Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group. Heparin in Acute Embolic Stroke Trial.
Patients with acute ischaemic stroke and atrial fibrillation have an increased risk of early stroke recurrence, and anticoagulant treatment with heparins has been widely advocated, despite missing data on the balance of risk and benefit.
                Heparin in Acute Embolic Stroke Trial (HAEST) was a multicentre, randomised, double-blind, and double-dummy trial on the effect of low-molecular-weight heparin (LMWH, dalteparin 100 IU/kg subcutaneously twice a day) or aspirin (160 mg every day) for the treatment of 449 patients with acute ischaemic stroke and atrial fibrillation. The primary aim was to test whether treatment with LMWH, started within 30 h of stroke onset, is superior to aspirin for the prevention of recurrent stroke during the first 14 days.
                The frequency of recurrent ischaemic stroke during the first 14 days was 19/244 (8.5%) in dalteparin-allocated patients versus 17/225 (7.5%) in aspirin-allocated patients (odds ratio=1.13, 95% CI 0.57-2.24). The secondary events during the first 14 days also revealed no benefit of dalteparin compared with aspirin: symptomatic cerebral haemorrhage 6/224 versus 4/225; symptomatic and asymptomatic cerebral haemorrhage 26/224 versus 32/225; progression of symptoms within the first 48 hours 24/224 versus 17/225; and death 21/224 versus 16/225. There were no significant differences in functional outcome or death at 14 days or 3 months.
                The present data do not provide any evidence that LMWH is superior to aspirin for the treatment of acute ischaemic stroke in patients with atrial fibrillation. However, the study could not exclude the possibility of smaller, but still worthwhile, effects of either of the trial drugs.
Anticoagulants offered no net advantages over antiplatelet agents in acute ischaemic stroke. The combination of low-dose UFH and aspirin appeared in a subgroup analysis to be associated with net benefits compared with aspirin alone, and this merits further research.