Association of pre-existing cardiovascular disease with cardiovascular and clinical outcomes in patients receiving immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are increasingly associated with cardiovascular complications. The association between pre-existing cardiovascular disease (CVD) and cardiovascular outcomes among patients receiving ICIs remains incompletely characterized, particularly in real-world settings. To evaluate the association between baseline CVD and cardiovascular and clinical outcomes among adult patients treated with ICIs. We conducted a retrospective multicenter cohort study at two tertiary hospitals in Saudi Arabia, including adult patients who received at least one ICI dose between January 2017 and January 2023. Baseline CVD was defined as documented cardiovascular disease before ICI initiation. The primary outcome was a composite of new cardiovascular events occurring after ICI initiation. The secondary outcome was all-cause mortality. We used multivariable logistic regression to identify factors independently associated with cardiovascular events, with sensitivity analyses incorporating additional cardiovascular risk factors. Among 608 patients, 54 (8.9%) had baseline CVD. Patients with baseline CVD were older and had a greater burden of comorbidities than those without baseline CVD. During follow-up, 69 patients (11.3%) experienced at least one cardiovascular event. Cardiovascular events occurred in 27 of 54 patients (50.0%) with baseline CVD compared with 42 of 554 patients (7.6%) without baseline CVD ( p < 0.001). Baseline CVD was independently associated with higher odds of cardiovascular events (adjusted OR, 9.46; 95% CI 4.92–18.17; p < 0.001), and increasing age was also independently associated with the outcome (adjusted OR per year, 1.04; 95% CI 1.01–1.06; p = 0.001). The association remained significant after additional adjustment for hypertension, diabetes mellitus, chronic kidney disease, and dyslipidemia (adjusted OR, 6.64; 95% CI 3.28–13.47; p < 0.001). All-cause mortality was higher among patients with baseline CVD (64.8% vs. 46.4%, p = 0.010), and unadjusted median overall survival was shorter (11.5 vs. 23.8 months; log-rank p = 0.022). Cardiovascular events were predominantly ischemic and heart failure-related, whereas myocarditis was rare, occurring in only one patient overall. In this multicenter cohort, pre-existing CVD was independently associated with higher cardiovascular event odds among ICI patients, even after adjusting for risk factors. These patients also had shorter OS, though survival analysis was unadjusted. Findings suggest baseline CVD patients are vulnerable and may benefit from thorough risk assessment and cardio-oncology care. However, as an observational study without a non-ICI comparator, these associations do not prove ICI caused or worsened CVD.