Apixaban reduces risk of complications of atrium fibrillation

Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial.

Literature - Al-Khatib SM, Thomas L, Wallentin L et al. - Eur Heart J. 2013 Apr 17

Al-Khatib SM, Thomas L, Wallentin L et al.
Eur Heart J. 2013 Apr 17


Stroke is a serious and common complication of atrial fibrillation (AF). It is unclear whether the risk of stroke depends on the type, duration and frequency of AF [1-3]. Practical guidelines on AF management are based on risk factors and do not specify types of AF. A large pooled analysis of the SPORTIF (Stroke Prevention with the Oral Thrombin Inhibitor in Atrial Fibrillation) III and V trials indeed showed similar risk of stroke in paroxysmal and persistent or permanent AF [4,5].
Recently, oral anticoagulants have become available as an alternative to vitamin K antagonists (e.g. warfarin) for stroke prevention.
The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thrombo-embolic Events in Atrial Fibrillation) trial found apixaban to be superior to warfarin at reducing the risk of stroke or systemic embolism, bleeding and mortality in patients with AF and at least one risk factor for stroke or systemic embolism [6,7]. This paper describes the pre-specified analysis of the ARISTOTLE trial data to compare outcomes of apixaban vs. Warfarin by AF type and duration.
2786 patients had paroxysmal AF and 15412 had persistent or permanent AF at study entry.

Main results

  • Apixaban gave a consistent reduction in stroke or systemic embolism, all-cause mortality and major bleeding as compared to warfarin, for both types of AF, and irrespective of the duration of AF at study entry.
  • Longer duration of AF up to 2 years was associated with a reduction in the risk of death (per year increase in duration HR: 0.83, 95%CI: 0.76-0.90, P<0.001 for up to 2 years duration, and HR: 1.01, 95%CI: 0.99-1.04, beyond 2 years).
  • When comparing paroxysmal and persistent or permanent AF, patients with paroxysmal AF suffered less from the composite endpoints of stroke or systemic embolism (HR: 0.65, 95%CI: 0.48-0.87, P=0.003), all-cause mortality (HR: 0.72, 95%CI: 0.61-0.85, P=0.0002) and major bleeding (HR:0.77, 95%CI: 0.68-0.87, P<0.0001).
  • After correction for potential confounding due to differences in baseline characteristics,  the risk of stroke or systematic embolism was still significantly lower for paroxysmal AF (HR: 0.70, 95%CI: 0.51-0.93, P=0.015). A trend towards a higher risk of all-cause mortality and the composite endpoint of stroke or systemic embolism, all-cause mortality and major bleeding was observed for patients with persistent or permanent AF.


In patients with AF and at least one risk factor for stroke, the risk of stroke, systemic embolism, all-cause mortality and major bleeding were decreased with apixaban, as compared to warfarin treatment, regardless of the type or duration of AF. Persistent or permanent AF was associated with a higher risk of stroke or systemic embolism and a trend towards higher risk of all-cause mortality than that seen in paroxysmal AF. Based on this and other studies, it appears that the benefits of new anticoagulants on stroke prevention are consistent regardless of the type of AF.
The observed risk reduction with longer duration AF may stem from selection bias of participation in a trial. Because of the potential clinical importance of this aspect, more studies should include duration of AF in their analysis.


1. Aboaf AP, Wolf PS. Paroxysmal atrial fibrillation. A common but neglected entity. Arch Intern Med 1996;156:362–367.
2. Petersen P, Godtfredsen J. Embolic complications in paroxysmal atrial fibrillation. Stroke 1986;17:622–626.
3. Hart RG, Pearce LA, Rothbart RM, et al. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 2000;35:183–187.
4. Nieuwlaat R, Dinh T, Olsson SB et al. Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation? Eur Heart J 2008;29:915–922.
5. SPORTIF Investigators. Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation. J Intern Med 2008;264:50–61.
6. Granger CB, Alexander JH, McMurray JV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365: 981–992.
7. Lopes RD, Alexander JH, Al-Khatib SM, et al. Apixaban for stroke prevention in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J 2010;159:331–339.

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