Comparative Risk of Cardiovascular Hospitalization With Immune Checkpoint Inhibitors Versus Chemotherapy

Area of Science:

• Oncology
• Cardiology
• Immunotherapy

Background:

• Immune checkpoint inhibitors (ICIs) are known for rare, acute myocarditis.
• The comparative impact of ICIs on chronic vascular events and heart failure versus chemotherapy is not well understood.

Purpose of the Study:

• To compare the 2-year risk of major adverse cardiovascular events (MACEs) hospitalization after initiating ICIs versus chemotherapy.
• To characterize risk heterogeneity across different ICI regimens.

Main Methods:

• 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 matched 1:1 to a historical chemotherapy cohort (1997-2011).
• The primary endpoint was hospitalization for MACE (heart failure, myocardial infarction, or ischemic stroke) within 24 months.

Main Results:

• ICI therapy was associated with a significantly higher risk of MACE hospitalization compared to chemotherapy (RR, 1.40; P < .001).
• This excess risk was consistent across heart failure (RR, 1.39), ischemic stroke (RR, 1.40), and myocardial infarction (RR, 1.33).
• Durvalumab showed the highest 2-year cumulative incidence of MACE hospitalization (16.2%), exceeding other ICIs.

Conclusions:

• ICIs are associated with a substantial excess burden of severe cardiovascular events compared to traditional chemotherapy.
• The cardiovascular risk associated with ICIs extends beyond acute myocarditis to include chronic vascular events.
• Combination ICI therapy and durvalumab present distinct high-risk signals, necessitating long-term cardiovascular surveillance.