guillaume cayla , service de cardiologie chu nîmes-pr messner
DESCRIPTION
Pourquoi la Bivaluridine et pourquoi pas les IIb - IIIa ?. Guillaume Cayla , Service de Cardiologie CHU Nîmes-Pr Messner Unité INSERM 937 La Pitié Salpetrière Pr Montalescot. COI: AstraZeneca , Abbott Vascular , Biotronik , CLS Behring, Daiichi Sankyo , Eli Lilly, Iroko Cardio. - PowerPoint PPT PresentationTRANSCRIPT
Guillaume Cayla, Service de Cardiologie CHU Nîmes-Pr Messner
Unité INSERM 937 La Pitié Salpetrière Pr Montalescot
Pourquoi la Bivaluridine et pourquoi pas les IIb-IIIa?
COI: AstraZeneca, Abbott Vascular, Biotronik, CLS Behring, Daiichi Sankyo, Eli Lilly, Iroko Cardio
Les Questions
1) Bivalirudine: Forces et Faiblesses?2) HNF/IIbIIIa comparateur, quid Enoxaparine?3) IIb/IIIa molécules anciennes, nouvelles
données?4) Conclusion: les questions en suspens….
HORIZON MIHarmonizing Outcomes with Revascularization and Stents in AMI
≥3400* pts with STEMI with symptom onset ≤12 hours
Emergent angiography, followed by triage to…
Primary PCICABG – Medical Rx–
UFH + GP IIb/IIIa inhibitor(abciximab or eptifibatide)
Bivalirudin monotherapy(± provisional GP IIb/IIIa)
Aspirin, thienopyridine R 1:1
3000 pts eligible for stent randomization R 1:3
Bare metal stent TAXUS paclitaxel-eluting stent
*To rand 3000 stent pts
Clinical FU at 30 days, 6 months,1 year, and then yearly through 5 years
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 ≤ 0.0001Psup ≤ 0.0001
Diff = -2.9% [-4.9, -0.8]RR = 0.76 [0.63, 0.92]
PNI ≤ 0.0001Psup = 0.006
Stone et al, NEJM 2008
@ 1 month
Cardiac mortality @ 3 yearsC
ardi
ac M
orta
lity
(%)
P=0.001
3-yr HR (95%CI) 0.56 (0.40, 0.80)
2.9%
0 12 15 18 21 24 27 30 33 36
Months3 6 9
0
1
6
5
4
3
2
3.8%
2.1%
5.1%
Bivalirudin alone (n=1800)Heparin + GPIIb/IIIa (n=1802)
Stone et al, Lancet 2011
UFH + GP IIb/IIIa(N=1802)
Bivalirudin(N=1800)
UFH pre randomization 76.3% 65.8%Antithrombin in CCL - UFH 98.9% 2.6% - Bivalirudin 0.2% 96.9% - Peak ACT 264 [228, 320] 357 [300, 402]GP IIb/IIIa in CCL 94.5%* 7.2%* - Bail-out per protocol** - 4.4% - Abciximab 49.9% 4.0% - Eptifibatide 44.4% 3.1% - Tirofiban 0.2% 0.1%
Stone et al, NEJM 2008* « Administration if No Reflow or Giant Thrombus post PCI »
Thrombose aigue de stent?
Impact de l’administration HNF
Impact de la dose de charge de clopidogrel
HORIZON MILes Points positifs
Réduction hémorragies+++
Large population (3602 patients)
Bénéfice mortalité court et long terme
Les Points négatifs
Thrombose aigue stent?
Pas de réduction événements ischémiques
Impact de la coadministration héparineDose de clopidogrel
Bail out IIB/IIIA 7%
Utilisation radiale: 6%....
Bivalirudine
ESC STEMI 2010
AHA 2011
Les Questions
1) Bivalirudine: Forces et Faiblesses?2) HNF(+IIbIIIa) comparateur, quid Enoxaparine?3) IIb/IIIa molécules anciennes, nouvelles
données?4) Conclusion: les questions en suspens….
ATOLL Trial design
STEMI Primary PCI
30-day results
Randomization as early as possible (MICU +++)Real life population (shock, cardiac arrest included) No anticoagulation and no lytic before RxSimilar antiplatelet therapy in both groups
ENOXAPARIN IV0.5 mg/kg
with or without GPIIbIIIa
UFH IV 50-70 IU with GP IIbIIIa
70-100IU without GP IIbIIIa(Dose ACT-adjusted)
IVRS
Primary PCI ENOXAPARIN SC UFH IV or SC
Montalescot et al Lancet 2011; 378: 693-703
33.7
28
0
5
10
15
20
25
30
35
40
UFHENOX
RRR = 17% P = 0.07
% o
f pat
ient
s
ATOLL studyDeath, Complication of MI, Procedure Failure or Major Bleeding
RRR=17%P=0.063
0 5 10 15 20 25 30
0.00
0.05
0.10
0.15
Days
Mai
n se
cond
ary
EP
rate UFH
ENOXLog-Rank Test
p=0.01 11.3%
6.7%
30d rate (%)
i 41%
Death, Recur MI/ACS or Urgent Revasc
Main Secondary Endpoint (ischemic)
Enoxaparine: ATOLL trialDeath, MI, Major bleeding
Montalescot G Lancet 2011; 378: 693-703
Les Questions
1) Bivalirudine: forces et faiblesses?2) HNF/IIbIIIa comparateur, quid Enoxaparine?3) IIb/IIIa molécules anciennes, nouvelles
données?4) Conclusion: les questions en suspens….
Amélioration flux TIMI-3Study or Sub-category EARLY (n/N) LATE (n/N) RELAx-MI 25/105 11/105 ERAMI 7/40 5/40 REOMOBILE 11/48 8/52 Rakowski et al. 8/25 3/30 ReoPro-BRIDGING 8/28 2/27 Zorman et al. 9/56 1/56 Subtotal (95% CI) 68/302 30/310
0.1 0.2 0.5 1 2 5 10 Favours Early GP IIb-IIIa inhibitors Favours Late GP IIb-IIIa inhibitors
Test for heterogeneity: Chi² = 3.56, df = 5 (P = 0.61), I² = 0% Test for overall effect: Z = 4.38 (P < 0.0001)
Emre et al. 10/32 4/35Cutlip et al. 7/23 6/30ON-TIME 46/243 36/244Subtotal (95% CI) 63/298 46/309
Weight (%) Peto OR (IPD) (95% CI)12.48 2.55 (1.24, 5.21)2.67 1.45 (0.31, 6.81)6.47 1.62 (0.60, 4.39)3.70 3.86 (1.04, 14.39)3.47 4.05 (1.04, 15.77)3.83 5.69 (1.56, 20.73)32.62 2.69 (1.73, 4.19)
INTAMI 18/53 5/49TITAN TIMI-34 41/171 27/142Subtotal (95% CI) 59/224 32/191
Test for heterogeneity: Chi² = 1.84, df = 2 (P = 0.40), I² = 0% Test for overall effect: Z = 2.11 (P=0.03)
Test for heterogeneity: Chi² = 3.74, df = 1 (P = 0.05), I² = 73.3% Test for overall effect: Z = 2.35 (P=0.02)
Test for heterogeneity: Chi² = 12.53, df = 10 (P = 0.25), I² = 20.2% Test for overall effect: Z = 5.08 (P < 0.00001)
Total (95% CI) 190/824 108/810
4.67 3.15 (0.98, 10.15)4.72 1.86 (0.58, 5.97)28.47 1.35 (0.84, 2.16)37.85 1.56 (1.03, 2.35)
7.48 3.85 (1.53, 9.70)22.05 1.34 (0.78, 2.29)29.53 1.75 (1.10, 2.79)
100 1.93 (1.50, 2.48)
Abc
ixim
abTi
rofib
anEp
tifib
atid
e
Adapted from De Luca et al. Heart 2008; Epub ahead of print
Risk Profile
Ischemic Time (min)(Symptom Onset - TTT)
60 120 180 240 300 360
High
Intermediate
Low
High Risk and long
delay
FINESSE
Low Risk and short delay
MISTRAL
High Risk and short delay
EUROTRANSFER
RELAX-AMIOn Time-2
FINESSE substudy
Studies with benefit of IIbIIIa inhibitors
Studies without benefit of IIbIIIa inhibitors
BRAVE-3Low Risk and long delay
IIb/IIIa Données Récentes: Impact du temps et du risque du patient
Les questions en 2012 ?
Voie intracoronaire?→ AIDA STEMINouveaux P2Y12 inhibiteurs?
Guidelines 2010
Utilisation plus sélective
Les Questions
1) Bivalirudine: forces et faiblesses?2) HNF/IIbIIIa comparateur, quid Enoxaparine?3) IIb/IIIa molécules anciennes, nouvelles
données?4) Conclusion: les questions en suspens….
Conclusion
UFH Enoxaparine Bivalirudine
Bleeding complications: HORIZON
Ischemic complications : ATOLL Study
UFH/IIbIIIa Enoxaparine/IIb/IIIa Bivalirudine
Radiale? (RIVAL/RIFLE)Prasugrel/Ticagrelor?Utilisation + selective IIb/IIIa?Enoxaparine?
BACK UP SLIDE
Euromax
RIVAL
S Jolly et al Lancet 2011; 377:1409-20
NACE MACCE Bleedings
femoral arm radial armp = 0.003
• Net Adverse Clinical Event (NACE) = MACCE + bleeding• Major Adverse Cardiac and Cerebrovascular event (MACCE) = composite of cardiac
death, myocardial infarction, target lesion revascularization, stroke
30-day NACE rate
p = 0.029 p = 0.02621.0%
11.4%
7.2%
12.2%
7.8%
13.6%
RIFLE STEAACS
N=1001
30-day bleeding rate
p = 1.000
12.2%
6.8%
2.6%5.4% 5.2%
p = 0.026
Bleedings Access site related Non access site related
femoral arm radial arm
7.8%
p = 0.002
RIFLE STEAACSN=1001
HORIZON MI
Transradial:n=200!!!
2-Year Stent Thrombosis(ARC Definite/Probable)
1611 1509 1475 1444 12061591 1482 1449 1386 1153
p= 0.73
HR [95%CI]=0.94 [0.67, 1.32]
4.3% 4.6%
Ste
nt T
hrom
bosi
s (%
)
0
1
2
3
4
5
6
0 3 6 9 12 15 18 21 24
Number at riskBivalirudin aloneHeparin+GPIIb/IIIa
Bivalirudin alone (n=1800)Heparin + GPIIb/IIIa (n=1802)
Months
2.2%
3.0%
1.5%
0.3%
HR [95%CI] = 1.73 [0.47-1.13]
P = 0.06
HR [95%CI] =5.93 [2.06-17.04]
P = 0.0002
16111591
1600 1562 1525 1506 1485 13551587 1521 1495 1476 1457 1315
Number at riskBivalirudinUFH+GPIIb/IIIa
Def
/Pro
b S
tent
Thr
ombo
sis
(%)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Time in Days
0 1 30 90 180 270 365
Thrombose de stent
Bivalirudin monotherapyHeparin + GPIIb/IIIa inhibitor