The decision to anticoagulate a patient with atrial fibrillation involves a balance between the risks of thromboembolism against those of haemorrhage, with both risks imperfectly predicted by even the best stratification scoring systems.  Although warfarin reduces the risk of stroke in patients with atrial fibrillation, its use remains limited by several limitations.  Apixaban is a novel direct factor Xa inhibitor, previously found to be superior to warfarin at prevention of stroke or systemic embolism in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial.

Lopes et al. attempted to determine how the results of anticoagulation with apixiban differed depending on the patients’ baseline risk of ischaemic events (CHADS2 & CHA2DS2-VASc) and bleeding (HAS-BLED) and found that apixaban consistently outperformed warfarin in terms of reducing the risk of clinical events (stroke, bleeding, and mortality) irrespective of CHADS2, CHA2DS2-VASc or HAS-BLED score.  In addition, Apixaban also appeared to be even more effective in reducing the risk of intracranial bleeding in patients with higher HAS-BLED scores. In individuals with HAS-BLED scores of >3, apixaban reduced the risk of intracranial bleeding 78% compared with warfarin, whereas the risk of intracranial bleeding was reduced 34% compared with warfarin in patients with HAS-BLED scores of 0 to 1.

Although apixaban is one of a number of novel oral anticoagulants that have been shown to have a clinical advantage over warfarin, it is the only one that has been shown to be associated with a reduction of both thromboembolism and haemorrhage, in addition to a reduction in all-cause mortality. This secondary analysis adds weight to the benefits of apixaban over warfarin in patients requiring anticoagulation for atrial fibrillation and reduction in intracranial bleeds in those with the highest risk of bleeding may provide physicians with an safer alternative therapy in these patients.

Conclusions:

Apixaban has benefits over warfarin that are consistent across the spectrum of stroke and bleeding risk, suggesting that the CHADS2,CHA2DS2VASc, and HAS-BLED scores may be less relevant for patients taking apixaban than they are for patients taking warfarin.

• Lopes RD, Al-Khatib SM, Wallentin L, et al. Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and bleeding in atrial fibrillation: a secondary analysis of a randomized controlled trial. Lancet 2012; DOI:10.1016/S0140-6736(12)60986-6.