Real-world burden of cardiovascular events following immune checkpoint inhibitor therapy: impact on mortality and treatment resumption in 29,503 patients.

BACKGROUND

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but can cause rare, severe cardiotoxicity. The real-world incidence and impact of a broader spectrum of cardiovascular events remains poorly defined. This study aims to evaluate the real-world incidence of cardiovascular events following ICI therapy, explore predictive biomarkers, and assess the impact of treatment interruptions.

METHODS

A retrospective observational study using Optum's de-identified Market Clarity Data was conducted in 29,503 patients receiving ICI therapy for any cancer type with a minimum follow-up of 6 months. Cardiovascular events including myocarditis, arrhythmias, and reduced left ventricular ejection fraction (LVEF < 50%), were analyzed. Kaplan-Meier survival curves were used to evaluate the timing of these events. Biomarkers such as NT-proBNP and troponin were evaluated for their predictive value.

RESULTS

Out of 29,503 ICI-treated patients, 27.6% experienced a cardiac event during the follow-up period (2 years). Patients with pre-existing cardiovascular conditions who were receiving cardioprotective treatment prior to ICI therapy had an increased risk of cardiovascular events (35% vs 20%, p < 0.001). Patients who experienced a cardiac event had a significantly higher mortality rate (39% vs 25.4%, p < 0.001). Elevated troponin and NT-proBNP levels were associated with increased mortality (p < 0.001).

CONCLUSIONS

Cardiovascular events are frequent in ICI-treated patients, particularly in those with pre-existing cardiac conditions. Elevated troponin and NT-proBNP levels may serve as useful biomarkers for predicting post-ICI cardiovascular events. These findings demonstrate that these events significantly interrupt ICI therapy and increase mortality. They support biomarker-guided risk stratification and prompt collaboration between oncologists and cardio-oncologists to preserve treatment integrity.