Efficacy of a Synthetic Pentasaccharide, a Pure Factor Xa Inhibitor, as an Antithrombotic Agent – A Pilot Study in the Setting of Coronary Angioplasty
Efficacy of a Synthetic Pentasaccharide, a Pure Factor Xa Inhibitor, as an Antithrombotic Agent – A Pilot Study in the Setting of Coronary Angioplasty
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合成五糖（一种纯 Xa 因子抑制剂）作为抗血栓剂的功效 – 冠状动脉血管成形术背景下的初步研究
DOI：
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发表时间：
1999
影响因子：
6.7
通讯作者：
J. Bassand
中科院分区：
文献类型：
--
作者：
Alain Vuillemenot;F. Schiele;N. Meneveau;S. Claudel;F. Donat;Sylvie Fontecave;R. Cariou;M. Samama;J. Bassand
研究目的总结。评估SR90107/ORG 31540的抗血栓形成特性，SR90107/ORG 31540是一种硫酸化五糖，在已知可促进动脉血栓形成（即冠状动脉血管成形术）的临床环境中特异性增强抗凝血酶III介导的因子Xa失活。方法和结果。经皮腔内冠状动脉成形术（PTCA）进行了传统的气球与单5分钟静脉输注的12毫克五糖，和500毫克静脉阿司匹林。术前、术中及术后24 h内均不允许使用肝素。主要终点是手术期间和术后24小时内血管突然闭合的发生率。样本量设定为60例可评价患者，以便能够以良好的置信水平（>95%）得出结论，即如果观察到少于3例突然血管闭合，则突然血管闭合率小于10%。71例患者被纳入研究，其中10例需要择期支架植入术，并且被认为疗效不可评价。剩余61例可评价患者中有2例在研究期间发生急性血管闭塞[3.28%，95%置信区间（0.4%; 11.4%）]。未发生大出血。注射五糖后10 min，血药浓度达到1.91 ± 0.39 mg/l，给药后2 h平均降至1.18 ± 0.27 mg/l，23 h降至0.36 ± 0.11 mg/l。活化凝血时间（ACT）和活化部分凝血活酶（aPTT）时间保持在正常范围内。注射受试药物后2 h，凝血酶-抗凝血酶复合物水平从22 ± 17.1 μg/ml降至4.5 ± 3.4 μg/ml，凝血酶原片段1+2水平从2.15 ± 1.01降至1.73 ± 0.87，活化因子VII水平从43.4 ± 16.8 mU/ml降至18.9 ± 7.3 mU/ml。结论.五糖给药导致凝血酶生成抑制，而不改变aPTT和ACT。血管突然闭合的发生率在历史系列报告的发生率范围内。因此，我们得出结论，五糖的抗血栓形成活性，如在冠状动脉血管成形术的设置中的这个试点试验中所示，值得进一步研究。
Summary Aim of the study. To assess the antithrombotic properties of SR90107/ORG31540, a sulfated pentasaccharide, which enhances specifically antithrombin III mediated inactivation of factor-Xa, in a clinical setting known to promote arterial thrombosis, i.e. coronary angioplasty. Methods and results. Percutaneous transluminal coronary angioplasty (PTCA) was carried out with conventional balloons with a single 5 min intravenous infusion of 12 mg pentasaccharide, and 500 mg intravenous aspirin. Heparin was not allowed before, during PTCA, and within 24 h after PTCA. The primary end point was the rate of abrupt vessel closure during and within 24 h after the procedure. The sample size was set at 60 evaluable patients, in order to be able to conclude with a good level of confidence (>95%) that the abrupt vessel closure rate was less than 10%, if less than 3 abrupt vessel closures were observed. Seventy-one patients were included in the study, of whom 10 needed elective stenting, and were not considered as evaluable for efficacy. Two out of the 61 remaining evaluable patients experienced acute vessel closure during the study period [3.28%, 95% confidence interval (0.4%; 11.4%)]. No major bleeding occurred. The drug plasma concentrations reached 1.91 ± 0.39 mg/l, 10 min after pentasaccharide injection, and decreased on average to 1.18 ± 0.27 mg/l at 2 h, and to 0.36 ± 0.11 mg/l at 23 h after administration of pentasaccharide. Activated clotting time (ACT) and activated partial thromboplastin (aPTT) time remained within normal range. Thrombinantithrombin complex levels fell from 22 ± 17.1 to 4.5 ± 3.4 μg/ml, prothrombin fragment 1+2 levels decreased from 2.15 ± 1.01 to 1.73 ± 0.87, and activated factor VII levels decreased from 43.4 ± 16.8 mU/ml to 18.9 ± 7.3 mU/ml respectively from baseline to 2 h following injection of the tested drug. Conclusions. Administration of pentasaccharide led to the inhibition of thrombin generation without modification of aPTT and ACT. The rate of abrupt vessel closure was within range of rates reported in historical series. Thus we conclude that the anti-thrombotic activity of pentasaccharide, as shown in this pilot trial in the setting of coronary angioplasty, deserves further investigation.
不稳定型心绞痛患者的冠状动脉血管镜检查。
DOI：
10.1056/nejm198610093151501
发表时间：
1986
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sherman,CT;Litvack,F;Grundfest,W;Lee,M;Hickey,A;Chaux,A;Kass,R;Blanche,C;Matloff,J;Morgenstern,L
通讯作者：
Morgenstern,L
急性心肌梗死患者溶栓和联合肝素治疗期间凝血酶的生成和活性。
影响因子：
24
作者：
Merlini,PA;Bauer,KA;Oltrona,L;Ardissino,D;Spinola,A;Cattaneo,M;Broccolino,M;Mannucci,PM;Rosenberg,RD
通讯作者：
Rosenberg,RD
不稳定型心绞痛亚型经皮腔内冠状动脉成形术的结果。
影响因子：
24
作者：
Bentivoglio,LG;Detre,K;Yeh,W;Williams,DO;Kelsey,SF;Faxon,DP
通讯作者：
Faxon,DP