Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.
BACKGROUND
Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects.


RESULTS
ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials.


CONCLUSIONS
ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.
Population Health Research Institute, Hamilton, Ontario, Canada. connostu@hhsc.ca
Connolly
S
S
Yusuf
S
S
Budaj
A
A
Camm
J
J
Chrolavicius
S
S
Commerford
P J
PJ
Flather
M
M
Fox
K A A
KA
Hart
R
R
Hohnloser
S
S
Joyner
C
C
Pfeffer
M
M
Anand
I
I
Arthur
H
H
Avezum
A
A
Bethala-Sithya
M
M
Blumenthal
M
M
Ceremuzynski
L
L
De Caterina
R
R
Diaz
R
R
Flaker
G
G
Frangin
G
G
Franzosi
M-G
MG
Gaudin
C
C
Golitsyn
S
S
Goldhaber
S
S
Granger
C
C
Halon
D
D
Hermosillo
A
A
Hunt
D
D
Jansky
P
P
Karatzas
N
N
Keltai
M
M
Lanas
F
F
Lau
C P
CP
Le Heuzey
J-Y
JY
Lewis
B S
BS
Morais
J
J
Morillo
C
C
Oto
A
A
Paolasso
E
E
Peters
R J
RJ
Pfisterer
M
M
Piegas
L
L
Pipillis
T
T
Proste
C
C
Sitkei
E
E
Swedberg
K
K
Synhorst
D
D
Talajic
M
M
Trégou
V
V
Valentin
V
V
van Mieghem
W
W
Weintraub
W
W
Varigos
J
J
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077405:Irbesartan; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D013777:Tetrazoles / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D000077405:Irbesartan; D013988:Ticlopidine