Newer Agents

Abstract

APIXABAN Patients with AF have a fivefold increased risk of stroke, particularly in patients with valvular heart disease and in the elderly. It is estimated that 15-20 % of all strokes are attributable to AF. Four new agents [apixaban, dabigatran, edoxa-ban, and rivaroxaban] are vying to replace or greatly reduce the use of the well-tried warfarin. There is little doubt that warfarin is underused and in many the international normalized ratio [INR] is not in the desired range 2-3. Apixaban is an oral direct factor Xa inhibitor. Bioavailability is high. Importantly, elimination is only 25 % renal , and half-life ≈ 12 h. Similar to rivaroxaban, cytochrome P450 3A4 is involved in the metabolism so that strong inhibitors substantially increase drug levels (Eikelboom and Weitz 2010). ARISTOTLE.Granger et al 2011 : [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial] In this double-blind design trial 18,201 patients with nonvalvular atrial fibrillation and at least one additional risk factor for stroke were enrolled and randomly assigned to receive the direct factor Xa inhibitor apixaban (at a dose of 5 mg twice daily) or warfarin (target INR, 2.0-3.0). Results: Apixaban was not only noninferior to warfarin, but actually superior, reducing the risk of stroke or systemic embolism by 21 % and the risk of major bleeding by 31 %. As compared with warfarin, apixaban significantly reduced the risk of death from any cause by 11 %. Apixaban is the 24