使用低分子肝素（舍托肝素）预防缺血性卒中患者的血栓性成及栓塞事件---PROTECT研究结果

Prophylaxis of Thrombotic and Embolic Events in Acute Ischemic Stroke With the Low-Molecular-Weight Heparin Certoparin
Results of the PROTECT Trial
Hans-Christoph Diener, MD; Erich B. Ringelstein, MD; Rüdiger von Kummer, MD; Helmut Landgraf, MD; Klaus Koppenhagen, MD; Job Harenberg, MD; Ivan Rektor, MD; Attila Csányi, MD; Dietmar Schneider, MD; Jürgen Klingelhöfer, MD; Joachim Brom, PhD; Gottfried Weidinger, PhD for the PROTECT Trial Group

From the University of Essen, Germany (H.C.D.), University of Münster, Germany (E.B.R.); Technical University of Dresden, Germany (R.v.K.); Hospital Friedrichshain, Berlin, Germany (H.L.); Benjamin Franklin Hospital, Berlin, Germany (K.K.); University of Mannheim, Germany (J.H.); Faculty Hospital, Brno, Czech Republic (I.R.); Petz Aladár County Hospital, Györ, Hungary (A.C.); University of Leipzig, Germany (D.S.); Hospital Chemnitz, Germany (J.K.); and Novartis Pharma, Nürnberg, Germany (J.B., G.W.).

Correspondence to Hans-Christoph Diener, MD, PhD, Neurologische Klinik und Poliklinik, Universitätsklinikum Essen, Hufelandstr. 55, D-45122 Essen, Germany. E-mail h.diener@uni-essen.de

Background and Purpose— Patients with stroke are at substantial risk of thromboembolic complications and therefore require antithrombotic prophylaxis. To show the noninferiority of the low-molecular-weight heparin certoparin to unfractionated heparin (UFH) for the prevention of thromboembolic complications, we performed a randomized, double-blind, active-controlled multicenter trial in patients with acute ischemic stroke.

Methods— Overall, 545 patients were randomized within 24 hours of stroke onset to treatment with certoparin (3000 U anti-Xa OD; n=272) or UFH (5000 U TID; n=273) for 12 to 16 days. Patients with paresis of a leg and an National Institutes of Health Stroke Scale score of 4 to 30 points were included. The primary end point was a composite outcome of proximal deep vein thrombosis, pulmonary embolism, or death related to venous thromboembolism during treatment. Computed tomography was performed at trial entry, after 7 days, and when clinical deterioration occurred.

Results— The per-protocol analysis revealed 17 (7.0%) primary events in the certoparin group compared with 24 (9.7%) in the UFH group, thereby demonstrating noninferiority (P=0.0011), confirmed by intention-to-treat analysis (6.6% versus 8.8%; P=0.008). Major bleeding occurred during treatment in 3 patients allocated to certoparin (1.1%) and 5 patients allocated to UFH (1.8%).

Conclusions— Certoparin (3000 U anti-Xa OD) is at least as effective and safe as UFH (TID) for the prevention of thromboembolic complications in patients with acute ischemic stroke.
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使用低分子肝素（舍托肝素）预防缺血性卒中患者的血栓性成及栓塞事件---PROTECT研究结果

背景和目的：卒中患者有后续发生血栓栓塞并发症的风险，需进行抗血栓预防。为了研究低分子肝素（舍托肝素）预防血栓栓塞的效果不比普通肝素差。本研究以缺血性卒中患者为研究对象，进行了多中心随机双盲对照研究。

方法：545名患者在卒中24小时内随机进入舍托肝素组（3000 U抗Xa, 每天一次，n=272）或者普通肝素组（5000 U 每天3次，n=273），持续12-16天。这些患者包括腿部局部麻痹患者和NISHH量表评分在4-30分的患者。主要终点为治疗过程中的近端深静脉血栓、肺栓塞、静脉血栓栓塞导致死亡的混合预后。研究开始时，7天和临床状态恶化时使用CT检查。

结果：总的诊断记录显示舍托肝素组和普通肝素组分别有17（7.0%）和24个（9.7%）主要终点事件，这反映出两种治疗方法无差异性（P=0.001）。此结果通过意向性分析证实（6.6% vs 8.8%;P=0.008）。舍托肝素和普通肝素组分别有3人和5人出现治疗过程中的严重出血。

结论：舍托肝素（3000U抗 Xa，每天一次）至少与普通肝素（每天3次）预防血栓栓塞并发症同样安全，有效。