AIM III is a prospective, randomized, double-blinded, placebo controlled trial. The study is directly connected to IRB 08-008161 as a specific aim of the National Institute of Health (NIH) grant. Participants may either consent to and qualify for AIM I and AIM II (IRB 08-008161) or have a cardiac catheterization with acetylcholine testing in the Cardiac Catheterization Laboratory at Mayo Clinic in Rochester, Minnesota to be considered for this study.

The main goal of AIM III is to assess and quantify the effect of long-term administration of darapladib 160 mg once a day, a selective, reversible, orally active inhibitor of plasma and vascular Lp-PLA2, on coronary endothelial function, progression of coronary atherosclerosis as determined by intravascular ultrasound (IVUS), and atherosclerosis in patients with early atherosclerosis. Patients with evidence of coronary endothelial dysfunction, as determined by intracoronary administration of acetylcholine during angiography and IVUS, will be followed for 6 months during once daily dosing of darapladib. Coronary endothelial function is determined by the changes in coronary artery diameter and coronary blood flow response to the intracoronary administration of acetylcholine and adenosine. The patients will be followed in clinic 6 months. They will have follow-up angiography, assessment of endothelial function, and IVUS during the six month visit.

Inclusion Criteria:

1. Patients undergoing coronary angiography including endothelial function testing with the medication acetylcholine in the cardiac catheterization laboratory at Mayo Clinic. Patients may be enrolled in AIM I and AIM II IRB 08-008161 :Lp-PLA2, Progenitor Cells and Atherosclerosis in Humans".
2. Male or female aged at least 18 years, inclusive, at screening. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator in accordance with local practice in relation to adequate contraception.
3. Age greater than 18 up to age 85

Exclusion Criteria:

1. Current severe heart failure New York Heart Association class III or IV with ejection fraction less than 40%
2. Unstable angina
3. Myocardial infarction or angioplasty within 6 months prior to entry into the study
4. Planned coronary revascularization (PCI or CABG)
5. Planned major surgical procedure
6. Patients with segments with endothelial dysfunction of less than 10 mm in length or complete occlusion will be excluded.
7. Angiographic exclusion criteria include left main disease with greater than 30% stenosis on angiogram, luminal diameter of the study vessel less than 2.5 mm, severe tortuousity of the study vessel, or any other relevant anatomical reasons that the investigator deems inappropriate for the study.
8. Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase > 1.5 x upper limit of normal (UNL); or alanine transaminase (ALT) or aspartate amino transferase (AST) > 2.5 x UNL or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
9. Chronic or acute kidney disease with serum creatinine greater than or equal to 2 mg/dL or estimated glomerular filtration rate <40 mL/min/1.73m2, renal transplant status, history of contrast nephropathy,
10. Poorly controlled hypertension despite lifestyle modifications and pharmacotherapy. (systolic BP >160 mm Hg and/or diastolic BP >110 mm Hg),
11. Poorly controlled diabetes mellitus (HbA1c >10%),
12. Current or within 1 month use of any form of corticosteroids,
13. Severe asthma that is poorly controlled on pharmacotherapy
14. History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions
15. Current life-threatening conditions other than vascular disease, alcohol or drug abuse within the last 6 months
16. Malignancy within the past 5 years,
17. Positive pregnancy test (all female subjects of childbearing potential must have a urine β-human chorionic gonadotropin (hCG) pregnancy test performed at Screening and/or within 7 days prior to randomization) or is known to be pregnant or lactating.
18. Current or planned chronic administration of strong oral or injectable cytochrome P-450 isoenzyme 3A4 (CYP3A4) inhibitors.
19. Subjects with both parents of Japanese, Chinese, or Korean ancestry must have a blood sample collected for assessment of Lp-PLA2 activity by the central laboratory prior to randomization. Those with Lp-PLA2 activity ≤10 nmol/min/mL will be excluded from participation in the study.
20. Previous exposure to darapladib (SB-480848).
21. Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of the study medication, or any subject the investigator deems unsuitable for the study
22. Patients who require treatment with positive inotropic agents other than digoxin during the study
23. Patients with cerebrovascular accident within 6 months prior to entry into the study
24. Significant endocrine, hepatic or renal disorders
25. Local or systemic infectious disease within 4 weeks prior to entry into study
26. Mental instability
27. Federal Medical Center inmates
28. Hemoglobin less than 12 mg/dL

The baseline characteristics table only includes subjects who completed the study.

6 months