On December 28th, 2012 the FDA announced the approval of Eliquis
(apixaban), an oral Factor Xa inhibitor, to reduce the risk of stroke and systemic embolism in
patients with non-valvular atrial fibrillation1. The approval of Eliquis was based on two
pivotal clinical trials, the ARISTOTLE and AVERROES trials.
The Apixaban for Reduction in
Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study was a randomized,
double-blind, head-to-head, non-inferiority trial of apixaban 5 mg twice daily versus warfarin
(target INR 2.0-3.0) conducted in 18,201 patients2. Results of the study established that apixaban
was not inferior to warfarin in the reduction of hemorrhagic stroke. Key secondary outcomes of the
trial showed apixaban superior to warfarin in preventing stroke or systemic embolism.2
The Apixaban Versus
Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are
Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial was a randomized, double-blind study
of 5,599 patients with atrial fibrillation who had increased risk for stroke and were unsuitable for
vitamin K antagonist therapy.3 Patients were randomized to either apixaban 5 mg
twice daily or aspirin 81 to 324 mg daily. The primary outcome was the occurrence of stroke or
systemic embolism3. Results of the trial showed apixaban reduced
the risk of stroke or systemic embolism compared to aspirin (51 and 113; P<0.001) and had
similar occurrence of major bleeding events (44 and 39; P=0.57).3
The recommended dose of apixaban
is 5mg twice daily, or 2.5 mg twice daily in patients with at least two of the following:
years of age, <60
kg, or SCr >1.5 mg/dL.4 Apixaban is metabolized mainly by CYP3A4 and is
a substrate of P-glycoprotein (P-gp), therefore the dose should be reduced to 2.5 mg or avoided
with strong dual inhibitors of CYP3A4 and P-gp and avoided completely with strong inducers of
CYP3A4 and P-gp. The major adverse effect is the increased risk of bleeding. Similar to other
inhibitors, apixaban does not require monitoring of INR and there is no reversal
agent available for the anti-coagulant effect.
Apixaban offers an alternative to other oral
anticoagulants in the treatment of atrial fibrillation, such as warfarin, dabigatran, and
rivaroxaban. Clinicians should use care in selecting appropriate therapy based on patient specific
factors and be mindful of apixaban’s potential for drug-drug interactions.
- Food and Administration. FDA approves Eliquis
to reduce the risk of stroke, blood clots in patients with non-valvular atrial fibrillation.
Retrieved from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333634.htm.
- Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial
fibrillation. N Engl J Med. 2011 Sep 15. 365(11):981-992.
- Connolly SJ, Eikelboom J,
Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011 Mar 3.
- Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb;