Burden of Cardiovascular Disease in Immune Checkpoint Inhibitor-Treated Patients: Reconciling Adjudicated and Coded Outcomes.

ABSTRACT

Background: There is growing recognition of the risk of cardiovascular (CV) events, particularly myocarditis, in the context of immune checkpoint inhibitor (ICI) therapy; however, true event rates in real-world populations and in the background of CV disease remain uncertain. Objectives: The authors sought to determine CV event occurrence in ICI-treated patients and assess the accuracy of diagnosis by International Classification of Diseases (ICD) code compared with adjudication using established definitions and full-source documentation review. Methods: Electronic medical record extraction identified potential CV events in ICI-treated patients in the University of Colorado Health system. Two cardiologists independently adjudicated events using standardized definitions. Agreement between ICD codes and adjudicated diagnoses was assessed using the kappa statistic. Results: The cohort comprised 1,813 ICI-treated patients with a mean follow-up of 4.6 ± 3.4 years (3.2 ± 3.2 years pre-ICI and 1.4 ± 1.4 years post-ICI). Venous thromboembolic events (VTEs) were the most common event, occurring in 11.4% of patients pre-ICI and 11.3% post-ICI therapy. Post-ICI therapy, the crude rates of myocardial infarction (MI), heart failure, and stroke were 3.0%, 2.8%, and 1.6%, respectively. Six patients (0.3%) developed myocarditis post-ICI. Agreement between the ICD code and adjudication was greater for VTE (κ = 0.82; 95% CI 0.79-0.85) and MI (κ = 0.74; 95% CI 0.66-0.82) and worse for myocarditis (κ = 0.50; 95% CI 0.20-0.80) and heart failure (κ = 0.47; 95% CI 0.40-0.54). Conclusions: ICD codes correlated well with adjudicated events for VTE and MI, but correlation was worse for heart failure and myocarditis. Adjudication with standardized definitions can enhance the understanding of the incidence of CV events related to ICI therapy.