hypothesis: baseline risk status of the patients and proximity to a recent cardiovascular event...
DESCRIPTION
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 Primary outcome event rate (%) Months since randomization Clopidogrel + ASA 7.3 % Placebo + ASA 8.8 % N=9,478TRANSCRIPT
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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).
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How do we interpret the data?
• Patients with documented vascular events, irrespective of inclusion group• Does baseline risk influence the treatment effect?
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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
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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).
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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
![Page 6: Hypothesis: baseline risk status of the patients and proximity to a recent cardiovascular event influence the response to dual anti-platelet therapy. Patients](https://reader035.vdocuments.net/reader035/viewer/2022062504/5a4d1b7d7f8b9ab0599b9aae/html5/thumbnails/6.jpg)
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
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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
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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).
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How do we interpret the data?
• Primary outcome by categories of included patients• Patients with included with documented MI or ischemic stroke
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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
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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
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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