Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal2Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal3Department of Cardiology, Hospital Garcia de Orta, Almada, Port.
Department of Ophthalmology, Hospital Santa Maria, Lisbon, Portugal.
JAMA Ophthalmol. 2015 Jul;133(7):834-9. doi: 10.1001/jamaophthalmol.2015.0985.
In noninferiority trials, novel oral anticoagulants (NOACs), also known as non-vitamin K oral anticoagulants, were at least noninferior to standard care in the prevention of most prothrombotic conditions. However, differences exist in the safety profile of antithrombotic drugs, and little is known about their intraocular bleeding risk.
To evaluate the risk of substantial intraocular bleeding associated with NOACs.
MEDLINE, Cochrane Library, SciELO collection, and Web of Science databases were searched from inception to November 2014, as well as other systematic reviews and regulatory agencies documentation.
All phase 3 randomized clinical trials (RCTs) comparing NOACs with any other control that reported intraocular bleeding events.
Data were extracted independently by 2 of the authors and pooled using random-effects meta-analysis. Heterogeneity was assessed with the I2 test.
Substantial intraocular bleeding was evaluated with pooled risk ratios (RRs) and 95% CIs.
Seventeen RCTs were included. In patients with atrial fibrillation, no difference was identified between NOACs and vitamin K antagonists (RR, 0.84; 95% CI, 0.59-1.19; I2 = 35%; 5 RCTs), and no increased risk was identified compared with acetylsalicylic acid (RR, 14.96; 95% CI, 0.85-262.00; 1 RCT). In patients with venous thromboembolism, no increased risk of substantial intraocular bleeding compared with sequential treatment with low-molecular-weight heparin and a vitamin K antagonist (RR, 0.67; 95% CI, 0.37-1.20; I2 = 0%; 5 RCTs) was identified. Regarding patients who underwent orthopedic surgery, the risk was not different between NOACs and low-molecular-weight heparin (RR, 2.13; 95% CI, 0.22-20.50; I2 = 0%; 5 RCTs).
Randomized data suggest that no differences exist in the risk of substantial intraocular bleeding between NOACs and other antithrombotic drugs. However, the number of events was scarce so that additional studies from larger databases that monitor patients under conditions of ophthalmologic routine clinical practice should be performed to better characterize the safety profile of NOACs.
在非劣效性试验中，新型口服抗凝剂（NOACs），也称为非维生素 K 口服抗凝剂，在预防大多数血栓前状态方面至少不劣于标准治疗。然而，抗血栓药物的安全性特征存在差异，对于它们的眼内出血风险知之甚少。
评估新型口服抗凝剂（NOACs）与标准治疗相比，发生严重眼内出血的风险。
从研究开始到 2014 年 11 月，我们在 MEDLINE、Cochrane 图书馆、SciELO 集合和 Web of Science 数据库中进行了搜索，同时还搜索了其他系统评价和监管机构的文件。
所有比较新型口服抗凝剂（NOACs）与任何其他控制因素并报告眼内出血事件的 3 期随机临床试验（RCT）。
由 2 名作者独立提取数据，并使用随机效应荟萃分析进行汇总。使用 I2 检验评估异质性。
严重眼内出血用汇总风险比（RR）和 95%置信区间（CI）评估。
纳入了 17 项 RCT。在房颤患者中，与维生素 K 拮抗剂相比，新型口服抗凝剂（NOACs）并未增加风险（RR，0.84；95%CI，0.59-1.19；I2=35%；5 项 RCT），与乙酰水杨酸相比也未增加风险（RR，14.96；95%CI，0.85-262.00；1 项 RCT）。与低分子肝素序贯治疗加维生素 K 拮抗剂相比，静脉血栓栓塞患者使用新型口服抗凝剂（NOACs）并未增加严重眼内出血的风险（RR，0.67；95%CI，0.37-1.20；I2=0%；5 项 RCT）。对于接受骨科手术的患者，新型口服抗凝剂（NOACs）与低分子肝素之间的风险无差异（RR，2.13；95%CI，0.22-20.50；I2=0%；5 项 RCT）。
随机数据表明，新型口服抗凝剂（NOACs）与其他抗血栓药物在严重眼内出血风险方面无差异。然而，事件数量较少，因此应从监测眼科常规临床实践下患者的更大数据库中开展额外研究，以更好地描述新型口服抗凝剂（NOACs）的安全性特征。
