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 InvestigatorsLancet Volume 367, Issue 9526, 10 June 2006-16 June 2006, Pages 1903-1912

Validity?

• Randomized• Double Blinded• Multicenter trial• Similar• Intention to treat

analysis

• Accountability: sponsored by – Sanofi-Aventis

• Avapro (Irbesartan)• Plavix (Clopidogrel)

– Bristol-Myers Squibb• Avapro (Irbesartan)• Coumadin (Warfarin)• Plavix (Clopidogrel)

7455 eligible6706 randomized

3371 3335Warfarin ASA

Clopidogrel

ASA 75-100mg+

Clopidogrel 75mg

3206 3101

165 234

Warfarin (n=3371) | Clopidogrel+ASA (3335)

No 1o

end point

Primary end point

32713276

10059

Warfarin (n=3371) | Clopidogrel+ASA (3335)

No stroke

Stroke

3278 3234

93 101

No majorbleeding

Major bleedingp=0.53

Warfarin (n=3371) | Clopidogrel+ASA (3335)

2816 2691

555 644

Nobleeding

Total bleeding

Warfarin (n=3371) | Clopidogrel+ASA (3335)

Results• Warfarin• 4.9% of patients achieved

a primary end point– ARR is 2.1%– NNT to prevent CV events:

48

• Stroke in 1.8%– ARR is 1.2%– NNT to prevent stroke is 84

• Bleeding in 16.5%

• Clopidogrel + ASA• 7.0% of patients achieved

a primary end point• Stroke in 3.0%

• Major bleeding not statistically significant

• 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• Double Blinded• Multicenter trial• Similar• Intention to treat

analysis

• Accountability: sponsored by – Sanofi-Aventis

• Avapro (Irbesartan)• Plavix (Clopidogrel)

– Bristol-Myers Squibb• Avapro (Irbesartan)• Coumadin (Warfarin)• Plavix (Clopidogrel)

7554 patients from33 countries,561 centers0.6% lost to

followup

3772 3782ASA ASA

Clopidogrel Placebo

ASA 75-100mg+

Clopidogrel 75mg

2940 2858

832 924

Clopidogrel+ASA placebo+ASA

No 1o

end point

Primary end point

3476 3374

296 408

Clopidogrel+ASA placebo+ASA

No stroke

Stroke

3521 3620

251 162

Clopidogrel+ASA placebo+ASA

No majorbleeding

Major bleeding

Results

• Clopidogrel + ASA• 22.0% of patients achieved

a primary end point– ARR is 2.4%– NNT to prevent CV events:

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

• ASA alone• 24.4% of patients

achieved a primary end point

• Stroke in 10.8%• Major bleeding in 4.3%

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.