The incidence and risk of cardiovascular events among gastroesophageal cancer patients receiving immune-checkpoint inhibitors.

Abstract

374 Background: Immune checkpoint inhibitors (ICIs) have been associated with an increased risk of cardiovascular events. However, these data were mostly derived from patients with lung cancer or melanoma. To date, there is limited data describing the incidence and risk of cardiovascular adverse events associated with the use of ICIs among patients with gastroesophageal cancers. Methods: We performed a propensity score-matched cohort study using the TriNetX Analytics Network database, which comprises de-identified data from over 120 participating institutions and 101 million individuals. We defined the ICI cohort as patients who received any of the ICIs and chemotherapy. We defined the control cohort as patients who received only chemotherapy but not an ICI. We matched 2 cohorts based on predetermined variables including age, race, gastroesophageal cancer-directed therapy, cardiovascular agents, underlying comorbidities, and surgical history. The outcomes were myocarditis, pericarditis, myocardial infarction, heart failure, cerebral ischemia/infarction, atrial fibrillation, conduction disorders, and venous thromboembolism (VTE). All outcomes were captured within 1-year of the start of ICI therapy and identified using the International Classification of Diseases (ICD)-10 codes. Results: We identified 2005 patients who received ICI and chemotherapy (ICI cohort) and 14048 patients who received chemotherapy only (control cohort). We matched 952 patients in 2 cohorts. The mean age was 62.8 ± 12.7 and 62.8 ± 12.3 for the ICI and chemotherapy cohorts, respectively. We observed a significant increase in cardiovascular events in the ICI cohort compared to the chemotherapy cohort. In particular, the risk of myocarditis (4 cases in the ICI cohort and no cases in the chemotherapy cohort), pericarditis (Hazard ratio (HR), 2.53 [95% CI: 1.52-4.19]), conduction disorders (HR, 1.64 [95% CI: 1.04-2.59]), and VTE (HR, 1.56 [95% CI: 1.17-2.10]) were higher in the ICI cohort than the chemotherapy cohort. Conclusions: The use of ICI was associated with an increased risk of cardiovascular events, particularly myocarditis, pericarditis, conduction disorders, and VTE among patients with gastroesophageal cancer. Further studies are needed to identify strategies to stratify patients at high risk of developing ICI-associated cardiovascular events. Outcomes ICI + Chemotherapy(ICI cohort) Chemotherapy only(Control cohort) Hazard ratio(95% CI) Cases At risk patients Cases At risk patients Myocarditis 4 952 0 952 - Pericarditis 52 952 21 952 2.53 (1.52-4.19) Myocardial infarction 18 952 12 952 1.49 (0.72-3.11) Cerebral Ischemia/Infarction 22 952 17 952 1.30 (0.69-2.44) Atrial fibrillation 56 952 48 952 1.16 (0.79-1.71) Conduction disorder 49 952 30 952 1.64 (1.04-2.59) Venous thromboembolism 112 952 73 952 1.56 (1.16-2.10) Heart Failure 118 952 114 952 1.04 (0.80-1.34)