Peripheral artery disease (PAD) often progresses silently and without classic leg pain. So it’s often not diagnosed until a patient presents with foot ulcers, infection, or limb-threatening ischemia. 

A new scientific statement from the American College of Cardiology (ACC) urges a rethinking of how aggressively clinicians screen for and manage PAD in people with diabetes. The authors underscored screening, developing clinical profiles, proper lifestyle and exercise, medical management, and surgical and interventional management.

“PAD in people with diabetes is often diagnosed late, after complications make amputation a significant risk,” said Sandeep R. Das, MD, MPH, one of the authors. “We have outlined a pragmatic approach to risk-based screening and preventive therapies [that] reduce adverse cardiovascular and limb events and can improve our patients’ quality of life.”

Das, who is a professor in the Department of Internal Medicine’s Division of Cardiology at UT Southwestern Medical Center in Dallas, added, “This statement is a call to consistently apply proven strategies, especially in vulnerable communities who bear the highest amputation rates.”

Screening and Evaluation

The ankle-brachial index is recommended for an initial test, with values ≤ 0.90 diagnostic of PAD, according to the statement. When arteries are noncompressible — a common finding with diabetes — more conclusive data can often be found through alternative assessments such as the toe brachial index, pulse volume recordings, or transcutaneous oxygen measurements.

In many patients, PAD may be the first outward sign of systemic atherosclerotic cardiovascular disease. Diabetes often involves distal and infrapopliteal vessels and frequently coexists with kidney disease, neuropathy, and retinopathy, each of which magnifies the risk for major adverse limb events.

Routine evaluation for these patients should include regular assessment of A1c, kidney function, neuropathy, retinopathy, hypertension, and lipid levels.

Daily foot inspections by patients or caregivers and at least one comprehensive foot examination by a clinician each year are recommended, with more frequent evaluation for those at elevated risk.

Lifestyle and Exercise

Smoking cessation is paramount because tobacco worsens PAD and sharply increases the risk for amputation, cardiovascular events, and death. The statement authors urge counseling combined with pharmacologic therapies such as nicotine replacement, varenicline, and bupropion because these interventions offer the best chance of long-term cessation.

Supervised exercise therapy is strongly recommended for improving symptoms and quality of life in patients with symptomatic PAD. Structured home- or community-based exercise regimens are reasonable alternatives.

Nutritional counseling should emphasize plant-forward, whole-food eating patterns consistent with American Diabetes Association and American Heart Association (AHA) recommendations, with particular attention to adequate protein and caloric intake in patients with wounds or chronic limb-threatening ischemia.

Medical Management

Pharmacologic therapy can lower the risk for major adverse cardiac events, prevent major adverse limb events, and preserve kidney function.

Dual-pathway inhibition with low-dose rivaroxaban (2.5 mg twice daily) plus low-dose aspirin are recommended, according to the statement. For patients at high bleeding risk, aspirin or clopidogrel monotherapy remains appropriate, though it has not been shown to reduce limb events.

Blood pressure should be treated to a target below 130/80 mm Hg, preferably with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers.

High-intensity statin therapy aiming for at least a 50% reduction in low-density lipoprotein (LDL) cholesterol and an absolute LDL goal below 55 mg/dL is recommended. Adjunctive therapies such as ezetimibe, PCSK9 inhibitors, or bempedoic acid may be needed.

For glycemic management, the statement prioritizes therapies with proven cardiovascular benefit. SGLT2 inhibitors reduce heart failure and kidney complications, while GLP-1 receptor agonists lower cardiovascular risk. Semaglutide has shown improvements in walking capacity, quality of life, and major adverse limb events in patients with PAD.

Surgical and Interventional Management

When PAD progresses to chronic limb-threatening ischemia, revascularization becomes central to limb preservation. In people with diabetes, neuropathy and microvascular disease can allow rapid, unpredictable deterioration, making early recognition essential.

The ACC stresses that amputation should rarely be the first option, and all patients with diabetes and limb-threatening ischemia should be evaluated by a multidisciplinary limb-salvage team.

Importantly, revascularization is not indicated for patients who have asymptomatic PAD. Around the time of intervention, careful blood sugar control is critical, as acute hyperglycemia — rather than A1c — has been linked to graft failure and adverse limb outcomes.

Filling a Gap

“The 2024 ACC/AHA PAD guideline is quite comprehensive but didn’t have a focus on the patients with both diabetes and PAD. This statement is basically the ‘missing chapter’ for the highest-risk PAD patients,” said Joshua Beckman, MD, MS, executive clinical director of cardiovascular services and chief of the Division of Vascular Medicine at the UT Southwestern Medical Center.

“It’s also landing at a moment when our therapeutic ‘center of gravity’ in diabetes continues to shift from glucose-centric to cardio-kidney-metabolic plus limb outcomes,” said Beckman, who was not involved in writing the new statement.

“The take-home message of the statement is essentially saying: Stop treating PAD-in-diabetes like a footnote. There are now outcome-driven levers we should be pulling systematically, and we’re not pulling them enough.”

The study was independently supported. Smith and Jones report no relevant financial relationships. Das reported having no financial relationships.

Journalist Lois Anzelowitz Levine is a freelance medical writer living in Dallas.