Atrial fibrillation is a major risk factor for first and recurrent ischaemic 
stroke, and anticoagulation, mainly by use of coumarin medications, is an 
effective strategy for reducing ischaemic stroke occurrence in these patients. 
However, the coumarin medications have disadvantages. Over the past decade, 
important strides have been made towards developing improved anticoagulant 
medications. This review discusses these new developments and what they mean for 
the future of primary and secondary ischaemic stroke prevention in patients with 
atrial fibrillation. Relevant papers were identified with electronic searches of 
the Medline and EMBASE databases. Ongoing trials were checked using the Trials 
Results Centre website. The direct thrombin inhibitors, and the factor Xa 
inhibitors are the two major new anticoagulant drug classes under development at 
present. In phase III trials, dabigatran and rivaroxaban demonstrated at least 
as good performance as warfarin at reducing the rate of ischaemic stroke, 
systemic embolus, and haemorrhagic ischaemic stroke, whilst maintaining a 
comparable or lower rate of major bleeding events. Drug level monitoring was not 
required due to stable pharmacodynamics. AZD0837, apixaban, YM-150, edoxaban and 
betrixaban all showed promising results in phase II trials, as did S35972 in 
animal, in vitro and ex vivo models. The future of these new anticoagulants 
looks encouraging, although there are still some significant challenges to 
overcome. We need to consider the accumulation of long-term safety and efficacy 
data, and the development of effective means of reversal of anticoagulation for 
the direct thrombin inhibitors and factor Xa inhibitors.