Risk factors associated with cardiovascular hospital admissions and all-cause mortality in cancer patients treated with immune checkpoint inhibitors

PURPOSE: Immune checkpoint inhibitors (ICIs) are highly effective cancer therapies. However, they are associated with considerable adverse cardiovascular (CV) outcomes. We investigated the risk factors for CV hospitalisations and all-cause mortality in oncology patients receiving ICIs. METHODS: A retrospective cohort study of adult patients administered ICIs between 1st January 2010 and 1st January 2020 in New South Wales, Australia. Electronic medical records were accessed to obtain demographic and clinical data. Univariate analysis included Chi-squared test for categorical variables and Student's t-test for continuous variables. Binary logistic regression was used for multivariate analysis. Mortality was analysed using Cox regression including (i) time-dependent Cox models with CV admission as a time-varying covariate and (ii) a 1-year landmark sensitivity analysis. RESULTS: Out of 1,080 patients receiving ICIs during the study period, 340 patients (31.5%) had at least one CV hospital admission, and 763 patients (70.6%) had died by the end of the follow-up period. On multivariable analysis, prior history of heart failure and/or cardiomyopathy (p < 0.001), arrhythmia (p < 0.001) and ischaemic heart disease (p < 0.001) were independently associated with an increased risk of CV hospital admission by approximately fourfold, while CV hospitalisation during follow-up (p < 0.001) was independently associated with an increased risk of all-cause mortality. In a time-dependent Cox model (n = 928; excluding CV admissions with missing admission timing), CV admission was associated with higher subsequent mortality (HR 3.29 [95% CI 2.70-4.02]; p < 0.001). In a 1-year landmark sensitivity analysis among patients alive at 365 days (n = 533), CV admission within 1 year was associated with higher subsequent mortality (HR 2.36 [95% CI 1.61-3.45]; p < 0.001). CONCLUSION: In cancer patients treated with ICIs, pre-existing CV risk factors significantly increase the risk of CV hospitalisations and all-cause mortality. Appropriate CV risk monitoring and management should be considered for people with cancer receiving ICI therapy.