Intravitreal anti-VEGF therapy tied to serious adverse drug reactions

Adverse drug reactions (ADRs) appear to be significantly increased following intravitreal anti-VEGF treatment, particularly cardiovascular and cerebrovascular events, according to a recent study. 

This pharmacovigilance study made use of VigiBase, a World Health Organization global safety database. A team of investigators compared the individual case safety reports (ICSRs) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment (ie, aflibercept, bevacizumab, brolucizumab, and ranibizumab) with those reported in the full database. 

From 2004 to 2023, the investigators found 23,129 ADRs following intravitreal anti-VEGF therapy and a total of 25,015,132 ADRs related to any drug (full database). 

Compared with the full database, anti-VEGF use correlated with a higher incidence of myocardial infarction (reporting odds ratio [ROR], 1.78, 95 percent confidence interval [CI], 1.70–1.86), angina pectoris (ROR, 1.61, 95 percent CI, 1.47–1.77), arrhythmias (such as atrial fibrillation, atrial flutter, ventricular fibrillation, and supraventricular tachycardia; ROR >1), hypertension (ROR, 4.91, 95 percent CI, 4.82–5.01), and hypertensive crisis (ROR, 4.49, 95 percent CI, 4.07–4.97). 

Anti-VEGFs also showed a significant association with an increased reporting of cerebrovascular ADRs, including cerebral infarction (ROR, 23.19, 95 percent CI, 22.10–24.34), carotid artery stenosis (ROR, 5.24, 95 percent CI, 3.98–6.89), cerebral haemorrhage (ROR, 5.38, 95 percent CI, 5.03–5.76), and subarachnoid haemorrhage (ROR, 4.81, 95 percent CI, 4.14–5.6). 

In interdrug comparisons, aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (ratio of OR [rOR], 0.55, 95 percent CI, 0.49–0.52), atrial fibrillation (rOR, 0.28, 95 percent CI, 0.23–0.35), cerebrovascular accident (rOR, 0.15, 95 percent CI, 0.14–0.17), and cerebral haemorrhage (rOR, 0.51, 95 percent CI, 0.40–0.65) relative to ranibizumab. 

“Although ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept,” the investigators said.