making sense of antithrombotic therapy in the cath lab€¦ · bivalirudin alone 1800 0 12 15 18 21...
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Making sense of antithrombotic therapy in the cath lab
Azfar Zaman Freeman Hospital
BCIS Cardiff 2010
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Risk profile for PCI
n stable angina (mortality <0.25%)
n unstable angina/NSTEMI (1-2%)
n STEMI (4-7%)
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Stable angina
n preloaded with ASA and clopidogrel (600mg) at least 6 hours pre-procedure¹ (AHA/ACC IC)
n which (if any) anticoagulant?
n dose?
n early mobilisation/day case
1. CREDO JAMA 2002;288:2411
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Heparin’s limitations
Heparin exhibits a nonlinear dose-response
Heparin dose
Clo
tting
tim
e
Heparin
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Coronary Interventions Antiplatelet-based Only (CIAO) Study
JACC 2008;52:1293
Simple type A lesions
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Viswanathan G et al Cardiovascular Therapeutics (in press)
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Viswanathan G et al Cardiovascular Therapeutics (in press)
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Stable Angina
n thrombus prevention : no or reduced anticoagulant
n thrombus treatment : any GPI or bivalirudin
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NSTE-ACS
n no upstream treatment
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Who benefits from GPI after 600mg clopidogrel loading?
n stable
n ACS
diabetes – X ISAR-SWEET¹
no diabetes X
NSTE – troponin negative X
NSTE – troponin positive √ ISAR REACT-2³
STEMI - ? 1 Circulation 2004:110;3527 2 NEJM 2004:350;232 3 JAMA 2006:295;1531
ISAR REACT²
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Primary PCI – ASA only
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ESC 2008 – Recommendations Class LOE
n Antiplatelet co-therapy • aspirin • clopidogrel loading dose • GPI antagonist
n abciximab n tirofiban n eptifibatide
n Antithrombin co-therapy • heparin • bivalirudin • fondaparinux
n Adjunctive devices • thrombus aspiration
I I
IIa IIb IIb I
IIa III
IIb
B C A B C C B B B
Primary PCI: Adjunctive therapies
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ACC/AHA 2007 – Recommendations Class LOE n Antiplatelet co-therapy
• abciximab • tirofiban • eptifibatide
n Antithrombin co-therapy • heparin • bivalirudin • fondaparinux
IIa IIb IIb I I
III
A B C C C C
Primary PCI: Adjunctive therapies
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In primary PCI, ReoPro delivers improvements in clinical outcomes
ReoPro improves 30-day clinical outcomes in primary PCI1–5
D = death; MI = myocardial infarction; TVR = target vessel revascularization; UTVR = urgent target vessel revascularization
RAPPORT1 CADILLAC2 ISAR-23 ADMIRAL4 ACE5
Placebo + PTCA (n=242) ReoPro + PTCA (n=241)
PTCA or stent (n=1030) ReoPro + PTCA or stent (n=1052)
Usual care + stent (n=200) ReoPro + stent (n=201)
Placebo + stent (n=151) ReoPro + stent (n=149)
Stent alone (n=200) ReoPro + stent (n=200)
p=0.03
p=0.01
p=0.038
p=0.01
p=0.023 11.2
5.8 7.0
4.6
10.5
5.0
14.6
6.0
10.5
4.5
Pat
ient
s (%
)
30 days D/MI/UTVR
30 days D/MI/TVR/stroke
30 days D/MI/TVR
30 days D/MI/UTVR
30 days D/MI/TVR/stroke
20-
18-
16-
14-
12-
10-
8-
6-
4-
2-
0-
1. RAPPORT. Circulation 1998;98:734–41. 2. CADILLAC. Circulation 2003;108:1316–23. 3. ISAR-2. J Am Coll Cardiol 2000;35:915–21. 4. ADMIRAL. N Engl J Med 2001;344:1895–903. 5. ACE. J Am Coll Cardiol 2003;42:1879–85.
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Stone G et al. N Engl J Med 2008;358:2218-2230
HORIZONS-AMI: Bivalirudin Alone v Heparin plus GPIIb/IIIa
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Three-Year All-Cause Mortality
P=0.03
3-yr HR [95%CI]= 0.75 [0.58, 0.97]
5.9%
7.7% A
ll-C
ause
Mor
talit
y (%
)
0 1 2 3 4 5 6
9 10
1611 1568
1660 1689 1670
1800 Bivalirudin alone
0 12 15 18 21 24 27 30 33 36
1098 1802 1643
Months 3 6 9
Number at risk
Heparin+GPIIb/IIIa 1633 1593
1574 1525 1043
0.71 [0.51, 0.98] P=0.04
1-yr HR [95%CI]=
Bivalirudin alone (n=1800) Heparin + GPIIb/IIIa (n=1802)
7 8
4.8%
3.4%
TCT Washington 2010
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What’s new?
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Oral antiplatelets in STEMI
n TRITON¹ (STEMI 26%) [prasugrel]
n PLATO-INVASIVE² (49.1%) [ticagrelor]
n CURRENT – OASIS³ (29.2%) [clopidogrel]
1. Montalescot et al Lancet. 2009;373:723 2. Cannon et al Lancet. 2010;375:283 3. Mehta et al N Engl J Med. 2010;363:930
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R Angiograpy TRITON
Prasugrel LD 60mg + MD 10mg
PCI
Clopidogrel LD 300mg + MD 75mg
R
Ticagrelor 180mg + MD 90mgx2
PCI PLATO
Clopidogrel LD 600mg (16%)
R CURRENT
Angiograpy
PCI Angiograpy
99%
Clopidogrel LD 300mg + MD 75mg
Clopidogrel LD 300mg + MD 75mg
Clopidogrel LD 600mg + MD 150mg
81% 64.3%
70%
99% n= 13,608
n= 18,624
n= 25,087
100%
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Zaman et al ATVB 2000:20:860
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B
OVERALL
No GPI GPI
DES BMS
DM No DM
>75 65-74
<65
Female Male
STEMI UA/NSTEMI
0.5 1 2 Prasugrel Better Clopidogrel Better HR
Age
Reduction in risk (%) 18
21 12
25 14 6
14 30
20 18
21 16
19
21
Pinter = NS
CV Death, MI, Stroke Major Subgroups
CrCl > 60 CrCl < 60 14
19
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Montalescot et al Lancet 2009;373:723
Prasugrel v Clopidogrel in STEMI : 30 day endpoints
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Prasugrel v Clopidogrel in STEMI : 15 month endpoints
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PLATO – Invasive Lancet 2010;375:283
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0.50 1.50
Overall NSTEMI/UA STEMI Male Female Age <= 65 yrs Age > 65 yrs Non-Diabetic Prev Diabetic No Inhosp GPIIb/IIIa GPIIb in hosp No Prot Pump Inhib Prot Pump Inhib Non-smoker Current Smoker ASA Low ASA High
17232 10886 6346 13009 4223 10975 6257 13400 3831 12288 4936 7675 5557 10845 6380 8620 8612
4.5 4.2 5.0 4.1 5.8 3.0 7.1 4.2 5.6 3.9 6.0 3.8 5.7 4.9 3.8 4.2 4.8
3.9 3.6 4.2 3.6 4.6 2.7 6.0 3.6 4.9 3.5 4.7 3.2 4.2 4.6 2.6 4.3 3.5
0.805 0.419 0.702 0.836 0.465 0.408 0.045 0.024
0.50 1.50
3.7 3.6 4.0 3.5 4.6 2.9 5.2 3.6 4.1 3.1 5.2 3.1 4.8 3.9 3.4 3.6 3.8
3.0 3.1 2.8 3.0 3.0 2.2 4.4 2.8 3.6 2.5 4.1 2.3 3.3 3.5 2.1 3.2 2.7
0.248 0.148 0.418 0.567 0.894 0.613 0.050 0.191
CV Death, MI or Stroke MI or Stent thrombosis
Clopidogrel: Double v Standard Dose PCI Cohort Subgroups
Std % Double % Std % Double % Intxn P Intxn P
Double Dose Better
Double Dose Better
Std Dose Better
Std Dose Better
2N
Mehta S, ESC 2009
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Days
Cum
ulat
ive
Haz
ard
0.0
0.01
0.
02
0.03
0.
04
0 3 6 9 12 15 18 21 24 27 30
Clopidogrel: Double vs Standard Dose Primary Outcome: PCI Patients
Clopidogrel Standard
Clopidogrel Double
HR 0.85 95% CI 0.74-0.99
P=0.036
15% RRR
CV Death, MI or Stroke
Mehta S, ESC 2009
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Anticoagulants in STEMI
n unfractionated heparin – no randomised controlled trials (ESC = IC)
n low molecular weight heparin - ATOLL¹
1. Montalescot et al presented at ESC Stockholm 2010
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ATOLL
Trial of UFH v LMWH in primary PCI [ESC Stockholm 2010]
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Antithrombotics in the cath lab: summary
n in stable angina : nil
n in ACS : GPI or bivalirudin for troponin positive only
n in STEMI : prasugrel/ticagrelor (low dose UFH or LMWH)
GPI/bivalirudin for visible thrombus after aspiration
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Thank you
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Krumholz, H. M. et al. JAMA 2009;302:767-773.
Change in Acute Myocardial Infarction 30-Day All-Cause Risk-Standardized Mortality From 1995 to 2006
18.8% (SD, 2.1%; range, 10.4%-27.5%) in 1995
15.8% (SD, 1.7%; range, 10.6%-21.6%) in 2006
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Intravenous antiplatelet therapy in STEMI - timing
APEX-AMI trial – retrospective analysis of patients receiving glycoprotein inhibitors revealed that preprocedure infusion significantly improved 90 day outcomes
1. Eur Heart J. 2010 Jul;31(14):1708-16. 2. JAMA. 2007;297:43