Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial

Background Low-molecular-weight heparins and heparinoids are superior to un fractionated heparin in the prevention and treatment of venous thromboembol ism, but their safety and efficacy in acute ischaemic stroke are inadequate ly 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; 5 08 patients), or aspirin (300 mg daily; 491 patients) started within 48 h o f acute ischaemic stroke and given for up to 10 days. Primary intracerebral haemorrhage was excluded by computed tomography. Outcome was assessed, wit h treatment allocation concealed, by the modified Rankin scale at 6 months (independence [scores 0-2] vs dependence or death [scores 3-6]). Findings Of 1486 randomised patients, two did not receive treatment and 46 were lost to follow-up. The proportions independent at 6 months were simila r In the groups assigned high-dose tinzaparin (194/468 [41.5%]), medium-dos e tinzaparin (206/486 [42.4%]), or aspirin (205/482 [42.5%]). There was no difference in effect in any predefined subgroup, including patients with pr esumed cardioembolic stroke. Other outcome measures were similar between th e treatment groups (disability, case-fatality, and neurological deteriorati on 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 tinza parin developed symptomatic intracerebral haemorrhage compared with one in the aspirin group. Interpretation Treatment with tinzaparin, at high or medium dose, within 48 h of acute ischaemic stroke did not improve functional outcome compared wi th aspirin. Although high-dose tinzaparin was superior in preventing deep-v ein thrombosis, it was associated with a higher rate of symptomatic intracr anial haemorrhage.