Peripheral arterial disease (PAD) is a condition where the blood vessels in the legs get blocked. It affects one out of every five adults over the age of 65. As it is the main cause of amputations, the NHS performs over 20,000 operations every year to prevent them. People with PAD benefit from tablets to thin their blood as this improves outcomes after surgery and prevents heart attacks and strokes. The main tablets for this purpose are aspirin and clopidogrel. These work in most people, but up to a third of patients do not get any benefit from them, as their bodies cannot process them. We call this resistance to therapy (RT).Because blood thinning is particularly important after operations people with RT may be at higher risk of their operation failing leading to amputation and/or problems such as heart attacks and strokes. Testing for RT has not traditionally been performed because it requires complex laboratory procedures. Recent development in technology now means that bedside tests are available for RT. We will use a simple beside test for RT in patients with severe PAD. We will use this test to see how many of these patients have RT and whether this affects their risk of complications after an operation. If we find that RT does affect outcomes for patients with PAD, the information obtained will be used to plan future research to determine if changing blood thinning therapy in people with CR improves their outcomes after surgery.

Patients with peripheral arterial disease, a condition whereby arteries in the legs become narrow or blocked, are not only at a higher risk of limb loss but also of suffering heart attacks and strokes. To manage this risk and to ensure surgery for the blocked arteries is successful, they are prescribed tablets to make their blood less sticky, called antiplatelet agents. Aspirin and clopidogrel are the two tablets most commonly prescribed for this purpose.

In some patients, these two tablets are not effective as expected, because of interactions with other medications they are on or because their bodies cannot process them. This is known as resistance to antiplatelet therapy.

The main aim of this study is to establish how common resistance to aspirin and clopidogrel is in patients with peripheral arterial disease.

Inclusion Criteria:

• Patients over the age of 18 years.
• Patients with severely symptomatic aorto-iliac and infra-inguinal peripheral arterial disease.
• Patients with the ability to provide written informed consent.
• Patients on antiplatelet therapy

Exclusion Criteria:

• Patients under the age of 18 years.
• Patients unable or unwilling to provide written informed consent.
• Patients with acute limb ischaemia of the lower limb.
• Patients with aneurysmal disease of the arteries of the lower limb.
• Patients with severe diabetic foot sepsis.
• Patients with a known history of clotting disorders
• Patients with inherited bleeding disorders

The population of interest is patients presenting electively or as an emergency with:

• Disabling intermittent claudication (Rutherford stage III)
• Ischaemic rest pain (Rutherford Stage IV)
• Minor tissue loss due to peripheral arterial disease (Rutherford Stage V)
• Ulceration or gangrene due to peripheral arterial disease (Rutherford Stage VI).

Patients presenting with diabetic foot infection or diabetic foot sepsis will not be considered for