Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial.
BACKGROUND
Low-molecular-weight heparins and heparinoids are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism, but their safety and efficacy in acute ischaemic stroke are inadequately defined.


METHODS
This randomised, double-blind, aspirin-controlled trial tested the safety and efficacy of treatment with high-dose tinzaparin (175 anti-Xa IU/kg daily; 487 patients), medium-dose tinzaparin (100 anti-Xa IU/kg daily; 508 patients), or aspirin (300 mg daily; 491 patients) started within 48 h of acute ischaemic stroke and given for up to 10 days. Primary intracerebral haemorrhage was excluded by computed tomography. Outcome was assessed, with treatment allocation concealed, by the modified Rankin scale at 6 months (independence [scores 0-2] vs dependence or death [scores 3-6]).


RESULTS
Of 1486 randomised patients, two did not receive treatment and 46 were lost to follow-up. The proportions independent at 6 months were similar in the groups assigned high-dose tinzaparin (194/468 [41.5%]), medium-dose tinzaparin (206/486 [42.4%]), or aspirin (205/482 [42.5%]). There was no difference in effect in any predefined subgroup, including patients with presumed cardioembolic stroke. Other outcome measures were similar between the treatment groups (disability, case-fatality, and neurological deterioration rates). During the in-hospital treatment period no patient assigned high-dose tinzaparin developed a symptomatic deep-vein thrombosis compared with nine assigned aspirin. Conversely, seven patients assigned high-dose tinzaparin developed symptomatic intracerebral haemorrhage compared with one in the aspirin group.


CONCLUSIONS
Treatment with tinzaparin, at high or medium dose, within 48 h of acute ischaemic stroke did not improve functional outcome compared with aspirin. Although high-dose tinzaparin was superior in preventing deep-vein thrombosis, it was associated with a higher rate of symptomatic intracranial haemorrhage.
Bath
P M
PM
Centre for Vascular Research, University of Nottingham, Nottingham, UK. philip.bath@nottingham.ac.uk
Lindenstrom
E
E
Boysen
G
G
De Deyn
P
P
Friis
P
P
Leys
D
D
Marttila
R
R
Olsson
J
J
O'Neill
D
D
Orgogozo
J
J
Ringelstein
B
B
van der Sande
J
J
Turpie
A G
AG
D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D000078222:Tinzaparin; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000517:prevention & control
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin; D001241:Aspirin