Pharmacogenomics of Antiplatelet Response - II (PARes-II)

Phase 4

Completed

Brief Summary: This clinical trial is examining the effect of 4-week aspirin therapy on platelet transcriptome in persons at high-risk for myocardial infarction or stroke due to family history of early-onset coronary artery disease.

Detailed Description: Platelet aggregation can initiate thrombosis on ulcerated arterial plaques resulting in acute coronary syndrome (ACS). There is large variation in platelet aggregation between individuals. As the genetic message to the cell machinery is conveyed through its transcriptome, we hypothesize that much of the variability in platelet function can be explained by transcriptome changes including differences in gene or isoform expression, altered splicing events, or allele-specific expression. Moreover, aspirin modifies gene expression in several cells, but whether it also affects platelet transcriptome has not yet been studied. Our goal is to characterize the platelet transcriptome and identify genes that are up- or down-regulated after 4-week aspirin therapy. A major strength of our study is that it enrolls individuals from European Americans and African Americans and thus will have the ability to study similarities and differences between the two. The study will produce innovative comparative genomic/platelet phenotype data and will provide a potential pharmacogenomic and diagnostic template for the future discovery of novel antiplatelet regimens to prevent thrombosis-related cardiovascular disease events.

Recruitment & Eligibility

Inclusion Criteria

Participants from the GeneSTAR cohort
Unaffected with no overt coronary artery disease or serious vascular event (stroke or peripheral vascular disease diagnosis
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).

Arm && Interventions

Group	Intervention	Description
Aspirin	Aspirin	Participants treated with aspirin - there is no control group. Participant's baseline will act as their control.

Primary Outcome Measures

Name	Time	Method
Changes in Platelet Transcriptome	4 weeks	Comparison of platelet transcriptome before aspirin therapy with platelet transcriptome after aspirin therapy. The expression levels of genes before aspirin therapy was compared with the expression level of the genes after aspirin therapy. The expression levels were measured using the FPKM unit (Fragments Per Kilobase of transcript per Million mapped reads). The gene with the highest difference (pre vs. post) in FPKM is being reported with name in the units area and the actual difference in the number area

Secondary Outcome Measures