Prophylaxis of thrombotic and embolic events in acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the PROTECT Trial.
OBJECTIVE
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.
Diener
Hans-Christoph
HC
University of Essen, Germany. h.diener@uni-essen.de
Ringelstein
Erich B
EB
von Kummer
Rüdiger
R
Landgraf
Helmut
H
Koppenhagen
Klaus
K
Harenberg
Job
J
Rektor
Ivan
I
Csányi
Attila
A
Schneider
Dietmar
D
Klingelhöfer
Jürgen
J
Brom
Joachim
J
Weidinger
Gottfried
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D006493:Heparin / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D007511:Ischemia / Q000628:therapy; D008875:Middle Aged; D015233:Models, Statistical; D011655:Pulmonary Embolism / Q000188:drug therapy / Q000401:mortality; D012306:Risk; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013923:Thromboembolism / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy
D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; C403769:certoparin