The primary objective of this study is to determine whether among symptomatic Peripheral Arterial Disease (PAD) patients with no known Coronary Artery Disease (CAD) who had undergone lower-extremity revascularization, a strategy of best medical therapy (BMT) plus selective coronary revascularization based on FFRct assessment of lesion-specific coronary ischemia can reduce adverse cardiac events and improve survival compared to BMT alone. Lesion-specific coronary ischemia is defined as FFRCT ≤0.80 distal to stenosis in a major (≥2 mm) coronary artery with severe ischemia defined as FFRCT ≤0.75.

This study targets a population of patients with symptomatic PAD (CLTI or severe claudication in 1:1 ratio) and no prior cardiac history, no myocardial infarction, no coronary angiography or coronary computed tomography angiography (CTA), and no coronary revascularization (PCI or CABG) who have undergone successful lower extremity revascularization with planned post-operative best medical therapy. Within 14 days following lower-extremity revascularization, patients will be randomly assigned to BMT alone or BMT plus coronary CT angiography (which must be completed within 14 days of randomization) and Fractional Flow Reserve Derived from CT (FFRct) analysis to determine the functional significance of coronary lesions identified on the CT scan. Results of the CT scan and FFRCT analysis in patients randomized to the CT-FFRct group, will be provided to treating physicians to help guide patient management with Heart Team consideration for coronary angiography and revascularization as appropriate for each patient. Coronary revascularisation (PCI or CABG), if indicated, is strongly recommended within 3 months from the randomisation. Clinical follow up (based on date of randomization) is planned 6 months, one and 2 years. Additional long-term follow up out to 5-years is planned for participating centers. An independent academic clinical events committee will adjudicate all endpoints in a blinded manner. The definition of outcome events will be in accordance with Academic Research Consortium-2 consensus document.

Inclusion Criteria:

1. Inform consent obtained before any study-related activities;
2. Age above or equal to 50 years with symptomatic lower extremity PAD (severe claudication or chronic limb-threatening ischemia, Rutherford 3,4,5) which has been successfully revascularized by open surgical or endovascular procedure within the past 14 days;
3. Willing and able to undergo coronary CTA scan within 14 days of randomization and agrees to submission of CTA data set for HeartFlow FFRct analysis with results made available to treating physician.

Exclusion Criteria:

1. Known CAD, history of MI, prior coronary revascularization (PCI or CABG);
2. Patient underwent coronary angiography or coronary CTA before the randomization;
3. Known history of 2nd or 3rd degree heart block; sick sinus syndrome; long QT syndrome;
4. History of severe asthma, severe or bronchodilator-dependent Chronic obstructive pulmonary disease (COPD);
5. Severe congestive heart failure (NYHA III or IV);
6. Severe arrhythmia, prior pacemaker or internal defibrillator lead implantation;
7. Impaired chronic renal function (EPI-Glomerular Filtration Rate (GFR)<30ml/min);
8. Subjects with known anaphylactic allergy to iodinated contrast;
9. Pregnancy or unknown pregnancy status in subject of childbearing potential;
10. Evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), cardiogenic shock, unstable blood pressure with systolic blood pressure <90 mmHg, or acute pulmonary edema;
11. Any active, serious, life-threatening disease with a life expectancy of less than 2 years;
12. Any active infection;
13. Inability to comply with study procedures;
14. Contraindication for guideline-guided longterm antiplatelet/anticoagulation regime after PCI/CABG;
15. Participation in any interventional clinical study within 30 days prior to screening.

Patients with symptomatic PAD (CLTI or severe claudication in 1:1 ratio) and no prior cardiac history, no myocardial infarction, no coronary angiography or coronary CTA, and no coronary revascularization (PCI or CABG) who have undergone successful lower extremity revascularization with planned post-operative best medical therapy.