What is the clinical evidence from this study?

Study design: Cohort. Population: Cancer (n=9541). Intervention: Immune checkpoint inhibitors vs. Reference groups (e.g., PD-1/PD-L1 monotherapy, melanoma, patients without specific comorbidities). Primary outcome: New-onset cardiovascular adverse event (CVAE) within one year.

What does this research mean for the field?

Among patients initiating immune checkpoint inhibitors, nearly one-quarter develop a new-onset cardiovascular adverse event within one year, with risk significantly increased by cardiometabolic comorbidities and triple checkpoint blockade. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

November 17, 2025Open Access

Real-world analysis of cardiovascular adverse events and risk factors after immune checkpoint inhibitor therapy

Key Result

Among 9,541 patients initiating immune checkpoint inhibitors, 24.3% developed a new-onset cardiovascular adverse event within one year, with cardiometabolic comorbidities and triple checkpoint blockade significantly increasing risk.

Study Design

Type

Cohort (n=9,541)

Multicenter

Yes

Structured PICO

Population

9,541 adult cancer patients initiating immune checkpoint inhibitors, free of prior cardiovascular adverse events, followed for up to one year to assess incident cardiovascular toxicity.

Exposure

Immune checkpoint inhibitor (ICI) therapy, including single, double, or triple checkpoint blockade (CTLA-4 + PD-(L)1 + LAG-3).

Outcome

New-onset cardiovascular adverse event (CVAE) within one year.safety

Cardiovascular adverse events occur frequently (24.3% within one year) after immune checkpoint inhibitor initiation, highlighting the need for cardiovascular risk assessment in cardio-oncology.

Limitations

Observational design subject to residual confounding and confounding by indication.
Lack of data on unmeasured factors such as cancer stage, tumor burden, performance status, inflammatory biomarkers, and concurrent or prior cardiotoxic therapies.
Reliance on administrative data may not capture uncoded pre-existing conditions, potentially misclassifying chronic cardiovascular diseases as new-onset.
Requirement for at least one year of follow-up may exclude early deaths or those lacking sufficient encounter data, introducing survivorship bias and potentially underestimating early-onset or fatal CVAEs.

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, offering significant survival benefits across diverse malignancies. However, growing evidence suggest an increased occurrence of cardiovascular adverse events (CVAEs) following ICI, which remain poorly characterized in large, real-world populations. OBJECTIVES: To quantify the incidence and spectrum of CVAEs following ICI initiation and identify demographic, clinical, and treatment-related risk factors for CVAE development. METHODS: We conducted a retrospective cohort study using electronic health record data from the OneFlorida + Clinical Research Network. Adult cancer patients (≥ 18 years) with cancer who started FDA-approved ICIs between January 1, 2018, and December 31, 2023, were included. Eligible patients had either ≥ 1 inpatient or ≥ 2 outpatient encounters after. The primary outcome was new-onset CVAE within one year. Kaplan-Meier survival analyses and multivariable Cox regression evaluated associations with risk factors. RESULTS: Among 9,541 patients initiating ICIs, 2,320 (24.3%) developed a CVAE within one year, with arrhythmia (15.7%), heart failure (5.2%), and stroke (4.1%) being the most common. Cardiometabolic comorbidities (hypertension, hyperlipidemia, diabetes, and obesity) were independently associated with increased CVAE risk. CVAE incidence varied significantly by cancer type, with highest risk observed in breast, liver, and lung cancers compared to melanoma. Triple checkpoint blockade (CTLA-4 + PD-(L)1 + LAG-3) conferred a modest but significant increase in CVAE risk. CONCLUSION: CVAEs occurred frequently after ICI initiation, with substantial variation by cancer type, comorbidities, and treatment regimen. These findings highlight the importance of cardiovascular risk assessment and monitoring to optimize outcomes in immuno-oncology.

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