Peri-Event Intravitreal Anti-VEGF and Systemic Outcomes After Stroke or Myocardial Infarction

Among patients receiving ongoing intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy who experience stroke or myocardial infarction (MI), evidence is limited on the systemic safety of continuing injections and whether treatment should be paused or modified.

To evaluate whether, among patients receiving intravitreal anti-VEGF therapy who experience cardiovascular events (CVE), there exist associations between anti-VEGF treatments administered shortly before or after CVE (peri-CVE) and mortality or major functional outcomes, and to evaluate whether systemic outcomes differ by anti-VEGF agents.

This was a retrospective cohort study of TriNetX network deidentified electronic health records (EHR) from 2005 to 2025. This study setting was a multicenter, EHR-based network analysis including individuals with stroke or MI with established anti-VEGF history (≥3 months pre-CVE), matched between those receiving 1 or more anti-VEGF injections within 14 days before or up to 6 weeks after CVE and those with no anti-VEGF from 3 months before to 3 months after. Propensity score matching (PSM) balanced demographics, comorbidities, procedures, systemic medications, laboratory values, and anti-VEGF agent history.

Exposures included intravitreal anti-VEGF during the peri-CVE window vs no peri-CVE anti-VEGF. Sensitivity analyses restricted exposure to 14 days or fewer pre-CVE and compared aflibercept, bevacizumab, or ranibizumab with other agents.

The primary outcomes were 3-month and 1-year all-cause mortality, poststroke neurologic deficits, and post-MI heart failure. Data were expressed in relative risks (RRs) with 95% CIs.

A total of 6073 and 5381 individuals with stroke or MI, respectively, were included before PSM. After PSM (1526 pairs with stroke; exposure [received peristroke anti-VEGF], mean [SD] age, 72.1 [12.9] years; 822 female [53.9%]; control [did not receive peristroke anti-VEGF], 72.7 [13.3] years; 840 female [55.0%]; and 1523 pairs with MI, exposure [received peri-MI anti-VEGF], 71.4 [13.5] years; 809 male [53.1%]; control [did not receive peri-MI anti-VEGF], 71.5 [13.3] years; 798 male [52.4%]), peristroke anti-VEGF was associated with lower mortality at 3 months (RR, 0.39; 95% CI, 0.29-0.53) and 1 year (RR, 0.52; 95% CI, 0.43-0.63) and fewer neurologic deficits at 3 months (RR, 0.64; 95% CI, 0.46-0.89) but not 1 year (RR, 0.79; 95% CI, 0.62-1.01). Peri-MI exposure was associated with lower mortality at 3 months (RR, 0.34; 95% CI, 0.26-0.43) and 1 year (RR, 0.58; 95% CI, 0.49-0.68) and lower heart failure at 3 months (RR, 0.65; 95% CI, 0.46-0.93) but not 1 year (RR, 0.87; 95% CI, 0.68-1.11). Timing-restricted analyses showed similar mortality findings without differences in neurologic deficits or heart failure. In agent-specific comparisons, there were no differences across aflibercept, bevacizumab, or ranibizumab for any outcome.

Results of this cohort study reveal that peri-CVE anti-VEGF was not associated with increased mortality or morbidity. Outcomes did not differ among commonly used agents, supporting the safety of continuing intravitreal anti-VEGF therapy without modification during the peri-CVE period.