Anti-VEGF Treatment does not Increase Cardiovascular Event Risk

While the advent of intravitreal anti-vascular endothelial growth factor (anti-VEGF) has transformed treatment for ocular diseases, it is unknown whether or not this family of treatment could increase the risk of negative cardiovascular events.

A team, led by Nadège Ngo Ntjam, MSc, Hospital Pharmacy, CHRU de Tours, compared the systemic adverse event (SAE) rates for patients treated with intravitreal anti-VEGF drugs with a cohort of patients with ocular diseases that were not treated with anti-VEGF.

Existing Trials

The researchers gathered trial data from several different databases from inception through July 7, 2020, selecting 74 randomized clinical trials in adults with retinal diseases who received intravitreal anti-VEGF treatment.

The investigators sought main outcomes of major cardiovascular events (MACEs) and total mortality, as well as secondary outcomes of nonocular hemorrhage, components of MACEs, other cardiovascular outcomes, serious systemic adverse events, and all systemic adverse events.

Of the 74 trials analyzed in the study, 43% (n = 32) included 14,190 patients with age-related macular degeneration (AMD), while 32% (n – 24) included 5424 patients with diabetic retinopathy (diabetic macular edema or proliferative diabetic retinopathy), 23% (n = 17) included 3757 patients with retinal vein occlusion, and 1% (n = 1) included 122 patients with myopic choroidal neovascularization.

The Risk of Adverse Events

After examined the data, the researchers said anti-VEGF administration did not increase the overall rate of MACEs compared to control agents (OR, 1.16; 95% CI, 0.85-1.58) or total mortality (OR, 1.27; 95% CI, 0.82-19.6).

However, the team identified an interaction (subgroup difference, P = 0.04) in mortality risk depending on the underlying disease with an overall increase (OR, 1.80; 95% CI, 1.03-3.16; P = 0.04) in the risk of death in diabetic retinopathy patients.

This increase was not found in patients with AMD or retinal vein occlusion.\

Anti-VEGF administration did increase the risk of nonocular hemorrhage (OR, 1.46; 95% CI, 1.01-2.10), but this was mainly prevalent in patients with AMD.

“Intravitreal anti-VEGF was not associated with an increase in MACEs in the trials examined herein,” the authors wrote. “Increased mortality in patients with diabetes and nonocular hemorrhages, especially in those with AMD, could represent a safety signal, but the evidence was not strong. However, continued surveillance of SAEs remains warranted.”

In recent years, anti-VEGF medications have greatly improved treatment for diabetic retinopathy, with clear indications of diabetic macular edema.

AAO Data on Anti-VEGF Treatment

In data presented at the American College of Ophthalmology (AAO) 2020 Virtual Conference, investigators examined new treatment patterns for patients with diabetic retinopathy.

The investigators found 22,484 (83.6%) patients who had PDR and diabetic macular edema (DME) that were treated with anti-VEGF medication. In addition, they found 4511 (68.7%) patients without DME that were treated.

PRP alone was performed in 8320 (31%) patients without DME and 2317 (35%) of patients without DME, while 7246 (22%) patients had vitrectomy surgery.

In addition, anti-VEGF treatment was used in 49.1% (n = 3571) of patients receiving vitrectomy and visual acuity results were similar in patients regardless of anti-VEGF use.

Overall, very little difference was found in visual acuity whether or not anti-VEGF medications were used.

The study, “Cardiovascular Adverse Events With Intravitreal Anti–Vascular Endothelial Growth Factor Drugs,” was published online in JAMA Ophthalmology.