1. In patients diagnosed with stage III or IV non-small cell lung cancer (NSCLC), immune checkpoint inhibitors were associated with a greater risk of atherosclerotic cardiovascular disease.

Evidence Rating Level: 2 (Good)

Tumor treatment has become significantly better, specifically with the start of immune checkpoint inhibitors (ICIs). ICIs can be used to target programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). An important biomarker is coronary artery calcium (CAC) as it can show direct proof of coronary atherosclerosis which has a high association with atherosclerotic cardiovascular disease (ASCVD).  The retrospective cohort study included 1458 individuals over 18 years with a diagnosis of stage III or IV non-small cell lung cancer (NSCLC). Of these participants, 487 (33.4) received ICI therapy whereas 971 (66.6%) did not. Patients in the non-ICI group had more advanced tumours (stage IV, 81.9% vs 71.7%, P<0.001) with the dominant type being adenocarcinoma. In contrast, the proportions of adenocarcinoma and squamous cell carcinoma were quite evenly split in the ICI group (76.4% and 18.0% vs. 44.6% and 48.3%, respectively; P < 0.001).  24 (4.9%) ASCVD events occurred in the ICI group whereas only 14 (1.4%) in the non-ICI group. Further, after propensity score matching (PSM), 24 (5.4%) ASCVD events occurred in the ICI group while 5 (1.1%) occurred in the non-ICI group. For the CAC imaging study cohort, 113 individuals with ICI therapy, and 133 without therapy were enrolled. After PSM, only 75 participants remained in each group. At 12 months, the ICI group had a significantly more severe CAC score progression than the non-ICI group (16.8% vs 6.8%; P = 0.013 before PSM; 20.0% vs 8.0%; P = 0.032 after PSM). In all, receiving ICI therapy was associated with a higher incidence of ASCVD events, possibly due to ICIs accelerating systemic atherosclerosis progression.

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