Association between intravitreal anti-vascular endothelial growth factor agents and hypertension: a meta-analysis

To compare the risk of hypertension between intravitreal anti-vascular endothelial growth factor (VEGF) agents and sham injections, and between different anti-VEGF agents.

A systematic search was performed on OVID MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials from January 2005 to August 2023. Inclusion criteria included published randomized clinical trials (RCTs) reporting on cases of hypertension as an adverse event for standard dose intravitreal anti-VEGF agents. Using random-effects modeling, risk ratios (RR) and 95% confidence intervals (CI) were used to estimate the frequency of hypertension between patients who received anti-VEGF agents versus sham injections.

Twenty RCTs with 11 196 patients were included. There were 189/2873 (6.6%) new cases of hypertension in the ranibizumab 0.5-mg group, 61/1448 (4.2%) in the bevacizumab 1.25-mg group, 287/3450 (8.3%) in the aflibercept 2-mg group, 32/412 (7.8%) in the brolucizumab 6-mg group, 99/2063 (4.8%) in the faricimab 6-mg group, and 73/950 (7.7%) new cases of hypertension in patients receiving sham injections. There was no significant difference in the risk of developing hypertension between any of the included anti-VEGF agents. Compared to sham injection, ranibizumab (RR = 1.02, 95% CI: [0.74 to 1.40]; p = 0.92) and aflibercept (RR = 0.77, 95% CI: [0.54 to 1.11]; p = 0.17) did not significantly increase the risk of developing hypertension.

This meta-analysis found no significant difference in hypertension risk between different intravitreal anti-VEGF agents or sham injection. These results reinforce the notion that these agents have similar and safe side effect profiles, and that the choice of agent should not be based on the risk of hypertension.