Stroke, Heart Disease Patients Who Undergo Anti-VEGF Therapy Face Greater Mortality

Ophthalmologist analyzing exam’s results in a monitor
Researchers evaluated data from a healthcare database of Taiwanese residents and found a higher mortality risk in patients in the anti-VEGF group.

A significantly higher mortality risk is associated with intravitreal injections (IVI) of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) patients with prior stroke or acute myocardial infarction (AMI), compared with patients with the same history without exposure to anti-VEGF, according to findings published in Eye.

Researchers conducted a population-based study that retrieved medical records from the Taiwan National Health Insurance Database (NHIRD), which contains health care information for all residents of Taiwan. The participants of the first group (IVI group, n=3384) had received IVI of anti-VEGF and had a diagnosis of stroke or AMI prior to their first injections, and the second group (non-IVI group, n=13,536) consisted of patients with the same criteria except for treatment with anti-VEGF. The study evaluated data recorded between 2005 and 2013, comparing the mortality of participants in the 2 groups.

The study found a significant increase in the mortality risk of those in the IVI group compared with those in the non-IVI group and that elevated mortality was significant when anti-VEGF was injected within 1 year after stroke or AMI.

The researchers explain that the inclusion of nAMD patients with prior stroke or AMI was a strength of the study.

“Stroke and AMI are both critical vascular diseases leading to high risks of mortality,” the study explains. “It is reasonable to postulate that the systemic effects of intravitreal anti-VEGF might further hinder the recovery of vascular damage and thus increase mortality. In addition, stroke and AMI have similar underlying risk factors and would be better considered as a whole.”

The study notes that the absence of visual acuity (VA) and data on dietary habits in the NHIRD is a potential confounder, and therefore a study limitation. Another limitation, the researchers explain, is the study’s assessment of all-cause mortality rather than cause-specific mortality. This was due to the difficulty of discerning the specific cause of death based on the NHIRD data. However, it is noted that the study computed mortality for different intervals between stroke/AMI and IVI.

“Our study revealed a higher risk of mortality when the interval was shorter,” the study explains. “We also found that if the interval is more than 1 year, a significant increase in mortality does not exist.”


Chen, YY, Lai YJ, Yen YF et al. Increased mortality after intravitreal injections of anti-VEGF for neovascular AMD among patients with prior stroke or acute myocardial infarction. Eye Published online March 2, 2021. doi:10.1038/s41433-021-01416-1