Thinggaard Benjamin Sommer, Frederiksen Katrine, Subhi Yousif, Möller Sören, Sørensen Torben Lykke, Kawasaki Ryo, Grauslund Jakob, Stokholm Lonny
Department of Ophthalmology, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Ophthalmol Sci. 2023 Dec 7;4(3):100446. doi: 10.1016/j.xops.2023.100446. eCollection 2024 May-Jun.
Controversy exists regarding the systemic safety of intravitreal VEGF inhibitors in the treatment of neovascular age-related macular degeneration (nAMD). We aimed to investigate the potential impact of VEGF inhibitor treatment on the risk of all-cause mortality and cardiovascular disease (CVD) among patients with nAMD.
A nationwide register-based cohort study with 16 years follow-up.
Patients with nAMD exposed with VEGF inhibitors (n = 37 733) and unexposed individuals without nAMD (n = 1 897 073) aged ≥ 65 years residing in Denmark between January 1, 2007, and December 31, 2022.
Cox proportional hazards analysis was conducted to assess the effect of intravitreal VEGF inhibitor treatment on all-cause mortality and incident CVD.
In a predefined analysis plan we defined primary outcomes as hazard ratios (HRs) of all-cause mortality and a composite CVD endpoint in patients with nAMD treated with VEGF inhibitors compared with individuals without nAMD. The secondary outcomes encompassed analyses that explored the impact of the number of doses and the association between exposure and outcome over a specific time period.
Overall, 63.7% of patients with nAMD were women with an average age of 69.9 years (interquartile range 65.0-76.0 years). Patients exposed to VEGF inhibitors demonstrated a reduced risk of all-cause mortality compared with individuals without nAMD (HR, 0.79; 95% confidence interval [CI], 0.78-0.81), and an increased risk of composite CVD (HR, 1.04; 95% CI, 1.01-1.07). The decreased risk of all-cause mortality persisted, but there was no significant association between VEGF inhibitor treatment and CVD when patients with nAMD were grouped by the number of doses or considered exposed within 60 days postinjection.
Our study revealed a decreased risk of all-cause mortality and a 4% increased risk of CVD among patients with nAMD exposed with VEGF inhibitors. The decreased risk of mortality is unlikely to be directly pathophysiologically related to VEGF inhibitor treatment. Instead, we speculate that patients undergoing VEGF inhibitor treatment are, on average, individuals in good health with adequate personal resources. Therefore, they also have a higher likelihood of overall survival. These findings strongly support the safety of VEGF inhibitor treatment in terms of all-cause mortality and CVD among patients with nAMD.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
玻璃体内注射血管内皮生长因子（VEGF）抑制剂治疗新生血管性年龄相关性黄斑变性（nAMD）的全身安全性存在争议。我们旨在研究VEGF抑制剂治疗对nAMD患者全因死亡率和心血管疾病（CVD）风险的潜在影响。
一项基于全国登记的队列研究，随访16年。
2007年1月1日至2022年12月31日期间居住在丹麦、年龄≥65岁、接受VEGF抑制剂治疗的nAMD患者（n = 37733）和未患nAMD的未暴露个体（n = 1897073）。
采用Cox比例风险分析评估玻璃体内注射VEGF抑制剂治疗对全因死亡率和新发CVD的影响。
在预先定义的分析计划中，我们将主要结局定义为接受VEGF抑制剂治疗的nAMD患者与未患nAMD个体相比的全因死亡率风险比（HR）和复合CVD终点。次要结局包括探索剂量数量的影响以及特定时间段内暴露与结局之间关联的分析。
总体而言，63.7%的nAMD患者为女性，平均年龄69.9岁（四分位间距65.0 - 76.0岁）。与未患nAMD的个体相比，接受VEGF抑制剂治疗的患者全因死亡率风险降低（HR，0.79；95%置信区间[CI]，0.78 - 0.81），复合CVD风险增加（HR，1.04；95% CI，1.01 - 1.07）。全因死亡率降低的风险持续存在，但按剂量数量对nAMD患者进行分组或考虑注射后60天内暴露时，VEGF抑制剂治疗与CVD之间无显著关联。
我们的研究显示，接受VEGF抑制剂治疗的nAMD患者全因死亡率风险降低，CVD风险增加4%。死亡率降低的风险不太可能与VEGF抑制剂治疗直接存在病理生理相关性。相反，我们推测接受VEGF抑制剂治疗的患者平均而言是健康状况良好且个人资源充足的个体。因此，他们总体生存的可能性也更高。这些发现有力地支持了VEGF抑制剂治疗在nAMD患者全因死亡率和CVD方面的安全性。
作者对本文讨论的任何材料均无所有权或商业利益。
