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Original Investigation
January 31, 2019

Association of Intravitreal Anti–Vascular Endothelial Growth Factor Therapy With Risk of Stroke, Myocardial Infarction, and Death in Patients With Exudative Age-Related Macular Degeneration

Author Affiliations
  • 1Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota
  • 2Mayo Clinic School of Medicine, Rochester, Minnesota
  • 3Department of Health Sciences Research/Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, Florida
  • 4Department of Neurology, Mayo Clinic, Rochester, Minnesota
JAMA Ophthalmol. Published online January 31, 2019. doi:10.1001/jamaophthalmol.2018.6891
Key Points

Question  Do patients receiving intravitreal anti–vascular endothelial growth factor injections for neovascular age-related macular degeneration have an increased incidence of cardiovascular events, such as myocardial infarction, stroke, and death compared with individuals not receiving the injections?

Findings  In this cohort study of 504 patients from Olmsted County, Minnesota, no consistent associations were found in the 5-year risk of stroke, myocardial infarction, or death among patients with age-related macular degeneration receiving intravitreal anti–vascular endothelial growth factor injections compared with control groups with and without age-related macular degeneration.

Meaning  This study suggests that intravitreal anti–vascular endothelial growth factor therapy for neovascular age-related macular degeneration is not associated with increased risk of stroke, myocardial infarction, or death.

Abstract

Importance  Current studies assessing the risk of stroke, myocardial infarction (MI), and death in patients undergoing intravitreal anti–vascular endothelial growth factor (VEGF) therapy are inconclusive. To our knowledge, no population-based studies have been performed to examine these potential risks.

Objective  To examine whether patients with exudative age-related macular degeneration (AMD) receiving intravitreal anti-VEGF injections have a higher incidence of MI, stroke, or death compared with control populations.

Design, Setting, and Participants  This population-based, retrospective cohort study included 504 patients from Olmsted County, Minnesota, identified through the Rochester Epidemiology Project (REP) database as receiving at least 1 intravitreal anti-VEGF injection for exudative AMD from January 1, 2004, to December 31, 2013. Three age- and sex-matched control groups of individuals who did not receive anti-VEGF treatment and were derived from the REP database were also studied: control individuals with exudative AMD in the era before anti-VEGF (January 1, 1990, to December 31, 2003), controls with dry AMD, and controls without AMD. Data analysis was performed from September 1, 2016, to September 1, 2017.

Main Outcomes and Measures  Five-year risk of stroke, MI, and death were assessed in patients compared with controls using Kaplan-Meier and multivariate analysis with Cox proportional hazards regression models.

Results  The study included 504 patients (321 female [63.7%]; mean [SD] age, 76.5 [10.0] years) who received at least 1 intravitreal anti-VEGF injection for exudative AMD during the study period. Kaplan-Meier analysis revealed a 5-year risk of 7.2% for stroke, 6.1% for MI, and 30.0% for death. Patients who received anti-VEGF had no increased risk of stroke or MI compared with controls with dry AMD (n = 504), controls with exudative AMD (n = 473), or controls without AMD (n = 504). There was an increased risk of mortality compared with controls with exudative AMD in the era prior to anti-VEGF therapy but not the other control groups on multivariate analysis (hazard ratio, 1.63; 95% CI, 1.30-2.04; P < .001).

Conclusions and Relevance  This population-based study revealed that intravitreal anti-VEGF therapy for exudative AMD was not associated with consistent increases in the risk of stroke, MI, or death compared with no therapy in patients with or without AMD. It appears to be likely the cardiac events these patients experience are not attributable to their anti-VEGF therapy.

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