Overview

Vascular Effects of Ezetimibe/Simvastatin and Simvastatin on Atherosclerosis

Status:
Completed

Trial end date:
2008-02-01

Target enrollment:
0

Participant gender:
All

Summary

Multiple clinical trials, using 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), have shown benefit in the primary and secondary prevention of atherosclerotic complications. However, till now, there is an incomplete understanding of all the mechanisms of the biologic effects of statins beyond LDL cholesterol (LDL-C) reduction, but there is accumulating evidence that the Rho-GTP/Rho-Kinase pathway (Rho/Rho-K) plays an important role and may be a strategic therapeutic target in cardiovascular diseases. With similar LDL-C reduction ability, the availability of Ezetimibe offers the potential to begin to address the question whether some of the benefits conferred by statins may accrue independently of their effects on LDL-C lowering. A better understanding of the role of the Rho/Rho-kinase signaling pathway in the pathogenesis of atherosclerosis in human is essential. Inhibition of Rho/Rho-kinase by statins may explain some of the biological beneficial effects of statins observed in clinical trials. This study aims to translate into patients important experimental discoveries regarding the initiation of inflammation in atherosclerosis in an attempt to improve upon the present treatment of cardiovascular diseases.

Phase:

Phase 4

Accepts Healthy Volunteers?

Details

Lead Sponsor:

National Cheng-Kung University Hospital

Treatments:

Ezetimibe
Ezetimibe, Simvastatin Drug Combination
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin

Criteria

Inclusion Criteria:

- Inclusion Criteria:

1. Male or female subjects aged 40 to 80 years

2. Documented stable atherosclerosis by angiography or vascular ultrasound (more
that 20% luminal narrowing), peripheral arterial disease or type 2 diabetes
mellitus (coronary heart disease (CHD) risk equivalent - Adult Treatment Program
(ATP)-III guidelines)

3. LDL-cholesterol >100mg/dL (indication to treat with statin)

4. Written informed consent

5. Primary care physician authorization letter to participate in the study.

- Exclusion criteria:

1. Inability to give consent

2. Pre-menopausal women

3. Current use of antibiotics, anti-inflammatory or immunosuppressant drugs

4. History of LFT >2 times the upper normal limit

5. History of myopathy / myositis or CPK > 10 times the upper normal limit

6. CPK above normal limits at study onset

7. Any evidence of inflammatory, infectious or neoplastic disease

8. History of CABG, PCI or acute ischemic syndrome in the preceding 3 months.