BACKGROUND: We sought to assess the occurrence of events after blinded study 
drug discontinuation and transition to open-label vitamin K antagonist (VKA) in 
ARISTOTLE.
METHODS: At the end of ARISTOTLE, blinded study drug was stopped, and open-label 
VKA was recommended. For patients completing the trial on blinded study drug, a 
2-day bridging period with apixaban or apixaban placebo was recommended (while 
beginning open-label VKA). Outcomes were assessed during the 30 days after 
stopping blinded study drug.
RESULTS: Of the 6,809 patients in the apixaban group and 6,588 in the warfarin 
group who completed the trial on study drug, there were 21 strokes or systemic 
emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban 
group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 
10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), 
with most of the imbalance between groups being after the first week. Similar 
results were seen in the first 30 days of the trial where warfarin-naive 
patients starting warfarin had a higher rate of stroke or systemic emboli 
(5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen 
when starting apixaban. No similar increase in events with apixaban versus 
warfarin was seen during temporary or permanent study drug discontinuation 
during the trial.
CONCLUSIONS: The excess in thrombotic and bleeding events in the apixaban group 
after study drug discontinuation appears to be related to an increased risk 
associated with the initiation of a VKA rather than a direct effect of apixaban. 
Whether ≥2 days of apixaban bridging improves outcomes during VKA transition is 
unknown and deserves further evaluation.