Apixaban in the elderly - McMaster University / Hamilton Heath

Apixaban versus Aspirin in Atrial Fibrillation Patients ≥ 75 years old:
An Analysis from the AVERROES Trial
Kuan H Ng, Olga O Shestakovska, John W. Eikelboom, Stuart J Connolly, Salim Yusuf, Robert G Hart
McMaster University, Hamilton, ON; Population Health Research Institute, Hamilton, ON;
Hamilton Health Sciences, Hamilton, ON
The AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA]
to Prevent Stroke In Atrial Fibrillation [AF] Patients Who
Have Failed or Are Unsuitable for Vitamin K Antagonist
[VKA] Treatment) trial (mean participant age 70 years)
compared aspirin with apixaban, a novel oral Xa inhibitor, in
patients at moderate-to-high risk of stroke due to atrial
fibrillation (AF) but were unsuitable for vitamin K antagonists
(VKA).1 Most AF patients in the community are older(≥ 75
years-old), and this age group has higher risks of both stroke
and bleeding during antithrombotic therapy than younger AF
Participants ≥ 75 years were more often female and at greater risk of strokes with higher CHADS2
scores and lower estimated glomerular filtration rate (eGFR). If bleeding risk scores for Vitamin K
antagonists were applied, older participants had higher ATRIA and HAS-BLED scores than
younger participants
The risk of strokes rises with age. The likelihood of strokes due
to cardiac embolism from AF increases with age. Most of the
effect of antiplatelets on stroke reduction appears to be on
non-embolic non-disabling strokes and appears to wane with
age. The benefit of anticoagulation with warfarin is preserved
with age. 3 Despite the clear benefits of anticoagulation for
stroke prevention, VKA remains underused. Older patients
with AF are often not on VKA due to increased risk of
bleeding and difficulties maintaining therapeutic levels of
When compared with aspirin, apixaban is more efficacious in
preventing strokes in older patients. The benefits of apixaban
are preserved with increasing age. Older participants were not
at greater risk of extracranial or intracranial hemorrhage with
apixaban compared to aspirin.
In these exploratory analyses, we set out to:
1. Determine the baseline characteristics of patient older
participants compared with younger participants in the
2. Further characterise the effects of aspirin and apixaban in
older participants.
The AVERROES trial (n=5599) included 1898 participants ≥ 75
years with AF. We compared baseline characteristics and
evaluated the effect of apixaban compared with aspirin on
stroke and major bleeding in participants ≥ 75 years versus
patients < 75 years.
Table 1. Baseline characteristics of older versus younger participants
The rates of stroke or systemic embolism, major hemorrhage and death were nearly three-fold
higher among older compared with younger participants. The absolute risk reduction for stroke
with apixaban over aspirin in AF patients ≥ 75 years was 3.9%/year compared with 0.7%/year in
AF patients <75. Apixaban was more efficacious for preventing strokes in patients ≥ 75 years
(relative risk reduction 67%) compared with patients < 75 years (relative risk reduction 32%; Pvalue for age interaction = 0.04). The benefit of apixaban was consistent across both age groups
with a trend towards a reduction in the primary outcome (P for age interaction = 0.06) and all
cause mortality (P for age interaction = 0.2) in older patients.
Whilst the risk of major bleeding was higher in patients ≥ 75 years (2.2%/year on aspirin and
2.6%/year on apixaban) compared with patients < 75 years (0.7%/year on aspirin and 0.8%/year
on apixaban), there was no significant interaction with age. The number needed to treat with
apixaban instead of aspirin to prevent a stroke or systemic embolus is 26.
Patients ≥ 75 years who are unsuitable for VKA treatment
have substantially greater benefit from apixaban than aspirin
compared with younger patients. Apixaban was not
associated with a disproportionately greater risk of bleeding
in patients ≥ 75 compared with younger patients despite the
greater absolute risk of major bleeding and worse renal
1. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn
S, et al. Apixaban in patients with atrial fibrillation. The New
England journal of medicine. 2011;364(9):806-17.
2. Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, Hart
RG.Prevalence, age distribution, and gender of patients with
atrial fibrillation. Analysis and implications. Archives of internal
medicine. 1995;155(5):469-73.
Figure 1. Participant flow diagram in AVERROES
Figure 2. Comparison of absolute rates of primary and secondary
outcomes on aspirin versus apixaban in older participants
3. van Walraven C, Hart RG, Connolly S, et al. Effect of age on
stroke prevention therapy in patients with atrial fibrillation: the
atrial fibrillation investigators. Stroke; a journal of cerebral
circulation 2009;40:1410-6.

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