Cardiovascular adverse events in patients with lung cancer treated with immune checkpoint inhibitors: a nationwide database study

BACKGROUND: Large, diverse cohort studies are essential for determining the incidence and risk factors of major adverse cardiovascular events (MACEs) associated with immune checkpoint inhibitors (ICIs). This study aimed to (1) compare the incidence of MACEs in primary lung cancer patients receiving ICIs versus those receiving non-ICI chemotherapy, and (2) identify risk factors for MACEs in ICI-treated patients. MATERIALS AND METHODS: We performed a retrospective analysis of primary lung cancer patients using a nationwide Japanese database. Patients were stratified by their use of ICIs, and after propensity score matching, outcomes were evaluated over 180 days. RESULTS: The study included 743 propensity-matched patients in each cohort. The median follow-up period was 329 days (interquartile range, 147-625). At 180 days, 4.0% of ICI-treated patients experienced MACEs, significantly higher than those treated with non-ICI chemotherapy (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.07-3.69; P-value = .030). Among MACEs, myocarditis and pericarditis occurred significantly more frequently in patients receiving ICI treatment than in those receiving non-ICI chemotherapy (P-value = .048 for both outcomes). No significant differences were observed in other MACE components. In multivariable analysis, chronic renal failure (HR, 2.16; 95% CI, 1.05-4.46; P-value = 0.038) and prior heart failure (HR, 3.08; 95% CI, 1.86-5.11; P-value < 0.001) were significant risk factors for MACEs. CONCLUSION: ICI treatment was associated with more frequent MACEs, primarily due to myocarditis and pericarditis. Additionally, prior heart failure and chronic renal failure were key risk factors for MACEs. CLINICAL TRIAL REGISTRATION: UMIN000051698.