Division of Cardiovascular Sciences, Department of Internal Medicine (A.J.L., J.N.M., N.T.), University of South Florida.
Division of Stroke and Vascular Neurology, Department of Neurology (D.Z.R., S.R., A.C.B., T.M., W.S.B.), University of South Florida.
Stroke. 2021 Apr;52(4):1164-1171. doi: 10.1161/STROKEAHA.120.030042. Epub 2021 Feb 25.
It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals.
AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (≥1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS.
Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, =0.78), death (4.9% versus 8.5%, =0.68), fatal strokes (2.4% versus 8.5%, =0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, =0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm.
Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02283294.
目前尚不清楚在房颤（AF）导致的急性缺血性脑卒中（AIS）后何时开始抗凝。早期抗凝可能预防再次梗死，但可能引发出血性转化，因为 AF 卒中通常更大且更容易发生出血性转化。晚期抗凝可能预防出血性转化，但在此时间段内增加了二次卒中的风险。我们的目的是比较在 AF 伴卒中和短暂性脑缺血发作（TIA）患者中，早期使用阿哌沙班与后期给予华法林的效果。
AREST（阿哌沙班用于预防复发性栓塞性卒中及出血性转化的早期干预）是一项开放标签、随机对照试验，比较了在 TIA 后 0 至 3 天、小面积 AIS（<1.5cm）后 3 至 5 天、大面积 AIS（≥1.5cm，除外皮质全部区域）后 7 至 9 天内早期使用阿哌沙班与华法林在 1 周后 TIA 或 2 周后 AIS 的安全性，采用 1:1 比例。
尽管 AREST 在全国指南重点更新后提前终止，该更新建议将直接口服抗凝剂替代华法林用于 AF，但结果显示阿哌沙班的复发性卒中和 TIA 发生率（14.6%对 19.2%，=0.78）、死亡率（4.9%对 8.5%，=0.68）、致死性卒中发生率（2.4%对 8.5%，=0.37）、症状性出血发生率（0%对 2.1%）和致死性卒中、复发性缺血性卒中和 TIA 的主要复合终点发生率（17.1%对 25.5%，=0.44）在统计学上相似，但数值上通常较低。华法林组发生 1 例症状性颅内出血，阿哌沙班组未发生。每组各有 5 例无症状性出血性转化。
在 AF 导致的 TIA、小面积或大面积 AIS 后早期开始抗凝似乎不会危及患者安全。更大规模的关键试验仍需确定早期抗凝的潜在疗效。
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