Search

Background In rare cases, immune checkpoint inhibitors (ICIs) cause immune-mediated myocarditis. However, the true incidence of other major adverse cardiovascular events (MACE) following ICI treatment remains unknown, mainly because late occurring side effects are rarely reported in prospective clinical trials. Purpose To identify the incidence and risk factors of MACE in a real-life ICI-treated cancer cohort and to compare the incidence with non-ICI-treated cancer patients and population controls. Methods In total, 672 ICI-treated patients were included. The primary endpoint was MACE, a composite of acute coronary syndrome, heart failure, stroke and transient ischemic attack. Secondary outcomes were acute coronary syndrome and heart failure separately. Incidence rates were compared between groups after matching according to age, sex, cardiovascular history and cancer type. Results Incidence of MACE was 10.3% during a median time of follow-up of 13 months (IQR 6 to 22). In multivariable analysis, a history of heart failure (hazard ratio (HR): 2.27; 95% confidence interval (CI): 1.03 to 5.04; p=0.043) and valvular heart disease (HR 3.01; 95% CI: 1.05 to 8.66; p=0.041) remained significantly associated with MACE. Cumulative incidence rates were significantly higher in the matched ICI group (rate at full range of follow-up (rate): 8.51; 95% CI: 6.18 to 11.4) compared with the cancer cohort not exposed to ICI (rate: 5.20; 95% CI: 3.56 to 7.35; p=0.032) and the population controls (rate: 2.55; 95% CI: 2.16 to 2.99; p Conclusions Cardiovascular events during and after ICI treatment are more common than currently appreciated. Patients at risk are those with a history of cardiovascular disease. Compared with matched cancer and population controls, MACE incidence rates are significantly higher, suggesting a potential harmful effect of ICI treatment besides the underlying risk. Funding Acknowledgement Type of funding sources: None.