We performed a systematic review and meta-analysis to evaluate the risks of cardiac adverse events in solid tumor patients treated with monotherapy of immune checkpoint inhibitors (ICIs) or combined therapy of ICIs plus chemotherapy.
Eligible studies were selected through the following databases: PubMed, Embase and clinical trials (
Among 2,551 studies, 25 clinical trials including 20,244 patients were qualified for the meta-analysis. Compared with PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy showed significant increase in grade 5 arrhythmology (OR 3.90, 95% CI: 1.08–14.06, p = 0.603). PD-1 inhibitor plus chemotherapy show significant increase in grades 1–5 myocardial disease (OR 5.09, 95% CI: 1.11–23.32, p = 1.000). Compared with chemotherapy, PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy show significant increase in grades 1–5 arrhythmology (OR 2.49, 95% CI: 1.30–4.78, p = 0.289).
Our meta-analysis demonstrated that PD-1 inhibitor plus CTLA-4 inhibitor can result in a higher risk of grade 5 arrhythmology in comparison with PD-1/CTLA-4 inhibitor alone, and a higher risk of grade 5 arrhythmology in comparison with chemotherapy. PD-1 inhibitor plus chemotherapy treatment could increase the risk of all-grade myocardial disease compared with chemotherapy. However, in most cases, there was no significant increase of risks of cardiovascular toxicity in PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor plus chemotherapy compared with chemotherapy alone.