Congestive heart failure and other cardiac adverse events after intravitreal anti-VEGF therapy: a systematic review and meta-analysis.

Authors

Michael Balas, Andrew Mihalache, Aaditeya Jhaveri, Shayaan Kaleem, Marko M Popovic, Peter J Kertes, Rajeev H Muni

Published in

Canadian journal of ophthalmology. Journal canadien d'ophtalmologie. Sep 21, 2026. Epub Sep 21, 2026.

Abstract

To evaluate congestive heart failure (CHF) and other cardiac adverse events (AEs) after intravitreal anti-vascular endothelial growth factor (VEGF) therapy for retinal vascular disease and compare risks across agents.
A systematic review and meta-analysis.
Registered review (PROSPERO CRD42022302658) searched Ovid MEDLINE, Embase, and the Cochrane Library from January 2005 to February 2024 for randomized controlled trials (RCTs) of intravitreal anti-VEGF therapy for neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion. Eligible trials compared an anti-VEGF agent with sham or another anti-VEGF agent and reported CHF (primary outcome) or other cardiac AEs (secondary outcomes: arrhythmias, heart failure/cardiomyopathy, inflammatory heart disease, ischemic heart disease, or valvular heart disease). Risk of bias was assessed with RoB 2, certainty with GRADE, and random-effects models generated risk ratios (RRs) with 95% confidence intervals (CIs).
Fourteen reports describing 20 trials (11,803 eyes; mean age 71 ± 12 years; 53% female) were included. CHF was uncommon overall: aflibercept 2.0% (84/4172), ranibizumab 2.2% (25/1158), faricimab 2.3% (44/1926), brolucizumab 2.5% (40/1612), and sham 3.8% (20/524). Ranibizumab did not differ from sham for CHF (RR = 1.53, 95% CI 0.46-5.06), whereas aflibercept was associated with higher CHF risk versus sham in 2 trials (RR = 2.08, 95% CI: 1.03-4.23). No significant CHF differences were detected between aflibercept and brolucizumab, faricimab, or ranibizumab. Other cardiac events were similar across agents.
CHF and other AEs after intravitreal anti-VEGF therapy were uncommon in RCTs and comparable across agents. The aflibercept-sham CHF signal was based on limited evidence and should be interpreted cautiously.

PMID:
42767615
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.

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