Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.
Mayo Clinic School of Medicine, Rochester, Minnesota.
JAMA Ophthalmol. 2019 May 1;137(5):483-490. doi: 10.1001/jamaophthalmol.2018.6891.
Current studies assessing the risk of stroke, myocardial infarction (MI), and death in patients undergoing intravitreal anti-vascular endothelial growth factor (VEGF) therapy are inconclusive. To our knowledge, no population-based studies have been performed to examine these potential risks.
To examine whether patients with exudative age-related macular degeneration (AMD) receiving intravitreal anti-VEGF injections have a higher incidence of MI, stroke, or death compared with control populations.
DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective cohort study included 504 patients from Olmsted County, Minnesota, identified through the Rochester Epidemiology Project (REP) database as receiving at least 1 intravitreal anti-VEGF injection for exudative AMD from January 1, 2004, to December 31, 2013. Three age- and sex-matched control groups of individuals who did not receive anti-VEGF treatment and were derived from the REP database were also studied: control individuals with exudative AMD in the era before anti-VEGF (January 1, 1990, to December 31, 2003), controls with dry AMD, and controls without AMD. Data analysis was performed from September 1, 2016, to September 1, 2017.
Five-year risk of stroke, MI, and death were assessed in patients compared with controls using Kaplan-Meier and multivariate analysis with Cox proportional hazards regression models.
The study included 504 patients (321 female [63.7%]; mean [SD] age, 76.5 [10.0] years) who received at least 1 intravitreal anti-VEGF injection for exudative AMD during the study period. Kaplan-Meier analysis revealed a 5-year risk of 7.2% for stroke, 6.1% for MI, and 30.0% for death. Patients who received anti-VEGF had no increased risk of stroke or MI compared with controls with dry AMD (n = 504), controls with exudative AMD (n = 473), or controls without AMD (n = 504). There was an increased risk of mortality compared with controls with exudative AMD in the era prior to anti-VEGF therapy but not the other control groups on multivariate analysis (hazard ratio, 1.63; 95% CI, 1.30-2.04; P < .001).
This population-based study revealed that intravitreal anti-VEGF therapy for exudative AMD was not associated with consistent increases in the risk of stroke, MI, or death compared with no therapy in patients with or without AMD. It appears to be likely the cardiac events these patients experience are not attributable to their anti-VEGF therapy.
目前评估接受玻璃体内抗血管内皮生长因子（VEGF）治疗的患者发生中风、心肌梗死（MI）和死亡风险的研究尚无定论。据我们所知，尚未进行基于人群的研究来检查这些潜在风险。
研究与对照人群相比，患有渗出性年龄相关性黄斑变性（AMD）的患者接受玻璃体内抗 VEGF 注射后 MI、中风或死亡的发生率是否更高。
设计、地点和参与者：这是一项基于人群的回顾性队列研究，共纳入明尼苏达州奥姆斯特德县的 504 名患者，这些患者通过罗切斯特流行病学项目（REP）数据库确定，他们在 2004 年 1 月 1 日至 2013 年 12 月 31 日期间至少接受过 1 次玻璃体内抗 VEGF 注射用于治疗渗出性 AMD。还研究了三个未接受抗 VEGF 治疗且来自 REP 数据库的年龄和性别匹配的对照组：在抗 VEGF 时代之前患有渗出性 AMD 的对照者（1990 年 1 月 1 日至 2003 年 12 月 31 日）、干性 AMD 的对照者和没有 AMD 的对照者。数据分析于 2016 年 9 月 1 日至 2017 年 9 月 1 日进行。
使用 Kaplan-Meier 法和 Cox 比例风险回归模型，对患者与对照组相比，评估中风、MI 和死亡的 5 年风险。
本研究纳入了 504 名患者（321 名女性[63.7%]；平均[标准差]年龄为 76.5[10.0]岁），他们在研究期间至少接受过 1 次玻璃体内抗 VEGF 注射治疗渗出性 AMD。Kaplan-Meier 分析显示，5 年中风风险为 7.2%，MI 风险为 6.1%，死亡率为 30.0%。与干性 AMD（n=504）、渗出性 AMD（n=473）或无 AMD（n=504）对照组相比，接受抗 VEGF 治疗的患者中风或 MI 风险无增加。与抗 VEGF 治疗前渗出性 AMD 时代的对照组相比，多变量分析显示死亡风险增加（风险比，1.63；95%CI，1.30-2.04；P<.001），但与其他对照组无差异。
这项基于人群的研究表明，与 AMD 患者或无 AMD 患者不接受治疗相比，玻璃体内抗 VEGF 治疗渗出性 AMD 并不会持续增加中风、MI 或死亡的风险。这些患者发生的心脏事件似乎不太可能归因于他们的抗 VEGF 治疗。
