Major Adverse Cardiovascular Events in Angiogenesis Inhibitor‐Based Cancer Therapy: A Systematic Review and Meta‐Analysis

Q: What are the key findings of this study?

Angiogenesis inhibitors significantly increased the incidence of hypertension compared to control treatments in patients with cancer (22.4% vs 6.6%; RR 3.28).

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Cancer (n=27639). Intervention: Angiogenesis inhibitors vs. Control (chemotherapy alone, placebo, hormone therapy alone, or other targeted therapy alone). Primary outcome: Hypertension events (RR 3.28, 95% CI 2.82-4.30, p=<0.001).

Q: What does this research mean for the field?

Angiogenesis inhibitor therapies significantly increase the risk of adverse cardiovascular events, including hypertension, myocardial ischemia, thrombosis, and left ventricular dysfunction, particularly when combined with chemotherapy or targeted therapies. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Yuxuan Tao; Wenyuan Song; Hui Xu; Jing Zeng; Haixia Li

doi:10.1161/jaha.125.042896

November 3, 2025Journal of the American Heart AssociationOpen Access

Major Adverse Cardiovascular Events in Angiogenesis Inhibitor‐Based Cancer Therapy: A Systematic Review and Meta‐Analysis

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Key result

Angiogenesis inhibitors increase hypertension risk ~3.3-fold compared to control therapy in cancer patients.

RR 3.28
95% CI 2.82-4.30
P<0.001
n=27,639

Figures

Graphical abstract published by Journal of the American Heart Association — Graphical abstract · Published by Journal of the American Heart Association · CC BY-NC-ND

Why the study?

Angiogenesis inhibitors are associated with significant cardiovascular toxicities that may increase when combined with other therapies, warranting an evaluation of the types, incidence, and severity of these adverse events.

Does angiogenesis inhibitor therapy increase major adverse cardiovascular events in patients with cancer?

Study Design

Type

Meta-Analysis (n=27,639)

Structured PICO

Does angiogenesis inhibitor therapy increase major adverse cardiovascular events in patients with cancer?

P

Population

27,639 patients with cancer across 64 randomized controlled trials evaluating the safety of angiogenesis inhibitor therapies.

I

Intervention

Angiogenesis inhibitors (AIs) therapy (alone or in combination with chemotherapy, hormone therapy, or other targeted therapies)

C

Comparator

Control treatments without angiogenesis inhibitors (chemotherapy alone, placebo, hormone therapy alone, or other targeted therapy alone)

O

Outcome

Major adverse cardiovascular events (MACEs) including hypertension, thrombosis, arrhythmia, myocardial ischemia or infarction, and left ventricular dysfunctionsafety

Main Result

Relative Risk: 3.28 (95% CI 2.82–4.3)

Absolute Event Rate: 22.4% vs 6.6%

p-value: p=<0.001

Angiogenesis inhibitors significantly increase the risk of major adverse cardiovascular events, including hypertension, myocardial ischemia, thrombosis, and left ventricular dysfunction in patients with cancer.

Limitations

Insufficient studies to analyze AIs combined with immunotherapy or radiotherapy
High heterogeneity due to the wide variety of AIs included (small-molecule multitarget inhibitors, large-molecule single-target inhibitors, pan-target inhibitors)
Some clinical trials reported data only on severe cardiovascular toxicities, potentially underestimating overall risk
Different AIs were grouped without stratification, preventing comparison of mechanisms and off-target profiles
Reporting across trials often did not allow consistent separation of all-grade versus high-grade adverse events
Lack of head-to-head drug comparisons precluded a network meta-analysis
Specific random sequence generation methods not reported in 26 studies
Performance bias (11 studies were open-label)
Small-study effects or publication bias noted for hypertension and thrombotic events
Substantial heterogeneity in some outcomes, particularly for hypertension
Lack of head-to-head comparisons between different angiogenesis inhibitor agents

Implication

Angiogenesis inhibitors warrant close BP and cardiac monitoring in cancer patients; confirms elevated hypertension, ischemia, and LV dysfunction risks across 64 RCTs.

Abstract

BACKGROUND: Angiogenesis inhibitors (AIs) are effective in cancer therapy due to their ability to suppress tumor vasculature. However, these agents are associated with significant cardiovascular toxicities, including hypertension, thrombosis, and heart failure, which may increase when combined with other cancer treatments, such as chemotherapy or immunotherapy. This meta-analysis aims to evaluate the cardiovascular adverse events linked to AIs, focusing on their types, incidence, and severity of these adverse events to provide a clearer understanding of the cardiovascular risks associated with AIs. METHODS: A systematic review was conducted for randomized controlled trials that assessed AI therapies. The data from 64 studies involving 27 639 patients were analyzed using a random-effects model. Major adverse cardiovascular events such as hypertension, thrombosis, arrhythmias, myocardial ischemia, and left ventricular dysfunction were the primary outcomes. RESULTS: The analysis revealed that AI treatment significantly increased the incidence of hypertension (relative risk [RR], 3.28 [95% CI, 2.82-4.30]), myocardial ischemia or infarction events (RR, 2.09 [95% CI, 1.05-4.17]), arrhythmia events (RR, 1.25 [95% CI, 0.90-1.74]), thrombotic events (RR, 1.46 [95% CI, 1.11-1.92]), and left ventricular dysfunction (RR, 2.00 [95% CI, 1.18-3.41]). Subgroup analyses indicated that the combination of AIs with chemotherapy or other targeted therapies heightened these risks. CONCLUSIONS: AIs significantly increase the risk of cardiovascular events in patients with cancer, particularly when combined with other treatments. Clinicians should balance the benefits and cardiovascular risks of AIs and consider strategies to reduce these adverse effects. Further research is needed to refine these insights.

Discussion

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Cite This Study

Tao et al. (2025) conducted a meta-analysis in Cancer (n=27,639). Angiogenesis inhibitors vs. Control (chemotherapy alone, placebo, hormone therapy alone, or other targeted therapy alone) was evaluated on Hypertension events (RR 3.28, 95% CI 2.82-4.30, p=<0.001). Angiogenesis inhibitors significantly increased the incidence of hypertension compared to control treatments in patients with cancer (22.4% vs 6.6%; RR 3.28).

synapsesocial.com/papers/6a84753ed7bfb55d357313ac https://doi.org/10.1161/jaha.125.042896

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Major Adverse Cardiovascular Events in Angiogenesis Inhibitor‐Based Cancer Therapy: A Systematic Review and Meta‐Analysis

Figures

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Major Adverse Cardiovascular Events in Angiogenesis Inhibitor‐Based Cancer Therapy: A Systematic Review and Meta‐Analysis

Figures

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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