Factors Associated with Adverse Cardiovascular Events in Cancer Patients Treated with Bevacizumab

Abstract

Background: Bevacizumab, a vascular endothelial growth factor (VEGF) monoclonal antibody commonly used for the treatment of various cancers, is often associated with adverse cardiovascular effects such as hypertension, cardiac and cerebral ischemia, thrombosis, and bleeding events. Factors associated with increased risks of adverse cardiovascular effects with bevacizumab have not been intensively studied. In this study, we determined factors associated with hospital admissions due to cardiovascular complications in patients who received bevacizumab for cancer treatment. Methods and Results: We retrospectively collected data for all patients treated with bevacizumab between the 1st January 2016 and the 31st December 2017 at the Hunter New England Local Health District. Patients’ characteristics and their medical history were obtained from hospital electronic medical records. Outcome data were sourced from the Institutional Cardiac and Stroke Outcomes Unit database. A total of n = 230 patients (mean age 65, males n = 124 (53.9%)) were treated with bevacizumab during the study period. N = 28 patients were admitted to hospital for a major cardiovascular-related event. Higher total treatment dose (p < 0.05), concomitant hypertension (p = 0.005), diabetes (p = 0.04), atrial fibrillation (p = 0.03), and lack of use of statin therapy (p = 0.03) were key contributors to hospital admission. Conclusions: Results of our study highlight the fact that patients with concomitant baseline cardiovascular disease/risk factors are at an increased risk of cardiovascular hospitalization related to bevacizumab treatment. Careful baseline cardiovascular assessment may be an essential step to minimize cardiovascular complications.

Cardiovascular safety of the tyrosine kinase inhibitor nintedanib

“…Remarkably, the incidence of CV events was lower in subsequent postmarketing analyses, which included subjects with a better CV risk profile as compared with those enrolled in the PACE trial, lending support to the consideration that there is an interaction between CV risk factors and the CV toxicity of TKI 61 . Other recent clinical reports have confirmed the clinical relevance of inhibition of VEGF and TK, and the association of the CV profile with the risk of adverse CV events 62–64 …”

Metformin alleviates bevacizumab-induced vascular endothelial injury by up-regulating GDF15 and activating the PI3K/AKT/FOXO/ PPARγ signaling pathway

“…In these patients, the number of patients who develop acute myocardial infarction, coronary artery disease, and thromboembolic event are 14.81%, 19.23%, and 17.86%, respectively (26). Additionally, a retrospective cohort study reported that in cancer patients (multiple types) treated with bevacizumab, 28 out of 230 patients were re-treated in hospital due to major cardiovascular-related events (27).…”

Mechanoregulation of Vascular Endothelial Growth Factor Receptor 2 in Angiogenesis

“…Finally, in ocular vascular degenerative disorders, several anti-VEGF therapies have been approved for clinical use but show limited improvements in many clinical trials (246). While some benefits have been observed in several studies for the various diseases and conditions discussed here, the side effects associated with anti-VEGF or anti-VEGFR-2 therapies can be severe and include heightened risk of arterial thromboembolic events, hypothyroidism, wound healing complications, GI perforations, neutropenia and hematological effects and increased risks for other cardiac adverse events (245,(247)(248)(249). If future treatments combine anti-VEGFR-2 and anti-mechanotransductive elements, additional side effects could be expected if the latter pathways are ubiquitous in healthy and diseased tissues.…”