Immune checkpoint inhibitors in cancer: the increased risk of atherosclerotic cardiovascular disease events and progression of coronary artery calcium

Background Immune checkpoint inhibitors (ICIs) have contributed to a significant advancement in the treatment of cancer, leading to improved clinical outcomes in many individuals with advanced disease. Both preclinical and clinical investigations have shown that ICIs are associated with atherosclerosis and other cardiovascular events; however, the exact mechanism underlying this relationship has not been clarified. Methods Patients diagnosed with stages III or IV non-small cell lung cancer (NSCLC) at the Wuhan Union Hospital from March 1, 2020, to April 30, 2022, were included in this retrospective study. Coronary artery calcium (CAC) volume and score were assessed in a subset of patients during non-ECG-gated chest CT scans at baseline and 3, 6, and 12 months after treatment. Propensity score matching (PSM) was performed in a 1:1 ratio to balance the baseline characteristics between the two groups. Results Overall, 1458 patients (487 with ICI therapy and 971 without ICI therapy) were enrolled in this cardiovascular cohort study. After PSM, 446 patients were included in each group. During the entire period of follow-up (median follow-up 23.1 months), 24 atherosclerotic cardiovascular disease (ASCVD) events (4.9%) occurred in the ICI group, and 14 ASCVD events (1.4%) in the non-ICI group, before PSM; 24 ASCVD events (5.4%) occurred in the ICI group and 5 ASCVD events (1.1%) in the non-ICI group after PSM. The CAC imaging study group comprised 113 patients with ICI therapy and 133 patients without ICI therapy. After PSM, each group consisted of 75 patients. In the ICI group, the CAC volume/score increased from 93.4 mm 3 /96.9 (baseline) to 125.1 mm 3 /132.8 (at 12 months). In the non-ICI group, the CAC volume/score was increased from 70.1 mm 3 /68.8 (baseline) to 84.4 mm 3 /87.9 (at 12 months). After PSM, the CAC volume/score was increased from 85.1 mm 3 /76.4 (baseline) to 111.8 mm 3 /121.1 (12 months) in the ICI group and was increased from 74.9 mm 3 /76.8 (baseline) to 109.3 mm 3 /98.7 (12 months) in the non-ICI group. Both cardiovascular events and CAC progression were increased after the initiation of ICIs. Conclusions Treatment with ICIs was associated with a higher rate of ASCVD events and a noticeable increase in CAC progression.