Adenosine-induced Myocardial Blood Flow in Peripheral Artery Disease Patients

The purpose of the study is to assess the effect of blood flow to the heart when subjects are treated with ticagrelor (Brilinta) or clopidogrel (antiplatelet drugs that stop the blood from clumping together) in patients with Peripheral Artery Disease (PAD).

The effects of ticagrelor and clopidogrel on adenosine-induced myocardial blood flow (MBF) will be evaluated by cardiac 13N- ammonia positron emission tomography (PET) at rest (baseline), acute dosing on Day 1, and at short term dosing on Day 7.

Subjects receiving ticagrelor will have additional pharmacokinetic (PK) blood samples collected at specific time points to measure ticagrelor concentration in the blood. Subjects' participation will be approximatetly 6 weeks.

Eligibility Criteria:
Inclusion Criteria:

* Symptomatic lower extremity PAD defined by:
* Symptoms at the time of screening including classic claudication, other exertional leg discomfort associated with physical limitations from PAD, AND Ankle brachial index (ABI) measurement at Visit 1 needs to be \< 0.90. OR, Prior lower extremity revascularization for symptomatic and haemodynamically significant PAD greater than 30 days prior to randomisation, irrespective of present leg symptoms and the Ankle Brachial Index (ABI).
* Male and female ≥ 18 years of age and less than 60 yrs.
* Subjects must be taking clopidogrel (75mg/day) for at least 30 days prior to entry to study.

Exclusion Criteria:

* Participation in another clinical study with an investigational product during the last 30 days.
* History of ACS within the last 1 year.
* Hypersensitivity or contraindications to clopidogrel or ticagrelor.
* Need for chronic oral anticoagulant therapy or chronic low- molecular-weight heparin or long-term treatment with fondaparinux, warfarin, apixaban, rivoroxaban, and parenteral anticoagulants such as enoxeparin, and bivalirudin.
* Life expectancy \< 6 months based on investigator's judgment.
* Planned lower extremity revascularization (surgical or endovascular) in any vascular territory within the next 3 months or with current ischemic ulcers or gangrene.
* Planned major amputation due to PAD within the next 3 months or major amputation due to PAD within the last 30 days.
* Subjects who have suffered a stroke during the past 3 months.
* Dementia likely to jeopardize understanding of information pertinent to study conduct or compliance to study procedures
* Severe hypertension that may put the subject at risk.
* Subjects considered to be at risk of bradycardic events (e.g., known sick sinus syndrome or second or third degree AV block unless already treated with a permanent pacemaker.
* Known severe liver disease (e.g., ascites and/or clinical signs of coagulopathy).
* Renal failure requiring dialysis
* A known bleeding diathesis, haemostatic or coagulation disorder, or systemic bleeding, whether resolved or ongoing
* History of previous intracranial bleed at any time, gastrointestinal bleed within the past 6 months, or major surgery within 30 days (if the surgical wound is judged to be associated with an increased risk of bleeding).
* History of thrombocytopenia or neutropenia
* Females of child-bearing potential (i.e., those who are not chemically or surgically sterilized, post-menopausal who are not willing to use an accepted method of treatment OR who have a positive pregnancy test at screening.
* Concern for inability of the subject to comply with study procedures and/or follow-up (e.g., alcohol or drug abuse).