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

OBJECTIVE: 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. DESIGN: A systematic review and meta-analysis. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.