Apixaban + DAPT in Lowering Platelet Reactivity and Thrombin Generation

Combination anti-platelet therapies particularly those combining aspirin with a P2Y12
antagonist (DAPT) are regarded as the current standard of care therapy for patients with
Acute Coronary Syndrome (ACS). As thrombin potently induces platelet dense granular release
and causes secondary adenosine 5'-diphosphate (ADP)-mediated P2Y12 receptor activation,
apixaban via inhibition of thrombin generation may exhibit synergistic activity with direct
P2Y12 receptor blockers such as clopidogrel or ticagrelor. The results from the study will
provide a clearer understanding of how these antithrombotic agents work in combination and
how the anti-Xa, apixaban, may reduce the contribution of thrombin and general platelet
reactivity when used alone and in combination with antiplatelet agents. This study does NOT
involve administration of medication to subjects. Experiments will be performed on donated
blood samples from participants.

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures (i.e.,
venipuncture).

2. Male or female at least 18 years of age but equal to or less than 75 years of age.

3. Females must be post-menopausal for at least one year or surgically sterile for at
least 6 months.

4. For ACS Subjects:

1. Documented prior history of ACS within the past 12 months.

2. Currently prescribed a DAPT medication regimen of aspirin (81mg) plus a P2Y12
inhibitor, clopidogrel or ticagrelor, and none of the excluded medications listed
in Exclusion Criteria #4.

3. Have taken DAPT medication for at least 7 days as prescribed prior to blood
collection.

5. For Healthy Subjects:

1. Currently not prescribed and/or taking any of the excluded medications listed in
Exclusion Criteria #4.

Exclusion Criteria:

1. Male or female less than 18 or greater than 75 years of age.

2. No prior history of ACS within 12 months (unless Healthy Subject)

3. Pregnancy

4. Currently prescribed and/or taking any of the following medications:

Within the last 1 month:

- PAR-1 antagonist (vorapaxar/Zontivity®)

- Coumadin®

- Heparin including low molecular weight heparin (enoxaparin/Lovenox®)

- Factor Xa inhibitors (rivaroxaban/Xarelto®, apixaban/Eliquis®, edoxaban/Savaysa®,
betrixaban/Bevyxxa®)

- Direct thrombin inhibitors (hirudin, bivalirudin/Angiomax®, dabigatran/Pradaxa®)

Within last 10 days:

- Glycoprotein IIb/IIIa inhibitors (Eptifibatide/Integrilin®, Tirofiban/Aggrastat®,
Abciximab/ReoPro®)

- Acetylsalicylic Acid/Aspirin products (Alka-Seltzer®, Goody Powder®, BC Powder®,
Pepto Bismol®, Aggrenox®) (except aspirin as prescribed for DAPT participants)

Within last 3 days:

- Phosphodiesterase inhibitors (cilostazol/Pletal®)

- Adenosine reuptake inhibitors (dipyridamole/Persantine®)

- NSAIDs

- Decongestants

- Antidepressants or Anti-anxiety medications:

- Selective Serotonin Reuptake Inhibitors (SSRI) (fluoxetine/Prozac®,
sertraline/Zoloft®, paroxetine/Paxil®)

- Selective Norepinephrine Reuptake Inhibitors (SNRI) (venlafaxine/Effexor® or
duloxetine/Cymbalta®)

5. Diagnosed with or possessing significant renal dysfunction as defined by the
physician/investigator.