Intravitreal vascular endothelial growth factor inhibition associates with decreased risk of all-cause mortality in patients with neovascular aged-related degeneration

Abstract

Purpose : Controversy exists regarding the systemic safety of intravitreal vascular endothelial growth factor (VEGF) inhibitors in treatment of neovascular aged-related macular degeneration (nAMD). In this cohort study, we examined whether VEGF inhibitory treatment affects the risk of cardiovascular disease (CVD) and all-cause mortality among patients with nAMD.

Methods : We performed a nationwide register-based study including all individuals aged 65 years or more with no previous CVD, alive and living in Denmark (2006-2018). Exposure was three or more injections of intravitreal VEGF inhibitors in patients with nAMD and primary endpoints were composite CVD and all-cause mortality. A Cox proportional hazards model using time-varying exposure examined the effect of VEGF inhibitors on CVD and all-cause mortality when adjusting for age, sex, marital status, Charlson Comorbidity Index score, diabetes, dyslipidemia, chronic obstructive pulmonary disease (COPD) and hypertension.

Results : We identified 16,239 patients with nAMD exposed to VEGF inhibitors and 1,428,537 unexposed individuals with no nAMD. Median age at diagnosis with nAMD was 70.9 (65.0-76.8) years and 66.6% were female among exposed while 56.2% were female among unexposed (p<0.001). Exposed had more diabetes, dyslipidemia, COPD, hypertension and were more likely to be divorced, widowed or never married than unexposed (p<0.001).
We identified 2956 events in 48,889 person-years at risk (PYR) and 337,777 events in 8,469,718 PYR of CVD among exposed and unexposed, respectively. The hazard of CVD was not higher among patients exposed to VEGF inhibitors than unexposed (adjusted HR 1.04 95% CI 1.00; 1.08).
In total, 5525 deaths in 88,198 PYR among exposed and 567,559 deaths in 12,674,281 PYR among unexposed were identified, giving a hazard of all-cause mortality significantly lower among exposed compared to unexposed (adjusted HR: 0.75 95% CI 0.73; 0.77).

Conclusions : In this nationwide cohort study of Danish citizens over 65 years, we found no association between intravitreal VEGF inhibitors and CVD, however we found a decreased risk of all-cause mortality associated with VEGF inhibitory treatment among patients with nAMD.
Overall, treatment with VEGF inhibitors in nAMD patients may by safe in terms of CVD and mortality according to real world data from a national cohort.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.