A retrospective analysis of cardiovascular adverse events associated with immune checkpoint inhibitors

Abstract Background Modern therapies in oncology have increased cancer survivorship, as well as the incidence of cardiovascular adverse events. While immune checkpoint inhibitors have shown significant clinical impact in several cancer types, the incidence of immune-related cardiovascular (CV) adverse events poses an additional health concern and has been reported. Methods We performed a retrospective analysis of the FDA Adverse Event Reporting System data of suspect product reports for immunotherapy and classical chemotherapy from January 2010–March 2020. We identified 90,740 total adverse event reports related to immune checkpoint inhibitors and classical chemotherapy. Results We found that myocarditis was significantly associated with patients receiving anti-program cell death protein 1 (PD-1) or anti-program death ligand 1 (PD-L1), odds ratio (OR) = 23.86 (95% confidence interval [CI] 11.76–48.42, (adjusted p -value) q < 0.001), and combination immunotherapy, OR = 7.29 (95% CI 1.03–51.89, q = 0.047). Heart failure was significantly associated in chemotherapy compared to PD-(L)1, OR = 0.50 (95% CI 0.37–0.69, q < 0.001), CTLA4, OR = 0.08 (95% CI 0.03–0.20, q < 0.001), and combination immunotherapy, OR = 0.25 (95% CI 0.13–0.48, q < 0.001). Additionally, we observe a sex-specificity towards males in cardiac adverse reports for arrhythmias, OR = 0.81 (95% CI 0.75–0.87, q < 0.001), coronary artery disease, 0.63 (95% CI 0.53–0.76, q < 0.001), myocardial infarction, OR = 0.60 (95% CI 0.53–0.67, q < 0.001), myocarditis, OR = 0.59 (95% CI 0.47–0.75, q < 0.001) and pericarditis, OR = 0.5 (95% CI 0.35–0.73, q < 0.001). Conclusion Our study provides the current risk estimates of cardiac adverse events in patients treated with immunotherapy compared to conventional chemotherapy. Understanding the clinical risk factors that predispose immunotherapy-treated cancer patients to often fatal CV adverse events will be crucial in Cardio-Oncology management.