Format

Send to

Choose Destination
Heart. 2017 Apr;103(8):623-628. doi: 10.1136/heartjnl-2016-309901. Epub 2016 Oct 24.

Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation.

Author information

1
INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina.
2
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
3
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
4
Bristol-Myers Squibb, Princeton, New Jersey, USA.
5
University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
6
Boston University Medical Center, Boston, Massachusetts, USA.
7
Heartcenter, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, Netherlands.
8
Tokai University School of Medicine, Isehara, Japan.

Abstract

OBJECTIVE:

We describe the incidence, location and management of non-major bleeding, and assess the association between non-major bleeding and clinical outcomes in patients with atrial fibrillation (AF) receiving anticoagulation therapy enrolled in Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE).

METHODS:

We included patients who received ≥1 dose of study drug (n=18 140). Non-major bleeding was defined as the first bleeding event considered to be clinically relevant non-major (CRNM) or minor bleeding, and not preceded by a major bleeding event.

RESULTS:

Non-major bleeding was three times more common than major bleeding (12.1% vs 3.8%). Like major bleeding, non-major bleeding was less frequent with apixaban (6.4 per 100 patient-years) than warfarin (9.4 per 100 patient-years) (adjusted HR 0.69, 95% CI 0.63 to 0.75). The most frequent sites of non-major bleeding were haematuria (16.4%), epistaxis (14.8%), gastrointestinal (13.3%), haematoma (11.5%) and bruising/ecchymosis (10.1%). Medical or surgical intervention was similar among patients with non-major bleeding on warfarin versus apixaban (24.7% vs 24.5%). A change in antithrombotic therapy (58.6% vs 50.0%) and permanent study drug discontinuation (5.1% (61) vs 3.6% (30), p=0.10) was numerically higher with warfarin than apixaban. CRNM bleeding was independently associated with an increased risk of overall death (adjusted HR 1.70, 95% CI 1.32 to 2.18) and subsequent major bleeding (adjusted HR 2.18, 95% CI 1.56 to 3.04).

CONCLUSIONS:

In ARISTOTLE, non-major bleeding was common and substantially less frequent with apixaban than with warfarin. CRNM bleeding was independently associated with a higher risk of death and subsequent major bleeding. Our results highlight the importance of any severity of bleeding in patients with AF treated with anticoagulation therapy and suggest that non-major bleeding, including minor bleeding, might not be minor.

TRIAL REGISTRATION NUMBER:

NCT00412984; post-results.

PMID:
27798052
PMCID:
PMC5529964
DOI:
10.1136/heartjnl-2016-309901
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center