Authors : Christopher B. Granger, Renato D. Lopes, Michael Hanna, Jack Ansell, Elaine M. Hylek, John H. Alexander, Laine Thomas, Junyuan Wang, M. Cecilia Bahit, Freek Verheug, Jack Lawrence, *Denis Xavier*, Lars Wallentin.
Publication Year : 2015
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. (Am Heart J 2015
https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.114.014807