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NEW ORAL ANTICOAGULANTS
ESC Congress in Paris: ARISTOTLE Trial showed superiority over warfarin in atrial fibrillation

On August 28, 2011, Granger C, Wallentin L et al. (1)  reported   the results of the ARISTOTLE trial (1,2) which evaluated the efficacy and safety of apixaban  (Bristol-Myers Squibb  and Pfizer) compared to warfarin in stroke prevention and systemic embolism in patients with nonvalvular atrial fibrillation and an additional risk factor for stroke. This randomized, multicenter trial included 18201 patients randomized to apixaban (5mg b.i.d.) or adjusted dose warfarin. The primary endpoint was stroke (ischemic or hemorrhagic)  or systemic embolism. The secondary endpoint included efficacy and major bleeding and death of any cause.

Apixaban was noninferior regarding the primary endpoint (1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group) and superior to warfarin for the secondary endpoint. The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001). The death rates were 3.52% in the apixaban group and 3.94% in the warfarin group. The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio,0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42). The predominant effect on stroke prevention was on hemorrhagic stroke ‘4 pts per 1000 and stroke of uncertain origin in 2 pts per 1000. The risk of bleeding was lower in the apixaban group than in the warfarin group including gastro-intestinal bleeding.
Comment:

This trial confirms that new anticoagulants are a valid alternative to warfarin treatment and are more practical to use as they do not require anticoagulation monitoring. Apixaban appeared safer than warfarin particularly with a reduction in hemorrhagic stroke.

One should be careful in comparing major trials on new oral anticoagulants as the trial design and patient population differs. For example the mean CHADS2 score was higher in the ROCKET Trial (3.5 ) than in the RE-LY trial (2.1) or ARISTOTLE Trial (2.1). Only a head to head comparison trial can compare the new anticoagulants and such trials are not at present available.

S. Lévy (No conflict of interest to declare)

1 .  Granger C et al. Efficacy and safety of apixaban compared to warfarin for prevention of stroke and systemic embolism in 18 202 patients with atrial fibrillation: primary results of the ARISTOTLE trial. Session Hot line 1. Congress of the European Society of Cardiology, Paris, August 28 2011.

2 .  Granger CB, Alexander JH, McMurray JJV et al. N Engl J Med 2011 ; DOI : 10.1056/NEJMoa1107039, September 12.