(Stroke. 2001;32:22.)
© 2001 American Heart Association, Inc.
Original Contributions |
Treatment of Acute Ischemic Stroke With the Low-Molecular-Weight Heparin Certoparin
Results of the TOPAS Trial
From Universitätsklinikum Essen (H.C.D.); Universität Münster (E.B.R.); Universität Dresden (R.von K.); Klinikum Fulda (H.D.L.); Krankenhaus Köln-Merheim (H.B.); Wenckebach-Krankenhaus, Berlin (H.L.); Universitätsklinikum Mannheim (M.H.); Universität Regensburg (D.W.); and Novartis Pharma, Nürnberg (M.G., J.B., G.W.) (Germany).
Correspondence to Professor Dr H.C. Diener, Neurologische Klinik und Poliklinik, Universitätsklinikum Essen, Hufelandstraße 55, 45122 Essen, Germany. E-mail h.diener{at}uni-essen.de
Background and Purpose—To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]).
Methods—We randomized
404 patients to 4 treatment groups within 12 hours of stroke onset:
3000 U anti–factor Xa (aXa) certoparin once daily (treatment group 1);
3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and
8000 U aXa twice daily (group 4). The primary efficacy variable was
the proportion of patients reaching a favorable functional outcome
(Barthel Index 
90 points) at 3 months. CT was performed at trial
entry, after 7 days, and on clinical
deterioration.
Results—The proportion
of patients with Barthel Index 90 was not different between treatment
arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively;
intent-to-treat population). European Stroke Scale scores improved in
all treatment groups within the first 14 days to a similar extent.
During the follow-up of 6 months, percentages of patients with
recurrent stroke/transient ischemic attack were 11.0%, 5.9%,
9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was
only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial
bleeding episode occurred in treatment group 1 versus 1 and 0 in group
2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During
certoparin treatment, 1 deep vein thrombosis but no pulmonary
embolism was observed.
Conclusions—Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.
Key Words: heparin • stroke, acute • stroke, ischemic • stroke management • thrombosis
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