Simvastatin With or Without Ezetimibe and Atherothrombotic Biomarker Assessment

1. To assess the ex vivo effects of ezetimibe/simvastatin (E/S) (Vytorin 10/40mg) and simvastatin (S) (Zocor 40mg) on platelet and inflammation biomarkers in patients with documented metabolic syndrome.
2. To compare platelet-related effects including PAR-1 receptor inhibition of E/S with those of the established anti-platelet agents including aspirin, clopidogrel, intravenous and oral glycoprotein IIb/IIIa inhibitors.
3. To determine whether the addition of ezetimibe will yield extra protection beyond lipid modulation in the reduction of inflammation and platelet activation.

• simvastatin (Drug), also known as zocor: Subjects will receive 6 weeks of simvastatin 40 mg, after which atherothrombotic biomarker assessment will be studied.
• ezetimibe/simvastatin (Drug), also known as vytorin: Subjects will receive 6 weeks of ezetimibe/simvastatin 10/40 mg, after which atherothrombotic biomarker assessment will be studied.

Primary outcomes

• Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression [6 weeks]: Measured using whole blood flow cytometry

Secondary outcomes

• Biomarkers of Inflammation [6 weeks]

Sex: All, ages: 21 Years to any, accepts healthy volunteers

Inclusion Criteria:

1. Men and women greater than or equal to 21 years of age
2. Diagnosis of metabolic syndrome. We defined the presence of metabolic syndrome based on the US National Cholesterol Education Program's Adult Treatment Panel III guidelines. Specifically, metabolic syndrome will be diagnosed and documented when 3 of the following 5 characteristics will be present:

   * abdominal obesity, given as waist circumference for men > 102 cm, and for women > 88 cm
   * triglycerides > 150 mg/dL
   * HDL cholesterol < 40 mg/dL for men, and < 50 mg/dL for women
   * blood pressure > 130/85 mm Hg
   * fasting glucose > 100 mg/dL

Exclusion Criteria:

1. Patients will be excluded for a history of bleeding diathesis
2. drug or alcohol abuse
3. prothrombin time greater than 1.5 times control
4. platelet count < 100,000/mm3
5. hematocrit < 25%
6. creatinine > 4.0 mg/dl
7. surgery or angioplasty performed within 3 months or planned for the future
8. history of gastrointestinal or other bleeding
9. history of drug-induced disorders
10. trauma, cancer, rheumatic diseases, coronary artery disease or stroke
11. Patients participating in other investigational drug trials within one month of completion will be also excluded
12. Patients treated with intravenous platelet glycoprotein IIb/IIIa inhibitors or thienopyridines, within past 6 months
13. Patients treated with statins or aspirin within past four weeks

Participant flow

Outcome results

• Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression (Primary), Mean, ng/dl: Simvastatin 35.4 +/- 5.2; Simvastatin/Ezetimibe 34.5 +/- 5.4
• Biomarkers of Inflammation (Secondary), Mean, mg/dl: Simvastatin 3.51 +/- .48; Simvastatin/Ezetimibe 3.57 +/- .34

Adverse events

Other adverse events by term

• MICHAEL MILLER, MD, Principal investigator, University of Maryland, College Park
• VICTOR L. Serebruany, MD, PhD, Study director, President, HeartDrug Research LLC