Qureshi Adnan I, Siddiqui Amir M, Hanel Ricardo A, Xavier Andrew R, Kim Stanley H, Kirmani Jawad F, Boulos Alan S, Hopkins L Nelson
Department of Neurology and Neurosciences, University of Medicine and Dentistry of New Jersey, H-506, 185 S. Orange Avenue, Newark, NJ 07103, USA.
Neurosurgery. 2004 Feb;54(2):307-16; discussion 316-7. doi: 10.1227/01.neu.0000103224.90865.2e.
Eptifibatide, a competitive platelet glycoprotein IIb-IIIa receptor inhibitor with high selectivity for platelet glycoprotein IIb-IIIa receptors and a short half-life, has been shown to reduce the risk of ischemic events associated with coronary interventions, particularly when used in high doses. However, its role in conjunction with neurointerventional procedures needs to be determined. We report the results of an open-label prospective registry to evaluate the safety (in terms of avoiding hemorrhagic complications) and effectiveness (in terms of preventing ischemic complications such as stroke) of administering high-dose eptifibatide during internal carotid artery angioplasty and stent placement (CAS) for extracranial carotid artery stenosis.
After femoral artery access was established and intravenous heparin (30 U/kg bolus) was administered, each patient was administered intravenous eptifibatide (two 180-microg/kg single-dose boluses before CAS, then a 2.0-microg/kg/min infusion for 20-24 hours thereafter). The primary end point was the 30-day composite occurrence of death, cerebral infarction, and unplanned or urgent endovascular or surgical intervention. The primary safety end point was bleeding, for which complications were classified according to the Thrombolysis in Myocardial Infarction scheme as major (hemoglobin decrease of more than 5 g/dl), minor (hemoglobin decrease of 3-5 g/dl), or insignificant. Platelet aggregation was measured in 13 consecutive patients with a rapid platelet-function analyzer.
Twenty-six patients (mean age, 68.1 +/- 9.4 yr; 16 men) underwent treatment. The infusion and the CAS procedure were discontinued in one patient who developed angioneurotic edema after being administered intravenous heparin and the first bolus dose of eptifibatide. Among the 25 patients who underwent the procedure, no intracerebral hemorrhages and one minor ischemic stroke occurred during the 1-month follow-up period. The minor stroke was observed on postprocedure Day 7 in a patient for whom antiplatelet therapy was discontinued before a coronary artery bypass graft operation was performed. Another patient was discharged after an uncomplicated hospitalization but died as a result of urinary sepsis 12 days after CAS. One episode of major bleeding from the femoral insertion site required surgical repair and blood transfusions. Minor bleeding occurred in one patient. Platelet aggregation measurements obtained in 13 patients revealed a high degree (mean, 96%; range, 86-100%) of platelet inhibition after the administration of the second bolus dose of intravenous eptifibatide.
High-dose eptifibatide administered as an adjunct to CAS seems to be safe. Further studies are required to analyze its effectiveness and role in neurointerventional procedures.
依替巴肽是一种对血小板糖蛋白IIb-IIIa受体具有高选择性且半衰期短的竞争性血小板糖蛋白IIb-IIIa受体抑制剂,已被证明可降低与冠状动脉介入治疗相关的缺血事件风险,尤其是大剂量使用时。然而,其在神经介入手术中的作用尚待确定。我们报告了一项开放标签前瞻性登记研究的结果,以评估在颅外颈动脉狭窄的颈内动脉血管成形术和支架置入术(CAS)期间给予大剂量依替巴肽的安全性(避免出血并发症方面)和有效性(预防缺血性并发症如中风方面)。
在建立股动脉通路并给予静脉肝素(30 U/kg推注)后,每位患者静脉给予依替巴肽(CAS前给予两次180 μg/kg单剂量推注,然后在此后20 - 24小时内以2.0 μg/kg/min的速度输注)。主要终点是30天内死亡、脑梗死以及计划外或紧急血管内或外科干预的复合发生率。主要安全终点是出血,并发症根据心肌梗死溶栓方案分为严重(血红蛋白下降超过5 g/dl)、轻微(血红蛋白下降3 - 5 g/dl)或不显著。使用快速血小板功能分析仪对13例连续患者进行血小板聚集测量。
26例患者(平均年龄68.1±9.4岁;16例男性)接受了治疗。1例患者在静脉给予肝素和首剂依替巴肽推注后出现血管性水肿,随后停止了输注和CAS手术。在接受手术的25例患者中,1个月随访期内未发生脑出血,发生1例轻微缺血性中风。轻微中风在术后第7天出现在1例患者中,该患者在冠状动脉搭桥手术前停用了抗血小板治疗。另1例患者住院过程顺利出院,但在CAS术后12天因尿脓毒症死亡。1例患者股动脉穿刺部位发生严重出血,需要手术修复和输血。1例患者发生轻微出血。对13例患者进行的血小板聚集测量显示,在静脉给予第二剂依替巴肽推注后,血小板抑制程度较高(平均96%;范围86 - 100%)。
作为CAS辅助用药的大剂量依替巴肽似乎是安全的。需要进一步研究来分析其在神经介入手术中的有效性和作用。