OBJECTIVES: The purpose of this study was to evaluate whether immune checkpoint 
inhibitors (ICIs) are associated with an increased risk of major adverse 
cardiovascular events (MACE) compared with non-ICI therapies in patients with 
lung cancer.
BACKGROUND: ICIs activate the host immune system to target cancer cells. Though 
uncommon, cardiovascular immune-related adverse events can be life-threatening.
METHODS: A retrospective single-institution cohort study of 252 patients with 
pathologically confirmed lung cancer who received ICI or non-ICI therapy was 
analyzed. The primary endpoint was MACE, defined as a composite of 
cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and 
hospitalization for heart failure.
RESULTS: During a median follow-up of 6 months, MACE occurred in 13.3% of 
ICI-treated patients, with a median time to event of 51 days, compared with 
10.3% and 64 days in non-ICI patients. ICIs were not associated with MACE 
(hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.57 to 2.43; p = 0.66) 
in a univariable Fine-Gray regression analysis incorporating noncardiovascular 
death as a competing risk. Multivariable regression analyses determined that 
patients treated with ICIs with elevated serum troponin I >0.01 ng/ml (HR: 7.27; 
95% CI: 2.72 to 19.43; p < 0.001) and B-type natriuretic peptide (BNP) >100 
pg/ml (HR: 2.65; 95% CI: 1.01 to 6.92; p = 0.047) had an increased risk of MACE. 
Patients pre-treated or receiving combined immunotherapy with ICIs and vascular 
endothelial growth factor inhibitors (VEGFIs) or tyrosine kinase inhibitors 
(TKIs) had an increased risk of MACE (HR: 2.15; 95% CI: 1.05 to 4.37; p = 0.04).
CONCLUSIONS: ICIs were not independently associated with an increased risk of 
MACE in patients with lung cancer, although power is an important limitation in 
these analyses. ICI-associated cardiotoxicity was associated with elevations in 
serum troponin and BNP, and combined immunotherapy with VEGFIs or TKIs. Future 
studies are needed to further define the role of cardiac biomarkers as a 
monitoring strategy with ICI therapy.