Vranckx P, Leebeek F W G, Tijssen J G P, Koolen J, Stammen F, Herman J-P R, de Winter R J, van T Hof A W J, Backx B, Lindeboom W, Kim S-Y, Kirsch B, van Eickels M, Misselwitz F, Verheugt F W A
Prof. Freek W. A. Verheugt MD, PhD, Department of Cardiology, Heartcenter, Oosterpark 9, AC Amsterdam 1091, the Netherlands, Tel.: + 31 20 5993421, Fax: +31 20 5993997, E-mail: f. w.
Thromb Haemost. 2015 Aug;114(2):258-67. doi: 10.1160/TH15-01-0061. Epub 2015 Apr 30.
Patients on rivaroxaban requiring percutaneous coronary intervention (PCI) represent a clinical conundrum. We aimed to investigate whether rivaroxaban, with or without an additional bolus of unfractionated heparin (UFH), effectively inhibits coagulation activation during PCI. Stable patients (n=108) undergoing elective PCI and on stable dual antiplatelet therapy were randomised (2:2:2:1) to a short treatment course of rivaroxaban 10 mg (n=30), rivaroxaban 20 mg (n=32), rivaroxaban 10 mg plus UFH (n=30) or standard peri-procedural UFH (n=16). Blood samples for markers of thrombin generation and coagulation activation were drawn prior to and at 0, 0.5, 2, 6-8 and 48 hours (h) after start of PCI. In patients treated with rivaroxaban (10 or 20 mg) and patients treated with rivaroxaban plus heparin, the levels of prothrombin fragment 1 + 2 at 2 h post-PCI were 0.16 [0.1] nmol/l (median) [interquartile range, IQR] and 0.17 [0.2] nmol/l, respectively. Thrombin-antithrombin complex values at 2 h post-PCI were 3.90 [6.8]µg/l and 3.90 [10.1] µg/l, respectively, remaining below the upper reference limit (URL) after PCI and stenting. This was comparable to the control group of UFH treatment alone. However, median values for thrombin-antithrombin complex passed above the URL with increasing tendency, starting at 2 h post-PCI in the UFH-alone arm but not in rivaroxaban-treated patients. In this exploratory trial, rivaroxaban effectively suppressed coagulation activation after elective PCI and stenting.
接受利伐沙班治疗且需要进行经皮冠状动脉介入治疗(PCI)的患者是一个临床难题。我们旨在研究利伐沙班(无论是否额外推注普通肝素[UFH])在PCI期间是否能有效抑制凝血激活。对108例接受择期PCI且正在接受稳定双联抗血小板治疗的稳定患者进行随机分组(2:2:2:1),分别给予10毫克利伐沙班短期治疗疗程(n = 30)、20毫克利伐沙班(n = 32)、10毫克利伐沙班加UFH(n = 30)或标准围手术期UFH(n = 16)。在PCI开始前以及开始后0、0.5、2、6 - 8和48小时(h)采集血样,检测凝血酶生成和凝血激活标志物。在接受利伐沙班(10或20毫克)治疗的患者以及接受利伐沙班加肝素治疗的患者中,PCI后2小时的凝血酶原片段1 + 2水平分别为0.16[0.1]纳摩尔/升(中位数)[四分位间距,IQR]和0.17[0.2]纳摩尔/升。PCI后2小时的凝血酶 - 抗凝血酶复合物值分别为3.90[6.8]微克/升和3.90[10.1]微克/升,在PCI和支架置入术后仍低于参考上限(URL)。这与单独使用UFH治疗的对照组相当。然而,单独使用UFH组在PCI后2小时凝血酶 - 抗凝血酶复合物的中位数开始超过URL并呈上升趋势,而利伐沙班治疗的患者则没有。在这项探索性试验中,利伐沙班有效抑制了择期PCI和支架置入术后的凝血激活。