User:Ewingdo/sandbox/ENHANCE trial

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ENHANCE Trial (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression)

The ENHANCE trial (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression) was a clinical study designed to assess the effect of combination therapy with ezetimibe and simvastatin on the progression of atherosclerosis in patients with familial hypercholesterolemia. The study aimed to determine whether adding ezetimibe to statin therapy would provide additional benefits in reducing atherosclerotic plaque compared to statin therapy alone.

Background

Familial hypercholesterolemia (FH) is a genetic disorder characterized by extremely high levels of low-density lipoprotein (LDL) cholesterol, leading to an increased risk of early-onset cardiovascular disease. Statins are the primary treatment for lowering LDL cholesterol, but many patients with FH do not achieve optimal LDL levels with statin therapy alone. Ezetimibe, a cholesterol absorption inhibitor, can further reduce LDL levels when added to statin therapy. The ENHANCE trial sought to evaluate whether this combination therapy could lead to greater regression of atherosclerosis.

Study Design

The ENHANCE trial was a randomized, double-blind, multicenter study that enrolled 720 patients with heterozygous familial hypercholesterolemia. Participants were randomized to receive either a combination of ezetimibe (10 mg daily) and simvastatin (80 mg daily) or simvastatin alone (80 mg daily).

The primary endpoint was the change in the mean carotid intima-media thickness (CIMT) over two years, measured by B-mode ultrasound. Secondary endpoints included changes in lipid levels (LDL cholesterol, high-density lipoprotein [HDL] cholesterol, and triglycerides) and safety outcomes.

Key Findings

The results of the ENHANCE trial, published in 2008, showed the following outcomes:

  • Primary Endpoint: There was no significant difference between the ezetimibe/simvastatin group and the simvastatin-alone group in the change in mean CIMT over two years. Both groups showed similar progression of atherosclerosis.
  • Lipid Levels: The combination therapy significantly reduced LDL cholesterol levels more than simvastatin alone. However, this did not translate into a significant difference in CIMT progression.
  • Safety: The safety profiles of both treatment regimens were similar, with no unexpected adverse events.

Clinical Implications

The findings of the ENHANCE trial had important implications for the use of combination therapy with ezetimibe and statins in managing familial hypercholesterolemia and cardiovascular risk:

  • Atherosclerosis Progression: Despite greater reductions in LDL cholesterol, the addition of ezetimibe did not significantly affect the progression of atherosclerosis as measured by CIMT.
  • Lipid Management: The trial highlighted the complexity of lipid management and the need for further research to understand the clinical benefits of LDL cholesterol reduction beyond traditional measures of atherosclerosis.

Long-Term Impact

The ENHANCE trial sparked significant debate within the medical community regarding the surrogate endpoints used in cardiovascular research and the interpretation of lipid-lowering therapies. It underscored the importance of outcome-based studies to assess the true clinical benefits of new treatments.

References

Kastelein, J. J., et al. (2008). "Simvastatin with or without ezetimibe in familial hypercholesterolemia." New England Journal of Medicine, 358(14), 1431-1443. Rosenson, R. S., et al. (2009). "Ezetimibe: mechanism of action and clinical update." Clinical Lipidology, 4(4), 453-463. Cannon, C. P., et al. (2015). "Ezetimibe added to statin therapy after acute coronary syndromes." New England Journal of Medicine, 372(25), 2387-2397.

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