Format

Send to

Choose Destination
Am Heart J. 2015 Jan;169(1):25-30. doi: 10.1016/j.ahj.2014.09.006. Epub 2014 Sep 28.

Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

Author information

1
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. Electronic address: christopher.granger@duke.edu.
2
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
3
Bristol-Myers Squibb, Princeton, NJ.
4
Lenox Hill Hospital, New York, NY.
5
Boston University Medical Center, Boston, MA.
6
INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina.
7
Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
8
St John's Medical College, Bangalore, India.
9
Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden.

Erratum in

  • Am Heart J. 2015 Apr;169(4):594.

Abstract

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.

PMID:
25497244
DOI:
10.1016/j.ahj.2014.09.006
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center