Does ezetimibe (Zetia) have a mortality benefit?

From the Guidelines

Ezetimibe has not been conclusively shown to provide a mortality benefit when used alone, and its primary role is as an adjunct therapy to statins for additional LDL reduction. The evidence for ezetimibe's impact on reducing death rates is limited, with the IMPROVE-IT trial demonstrating modest reductions in cardiovascular events but no statistically significant reduction in overall mortality when added to simvastatin therapy in high-risk patients with acute coronary syndrome 1. Key points to consider include:

• Ezetimibe effectively lowers LDL cholesterol by inhibiting intestinal cholesterol absorption
• The medication is generally well-tolerated with minimal side effects, typically dosed at 10 mg once daily with or without food
• Current evidence suggests that statins remain the primary lipid-lowering agents with established mortality benefits, while ezetimibe serves as a complementary therapy for additional LDL reduction without proven independent survival advantage 1
• The use of ezetimibe may be considered in patients with diabetes and a high risk of atherosclerotic cardiovascular disease, especially those with multiple risk factors or aged 50–70 years, to reduce LDL cholesterol levels by 50% or more when added to maximally tolerated statin therapy 1.

From the Research

Ezetimibe Mortality Benefit

• The study published in the Journal of clinical medicine research 2 found that ezetimibe in combination with a statin does not reduce all-cause mortality.
• A systematic review and meta-analysis published in The Cochrane database of systematic reviews 3 found that ezetimibe with statins probably reduces the risk of major adverse cardiovascular events, but has little or no effect on all-cause mortality.
• The IMPROVE-IT trial, cited in the study published in Cardiology research and practice 4, demonstrated a reduction in CV outcomes with ezetimibe when added to statin therapy, but did not specifically address all-cause mortality.
• The studies published in Clinical research in cardiology 5 and American journal of cardiovascular drugs 6 focused on the lipid-lowering efficacy of ezetimibe in combination with statins, but did not provide direct evidence on mortality benefit.

Key Findings

• Ezetimibe may reduce the risk of major adverse cardiovascular events when added to statin therapy 4, 3.
• Ezetimibe has little or no effect on all-cause mortality 2, 3.
• The combination of ezetimibe and statin is generally well tolerated 6.

Cardiovascular Events

• Ezetimibe with statins probably reduces the risk of non-fatal myocardial infarction and non-fatal stroke 3.
• The addition of ezetimibe to statin therapy may reduce the need for coronary revascularisation 3.