Breaking barriers in PAD treatment

Primary care physicians have new evidence-based options for managing patients with peripheral artery disease (PAD), a condition that affects an estimated 10 to 12 million U.S. adults over age 40.

In 2024, the American College of Cardiology (ACC), American Heart Association (AHA), and other societies released an updated guideline for the management of lower-extremity PAD that includes the first new preventive medical therapy in decades, along with the latest thinking on effective screening, diagnosis, treatment, and risk management strategies.

“A combination of rivaroxaban, 2.5 mg twice daily, with low-dose aspirin is a Class I recommendation for patients with PAD, either those with stable symptoms or those who've had revascularization,” said Heather Gornik, MD, chair of the guideline's writing committee and co-director of the Harrington Heart & Vascular Institute at University Hospitals in Cleveland. “Primary care physicians can be champions for getting appropriate patients started on this regimen, which can prevent major adverse limb and cardiovascular events.”

The latest guidance, which was last updated in 2016, highlights the impact of racial and ethnic disparities on PAD care and outcomes. The U.S. prevalence of PAD is higher among Black versus White patients, experts note, and Black patients have higher rates of high-risk comorbidities, such as hypertension and diabetes, and worse outcomes.

PAD management should consider the impact of certain social determinants of health, such as insurance coverage, access to care, and language barriers, said Dr. Gornik. Studies have shown a disproportionately higher risk of amputation versus revascularization among Black and Hispanic patients with severe limb ischemia, for example, which may be driven in part by systemic bias and fragmented access to care.

By recognizing and diagnosing PAD, and effectively managing risk factors with recommended medical and exercise therapies, primary care physicians can help reduce disparities and improve overall outcomes, she said. “Our hope is that the internal medicine community will use this guideline as a blueprint to manage patients with PAD in their practices.”

Recognizing PAD

Screening for PAD begins with a careful history and physical exam, the guideline states. Major risk factors include age older than 65 years, diabetes, history of smoking, hypertension, dyslipidemia, chronic kidney disease, and a family history of PAD.

Patients with one or more of these risk factors should be assessed for lower-extremity symptoms and signs of disease (such as abnormal pulses), even if they don't report leg pain, the authors note. The guideline cites data showing that 20% to 59% of patients with PAD did not report symptoms, but a significant percentage experienced leg pain during a walking test.

In fact, the term “asymptomatic” can be misleading, according to an editorial in Circulation that accompanied the guidelines, because “it fails to communicate the reality that such patients often have important, yet unrecognized, functional limitations, and also are at high risk for adverse outcomes. … just because a clinician and patient does not recognize symptoms does not mean the patient is asymptomatic.”

Patients in this category may have adapted their everyday activity levels to avoid pain, so it's important to probe deeper, experts said. For example, instead of asking if a patient has leg pain, ask how far they can walk, what limits their walking, or why they're not walking.

Hearing a patient say that they “never walk” is a big red flag, said Pulkit Chaudhury, MD, FACP, a cardiologist at Cleveland Clinic in Cleveland. “There should be a very good reason why somebody's not walking or not able to be as physically active as they would like. You should have a very low threshold for doing an ABI [ankle-brachial index] in these patients.”

Some patients may report chronic symptoms that they associate with other conditions, such as arthritis or neuropathy, said Amy Pollak, MD, a cardiologist at Mayo Clinic's Jacksonville, Fla., campus. As a result, underlying PAD may be missed.

“Patients might talk about very broad symptoms, such as fatigue, cramping, or an aching pain in the legs,” she said. “It's important to ask when these symptoms occur and whether they get worse with walking or go away with rest.”

The physical exam should always include taking a foot pulse on the patient's bare foot, said Maya Salameh, MD, associate director of the Johns Hopkins Center for Vascular Medicine in Baltimore.

A weak foot pulse should be followed up with a diagnostic ABI, she said. Other symptoms that strongly suggest PAD include vascular bruits over the abdomen and groin, absent or asymmetric hair growth on the legs, nail bed changes, nonhealing wounds, and elevation pallor (feet become pale when raised).

The ABI is the gold standard diagnostic test for PAD and can be used as a screening test in patients with risk factors, said Dr. Gornik.

“The ABI is a simple, safe test that can be done in the office with a blood pressure cuff and a handheld Doppler, with the patient lying down flat on an exam table,” she said. “However, in the guideline, we advocate for a vascular lab-based test where you actually measure the ABI but also obtain Doppler waveforms or pulse volume recordings to get a more accurate assessment of the severity of disease. There are some situations where the ABI may not accurately diagnose the presence of PAD, such as among patients with diabetes or wounds.”

Managing risk

Effective PAD management requires a multidisciplinary approach that can include vascular specialists, podiatrists, cardiologists, and others, according to the guideline. However, much can be done in the primary care setting to control risk factors following a diagnosis.

“PAD isn't just about treating claudication but preventing bad things from happening,” said Anuj Gupta, MD, an interventional cardiologist and associate professor of medicine at the University of Maryland School of Medicine in Baltimore. “These are very sick patients, and we want to keep them as healthy as possible by managing risk.”

Standard PAD management includes recommended medications (single antiplatelet, antithrombotic, lipid-lowering, and antihypertensive therapies) and a supervised exercise program to prevent major adverse cardiovascular and limb events, according to the guideline. Patients may also require diabetes and smoking cessation management.

For the first time, the ACC/AHA guidance also recommends a combination of rivaroxaban (2.5 mg twice daily) and low-dose aspirin (81 mg daily) for patients who are not at risk for bleeding. The recommendation is based on evidence from the COMPASS and VOYAGER PAD trials, which found that the combination significantly reduced the risk of both major adverse cardiovascular and lower-limb events.

“Combination therapy is a great option, but it's not for every patient,” said Dr. Salameh. “It's best for high-risk patients with multiple complications who are at a low risk for bleeding. Aspirin alone is usually sufficient for those with a mildly abnormal ABI and fewer risk factors.”

While adding rivaroxaban was beneficial in patients with symptomatic claudication, according to the trial results, it shouldn't be a first step, agreed Dr. Gupta.

“Controlling risk factors intensively is key to initial management,” he said. “Diabetes, smoking, and blood pressure are the first critical things to address, and they are issues that internists manage every day.”

Also new in the updated guideline is a Class I recommendation for the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with PAD and type 2 diabetes, based on evidence from recent trials showing that the medications led to reduced incidence of major adverse cardiac events (MACEs) in this patient population.

Structured exercise, including supervised and community- or home-based programs, is a core component of PAD management but isn't always emphasized in primary care, said Dr. Gornik.

“Even though supervised exercise therapy is now covered under Medicare, the service is woefully underutilized in primary care,” she said. “Copays and financial barriers are part of the reason, but it's also underprescribed. As soon as the general internist makes a diagnosis of PAD, they should be making a referral to PAD rehab.”

When to refer

While many PAD risk factors can be addressed in primary care, physicians should always establish a reliable referral network, said Dr. Chaudhury.

“Things like resting leg pain and nonhealing wounds require escalation of care,” he said. “If you don't have a network set up, it can take weeks to connect with a specialist, which is a disservice to the patient.”

Other common red flags for serious complications include discoloration of toes, which can be the first sign of chronic limb-threatening ischemia and acute-onset leg pain that doesn't go away with rest, he said. Such issues “are limb- or possibly life-threatening events that need to be acted on in the order of days or weeks.”

Escalation of care is necessary when patients move into the third or fourth of the four clinical subsets outlined in the guideline, experts said. Patients who have asymptomatic PAD, the first subset, may have functional impairment but report no leg symptoms or may limit their activity to avoid pain. The second subset, chronic symptomatic PAD—characterized by exertional leg symptoms—is the largest and most common subtype managed in primary care.

A smaller percentage of patients will move into the latter two subsets, chronic limb-threatening ischemia (CLTI) and acute limb ischemia (ALI), which are much more severe. CLTI manifests as rest pain or nonhealing wounds/ulcers or symptoms of gangrene and can result in limb amputations. ALI, the most serious subset, is indicated by acute pain, pallor, very weak pulse, and sudden decrease in arterial blood flow.

Physicians should talk to patients about symptoms that put them at risk for CLTI or ALI, said Dr. Pollak.

“Describing it as a ‘leg attack’ is easier to grasp for most patients,” she said. “Educate patients about potential symptoms, such as their foot, leg, or toes suddenly changing color or going cold, that need to be treated in the ED and potentially seen by a vascular surgeon or other specialist.”

Proper foot care is very important to prevent risk factors from worsening, especially in patients with diabetes, said Shahab Toursavadkohi, MD, a vascular surgeon and associate professor of medicine at the University of Maryland School of Medicine.

General internal medicine physicians can diagnose precardiovascular occlusive disease by examining the bottom of the foot for sores and looking for any kind of pathology around the toes, he said. They can then prescribe diabetic shoes and socks that reduce the risk of foot ulcers and amputation.

Patients with diabetes and PAD require attention by a multispecialty team, said Dr. Pollak, including a podiatrist, a wound care specialist with expertise in PAD, a vascular surgeon, an endocrinologist, and a cardiologist.

“There's a wide range of team members that can be involved in care,” she said. “Many specialists have expertise in PAD, and those that are important for any particular patient will depend on which clinical subset of PAD the patient has.”

Impact of health disparities

Significant disparities in PAD diagnosis, treatment, and outcomes are well established, the guideline states. For example, rates of major adverse limb events are disproportionately higher among Black and Hispanic patients, as well as patients with lower incomes and those who live in rural areas.

“Certain minority groups are not only disproportionately affected by PAD but also experience significant disparities in care,” said Dr. Gornik. “Primary care physicians can help improve outcomes by recognizing the impact of certain social determinants of health, such as language barriers or whether people have access to appropriate care or can afford their prescribed medications.”

The guideline notes that factors such as low-quality schools, low-wage jobs, and limited access to affordable foods, health insurance, and consistent medical care, collectively, result in a fourfold higher rate of major limb amputation, a 30% higher rate of cardiovascular disease (CVD) mortality, and a 45% higher rate of stroke among Black patients compared with non-Hispanic White patients.

Black patients tend to be diagnosed at later stages of disease and their condition tends to decline more rapidly, including loss of mobility, compared with White patients, the guideline continues. They are also less likely to be prescribed recommended medications, including antiplatelet and statin therapy, and are less likely to participate in supervised exercise programs.

“The statistics are pretty staggering,” said Dr. Pollak. “Your chance of having an amputation related to PAD varies significantly depending upon your race or ethnicity and where you live in the United States.”

To address disparities, physicians should look for signs and symptoms of PAD in patients from disenfranchised, at-risk populations and conduct regular physical exams that include assessing the pulse, legs, and feet, the guideline recommends. After a diagnosis, socioeconomic and other factors must be considered when implementing a care plan.

For example, patients who live in rural or remote areas might not have access to supervised exercise or rehabilitation facilities, said Dr. Salameh. Talking to those patients about the importance of home exercise is critical.

She suggests recommending that patients record their activities to stay on track. For example, smartphone-based fitness trackers that log steps can help patients monitor their progress at home.

Recognizing barriers and modifying care plans accordingly can slow disease progression and prevent the most serious adverse outcomes in many patients, said Dr. Gupta.

“If we can turn down the flow of PAD patients into emergency rooms and vascular surgery centers by controlling risk across our patient populations, it will be hugely beneficial,” he said. “I'm really glad the [new guideline] is highlighting these disparities because we've got to think about them with every patient that comes through the door.”