Intravitreal anti-vascular endothelial growth factor treatment and the risk of thromboembolism

Purpose — To evaluate the subsequent risk of thromboembolic events in patients receiving intravitreal ranibizumab and bevacizumab for age-related macular degeneration or macular edema.

Design — Population-based crossover analysis with self-matched historical control data.

Setting — Ontario, Canada, between April 1, 2006, and March 31, 2013.

Study Population — Consecutive patients 65 and older who initiated intravitreal treatment (N=57,919).

Intervention — Intravitreal injection of ranibizumab or bevacizumab.

Main Outcome Measures — Emergency visits for thromboembolic events spanning one to four years before treatment were compared to one year after treatment. We also examined other secondary events including hip fractures, congestive heart failure, angina, falls, depression, and total emergencies, as well as a control group.

Results — A total of 57,919 patients were included who accounted for 1,858 thromboembolic emergencies (48 per month) during the three-year Baseline interval and 1,077 thromboembolic emergencies (83 per month) during the one-year Subsequent interval after initiating treatment. The absolute change in risk equaled an increase from 10.7 to 18.6 per 1,000 patients annually after initiation of treatment (rate ratio 1.74; 95% confidence interval 1.58-1.92; p<0.0001). The relative increase was particularly pronounced for ischemic stroke (rate ratio 2.18; 95% confidence interval 1.94-2.46; p<0.0001). The observed increase exceeded trends due to aging, applied across patients with diverse characteristics, occurred with each medication (ranibizumab and bevacizumab), was not apparent for emergencies unrelated to thromboembolic events, and did not occur in a control group following cataract surgery.

Conclusions — Intravitreal anti-vascular endothelial growth factor medications ranibizumab and bevacizumab may contribute to systemic thromboembolic events in patients 65 years or older.