Published Online
on November 23, 2005

A more recent version of this article appeared on January 1, 2006

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Submitted on March 16, 2005
Revised on August 1, 2005
Accepted on September 8, 2005

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.).

^* To whom correspondence should be addressed. E-mail: h.diener{at}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.

Key words: cerebrovascular accident • heparin • venous thrombosis

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