JCO oncology practice · 2026
Comparative Risk of Cardiovascular Hospitalization With Immune Checkpoint Inhibitors Versus Chemotherapy.
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Vosooghi Aidan, Mahadevan Aditya, Arora Jagmeet, Farhat Theresa, Vasbinder Alexi, Hayek Salim S
Аннотация
PURPOSE: While immune checkpoint inhibitors (ICIs) are associated with rare, acute myocarditis, their comparative impact on chronic vascular events and heart failure versus conventional chemotherapy remains ill-defined. We compared the 2-year risk of hospitalization for major adverse cardiovascular events (MACEs) after ICI initiation versus chemotherapy and characterized risk heterogeneity across ICI regimens.
METHODS: We performed a global, propensity-matched cohort study using a federated electronic health record network (TriNetX). Patients initiating ICIs (2011-2024) for lung, skin, GI, or urinary malignancies were 1:1 matched to a historical cohort (1997-2011) treated with guideline-endorsed chemotherapy to benchmark toxicity against a standard-of-care control. The primary end point was hospitalization for MACE (heart failure, myocardial infarction, or ischemic stroke) within 24 months.
RESULTS: 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 [RR], 1.40 [95% CI, 1.26 to 1.56]; P < .001). This excess risk was consistent across heart failure (RR, 1.39), ischemic stroke (RR, 1.40), and myocardial infarction (RR, 1.33). Combination of ipilimumab plus nivolumab carried the highest early risk (0-6 months). However, durvalumab was associated with the highest 2-year cumulative incidence of MACE hospitalization (16.2%), significantly exceeding that of pembrolizumab and atezolizumab.
CONCLUSION: In this large real-world cohort, ICIs were associated with a substantial excess burden of severe cardiovascular events compared with traditional chemotherapy. The risk extends beyond acute myocarditis to include chronic vascular events, with distinct high-risk signals for combination therapy and durvalumab, underscoring the need for long-term cardiovascular surveillance.
METHODS: We performed a global, propensity-matched cohort study using a federated electronic health record network (TriNetX). Patients initiating ICIs (2011-2024) for lung, skin, GI, or urinary malignancies were 1:1 matched to a historical cohort (1997-2011) treated with guideline-endorsed chemotherapy to benchmark toxicity against a standard-of-care control. The primary end point was hospitalization for MACE (heart failure, myocardial infarction, or ischemic stroke) within 24 months.
RESULTS: 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 [RR], 1.40 [95% CI, 1.26 to 1.56]; P < .001). This excess risk was consistent across heart failure (RR, 1.39), ischemic stroke (RR, 1.40), and myocardial infarction (RR, 1.33). Combination of ipilimumab plus nivolumab carried the highest early risk (0-6 months). However, durvalumab was associated with the highest 2-year cumulative incidence of MACE hospitalization (16.2%), significantly exceeding that of pembrolizumab and atezolizumab.
CONCLUSION: In this large real-world cohort, ICIs were associated with a substantial excess burden of severe cardiovascular events compared with traditional chemotherapy. The risk extends beyond acute myocarditis to include chronic vascular events, with distinct high-risk signals for combination therapy and durvalumab, underscoring the need for long-term cardiovascular surveillance.