TY - JOUR
T1 - Cardiovascular and Cerebrovascular Adverse Events Associated with Intravitreal Anti-VEGF Monoclonal Antibodies
T2 - A World Health Organization Pharmacovigilance Study
AU - Yang, Jee Myung
AU - Jung, Se Yong
AU - Kim, Min Seo
AU - Lee, Seung Won
AU - Yon, Dong Keon
AU - Shin, Jae Il
AU - Lee, Joo Yong
N1 - Publisher Copyright:
© 2024
PY - 2025/1
Y1 - 2025/1
N2 - Purpose: To analyze cardiovascular and cerebrovascular adverse drug reactions (ADRs) after intravitreal anti–VEGF (aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. Participants: VigiBase, a World Health Organization (WHO) global safety report database. Design: Pharmacovigilance study. Methods: The individual case safety reports (ICSRs) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, there were 23 129 ADRs after intravitreal anti-VEGF therapy and 25 015 132 ADRs associated with any drug (full database). Main Outcome Measures: The reporting odds ratio (ROR) and information components (ICs) were calculated, and the 95% lower credibility interval end point of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odds ratio (rOR). Results: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI, 1.70–1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI, 1.47–1.77]), arrhythmias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 > 0, ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI, 4.82–5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI, 4.07–4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI, 22.10–24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI, 3.98–6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI, 5.03–5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI, 4.14–5.6]). Inter-drug comparison indicated that compared with ranibizumab, patients receiving aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI, 0.49–0.52]), atrial fibrillation (rOR 0.28 [95% CI, 0.23–0.35]), cerebrovascular accident (rOR, 0.15 [95% CI, 0.14–0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI, 0.40–0.65]). Conclusions: In this pharmacovigilance case-noncase study, there was significantly increased reporting of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment. 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. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
AB - Purpose: To analyze cardiovascular and cerebrovascular adverse drug reactions (ADRs) after intravitreal anti–VEGF (aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. Participants: VigiBase, a World Health Organization (WHO) global safety report database. Design: Pharmacovigilance study. Methods: The individual case safety reports (ICSRs) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, there were 23 129 ADRs after intravitreal anti-VEGF therapy and 25 015 132 ADRs associated with any drug (full database). Main Outcome Measures: The reporting odds ratio (ROR) and information components (ICs) were calculated, and the 95% lower credibility interval end point of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odds ratio (rOR). Results: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI, 1.70–1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI, 1.47–1.77]), arrhythmias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 > 0, ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI, 4.82–5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI, 4.07–4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI, 22.10–24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI, 3.98–6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI, 5.03–5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI, 4.14–5.6]). Inter-drug comparison indicated that compared with ranibizumab, patients receiving aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI, 0.49–0.52]), atrial fibrillation (rOR 0.28 [95% CI, 0.23–0.35]), cerebrovascular accident (rOR, 0.15 [95% CI, 0.14–0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI, 0.40–0.65]). Conclusions: In this pharmacovigilance case-noncase study, there was significantly increased reporting of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment. 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. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
KW - Anti-VEGF
KW - Cardiovascular adverse drug reaction
KW - Cerebrovascular adverse drug reaction
KW - Intravitreal injection
KW - VigiBase
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U2 - 10.1016/j.ophtha.2024.07.008
DO - 10.1016/j.ophtha.2024.07.008
M3 - Article
C2 - 39004231
AN - SCOPUS:85205883738
SN - 0161-6420
VL - 132
SP - 62
EP - 78
JO - Ophthalmology
JF - Ophthalmology
IS - 1
ER -