ICIs Linked to Increased Risk of PAD and Amputation in Patients With Cancer

While immune checkpoint inhibitors (ICIs) have revolutionized the oncology landscape, new data suggests these life-saving therapies may carry a hidden cost to vascular health. For oncology nurses, who serve as the frontline of patient assessment, understanding the emerging link between immunotherapy and peripheral artery disease (PAD) is now critical to preventing severe complications, including limb loss.

A landmark study led by researchers at Keck Medicine of USC, recently published in the Journal of Vascular Surgery, indicates that ICIs are associated with a significant increase in PAD and, in some instances, lower extremity amputation (LEA).

Study methodology and findings

Researchers utilized the TriNetX Analytics platform to conduct a large-scale analysis of more than 130,000 patients treated for cancer between 2005 and 2025. The study compared patients receiving ICIs, specifically PD-1, PD-L1, and CTLA-4 inhibitors, against a matched control group receiving alternative therapies.

The data revealed that ICI treatment was associated with a 59% to 64% increased risk of PAD. This association remained consistent across all major classes of checkpoint inhibitors. However, the risk was most pronounced in patients with pre-existing comorbidities such as smoking history, diabetes, hypertension, or hypercholesterolemia. In this high-risk subgroup, the use of ICIs was associated with an 85% increased risk of LEA.

Pathophysiology: The "off-target" effect

PAD occurs when the arteries supplying blood to the lower extremities become narrowed or obstructed by plaque buildup, a process known as atherosclerosis.

While the exact mechanism by which ICIs accelerate vascular damage is still under investigation, experts believe the same immune activation used to target malignant cells may inadvertently trigger inflammation within the arterial walls. This systemic inflammation can exacerbate existing atherosclerosis or promote the development of new arterial blockages.

The role of the oncology nurse

Because ICIs remain a primary tool in cancer treatment, the goal of this research is not to discourage their use, but to refine clinical monitoring. Oncology nurses are uniquely positioned to identify early warning signs of vascular compromise during routine infusions and follow-up appointments.

Nurses should monitor patients for the following symptoms of PAD:

• Intermittent claudication (painful cramping in the hips, thighs, or calves during activity).
• Lower extremity numbness or weakness.
• Noticeable coldness in the lower leg or foot compared to other body parts.
• Sores or ulcers on the toes or feet that are slow to heal or non-healing.

By identifying these risks early, the care team can implement preventive strategies, including aggressive management of blood pressure and cholesterol, ensuring that survivors maintain both their longevity and their mobility.

Reference

1. Tan TW, Armstrong DG, et al. Association between immune checkpoint inhibitors and peripheral artery disease. J Vasc Surg.