Cardiovascular and Cerebrovascular Safety of Ranibizumab, Bevacizumab, and Aflibercept in Ocular Diseases: An Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) Database

Abstract

AbstractThe cardiovascular and cerebrovascular safety of ranibizumab, bevacizumab, and aflibercept for ocular diseases is unclear. This study aimed to evaluate and compare the cardiovascular and cerebrovascular safety in patients receiving ranibizumab, bevacizumab, and aflibercept for ocular disease. A cross‐sectional study was conducted from 2017 (Q1) to 2021 (Q4) in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. The outcomes of interest were central nervous system vascular disorders, ischemic heart disease, hypertension, pulmonary hypertension, torsade de pointes/QT prolongation, embolic and thrombotic events, cardiac arrhythmias, cardiac failure, and cardiomyopathy. Data mining was performed by a disproportional method with a compression, using compressed reporting odds ratios (sRORs) with 95% confidence intervals (CIs) to measure signals. The results showed 1462 cardiovascular and cerebrovascular events associated with aflibercept, 834 with ranibizumab, and 150 with bevacizumab. Ranibizumab, bevacizumab, and aflibercept were linked to central nervous system vascular disorders (sROR, 5.57[95%CI, 4.95‐6.26] vs sROR, 2.23 [95%CI, 1.75‐2.85] vs sROR, 2.73[95%CI, 2.43–3.06]), ischemic heart disease (sROR, 3.31[95%CI, 2.65–4.13] vs sROR, 1.98 [95%CI, 1.24‐3.16] vs sROR, 3.00 [95%CI, 2.46‐3.65]), embolic and thrombotic (sROR, 3.36 [95%CI, 3.04‐3.72] vs sROR, 2.16 [95%CI, 1.70‐2.74] vs sROR, 5.25 [95%CI, 4.82‐5.72]). Both ranibizumab and bevacizumab produced hypertension (sROR, 1.73 [95%CI, 1.41‐2.12] vs sROR, 1.46 [95%CI, 1.03‐2.06]) and arrhythmias (sROR, 2.82 [95%CI, 1.99‐3.99] vs sROR, 2.13 [95%CI, 1.08‐4.22]) signals. The signals of heart failure were detected in ranibizumab (sROR, 5.64 [95%CI, 4.08‐7.79]) and aflibercept (sROR, 2.80 [95%CI, 2.03‐3.86]). Ranibizumab, bevacizumab, and aflibercept for ocular disease have different safety profiles in cardiovascular and cerebrovascular. The overall cardiovascular and cerebrovascular risk of the patient should be thoroughly assessed in order to select the safest drug for treatment.