Inhibidores de puntos de control inmunitario asociados con enfermedad arterial periférica en pacientes con cáncer

Immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy and improved survival across multiple malignancies. Although associations with cardiovascular events have been described, the relationship between ICIs and peripheral artery disease (PAD) remains unclear. The study aimed to determine whether ICI treatment is associated with PAD, chronic limb-threatening ischemia (CLTI), or lower extremity amputation (LEA) in patients with cancer.

We conducted a retrospective multicenter cohort study using the TriNetX Analytics platform to identify cancer patients treated with ICIs or non-ICI therapies between 2005-2025. Propensity score matching (1:1) was performed to balance baseline characteristics. Outcomes included PAD, CLTI, LEA within five years. Kaplan-Meier (KM) analyses assessed survival probabilities, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox Models. Subgroup analyses evaluated outcomes across different ICI classes and within at-risk groups with hypertension, hyperlipidemia, diabetes, or smoking history.

The matched cohort included 66,766 patients treated with ICIs and 66,766 controls. KM showed a lower 5-year PAD-free survival in the ICI group (73.6% vs. 81.7%, P < 0.001). In multivariable analysis, although the risk of CLTI and LEA were similar, ICI treatment was associated with increased risk of PAD (HR 1.59, 95% CI: 1.53-1.64). Consistently, an increased risk of PAD was demonstrated across all ICI classes: programmed cell death protein 1 (PD-1) inhibitors (HR 1.56, 95% CI: 1.47-1.55), programmed cell death ligand 1 (PD-L1) inhibitors (HR 1.48, 95% CI: 1.36-1.61), cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors (HR 1.58, 95% CI: 1.43-1.74). Among at-risk patients (N = 27,932), KM showed a lower 5-year PAD-free survival in the ICI group (70.3% vs 80.2%, P < 0.001) and ICI treatment was associated with increased risk of PAD (HR 1.64, 95% CI: 1.58-1.71) and LEA (HR 1.85, 95% CI: 1.32-2.61). Furthermore, increased risk of PAD was demonstrated across each ICI class among at-risk patients: PD-1 inhibitors (HR 1.64, 95% CI: 1.57-1.71), PD-L1 inhibitors (HR 1.64, 95% CI: 1.51-1.78), CTLA-4 inhibitors (HR 1.82, 95% CI: 1.60-2.06).

In this multicenter cohort of adults with cancer, ICI therapy appears to be associated with increased risks of PAD and LEA, particularly among individuals with pre-existing vascular risk factors. These findings suggest that ICI may contribute to PAD and highlight the need for vascular assessment and monitoring in patients receiving ICIs.