CAT: ACTIVE-A & W
A-fib Clopidogrel Trial w/
Irbesartan for prevention of
Vascular Events
ASA, Warfarin
Clinton Pong

Clinical Question
• What are the treatment options for
reducing cerebrovascular complications in
elderly patients with atrial fibrillation?
http://cardiology.ucsf.edu/ep/debris/ecg.htm

Source: ACTIVE-W
• Clopidogrel plus aspirin versus oral
anticoagulation for atrial fibrillation in
the Atrial fibrillation Clopidogrel Trial
with Irbesartan for prevention of
Vascular Events (ACTIVE W): a
randomised controlled trial
The ACTIVE Writing Group on behalf of
the ACTIVE Investigators
Lancet Volume 367, Issue 9526, 10 June
2006-16 June 2006, Pages 1903-1912

Validity?
• Randomized • Accountability:
• Double Blinded sponsored by
• Multicenter trial – Sanofi-Aventis
• Avapro (Irbesartan)
• Similar • Plavix (Clopidogrel)
• Intention to treat – Bristol-Myers Squibb
analysis • Avapro (Irbesartan)
• Coumadin (Warfarin)
• Plavix (Clopidogrel)

7455 eligible
6706 randomized
3371 3335
Warfarin ASA
Clopidogrel
ASA 75-100mg
+
Clopidogrel 75mg

Warfarin (n=3371)
| Clopidogrel+ASA (3335)
No 1o
3206 3101
end
point
Primary
end 165 234
point

Warfarin (n=3371)
| Clopidogrel+ASA (3335)
No
3276 3271
stroke
Stroke 59 100

Warfarin (n=3371)
| Clopidogrel+ASA (3335)
No major
bleeding 3278 3234
Major
bleeding 93 101
p=0.53
Warfarin (n=3371)
| Clopidogrel+ASA (3335)
No
2816 2691
bleeding
Total 555 644
bleeding

Results
• Warfarin
• Clopidogrel + ASA
• 4.9% of patients achieved
a primary end point • 7.0% of patients achieved
– ARR is 2.1%
a primary end point
– NNT to prevent CV events: • Stroke in 3.0%
48
• Stroke in 1.8%
– ARR is 1.2%
• Major bleeding not
– NNT to prevent stroke is 84
statistically significant
• Bleeding in 16.5% • Bleeding in 19.3%
– ARR is 2.8%
– NNH is 35

Summary statement:
• Warfarin is superior to Clopidogrel (75mg)
plus Aspirin (75-100mg) for patients with
atrial fibrillation to prevent CV events.
In addition, the bleeding risk is higher
in the C+A group when compared to the
warfarin group for all bleeding events,
while there was no significant difference in
severe bleeds.

Source: ACTIVE-A
• Effect of Clopidogrel Added to Aspirin
in Patients with Atrial Fibrillation
(ACTIVE-A)
The ACTIVE Investigators NEJM Volume
360:2066-2078 May 14, 2009 Number 20

Validity?
• Randomized • Accountability:
• Double Blinded sponsored by
• Multicenter trial – Sanofi-Aventis
• Avapro (Irbesartan)
• Similar • Plavix (Clopidogrel)
• Intention to treat – Bristol-Myers Squibb
analysis • Avapro (Irbesartan)
• Coumadin (Warfarin)
• Plavix (Clopidogrel)

7554 patients from
33 countries,
561 centers
0.6% lost to
followup
3772 3782
ASA ASA
Clopidogrel Placebo
ASA 75-100mg
+
Clopidogrel 75mg

Clopidogrel+ASA placebo+ASA
No 1o
2940 2858
end
point
Primary
end 832 924
point

Clopidogrel+ASA placebo+ASA
No
3476 3374
stroke
Stroke 296 408

Clopidogrel+ASA placebo+ASA
No major
3521 3620
bleeding
Major 251 162
bleeding

Results
• Clopidogrel + ASA • ASA alone
• 22.0% of patients • 24.4% of patients
achieved a primary end achieved a primary end
point point
– ARR is 2.4% • Stroke in 10.8%
– NNT to prevent CV events: • Major bleeding in 4.3%
43
• Stroke in 7.8%
– ARR is 2.9%
– NNT to prevent stroke is 34
• Major bleeding in 6.7%
– ARR is 2.4%
– NNH is 42

Summary statement:
• Clopidogrel (75mg) plus aspirin
(75-100mg) is an alternative to warfarin for
patients with atrial fibrillation to prevent CV
events. However, this must be balanced
with the consideration for major bleeding
as the NNT is equal to the NNH.