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