Department of Ophthalmology, Chi Mei Medical Center, Tainan, Taiwan.
School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
BioDrugs. 2022 Mar;36(2):205-216. doi: 10.1007/s40259-022-00516-y. Epub 2022 Mar 1.
The association between intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment and the risk of major thromboembolic adverse events (TAEs) remains under debate. This study aimed to examine associated risks of TAEs in patients receiving intravitreal anti-VEGF treatment, and effect modification by different indications.
This retrospective cohort study analyzed Taiwan's National Health Insurance Database during 2011-2017 to identify neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) patients newly receiving intravitreal aflibercept or ranibizumab. We followed up patients for 2 years, or until the occurrence of TAEs, including ischemic heart disease, ischemic stroke, transient ischemic attack, deep vein thrombosis, and pulmonary embolism, death, or the end of the study period (i.e., 31 December 2018). We compared the risk of TAEs between patients with aflibercept and ranibizumab using Cox-proportional hazard models. We examined statistical interactions between the anti-VEGF treatment (i.e., ranibizumab and aflibercept) and indications (i.e., nAMD and DME) with regard to the outcome of TAEs.
We included 12,215 nAMD and 7532 DME patients. Among nAMD patients, those receiving aflibercept had lower risk of TAEs (adjusted hazard ratio [HR] 0.85; 95% CI 0.77-0.94) compared with those receiving ranibizumab. However, among DME patients, those receiving aflibercept had no differences in the risk of TAEs (1.14; 0.97-1.35) compared with those receiving ranibizumab. Among patients treated with ranibizumab, the DME group had a higher risk of TAEs than the nAMD group (HR 1.15; 95% CI 1.03-1.28); similar results were observed in patients treated with aflibercept (HR 1.53; 95% CI 1.27-1.85). When DME patients were treated with aflibercept, the risk of TAEs was 31% higher than when nAMD patients were treated with ranibizumab (HR 1.31; 95% CI 1.09-1.56; p < 0.05). The p-value for statistical interaction between the anti-VEGF treatment and indications was 0.0033.
Patients treated with aflibercept or ranibizumab for different indications may be associated with varying risk of TAEs. The findings provide evidence to support treatment selection, taking indications and TAE risk into consideration.
玻璃体内抗血管内皮生长因子（anti-VEGF）治疗与主要血栓栓塞不良事件（TAE）风险之间的关联仍存在争议。本研究旨在研究接受玻璃体内抗 VEGF 治疗的患者发生 TAE 的相关风险，并探讨不同适应证的影响。
本回顾性队列研究分析了 2011 年至 2017 年台湾全民健康保险数据库，以确定新接受玻璃体内阿柏西普或雷珠单抗治疗的新生血管性年龄相关性黄斑变性（nAMD）或糖尿病性黄斑水肿（DME）患者。我们对患者进行了 2 年的随访，或直至发生 TAE，包括缺血性心脏病、缺血性中风、短暂性脑缺血发作、深静脉血栓形成和肺栓塞、死亡或研究期结束（即 2018 年 12 月 31 日）。我们使用 Cox 比例风险模型比较了阿柏西普和雷珠单抗治疗患者发生 TAE 的风险。我们检验了抗 VEGF 治疗（即雷珠单抗和阿柏西普）与适应证（即 nAMD 和 DME）之间在 TAE 结局方面的统计学交互作用。
我们纳入了 12215 例 nAMD 和 7532 例 DME 患者。在 nAMD 患者中，与接受雷珠单抗治疗的患者相比，接受阿柏西普治疗的患者发生 TAE 的风险较低（校正风险比[HR]0.85；95%CI0.77-0.94）。然而，在 DME 患者中，与接受雷珠单抗治疗的患者相比，接受阿柏西普治疗的患者发生 TAE 的风险无差异（1.14；0.97-1.35）。在接受雷珠单抗治疗的患者中，DME 组发生 TAE 的风险高于 nAMD 组（HR1.15；95%CI1.03-1.28）；在接受阿柏西普治疗的患者中也观察到了类似的结果（HR1.53；95%CI1.27-1.85）。当 DME 患者接受阿柏西普治疗时，与 nAMD 患者接受雷珠单抗治疗相比，发生 TAE 的风险高 31%（HR1.31；95%CI1.09-1.56；p<0.05）。抗 VEGF 治疗与适应证之间的统计学交互作用的 p 值为 0.0033。
针对不同适应证接受阿柏西普或雷珠单抗治疗的患者可能具有不同的 TAE 风险。这些发现为支持治疗选择提供了证据，即需要考虑适应证和 TAE 风险。
