Risk of Hypertension Associated with Antivascular Endothelial Growth Factor Monoclonal Antibodies: A Meta-Analysis From 51088 Patients with Cancer

Context: Hypertension events are the dominant adverse events observed in patients receiving the antivascular endothelial growth factor (anti-VEGF) monoclonal antibodies bevacizumab and ramucirumab treatment, which severe hypertension, particularly hypertensive emergencies, may cause acute target organ injury and major cardiovascular events, that has limited the administration of anti-VEGF monoclonal antibodies. The current meta-analysis aimed to examine the relative risk (RR) of hypertension associated with anti-VEGF monoclonal antibodies. Evidence Acquisition: PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library, and Clinical Trials.gov were searched until July 2019 for relevant phase II and III randomized controlled trials (RCTs). Statistical analyses were performed to examine the RR (with 95% confidence intervals (CIs)) of hypertension associated with the anti-VEGF monoclonal antibodies. Results: Ninety four RCTs and 51088 patients were included in the current meta-analysis. According to the results, compared with the control arms, anti-VEGF monoclonal antibodies increased the risk of all-grade (RR: 3.45, 95% CI: 2.98 - 4.00) and high-grade (RR: 5.63, 95% CI: 5.05 - 6.26) hypertension. In the subgroup analyses, the risk of high-grade hypertension varied significantly with cancer type, so that the highestRRwas for patients with ovarian cancer (17.27, 95% CI: 8.50 - 35.08), whereas the risk of all-grade hypertension did not vary significantly. When stratified based on drug types and drug dose, no significant difference was discovered. Conclusions: Anti-VEGF monoclonal antibodies significantly increased the risk of hypertension. The risk may vary with tumor type. Clinicians should be aware of the adverse reaction and clinical monitoring as well as effective management of such situations, particularly for high-risk patients.