly beneficial for high-risk patients who need additional LDL-C lowering beyond what can be achieved with statin monotherapy 3, 6

Conclusion

The combination of ezetimibe and atorvastatin represents an effective approach for enhanced lipid management, particularly for patients who cannot achieve target LDL-C levels with statin monotherapy alone. This combination leverages complementary mechanisms of action to provide superior lipid-lowering effects with an acceptable safety profile.