Perspective:

This secondary analysis of the ARISTOTLE study confirms that in this large, international, randomized trial, the benefits of apixaban versus warfarin, both in terms of stroke risk reduction and bleeding complications, extend across the range of pretreatment patient risk. (Of particular note is the dramatic reduction in risk of intracranial hemorrhage associated with apixaban use compared with warfarin). It is important to note, however, that for patients at lowest risk for stroke or systemic embolization (CHADS₂, score of 1 or CHA₂DS₂VASc score of 1), apixaban was no better than warfarin. As the benefits of any anticoagulation for these low-risk patients are not clear, the current study does not suggest that low-risk patients should be treated with apixaban any more than with warfarin. (Although the aggregate outcomes were better for apixaban in low-risk patients, this is only when bleeding complications were included as well). For now, these data suggest that apixaban may be safer and more effective than warfarin—across all risk groups. As the authors point out, better stratifying stroke risk in patients with atrial fibrillation to determine which patients would benefit from anticoagulation remains a persistent challenge. The conclusion that the risk scores studied may be ‘less relevant’ for ‘tailoring’ apixaban treatment than warfarin treatment is not supported by the study, however. What we have learned is that the relative benefit of apixaban over warfarin applies to all patients. We have not learned whether CHADS₂, CHA₂DS₂VASc, and HAS-BLED scores are any better or worse at identifying appropriate candidates for apixaban treatment than for warfarin treatment.