charisma: the “caprie-like” cohort deepak l. bhatt md, facc, fscai, fesc, facp associate...
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CHARISMA: CHARISMA: The “CAPRIE-like” CohortThe “CAPRIE-like” Cohort
Deepak L. Bhatt MD, FACC, FSCAI, FESC, FACP
Associate Director, Cleveland Clinic Cardiovascular Coordinating Center
Staff, Cardiac, Peripheral, and Carotid Intervention
Associate Professor of Medicine
Disclosure
Dr. Bhatt has served as a consultant to: Astra Zeneca, Bristol-Myers Squibb, Cardax, Cogentus, Daiichi Sankyo, Eli Lilly, Eisai, Glaxo Smith Kline, Johnson & Johnson, Medtronic, Millennium, Otsuka, Paringenix, PDL, sanofi aventis, Schering Plough, The Medicines Company, tns Healthcare, Vertex.
Honoraria are donated to NPOs.
Principal Investigator for CHARISMA, co-PI of CHAMPION, and co-chair of REACH, as well as other potentially related studies – no personal compensation, though the Cleveland Clinic does receive research funding.
This presentation discusses off-label and/or investigational uses of aspirin, AZD6140, cangrelor, clopidogrel, prasugrel, drug-eluting stents.
Sponsors – C5Sponsors – C5
• Abraxis
• Alexion Pharma
• AstraZeneca
• Atherogenics
• Aventis
• Biosense Webster
• Biosite
• Boehringer Ingelheim
• Boston Scientific
• Bristol-Myers Squibb (BMS)
• Cardionet
• Centocor
• Converge Medical Inc.
• Cordis
• Dr. Reddy’s
• Abraxis
• Alexion Pharma
• AstraZeneca
• Atherogenics
• Aventis
• Biosense Webster
• Biosite
• Boehringer Ingelheim
• Boston Scientific
• Bristol-Myers Squibb (BMS)
• Cardionet
• Centocor
• Converge Medical Inc.
• Cordis
• Dr. Reddy’s
• Edwards Lifesciences
• Esperion
• GE Medical
• Genentech
• Gilford
• GSK
• Guidant
• J&J
• Kensey-Nash
• Lilly
• Medtronic
• Merck
• Mytogen
• Novartis
• Edwards Lifesciences
• Esperion
• GE Medical
• Genentech
• Gilford
• GSK
• Guidant
• J&J
• Kensey-Nash
• Lilly
• Medtronic
• Merck
• Mytogen
• Novartis
• Novo Nordisk
• Orphan Therapeutics
• P&G Pharma
• Pfizer
• Roche
• Sankyo
• Sanofi-Aventis
• Schering-Plough
• Scios
• St. Jude Medical
• Takeda
• TMC
• VasoGenix
• Viacor
• Novo Nordisk
• Orphan Therapeutics
• P&G Pharma
• Pfizer
• Roche
• Sankyo
• Sanofi-Aventis
• Schering-Plough
• Scios
• St. Jude Medical
• Takeda
• TMC
• VasoGenix
• Viacor
CAPRIE: Superior Efficacy of Clopidogrel versus ASA
*MI, ischemic stroke or vascular death†Intent-to-treat analysis (n=19,185)
CAPRIE Steering Committee. Lancet 1996; 348: 1329–1339.
0
4
8
12
16
0 3 6 9 12 15 18 21 24 27 30 33 36
Months of follow-up
Cu
mu
lati
ve e
ven
t ra
te*
(%)
ASA
Clopidogrel
8.7%† RRR (p=0.043)
20
Patients with recent ischemic stroke, recent MI or symptomatic PAD
CAPRIE: Clopidogrel Provides Amplified Benefit in Patients with High Vascular Risk
Ringleb PA, Bhatt DL, Hirsch AT, et al. Stroke 2004; 35: 528–532.
*MI, ischemic stroke or vascular death;mean duration of treatment was 1.6 years
5.8%
10.2%
5.3%
8.8%
0
2
4
6
8
10
All CAPRIE patients
(n=19,099)
Prior history of major acute event
(MI or stroke; n=4496)
Eve
nt
rate
/yea
r* (
%)
ASA
Clopidogrel
12
p=0.043
RRR 8.7%
RRR 14.9%
p=0.045
Months of Follow-up
Yusuf S, et al. N Engl J Med. 2001;345:494-502.
CURE Study: Primary End Point: MI/Stroke/CV Death
Clopidogrel + Aspirin(n=6259)
Placebo + Aspirin(n=6303)
P <.001N=12,562
3 6 90 12
20%Relative RiskReduction
0.12
0.14
0.10
0.06
0.08
0.00
0.04
0.02
Cu
mu
lati
ve H
aza
rd R
ate
Mehta SR, et al. Lancet. 2001;358:527-533.
.00
.05
.10
.15
0 10 100 300 400200
Cu
mu
lati
ve H
aza
rd R
ate
Clopidogrel + Aspirin(n=1313)
31% RelativeRisk Reduction
Placebo + Aspirin(n=1345)Median
time to PCI
Days of Follow-up
12.6%
8.8%
P=.002
PCI-CURE Study: CV Death or MIFrom Randomization
CLARITY: Incidence of CV Death, MI, RI Urgent Revascularization
Sabatine MS, Cannon CP, Gibson CM, et al. N Engl J Med. 2005;352:1179-89.
Days
En
d p
oin
t (%
)
0
5
10
15
0 5 10 15 20 25 30
Placebo + ASA
Clopidogrel + ASA
Odds ratio 0.80(95% CI, 0.65-0.97)
P=0.026
20%
Days since randomization
Eve
nt
(%) 9% relative risk reduction
(P=0.002)
Placebo: 2310 events (10.1%)
Clopidogrel: 2121 events (9.2%)
COMMIT: Incidence of Death, Re-MI, or Stroke at 28 Days
07 14 2821
1
2
3
4
5
6
7
9
8
0
COMMIT Collaborative Group. Lancet. 2005;366:1607.
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
Pri
mar
y O
utc
om
e E
ven
t R
ate
(%)
0
2
4
6
8
10
Months Since Randomization
0 6 12 18 24 30
Clopidogrel + ASAPlacebo + ASA
N=9,478
* Post hoc analysis.
Bhatt DL, Flather MD, Hacke W, et al. J Am Coll Cardiol. 2007;49:1982-1988.
8.8%8.8%
7.3%7.3%
Primary Endpoint (MI/Stroke/CV Death) in Patients With Previous MI, IS, or PAD*
“CAPRIE-like Cohort”
*Post hoc analysis.
Cardiovascular Death/MI/StrokePlacebo Clopidogrel HR (95% CI) P value
Prior MI 8.3% 6.6% 0.774 (0.613, 0.978)
0.031
Prior IS 10.7% 8.4% 0.780 (0.624, 0.976)
0.029
Prior PAD 8.7% 7.6% 0.869 (0.671, 1.125)
0.085
Entire Cohort 8.8% 7.3% 0.829 (0.719, 0.956)
0.010
0.5 1 2
Placebo Clopidogrel P value
Prior MI 8.3% 6.6% 0.774 (0.613, 0.978)
0.031
Prior IS 10.7% 8.4% 0.780 (0.624, 0.976)
0.029
Prior PAD 8.7% 7.6% 0.869 (0.671, 1.125)
0.085
Entire Cohort 8.8% 7.3% 0.829 (0.719, 0.956)
0.010
0.5 1 2
Bhatt DL, Flather MD, Hacke W, et al. J Am Coll Cardiol. 2007;49:1982-1988.
10
8
6
4
2
0
CHARISMA―Prior MI
0 6 12 18 24 30
HR=0.774 (95% CI [0.613–0.978])
P=0.031
N=3,846
Pri
mar
y O
utc
om
e E
ven
t R
ate
(%)
Months Since Randomization
8.3%
6.6%
Placebo + ASA
Clopidogrel + ASA
Bhatt DL, Flather MD, Hacke W, et al. J Am Coll Cardiol. 2007;49:1982-1988.
CHARISMA―CAD Without Prior MI
10
8
6
4
2
00 6 12 18 24 30
HR=1.103 (95% CI (0.770–1.580])
P=0.593
N=1,989
Pri
mar
y O
utc
om
e E
ven
t R
ate
(%)
Months Since Randomization
6.3%
5.7%
Placebo + ASA
Clopidogrel + ASA
Bhatt DL, Flather MD, Hacke W, et al. J Am Coll Cardiol. 2007;49:1982-1988.
Timing of Severe or Moderate Bleeding
Placebo + ASA
Clopidogrel + ASA
Days Since Randomization
15 60 135 270 450 630 810
0.00008
0.00007
0.00006
0.00005
0.00004
0.00003
0.00002
0.00001
0
Haz
ard
Fu
nct
ion
/d
Bhatt DL, Flather MD, Hacke W, et al. J Am Coll Cardiol. 2007;49:1982-1988.
Median Time of Late Stent Thrombosis
p = 0.04p = 0.0003 p = 0.0052
Months
Bavry, Kumbhani, Helton, Borek, Mood, Bhatt. AJM 2006.
0
4
8
12
16
20
DES/BMS SES/BMS PES/BMS
Clinical Presentation of Bare Metal In-stent Restenosis
Clinical Presentation of Bare Metal In-stent Restenosis
Chen MS, John JM, Chew DP, Lee DS, Ellis SG, Bhatt DL. Am Heart J. 2006;151:1260-1264.
Clopidogrel Use and Long-term Clinical Outcomes after DES - Duke Registry
3.1%
7.2%
5.5%6.0%
0%
2%
4%
6%
8%
10%
DES + Clop DES - Clop BMS + Clop BMS - Clop
En
dp
oin
t (
%)
• Adjusted outcomes were analyzed at 24 months
• Patients in the DES with clop. group had significantly lower rates of death or MI than did patients in the DES without clopidogrel group
• Among BMS patients, there were no differences in death or MI
Adjusted rates of death or MI starting at 6 months
Difference = -4.1 ± 3.5
P=.02
Difference = -0.5 ± 2 .7
P=.70
Eisenstein EL, et al. JAMA. 2007;10;297(2):159-168.
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