Angiogenesis inhibitors and cardiovascular outcomes in cancer: Real-world, population-based, matched cohort study.

Abstract

e24024 Background: Angiogenesis inhibitors (AI) have vascular side effects and are now recognized forcardiovascular adverse events (CVAEs). Clinical trial outcomes can underestimate treatment-related adverse events due to restrictive eligibility criteria, limited sample size, and failure to anticipate specific toxicities. In contrast, observational studies have small sample sizes and insufficient adjustment of confounding covariates. In addition, prospective high-quality evidence in real-world settings is scarce. We evaluated the incidence of CVAEs in real-world populations on AI therapy. Methods: This large retrospective cohort study was conducted using the TriNetX database and included adult patients ( > 18 years) with new cancer diagnoses. We performed 1:1 propensity score matching (PSM) for demographics, BMI, nicotine dependence, comorbidities, cancer type, and medications to similar controls as cancer patients never treated with AIs. The primary outcome was the new incidence of CVAEs-like heart failure (HF), major adverse cardiovascular events (MACE; coronary artery intervention myocardial infarction, or unstable angina), arrhythmia, ischemic heart disease (IHD), venous thromboembolism (VT), and cerebrovascular events (CVE cerebral infarction, carotid intervention, stroke, transient ischemic attack). Sensitivity analysis assessed statistical robustness. Hazard ratios (HR) were calculated to compare the AI therapy association with incident CVAEs. Results: We identified 1,170,667 patients with diagnoses of colorectal, cervical, kidney, liver, nonsmall cell lung, or ovarian cancer between 2010 and 2022. Among these, 59,890 had an AI treatment history, and 110,777 did not, with a median follow-up time of 3.1 years. After PSM, both cohorts (59545 each) were well-matched. In the adjusted analysis, AI therapy was associated with higher risks of MACE (HR, 1.23; 95% CI 1.16 -1.31), HF (HR, 1.16; 95% CI 1.08 - 1.25), and VT (HR 2.07; 95% CI 1.95 - 2.19), IHD (HR 1.23; 95% CI 1.16- 1.31), arrhythmias (HR 1.19; 95% CI 1.12-1.27), CVEs (HR, 1.30; 95% CI 1.21- 1.40) at 1 year of exposure. These outcomes were still significantly higher “increased,” suggesting causation; this is an association at follow-up by increasing the lag exposure. Sensitivity analysis results were consistent, and all statistically significant associations remained unchanged. Conclusions: Angiogenesis inhibitor treatment was associated with a significantly higher risk of CVAEs and various malignancies. The increased risk ranges from approximately 1.16 to 2.07 fold, indicating a substantial elevation in risk. These findings highlight the importance of risk stratification and cardiovascular monitoring during and after AI therapy. There is an unmet need to define strategies for CVAE prevention in this high-risk population.