Rationale and design of AVERROES: apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment.
BACKGROUND
Many patients with atrial fibrillation (AF) at moderate or high risk for stroke are not treated with a vitamin K antagonist (VKA). Presently, the only alternative to a VKA with a labeled indication for AF is antiplatelet therapy with acetylsalicylic acid (ASA), which is much less effective than a VKA for prevention of stroke. The novel oral factor Xa inhibitor, apixaban, is being developed for prevention of stroke in AF. A noninferiority trial of apixaban versus a VKA (warfarin) is being conducted but does not address the large unmet need of AF patients at risk of stroke who are unsuitable for or unwilling to take a VKA. Apixaban may be an attractive alternative to ASA for prevention of stroke in patients with AF who cannot or will not take a VKA.


METHODS
AVERROES is a double-blind, double-dummy superiority trial of apixaban 5 mg twice daily (2.5 mg twice daily in selected patients) compared with ASA 81 to 324 mg once daily in patients with AF and at least 1 risk factor for stroke who have failed or are unsuitable for VKA therapy. The primary outcome is stroke or systemic embolism, and the primary safety outcome is major bleeding. The trial is event driven and is expected to enroll at least 5,600 patients.


CONCLUSIONS
By evaluating the use of apixaban as a replacement for ASA in AF patients who are not treated with a VKA, the AVERROES study is addressing an important unmet clinical need. The results of AVERROES will be complementary to those of a parallel noninferiority trial comparing apixaban with VKA therapy in patients with AF who are able to receive a VKA.
Eikelboom
John W
JW
Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada L8L 2X2. eikelbj@mcmaster.ca
O'Donnell
Martin
M
Yusuf
Salim
S
Diaz
Rafael
R
Flaker
Greg
G
Hart
Robert
R
Hohnloser
Stefan
S
Joyner
Campbell
C
Lawrence
Jack
J
Pais
Prem
P
Pogue
Janice
J
Synhorst
David
D
Connolly
Stuart J
SJ
D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D019233:Retreatment; D020521:Stroke / Q000517:prevention & control*; D017211:Treatment Failure; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D011728:Pyridones; D014812:Vitamin K; C522181:apixaban; D014859:Warfarin; D001241:Aspirin