Top Things to Know: Defining Cardiovascular Endpoints in Oncology Trials: Challenges and Opportunities
Updated: June 15, 2026
Prepared by Nicholas Brownell MD PhD Clinical Instructor in Medicine UCLA Division of Cardiology
- Because antineoplastic agents can have unanticipated cardiovascular (CV) effects, clinical trials offer a unique opportunity to identify and characterize toxicities, assess risk factors, and evaluate the balance between oncologic efficacy and CV risk.
- This statement offers a standardized framework for selecting, defining, and adjudicating CV endpoints in oncology trials.
- Identifying clinical CV endpoints requires an understanding of the potential mechanism of how a therapy may affect the CV system, using standardized criteria for the definition of the endpoint and robust event ascertainment processes to ensure consistent validity, interpretability, and regulatory acceptability.
- Biomarkers can be considered validated surrogate CV endpoints only when robust data demonstrate that changes in the biomarker consistently predict changes in true clinical outcomes with both biologic plausibility and statistically confirmed trial-level correlations; examples include severity of LVEF decline or seriousness of QT prolongation.
- Incorporating patient-reported outcomes into oncology trials can provide patient-centered insights into cancer- and CV-related symptoms, function, and treatment effects, but must be carefully designed and implemented to meet scientific and regulatory standards.
- Baseline CV testing is warranted in the screening phase of a trial to inform CV risk stratification, with CV events evaluated throughout the treatment phase and throughout post-treatment surveillance.
- Consistency in CV endpoint definitions may allow for pooling results across trials, when individual studies may be underpowered for rare CV events such as myocarditis.
- Integration of CV and oncology outcomes into composite endpoints such as CV-disease free survival and progression-free and CV event-free survival, balance oncologic efficacy and CV safety and provide a “net clinical benefit measure” for use in trials.
- When trials seek to support CV safety or efficacy claims in drug labeling, pre-specified statistical analyses are essential.
- Future trials will required enhanced collaboration between oncology and cardiology, along with transparent reporting and stakeholder alignment on the value of CV endpoints.
Citation
Barac A, Guha A, Fleming TR, Bonaca M, Thavendiranathan P, Deswal A, Amiri-Kordestani L, Bhatnagar V, Cordoba R, Hurvitz S, Adjei AA, Agarwal N; on behalf of the American Heart Association Cardio-Oncology Committee of the Council on Clinical Cardiology and Council on Genomic and Precision Medicine; Council on Cardiovascular and Stroke Nursing; and Council on Peripheral Vascular Disease. Defining cardiovascular endpoints in oncology trials: challenges and opportunities: a scientific statement from the American Heart Association. Circulation. Published online June 15, 2026. doi: 10.1161/CIR.0000000000001417.