Establishing the Microcirculatory Effects of Ticagrelor on Tissue Perfusion in Critical Limb Ischemia

Enrollment into the study will require severe symptomatic CLI without wounds (Rutherford
Stage IV) or CLI with concomitant vascular insufficiency wounds (Rutherford Stage V-VI PAD).

Potential participants will be identified and screened prior to discharge or at the time of
the first out-patient visit (within 2 weeks after discharge) after a percutaneous lower
extremity arterial angiography with arterial intervention (stent or balloon angioplasty) for
the presence of lower extremity vascular insufficiency. Participants will be classified as
Rutherford Class IV - VI (with or without ulcerations). A total of 60 patients will be
randomized into 2 treatment groups in a 1:1 ratio (ticagrelor to clopidogrel). Patients are
placed on clopidogrel after their arterial intervention per standard of care. They will
remain on clopidogrel up to the time that randomization occurs. For patients that are
randomized to ticagrelor, the clopidogrel will be stopped.

Patients will be randomized to either ticagrelor 90mg by mouth twice daily or clopidogrel
75mg by mouth daily.

Inclusion Criteria:

1. Adults age 18-100 years with Rutherford Classification Stage IV through VI PAD with a
recent percutaneous lower extremity arterial angiography with arterial intervention in
the past 2 weeks

2. Willingness to sign informed consent

3. Ability to return for follow up visits

4. A female patient of childbearing potential who is sexually active must agree to use
adequate contraception from screening until 30 days after receiving the last dose of
study drug. Women not of childbearing potential are defined as those who have
surgically sterilized (hysterectomy, bilateral oophorectomy, or tubal ligation) or who
are post menopausal (defined as at least 2 years since last regular menses). The
female patient should not be lactating and must have a negative pregnancy test at
screening.

Exclusion Criteria:

Patients will be ineligible for this study if they meet any one of the following criteria:

1. Intolerance to thienopyridines

2. Hypersensitivity to ticagrelor or any component of the product.

3. Concomitant use of oral anticoagulation with vitamin K antagonist, factor Xa
inhibitor, or direct thrombin inhibitor

4. History of intracranial hemorrhage

5. History of severe hepatic impairment defined by baseline transaminase greater than or
equal to 3x ULN or any elevation in bilirubin

6. Active bleeding

7. Allergy to aspirin

8. Baseline TcPO2 < 10 mmHg post angiography

9. Resting, pre- procedure heart rate <50 beats-per-minute without a permanent pacemaker
and not on an atrioventricular nodal blocking agent

10. Severe COPD on home oxygen therapy -