Programmed Cell Death 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) inhibitors and adverse cardiovascular events: a population-based study

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf Cardiovascular Analytics Group Background Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are major classes of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, they are associated with adverse cardiovascular events. Purpose To evaluate the cardiotoxicity of PD-1 and PD-L1 inhibitors, the present study aims to examine the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors. Methods Patients receiving PD-1 or PD-L1 inhibitors since their launch up to December 31st, 2019 without pre-existing cardiac complications were included. Patient data were obtained using a territory-wide electronic health record database. The primary outcome was a composite of incident heart failure (HF), acute myocardial infarction (AMI), atrial fibrillation (AF) or atrial flutter followed up to August 31st, 2020. Propensity score matching between PD-L1 and PD-1 inhibitor use with a 1:1 ratio for patient demographics and comorbidities was performed. Results A total of 1925 patients were included. Over a median follow-up of 136 days (interquartile range [IQR]: 42-279), 318 (16.51%) patients met the primary outcome after PD-1/PD-L1 treatment: 242 (incidence rate [IR]: 12.57%) with HF, 38 (IR: 1.97%) with AMI, 53 (IR: 2.75%) with AF, 6 (IR: 0.31%) with atrial flutter. Compared with PD-1 inhibitor treatment, PD-L1 inhibitor treatment was significantly associated with a lower risk of composite outcome after matching (HR: 0.78, 95% CI: [0.62-0.99], P value = 0.0417). Patients who developed cardiovascular complications had shorter average readmission intervals and more hospitalization episodes after treatment with PD-1/PD-L1 inhibitors both before and after matching (P value < 0.0001). Conclusions Compared with PD-1 inhibitor users, PD-L1 inhibitor users had a significantly lower risk of new-onset composite cardiovascular complications. Abstract Figure. Kaplan-Meier survival curve