Pharmacogenomics of Antiplatelet Response - I
Condition: Platelet Aggregation; Platelet Transcriptome; Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Intervention: Clopidogrel; Aspirin
Intervention description: Clopidogrel 75 mg daily; Aspirin 81 mg daily
Intervention MeSH terms: Aspirin; Clopidogrel
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 45 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Platelet aggregation; Clopidogrel; Platelet transcriptome

Summary:

      This clinical trial is examining the role of genetic polymorphism on the effect of
      clopidogrel (with or without aspirin) on platelet response in persons at high-risk for
      myocardial infarction or stroke due to family history of early-onset coronary artery disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants from the GeneSTAR cohort

          -  Unaffected with no overt coronary artery disease or serious vascular event (stroke or
             peripheral vascular disease diagnosis

          -  Presence of an occult coronary artery disease phenotype as defined by coronary artery
             calcium scores about the MESA (Multiethnic Study of Atherosclerosis) 75th percentile
             for age sex, and race or ≥ 1 stenoses in any of the major coronary arteries or main
             branches of > 50%, or coronary plaque volumetric scores above our own 75th percentile,
             or any combination on cardiac computed tomographic angiography (performed recently as
             part of the GeneSTAR study and present for all persons being recruited)/

          -  Presence of occult cerebrovascular disease defined as presence of white matter
             hyperintensities (WMH) thought to represent ischemic small vessel cerebrovascular
             disease, and /or the presence of lacunes (old small strokes), or the presence of an
             Atherosclerosis Risk in Communities Study (ARIC) silent stroke score on a visual
             analogue scales of 4 or more (on a scale of 0-9).

          -  Women who are postmenopausal.

          -  Women who use a reliable contraceptive method; a reliable contraceptive method will be
             defined as personal history of tubal ligation, ongoing use of intra-uterine device, or
             ongoing use of oral contraceptive pills.

        Exclusion Criteria:

          -  Presence of any CAD or stroke, transient ischemic attacks, peripheral arterial disease

          -  Persons taking aspirin, NSAIDS, or any anti-coagulants who are medically unable to
             stop them for a two week pre-trial

          -  A history of allergy to aspirin or clopidogrel

          -  Weight < 60kg

          -  Age < 45 and > 75 years of age

          -  A history of recent or any active bleeding

          -  Serious or current co-morbidity (AIDS, cancer)

          -  Pregnant women as determined by urine dipstick pregnancy test

          -  Any aneurysms on cranial magnetic resonance imaging/magnetic resonance angiography
             (obtained recently in the GeneSTAR participants)

          -  Blood pressure above >=159/95mmHg

          -  History of a gastric or duodenal ulcer, or significant gastrointestinal disease, like
             regional enteritis

          -  Mental incompetence to make a decision to participate (developmentally disabled, and
             persons with diagnosed psychiatric disorders-documented in primary care records).