Guidelines on the Management of Patients with PAD

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Dr. Hess:
Hello. My name is Connie Hess. I'm an Interventional Cardiologist at the University of Colorado. I'll be speaking about PAD stage, risk assessment, and comorbidities.

The 2024 PAD guidelines define four clinical subsets of patients with objectively confirmed PAD. The first includes asymptomatic PAD, which includes patients with objective evidence of PAD but who report no leg symptoms. Now, these patients may self-limit activity to avoid leg pain. And although they are classified as asymptomatic from a leg symptom standpoint, it's important to note that they do have functional impairment, similar to patients with claudication.

The second group includes patients with chronic symptomatic PAD. This is the most common clinically evident subgroup of PAD and includes patients with claudication or other non-joint-related exertional leg symptoms occurring consistently with walking and often relieved within 10 minutes of rest. These patients do have significant functional impairment and reduced quality of life.

Chronic limb-threatening ischemia is a severe clinical subset of PAD that manifests as ischemic rest pain, non-healing wounds or ulcers or gangrene with symptoms present for more than 2 weeks. CLTI is responsible for most PAD-related amputations.

Acute limb ischemia is another severe clinical subset of PAD that is caused by a sudden decrease in leg perfusion that threatens limb viability. Patients often present with acute symptoms less than 2 weeks in duration, and may present with the 6 P’s of pain, pallor, pulselessness, poikilothermia, paresthesias and paralysis.

Now, patients may develop different symptoms over time, and they can move into or out of different clinical subsets. Patients with PAD are at risk for ischemic events such as myocardial infarction, stroke, or cardiovascular death, collectively termed major adverse cardiovascular events, or MACE. And you can see on the left that patients with PAD have a higher risk of MACE than patients with MI or stroke and no prior PAD. On the right, you can see that patients with PAD are also at risk for major adverse limb events, or termed MALE, including peripheral revascularization, amputation, and acute limb ischemia, and the incidence of limb events is greater than that of systemic atherothrombotic events.

Now, although all patients with PAD are at risk for MACE and MALE, certain factors and comorbidities have been identified that can escalate this risk. Patients with older age have a higher prevalence of comorbid conditions, and geriatric syndromes such as frailty and sarcopenia are associated with greater risk of MACE, MALE, and death. Although diabetes and chronic kidney disease are risk factors for the development of PAD, their presence in PAD also is associated with increased risk for MACE and lower extremity amputation. Ongoing smoking or tobacco use is not only associated with MACE and MALE, but also reduced patency of revascularization procedures. And microvascular disease is associated with greater risk for MALE in PAD. Finally, greater risk for MACE, amputation, and mortality has been observed in patients with PAD and depression.

Important risk amplifiers in PAD also include polyvascular disease, defined as atherosclerosis, in multiple vascular territories. And as shown on the left, you can see that patients with three involved vascular territories are at highest risk for MACE. Prior peripheral revascularization is another important amplifier and in chronic PAD is associated with a four- to fivefold increased risk for acute limb ischemia. The period after a recent revascularization procedure is also particularly high risk for MALE with the risk increasing quickly and beginning immediately post procedure.

It's important to note that the drivers of risk for MACE and MALE are different in PAD. A strong driver for MACE is polyvascular disease, with patients with a recent acute coronary syndrome at highest risk, and beyond the risk amplifiers discussed, the defined clinical subsets of PAD are also associated with differential risk for MALE, as illustrated on the spectrum on the bottom of the slide. And patients undergoing recent revascularization for acute limb ischemia are at particularly high risk for MALE.

In summary, four clinical subsets of PAD have been defined. PAD is associated with increased risk for cardiovascular and limb events, as well as impaired functional status and reduced quality of life. Important amplifiers of risk have been identified, and therefore, providers should assess for these risk amplifiers and account for their presence when developing individual treatment plans for patients with PAD

Thank you.

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