hypothesis: baseline risk status of the patients and proximity to a recent cardiovascular event...

• Hypothesis: baseline risk status of the patients and proximity to a recent cardiovascular event influence the response to dual anti-platelet therapy.

• Patients with symptomatic CAD, CVD or PAD and all those with a history of CV events were included in this analysis (n=13,434).

How do we interpret the data?

• Patients with documented vascular events, irrespective of inclusion group• Does baseline risk influence the treatment effect?

Primary Endpoint (MI/Stroke/CV Death) in Patients with Previous MI, IS, or PAD“CAPRIE-like Cohort”

RRR: 17.1 % [95% CI: 4.4%, 28.1%]p=0.01

Prim

ary

outc

ome

even

t rat

e (%

)

0

2

4

6

8

10

Months since randomization

0 6 12 18 24 30

Clopidogrel + ASA7.3 %

Placebo + ASA8.8 %

N=9,478

Death/MI/stroke % Quartile 1

Quartile 2

Quartile 3

Quartile 4

Clopidogrel +Aspirin 1.4 3.0 6.0 18.4

Placebo+Aspirin 1.2 3.0 5.3 21.0

Hazard Ratio 1.11 0.98 1.15 0.86

p value 0.73 0.91 0.35 0.052

Cardiovascular outcomes according to quartiles of baseline CV risk.

Q4: severe bleeds: 3.1% C vs 3.2% P and ICH 1.0%C vs 1.0%P moderate bleeds 4.2%C vs 2.6% P, (p=0.02).

How do we interpret the data?

• Patients with documented vascular events, irrespective of inclusion group• Does baseline risk influence the treatment effect?• The impact of proximity to a CV event

Documented CV Disease Patients: Primary Outcome (MI/Stroke/CV Death)

Cerebrovascular (n=4320)

Placebo +ASA(9.6%)

RRR: 16.0% p=0.088

Clopidogrel+ ASA(8.1%)

0

2

4

6

8

10

12

Months since randomization 0 6 12 18 24 30

Cardiovascular (n=5835)

Clopidogrel + ASA (6.5%)

Placebo + ASA (7.4%)

Prim

ary

outc

ome

even

t rat

e (%

)

Months since randomization

RRR: 13.9% p=0.130

0

2

4

6

8

10

12

0 6 12 18 24 30

PAD (n=2838)

Placebo + ASA(8.7%)

Clopidogrel+ ASA(7.6%)

RRR: 13.1% p=0.285

0

2

4

6

8

10

12

Months since randomization 0 6 12 18 24 30

Bhatt DL, Fox KA, Hacke W, et al. N Engl J Med. 2006: 354; 1-12

Median time from qualifying event to randomization:23.3 months 3.5 months 23 months

Enrolled within 6/12 of event

10.810.8

55

3.83.83.43.4

5.65.6

8.28.2

5.35.3

3.43.4

2.52.5

44

0

2

4

6

8

10

12

Death/MI/Stroke Death (all) CV death MI Stroke

perc

ent

PlaceboPlaceboClopidogrelClopidogrel

p= 0.031p= 0.031

p= 0.06p= 0.06

Proximity to a recent CV event (MI/stroke) was associated with significant benefit with clopidogrel.

For those randomized within 6 months of MI or stroke, the frequency further MI/stroke or death was 8.2% C vs 10.8% P (HR 0.76, 95%CI 0.59-0.98, p=0.034).

In those patients who had a documented prior vascular event or with confirmed PAD (n=9478) the risk of death/MI/stroke was 7.3%C vs 8.8%P (HR 0.83, 95% CI 0.72-0.96, p=0.01).

How do we interpret the data?

• Primary outcome by categories of included patients• Patients with included with documented MI or ischemic stroke

Event rate over time for primary outcome in CAD patients with inclusion MI vs coronary inclusion criteria other than MI

RRR [95%CI]: 22.6 % [2.2, 38.7]

p = 0.031

RRR [95%CI]: -10.3 % [-58.0, 23.0]

p = 0.593

CAD patients with qualifying MI (N=3846)

PGM= SR25990C/EFC4505/CSR/us00145/PGM_RPT/i6effkmmi.sas OUT= OUTPUT/i6effkmmi.doc (31JAN2006 - 17:37)

CLOP PLAC

Prim

ary ou

tcome

even

t rate

(%)

0

2

4

6

8

10

Months since randomization

0C: 1903P: 1943

6 1873 1891

12 1842 1855

18 1807 1810

24 1500 1483

30 996 947

CAD patients without qualifying MI (N=1989)

PGM= SR25990C/EFC4505/CSR/us00145/PGM_RPT/i6effkmothcad.sas OUT= OUTPUT/i6effkmothcad.doc (31JAN2006 - 18:26)

CLOP PLAC

Prim

ary ou

tcome

even

t rate

(%)

0

2

4

6

8

10

Months since randomization

0C: 989P: 1000

6 974 985

12 956 969

18 947 953

24 776 800

30 435 446

Event rate over time for primary outcome in CVD patients with qualifying IS vs qualifying TIA

RRR [95%CI]: 22.0 % [2.4, 37.6]

p = 0.029

RRR [95%CI]: -14.7 % [-74.4, 24.6]

p = 0.520

CVD patients with qualifying IS (N=3245)

CVD patients with qualifying TIA (N=1233)

PGM= SR25990C/EFC4505/CSR/us00145/PGM_RPT/i6effkmis.sas OUT= OUTPUT/i6effkmis.doc (31JAN2006 - 17:54)

CLOP PLAC

Prim

ary ou

tcome

even

t rate

(%)

0

2

4

6

8

10

12

14

Months since randomization

0C: 1634P: 1611

6 1583 1557

12 1548 1509

18 1513 1464

24 982 924

30 368 376

PGM= SR25990C/EFC4505/CSR/us00145/PGM_RPT/i6effkmtia.sas OUT= OUTPUT/i6effkmtia.doc (31JAN2006 - 19:11)

CLOP PLAC

Prim

ary ou

tcome

even

t rate

(%)

0

2

4

6

8

10

Months since randomization

0C: 617P: 616

6 599 606

12 588 592

18 581 581

24 365 379

30 156 143

Conclusions:

• For the overall population the trend for benefit (7% RR) was non-significant

• Commencing therapy with clopidogrel within 6 months of a stroke or MI suggests evidence of benefit on rates of future death/MI/stroke.

• Higher risk groups, including those with clear evidence of vascular disease and recent vascular events, suggests the potential for greater benefit