Introduction

Have you ever had an interest in understanding diseases associated with our arteries? Ever wondered about the differences between the different pathologies? In this article, we will be reviewing a particular case known as Peripheral Artery Disease (PAD).

About 8 to 12 million people in the US suffer from peripheral arterial disease (PAD), a very common atherosclerotic illness that is linked to substantial morbidity and mortality.¹ So, what is PAD? Any condition that causes stenosis or blockage of the lower limb arteries can result in PAD, with atherosclerotic disease being the most prevalent cause.²

This issue is sometimes known as "poor circulation" or peripheral vascular disease (PVD).³ In order to have a better understanding of this, it is important to understand atherosclerosis; it is a multifactorial, immunoinflammatory and smouldering disease driven by lipids that affects medium and large-sized arteries.⁴ We can classify atherosclerosis into different groups:

• Atherosclerosis of the heart arteries: causes angina and myocardial infarction. It is known as coronary artery disease³
• Atherosclerosis of the neck and brain arteries: causes strokes. It is known as cerebrovascular disease³
• Atherosclerosis of the arm and leg arteries as well as aorta: it is known as PAD³

Physicians are realising that PAD is far more common than previously believed. Research that has been published indicates that more than 1 in 5 adults over 70 have PAD.³ Less than half of PAD sufferers are aware that they have an issue. Furthermore, many patients with PAD do not exhibit symptoms in their legs, and the only way to detect the condition is through an Ankle-Brachial Index (ABI) test or a doctor's examination.³

Individuals suffering from PAD-related leg pain may find it difficult to exercise, walk, go shopping, work, or clean their houses. One's quality of life may deteriorate due to PAD-related leg pain. More importantly, individuals with PAD probably have blockages in other bodily arteries, particularly in the heart and brain arteries.³ Compared to those without PAD, PAD patients have a 3–6 times higher risk of experiencing a heart attack or stroke.³ Hence, it is important to manage PAD and diagnose it for proper treatment.

One of the treatment options for PAD is something called antiplatelet therapy; according to data from the Antithrombotic Trialists' Collaboration, antiplatelet therapy lowers the risk of unfavourable cardiovascular events in patients with PAD by 23%.² Drugs that disrupt the function of platelets can be classified into three groups:

1. Primary prevention which prevents cardiovascular disease⁵
2. Drugs that treat acute disease⁵
3. Secondary prevention which treats chronic disease⁵

These drugs can be administered orally or intravenously and are used to treat patients with cerebrovascular and cardiac illnesses.⁵

Understanding peripheral artery disease

Causes and risk factors

These can be summarised into 2 categories: non-modifiable risk factors and modifiable risk factors.

Table 1. Modifiable and non-modifiable risk factors for PAD.²

Symptoms

Many people with PAD are asymptomatic, even moderately severe cases, however, some symptoms include:²

1. Intermittent claudication (IC): most common symptom. It represents pain/weakness of leg muscles during activity and elevated during rest
2. Rest pain: in more severe cases, often at night. Pain in the feet/toes during rest is a symptom
3. Coolness/weakness of legs
4. Changes to skin colour

Diagnosis

Diagnosis and assessment of PAD can be summarised below:²

1. Physical assessment
2. Hand-held Doppler
3. Ankle-Brachial Index
4. Blood tests
5. Magnetic Resonance Angiography (MRA) or Computed Tomography Angiography (CTA)

Role of platelets in peripheral artery disease

Platelets have a vital role in normal and pathological states of the body. Normally, platelets contribute to blood vessel constriction and repair to decrease bleeding and host defence.⁶ However, with the communication of other cells (e.g. white blood cells, smooth muscle cells), platelets can have a role in promoting atherosclerosis; in atherosclerosis, inflammatory reactions take place and stimulate endothelial activation, which leads to the activation of platelets and their attachment.^6,7

Following this, platelets play an important role in recruiting different types of cells to the lesion sight and promote coagulation, proteolysis, chemokine and proinflammatory cytokine synthesis which lead to increased inflammation and the formation of a plaque.⁷

Overview of antiplatelet therapy

Antiplatelet therapy is a widely used approach as primary and secondary prevention for ischemic events that are linked to coronary atherosclerotic disease.⁸ The most common type of drug used in this therapy is aspirin due to its benefits and low cost.⁹ However, there are other agents used, and their mechanism of action and side effects are summarised in Table 2.

Table 2. FDA-approved antiplatelet agents.⁹

Evidence supporting antiplatelet therapy for PAD

Antiplatelet therapy did not show improvement of claudication in patients but was able to reduce the risk of cardiovascular disease linked to atherosclerosis/PAD.² There were multiple trials and studies that demonstrated the ability of antiplatelet agents to decrease the risk of myocardial infarction (MI), stroke, or vascular-related deaths such seen in CAPRIE study, CHARISMA, WAVE, and Asymptomatic Atherosclerosis (AAA) trials.^2,10

Guidelines for antiplatelet therapy in peripheral artery disease

The guidelines for antiplatelet therapy will be summarised in Table 3.

Table 3. Guidelines for antiplatelet therapy in patients with PAD.¹⁰

Potential side effects and considerations

Potential side effects are considered with any medication taken and this treatment is no different. The majority of side effects are summarised in Table 2. However, some things to keep in mind include the interaction of these drugs with other medications that the patient is taking.

Patient education and adherence

It is important to make sure that patients are well-informed and educated about their therapy prior to administration. This can help the patient and their examiner to avoid confusion and answer common concerns or questions the patient might have. Additionally, knowing the patient’s history will help prevent the administration of medications that might be a cause of an allergic reaction in some patients. Furthermore, it is important for the patients to adhere and stick to their prescribed treatment as side effects (Table 2) can have an impact on the patient’s well-being.¹¹

Future directions in antiplatelet therapy for PAD

Future works in antiplatelet therapy are still being studied in the hopes of improving current treatment; this is to provide proper treatment with decreased risk of life-threatening bleeding in patients.¹¹ Some of the potential directions for therapy include:

1. Development of new antiplatelet agents⁹
2. Dual antiplatelet therapy (DAPT)¹¹
3. Personalised treatment which includes tailoring the therapy to the person’s genetic profile¹¹
4. Anticoagulant combinational therapy¹¹

Summary

In patients with a history of atherosclerotic illness, antiplatelet therapy is a crucial part of cardiovascular and cerebrovascular prophylaxis. Contemporary antiplatelet medications, either alone or in combination, can effectively prevent thrombotic consequences.

However, it is important for patients to adhere to the guidelines provided by their physician for a smooth process, hence, it is important to educate people in this domain. Additionally, treatment and therapy in this area are still being studied in the hopes of more effective and personalised treatments in the future.