In the trial (the ARISTOTLE trial), presented on August 28, 2011, at the European Society of Cardiology (ESC) 2011 Congress and simultaneously published online in the New England Journal of Medicine, apixaban was superior to warfarin in preventing stroke or systolic embolism (the primary end point) and was also associated with less bleeding and lower mortality than warfarin.
The results have been positioned as the most positive yet for one of the new oral anticoagulants in atrial fibrillation (AF) and appear to give apixaban the edge over its two major competitors, dabigatran (Pradaxa) and rivaroxaban (Xarelto). Both dabigatran and rivaroxaban have also shown benefits over warfarin in the RE-LY and ROCKET-AF trials respectively, but apixaban is the first of these three agents to have shown definite reductions in each of the major outcomes of stroke, bleeding, and mortality.
The ARISTOTLE trial randomized 18, 201 patients with atrial fibrillation to apixaban (5 mg orally twice daily) or warfarin (target INR of 2.0 to 3.0). After a median follow-up of 1.8 years, results showed that apixaban was associated with a 21% reduction in the risk of stroke or systemic embolism, a 31% reduction in bleeding, and an 11% reduction in all-cause mortality.
Addressing the question of whether these new oral agents will completely replace warfarin, Mega points out that that they overcome the need for monitoring with warfarin and have shown encouraging results in many different subgroups, but “switching to a newer agent may not be necessary for the individual patient in whom the INR has been well controlled with warfarin for years.”
The superior data for these new drugs presents a challenge for anyone to continue on warfarin. However, switching to a newer agent may not be necessary for the individual patient in whom the INR has been well controlled with warfarin for years. Another important issue that might prevent people from switching is cost. These new drugs will be much more expensive. It would be more reasonable to give these new drugs to new patients and switch over those not managing well on warfarin.