Propensity-matched cohort study of comparative risk of cardiovascular hospitalization with ICIs versus chemotherapy

While immune checkpoint inhibitors (ICIs) are associated with rare, acute myocarditis, their comparative impact on chronic ascular events and heart failure versus conventional chemotherapy is not clear. A propensity-matched cohort study using the TriNetX database compared the 2-year risk of cardiovascular hospitalization in patients intiating ICIs (2011-2024) for lung, skin, GI, or urinary malignancies 1:1 matched to a historical cohort (1997-2011) treated with guideline-endorsed chemotherapy. The primary endpoint was hospitalization for major adverse cardiovascular events (MACEs; heart failure, myocardial infarction, or ischemic stroke) within 24 months. The final cohort included 30,720 matched patients (15,360 per group). At 2 years, ICI therapy was associated with a significantly higher risk of MACE hospitalization compared with chemotherapy (risk ratio 1.40; p<0.001). This excess risk was consistent across heart failure (RR 1.39), myocardial infarction (RR 1.33), and ischemic stroke (RR 1.40). Combination of ipilimumab plus nivolumab carried the highest early risk (0-6 months), whereas durvalumab was associated with the higher 2-year cumulative incidence of MACE hospitalization (16.2%), significantly exceeding that of pembrolizumab and atezolizumab. The authors conclude that in this large real-world, ICIs were associated with a substantial excess burden of severe cardiovascular events compared with traditional chemotherapy.