ACS Critical Pathways 2007 Teleconferences This activity is supported by an educational grant from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. This activity is co-provided by the Network for Continuing Medical Education and EduPro Resources LLC. October 31, 2007
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ACS Critical Pathways 2007 Teleconferences
This activity is supported by an educational grant from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership.
This activity is co-provided by the Network for Continuing Medical Educationand EduPro Resources LLC.
October 31, 2007
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Faculty
Gregg C. Fonarow, MDEliot Corday Professor of Medicine
and Cardiovascular Science
Director, Ahmanson-UCLA Cardiomyopathy Center
UCLA Division of Cardiology
UCLA Medical Center
Los Angeles, California
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The Network for Continuing Medical Education and
EduPro Resources LLC require that CME/CNE faculty
disclose, during the planning of an activity, the existence
of any personal financial or other relationships they or
their spouses/partners have with the commercial
supporter of the activity or with the manufacturer of any
commercial product or service discussed in the activity.
Disclosure Statement
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Faculty Disclosure Statement
Gregg C. Fonarow, MD, has served as a consultant to and has received research support and honoraria from Bristol-Myers Squibb Company, GlaxoSmithKline, Merck & Co., Inc., Pfizer Inc, and sanofi-aventis.
Deborah Murphy reports no such relationships.
The staff of NCME reports no such relationships.
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Report From Transcatheter Cardiovascular Therapeutics
(TCT) 2007
Gregg C. Fonarow, MD
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Polling Question #1Where do you currently stand on using DES?
1) In light of SCAAR and other recent data, my use of DES is increasing since earlier in 2007
2) In light of the GRACE Registry and other recent data, my use of DES is decreasing since earlier in 2007
3) My practice has not changed since earlier in 2007 with regard to DES
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Highlights From TCT 2007● ARMYDA-4: 600 mg clopidogrel loading dose prior to PCI in patients
on chronic clopidogrel therapy
● ARMYDA-5: antiplatelet therapy for reduction of myocardial damage during angioplasty
● HORIZONS AMI: bivalirudin vs heparin + GP IIb/IIIa inhibitors during primary angioplasty in AMI
● SPIRIT III: 1-year follow-up stent data
● Endeavor IV: 9- and 12-months results, Endeavor vs TAXUS stents
● EVENT Registry: Implications of changing stent practice from 2004 to 2006
● SCAAR: Swedish Coronary Angiography and Angioplasty Registry
● NY State Database and STENT Registry: Comparison of DES vs BMS
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Per
cent
age 7
8
P=.96
Patti G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
ARMYDA-4: Composite Primary End Point of 30-day Death, MI, TVR
0
3
6
9
12
Placebo
600 mg clopidogrel reload
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Patti G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
78
Per
cent
age
600 mg clopidogrel reload
Placebo
ARMYDA-4: Individual Events at 30 Days
0
2
4
6
8
10
Death MI TVR
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Patti G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
ARMYDA-4: Bleeding Rates
600 mg clopidogrel reload
Placebo4 4
0 0
Per
cent
age
0
2
4
6
Major bleeding Minor bleeding
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ARMYDA-5: Study Design
Patients scheduled for angiography randomized to:
– 600 mg clopidogrel loading dose (n=174) 4 to 8 hours prior to angiography or
– Loading with clopidogrel in the cath lab once the coronary anatomy was defined and PCI was definite (n=176)
– Not included: 35 patients who underwent CABG and 53 patients treated with medical therapy
Primary end point: death, MI, or TVR at 30 days
44% of patients had NSTEMI; 36% had a prior MI
Di Sciascio G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
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ARMYDA-5: Results
NS5%4%Minor bleeding
.04
.005
272 PRUs
245 PRUs
241 PRUs
186 PRUs
Platelet reactivity at PCI
At 2 hours:
.5611%8%Death, MI, or TVR at 30 days
P ValueCath-lab treatment
Pretreatment
PRUs = platelet reactivity units.
Di Sciascio G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
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HORIZONS AMI: 2 Primary End Points at 30 DaysHORIZONS AMI: 2 Primary End Points at 30 Days
1) Net Adverse Clinical Events
2) Major Bleeding (non-CABG)
• Intracranial bleeding
• Intraocular bleeding
• Retroperitoneal bleeding
• Access site bleed requiringintervention/surgery
• Hematoma ≥5 cm
• Hgb ⇓ ≥3 g/dL with an overt source
• Hgb ⇓ ≥4 g/dL w/o overt source
• Reoperation for bleeding
• Blood product transfusion
andand
Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
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HORIZONS AMI: 2 Primary End Points at HORIZONS AMI: 2 Primary End Points at 30 Days (cont)30 Days (cont)
==
or
• All-cause death• Reinfarction
• Ischemic TVR• Stroke
Major adversecardiovascular events(major secondary end point)
Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
1) Net Adverse Clinical Events
2) Major Bleeding (non-CABG)
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HORIZONS AMI: Study DrugsHORIZONS AMI: Study Drugs
UFH + GP IIb/IIIa(N=1802)
Bivalirudin(N=1800)
UFH prerandomization 65.6% 65.6%
Antithrombin in CCL
- UFH 98.9% 4.1%
- Bivalirudin 0.4% 96.9%
- Peak ACT 264 [228, 320] 357 [300, 402]
GP IIb/IIIa in CCL 94.5%a 7.2%a
- Bail-out per protocolb - 4.4%
- Abciximab 49.9% 4.0%
- Eptifibatide 44.4% 3.1%
- Tirofiban 0.2% 0.1%
a97.7% and 7.5% during PCI; bFor giant thrombus or refractory no reflow after PCI. CCL = cardiac catheterization laboratory.
Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
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Primary Outcome Measures (ITT)
aNot related to CABG; bMACE = All-cause death, reinfarction, ischemic TVR or stroke.
Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
Diff = 0.0% [-1.6, 1.5] RR = 0.99 [0.76, 1.30]
Psup = 1.00
Diff = -3.3% [-5.0, -1.6] RR = 0.60 [0.46, 0.77]
PNI ≤ .0001
Psup ≤ .0001
Diff = -2.9% [-4.9, -0.8]RR = 0.76 [0.63, 0.92]
PNI ≤ .0001
Psup = .006
1° end point 1° end point0
5
10
20
15
12.1
9.2 8.3
4.9 5.5 5.4
Net adverse clinical events
Major bleedinga MACEb
30-d
ay e
vent
rat
es (
%)
Bivalirudin monotherapy (N=1800)Heparin + GP IIb/IIIa inhibitor (N=1802)
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30-day Net Adverse Clinical Events
Number at risk
Bivalirudin 1800 1660 1633 16261620 1607 1544
Heparin + GP IIb/IIIa 1802 1635 1591 15781569 1552 1482
Pri
ma
ry E
nd
Po
int
Ne
t adv
ers
e cl
inic
al e
ven
ts (
%)
Time in Days
12.2%
9.3%
HR [95%CI] = 0.75 [0.62, 0.92] P=.006
Heparin + GP IIb/IIIa inhibitor (n=1802)Bivalirudin monotherapy (n=1800)
Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
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30-day Major Bleeding (non-CABG)
Number at risk
Bivalirudin 1800 1697 1675 16681664 1653 1590
Heparin + GP IIb/IIIa 1802 1651 1617 16061598 1581 1511
Pri
ma
ry E
nd
Po
int
Ma
jor
ble
edi
ng (
%)
Time in Days
8.4%
5.0%
HR [95%CI] = 0.59 [0.45, 0.76]P<.0001
Heparin + GP IIb/IIIa inhibitor (n=1802)
Bivalirudin monotherapy (n=1800)
Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
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30-day Bleeding End Points30-day Bleeding End Points
UFH + GP IIb/IIIa(N=1802)
Bivalirudin(N=1800)
P Value
Protocol Major, non-CABGa 8.3% 4.9% <.0001
Protocol Major, All 10.8% 6.8% <.0001
Protocol Minor 15.4% 8.6% <.0001
Blood transfusion 3.5% 2.1% .01
TIMI Major 5.0% 3.1% .003
TIMI Minor 4.6% 2.8% .008
TIMI Major or Minor 9.6% 5.9% <.0001
GUSTO LTb or Severe 0.6% 0.4% .65
GUSTO Moderate 5.0% 3.1% .003
GUSTO LT or Sev or Mod 5.6% 3.5% .003
aPrimary end point; blife threatening.
Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
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30-day MACE Components30-day MACE Componentsaa
UFH + GP IIb/IIIa(N=1802)
Bivalirudin(N=1800)
P Value
Death 3.1% 2.1% .058
- Cardiac 2.9% 1.8% .035
- Noncardiac 0.2% 0.3% .75
Reinfarction 1.8% 1.8% .90
- Q wave 1.2% 1.4% .66
- Non–Q wave 0.7% 0.4% .50
Ischemic TVR 1.9% 2.6% .18
- Ischemic TLR 1.8% 2.5% .14
- Ischemic remote TVR 0.3% 0.3% 1.0
Stroke 0.6% 0.7% .69
aCEC adjudicated.
Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
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SPIRIT III: MACE Through 365 Days
MACE = cardiac death, MI, or ischemia-driven TLR.
Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
0
3
6
12
9
MA
CE
(%
)
0 90 180 270 365Days
9.9%
5.8%
TAXUS XIENCE
HR = 0.57 [0.36 – 0.90]Plogrank = .01
Number at risk
XIENCE 669 651 642 626 614
TAXUS 332 312 309 292 287
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Leon MB, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
P for Noninferiority <.001∆ = 3.8%
6.6% 7.2%
Endeavor(n=50/758)
Taxus(n=54/759)
TV
F R
ate
Target Vessel Failure
Endeavor IV: Primary End PointResult at 9 Months
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aDay 83, 145, 171.
Leon MB, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
.2679.4 (707.7 (58)TVF – % (#)
1.0006.6 (49)6.5 (49)MACE – % (#)
.7536.7 (50)6.3 (47)TVR – % (#)
.0854.2 (31)2.5 (19)TVR (non-TL) – % (#)
.2283.2 (24)4.5 (34)TLR – % (#)
.25000.4a (3) 31-360 days
.6250.1 (1)0.4 (3) 0-30 days
.1240.1 (1)0.8 (6)Stent Thrombosis (all) – % (#)
.2603.1 (23)2.1 (16)Death (cardiac) + MI (all) – % (#)
.1312.4 (18)1.3 (10) Non–Q wave
1.0000.1 (1)0.3 (2) Q Wave
.2082.6 (19)1.6 (12)MI (all) – % (#)
1.0000.5 (4)0.5 (4) Cardiac
1.0001.1 (8)1.1 (8)Death (all) – % (#)
P ValueTaxusn=741
Endeavorn=749
Endeavor IV: Clinical Eventsat 12 Months
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EVENT Registry: Bleeding Complications
Kleiman N, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
0.6
0.0%
2.0%
4.0%
6.0%
TIMI Major
WAVE 2
WAVE 1
WAVE 3
0.2 0.2
1.0 0.80.5
3.5
2.0 1.8
5.2
4.1
3.4
TIMI Minor Transfusion Any bleed ortransfusion
Not mutually exclusive
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EVENT Registry: Adjudicated Stent Thrombosis From Procedure to 1 Year Follow-up
Kleiman N, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.
2.2%
0%
WAVE 2
WAVE 1
WAVE 3
P=.046
P=.027
(Logistic regression)
In Hospital 6 Months 12 Months
Wave 2 is ARC Probable; Wave 3 is ARC Definite or Probable
Wave 1 to Wave 3
1.1
0.80.9
1.9
1.01.2
(Log rank)
0.40.2
0.1
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Carlsson J, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.