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首页> 外文学位 >Arterial Thromboembolic Events following Intravitreal Vascular Endothelial Growth Factor Inhibitor Therapy for Age-Related Macular Degeneration in Regular Clinical Practice.
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Arterial Thromboembolic Events following Intravitreal Vascular Endothelial Growth Factor Inhibitor Therapy for Age-Related Macular Degeneration in Regular Clinical Practice.

机译：在常规临床实践中，玻璃体内血管内皮生长因子抑制剂治疗与年龄相关的黄斑变性的动脉血栓栓塞事件。

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摘要

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is currently the best treatment for neovascular age-related macular degeneration (nvAMD). Anti-VEGF use is associated with concerns about adverse events in the elderly. Some adverse events such as arterial thromboembolic (AT) events, though rare, are potentially fatal. Investigations of AT event risk are typically a secondary objective in clinical trials of anti-VEGF agents. Some studies show increased risk of AT adverse events, while other studies show no appreciable difference in risk.;The MarketScanRTM insurance claims database provided 90% power to detect differences as low as 5%, and encompassed a nationally representative population, to enable the investigation of rare AT adverse events. I analyzed insurance claims data for 153,019 newly-diagnosed nvAMD patients aged 50 years or older continuously enrolled between 2006-2012. Of the study participants 41,336 (27.0%) had AT events during the study period, and 76,014 (49.7%) of the study participants received anti-VEGF injections.;I used Cox regression models, with adjustments for selected covariates and propensity score (PS) weighting, to assess the risk factors for AT adverse events associated with anti-VEGF therapy. I also used logistic regression methods to investigate the odds of AT events associated with any anti-VEGF therapy, and used Cox proportional hazards to assess AT event risk for patients in treatment subgroups for each of the three currently used drugs, Bevacizumab (Avastin), Ranibizumab (Lucentis) and Aflibercept (Eylea).;I found a three-fold increase of the risk of new AT adverse events in patients with a history of AT events prior to their nvAMD diagnosis (Hazard ratio [HR] 3.28, 95% confidence interval [CI] 3.21, 3.38). Other covariates associated with higher AT adverse event risk were the medication Plavix (HR 1.59), peripheral arterial disease (HR 1.39), diabetes (HR 1.27), renal disease (HR 1.17), dementia (HR 1.08), Preferred Provider health insurance subscription (HR 1.06), and age (HR 1.17).;The marginal odds ratio I observed for AT events in association with any anti-VEGF therapy was 20% lower (Odds ratio 0.79, 95%CI 0.77, 0.81) than without therapy, in a logistic regression model adjusted for potential confounders. When I included patient time and propensity score weights in the logistic regression, the estimated odds was 1.18 (95% CI 2.2, 1.2), indicating almost 20% marginal increased odds of AT adverse event in association with anti-VEGF, and suggesting that the time element and confounding by indication, are important in consideration of anti-VEGF-associated AT adverse event risk.;Cox regression showed that AT events are up to 20% less likely to occur within the first 30 days, and 10% less likely in days 31-60 after nvAMD diagnosis in patients who received any anti-VEGF, compared to those who did not. AT events were more likely to occur when follow-up was longer, and my Kaplan-Meier curves portrayed a switch from negative to null risk after 90 days, with no further effect of anti-VEGF after approximately 90 days.;There were no marked differences in AT adverse event risk associated with the individual anti-VEGF medications. Avastin and Lucentis lowered AT event risk in the first 90 days after nvAMD diagnosis by about 10%, and there was no difference in AT risk over the same time period between those who did, or did not receive Eylea.;In conclusion, I identified that a history of AT events prior to the use of anti-VEGF, use of Plavix, peripheral arterial disease, diabetes, renal disease, dementia, Preferred Provider health insurance subscription, and age, were associated with a higher risk of AT events. My observation of change in direction of effect estimates from odds ratio 0.77 to odds ratio 1.18 before and after accounting for patient time on the study, and for confounding by clinical indication (using propensity scores), illustrated the importance of these factors in interpreting any assessment of AT adverse events from insurance claims data. The data in fact indicated a negative risk of AT events associated with anti-VEGF in the first 90 days that switched to a positive risk thereafter - possibly due to increased recognition and preventive treatment for patients on anti-VEGF therapy, compared to patients who were not on treatment.
机译：玻璃体内注射抗血管内皮生长因子（anti-VEGF）是目前治疗新生血管性年龄相关性黄斑变性（nvAMD）的最佳方法。抗VEGF的使用与对老年人不良事件的担忧有关。某些不良事件（例如动脉血栓栓塞（AT）事件）虽然很少见，但可能致命。 AT事件风险的研究通常是抗VEGF药物临床试验中的次要目标。一些研究显示AT不良事件的风险增加，而其他研究则显示风险没有明显差异; MarketScanRTM保险理赔数据库提供90％的能力来检测低至5％的差异，并涵盖了具有全国代表性的人群，以进行调查罕见的AT不良事件。我分析了2006年至2012年之间连续登记的153,019名50岁以上的nvAMD新患者的保险索赔数据。在研究参与者中，有41,336名（27.0％）在研究期间发生了AT事件，而76,014名（49.7％）的研究参与者接受了抗VEGF注射。我使用了Cox回归模型，并对选定的协变量和倾向评分（PS）进行了调整）权重，以评估与抗VEGF治疗相关的AT不良事件的危险因素。我还使用了Logistic回归方法研究了与任何抗VEGF治疗相关的AT事件的几率，并使用Cox比例风险评估了目前使用的三种药物贝伐单抗（Avastin）中每种治疗亚组患者的AT事件风险， Ranibizumab（Lucentis）和Aflibercept（Eylea）。；在有nvAMD诊断之前有AT事件史的患者中，发现新的AT不良事件的风险增加了三倍（危险比[HR] 3.28，95％的置信度区间[CI] 3.21、3.38）。与更高的AT不良事件风险相关的其他协变量是药物Plavix（HR 1.59），外周动脉疾病（HR 1.39），糖尿病（HR 1.27），肾病（HR 1.17），痴呆症（HR 1.08），首选提供者医疗保险（HR 1.06）和年龄（HR 1.17）。；与任何抗VEGF治疗相关的AT事件的边际优势比I均比未治疗低20％（几率0.79、95％CI 0.77、0.81），在针对潜在混杂因素进行调整的逻辑回归模型中。当我在logistic回归中包括患者时​​间和倾向评分权重时，估计的几率是1.18（95％CI 2.2、1.2），表明与抗VEGF相关的AT不良事件的几率增加了近20％，这表明考虑到抗VEGF相关的AT不良事件的发生风险，时间因素和指征混淆很重要。; Cox回归显示，AT事件在头30天内发生的可能性降低了20％，而在30天内发生的可能性降低了10％。与未接受抗VEGF的患者相比，在接受nvAMD诊断后的第31至60天接受抗VEGF的患者。当随访时间更长时，AT事件更有可能发生，我的Kaplan-Meier曲线显示90天后从阴性风险变为无效风险，约90天后抗VEGF作用进一步减弱。与单独的抗VEGF药物相关的AT不良事件风险的差异。 Avastin和Lucentis在nvAMD诊断后的前90天内将AT事件的风险降低了约10％，并且在同一时间段内接受或未接受Eylea的患者的AT风险没有差异。在使用抗VEGF，使用Plavix，外周动脉疾病，糖尿病，肾病，痴呆，首选医疗提供者医疗保险和年龄之前发生AT事件的历史与较高的AT事件风险相关。我观察到考虑到患者在研究上的时间前后以及因临床指征（使用倾向评分）造成的混淆，从效果比估计值的比值从0.77降低到比值1.18的观察，说明了这些因素在解释任何评估中的重要性保险理赔数据中的AT不良事件。实际上，数据表明与抗VEGF相关的AT事件在90天内具有负风险，此后转为正风险-与接受抗VEGF治疗的患者相比，这可能是由于接受抗VEGF治疗的患者认识和预防治疗增加不接受治疗。

著录项

  • 作者

    Fafowora, Oluwatoyin Folasade.;

  • 作者单位

    University of California, Los Angeles.;

  • 授予单位 University of California, Los Angeles.;
  • 学科 Epidemiology.;Pharmacology.;Ophthalmology.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 131 p.
  • 总页数 131
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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