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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

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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, SalimYusuf, Robert G Hart

McMaster University, Hamilton, ON; Population Health Research Institute, Hamilton, ON;

Hamilton Health Sciences, Hamilton, ON




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 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%; P-value 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.

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.3Despite 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 anticoagulation.

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.

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).1Most 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 patients.2


In these exploratory analyses, we set out to:

Determine the baseline characteristics of patient older participants compared with younger participants in the AVERROES trial.

Further characterise the effects of aspirin and apixaban in older participants.


Table 1. Baseline characteristics of older versus younger participants

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 function.


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.


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.

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.

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.

Figure 2. Comparison of absolute rates of primary and secondary outcomes on aspirin versus apixaban in older participants

Figure 1. Participant flow diagram in AVERROES