Pourquoi la Bivaluridine et pourquoi pas les IIb-IIIa?

Présentation au sujet: "Pourquoi la Bivaluridine et pourquoi pas les IIb-IIIa?"— Transcription de la présentation:

1 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

2 Les Questions Bivalirudine: Forces et Faiblesses?
HNF/IIbIIIa comparateur, quid Enoxaparine? IIb/IIIa molécules anciennes, nouvelles données? Conclusion: les questions en suspens….

3 Harmonizing Outcomes with Revascularization and Stents in AMI
HORIZON MI Harmonizing Outcomes with Revascularization and Stents in AMI ≥3400* pts with STEMI with symptom onset ≤12 hours UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide) Bivalirudin monotherapy (± provisional GP IIb/IIIa) Aspirin, thienopyridine R 1:1 Emergent angiography, followed by triage to… Primary PCI CABG – Medical Rx 3000 pts eligible for stent randomization R 1:3 Bare metal stent TAXUS paclitaxel-eluting stent Clinical FU at 30 days, 6 months, 1 year, and then yearly through 5 years *To rand 3000 stent pts

4 @ 1 month PNI ≤ 0.0001 Psup ≤ 0.0001 Psup = 1.00 PNI ≤ 0.0001
Diff = -3.3% [-5.0, -1.6] RR = 0.60 [0.46, 0.77] PNI ≤ Psup ≤ Diff = 0.0% [-1.6, 1.5] RR = 0.99 [0.76, 1.30] Psup = 1.00 Diff = -2.9% [-4.9, -0.8] RR = 0.76 [0.63, 0.92] PNI ≤ Psup = 0.006 Stone et al, NEJM 2008

5 Cardiac mortality @ 3 years
Heparin + GPIIb/IIIa (n=1802) Bivalirudin alone (n=1800) Cardiac Mortality (%) P=0.001 3-yr HR (95%CI) 0.56 (0.40, 0.80) 2.9% 12 15 18 21 24 27 30 33 36 Months 3 6 9 1 5 4 2 3.8% 2.1% 5.1% Stone et al, Lancet 2011

6 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 0.1% * « Administration if No Reflow or Giant Thrombus post PCI » Stone et al, NEJM 2008

7 Thrombose aigue de stent?
Impact de l’administration HNF Impact de la dose de charge de clopidogrel

8 HORIZON MI Les Points positifs Les Points négatifs
Thrombose aigue stent? Pas de réduction événements ischémiques Impact de la coadministration héparine Dose de clopidogrel Bail out IIB/IIIA 7% Utilisation radiale: 6%.... Large population (3602 patients) Réduction hémorragies+++ Bénéfice mortalité court et long terme

9 Bivalirudine ESC STEMI 2010 AHA 2011

10 Les Questions Bivalirudine: Forces et Faiblesses?
HNF(+IIbIIIa) comparateur, quid Enoxaparine? IIb/IIIa molécules anciennes, nouvelles données? Conclusion: les questions en suspens….

11 with or without GPIIbIIIa
ATOLL Trial design Randomization as early as possible (MICU +++) Real life population (shock, cardiac arrest included) No anticoagulation and no lytic before Rx Similar antiplatelet therapy in both groups STEMI  Primary PCI ENOXAPARIN IV 0.5 mg/kg with or without GPIIbIIIa UFH IV 50-70 IU with GP IIbIIIa 70-100IU without GP IIbIIIa (Dose ACT-adjusted) IVRS 30-day results Primary PCI ENOXAPARIN SC UFH IV or SC Montalescot et al Lancet 2011; 378:

12 ATOLL study Death, Complication of MI, Procedure Failure or Major Bleeding RRR=17% P=0.063

13 Main Secondary Endpoint (ischemic)
Death, Recur MI/ACS or Urgent Revasc Main Secondary Endpoint (ischemic)

14 Enoxaparine: ATOLL trial
Death, MI, Major bleeding Montalescot G Lancet 2011; 378:

15 Les Questions Bivalirudine: forces et faiblesses?
HNF/IIbIIIa comparateur, quid Enoxaparine? IIb/IIIa molécules anciennes, nouvelles données? Conclusion: les questions en suspens….

16 Amélioration flux TIMI-3
Study 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 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) Abciximab Test for heterogeneity: Chi² = 3.56, df = 5 (P = 0.61), I² = 0% Test for overall effect: Z = 4.38 (P < ) Emre et al. 10/32 4/35 Cutlip et al. 7/23 6/30 ON-TIME 46/243 36/244 Subtotal (95% CI) 63/298 46/309 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) Tirofiban Test for heterogeneity: Chi² = 1.84, df = 2 (P = 0.40), I² = 0% Test for overall effect: Z = 2.11 (P=0.03) INTAMI 18/53 5/49 TITAN TIMI-34 41/171 27/142 Subtotal (95% CI) 59/224 32/191 7.48 3.85 (1.53, 9.70) 22.05 1.34 (0.78, 2.29) 29.53 1.75 (1.10, 2.79) Eptifibatide Test for heterogeneity: Chi² = 3.74, df = 1 (P = 0.05), I² = 73.3% Test for overall effect: Z = 2.35 (P=0.02) Total (95% CI) 190/824 108/810 100 1.93 (1.50, 2.48) Test for heterogeneity: Chi² = 12.53, df = 10 (P = 0.25), I² = 20.2% Test for overall effect: Z = 5.08 (P < ) Favours Late GP IIb-IIIa inhibitors 0.1 0.2 0.5 1 2 5 10 Favours Early GP IIb-IIIa inhibitors Adapted from De Luca et al. Heart 2008; Epub ahead of print

17 IIb/IIIa Données Récentes: Impact du temps et du risque du patient
High Risk and short delay EUROTRANSFER RELAX-AMI On Time-2 FINESSE substudy Risk Profile High Intermediate Low High Risk and long delay FINESSE BRAVE-3 Low Risk and long delay Low Risk and short delay MISTRAL Ischemic Time (min) (Symptom Onset - TTT) Studies with benefit of IIbIIIa inhibitors Studies without benefit of IIbIIIa inhibitors

18 Les questions en 2012 ? Voie intracoronaire?→ AIDA STEMI
Nouveaux P2Y12 inhibiteurs?

19 Guidelines 2010 Utilisation plus sélective

20 Les Questions Bivalirudine: forces et faiblesses?
HNF/IIbIIIa comparateur, quid Enoxaparine? IIb/IIIa molécules anciennes, nouvelles données? Conclusion: les questions en suspens….

21 Ischemic complications : ATOLL Study Bleeding complications: HORIZON
Conclusion Radiale? (RIVAL/RIFLE) UFH Enoxaparine Bivalirudine Prasugrel/Ticagrelor? Utilisation + selective IIb/IIIa? Ischemic complications : ATOLL Study Enoxaparine? UFH/IIbIIIa Enoxaparine/IIb/IIIa Bivalirudine Bleeding complications: HORIZON

22 BACK UP SLIDE

23 Euromax

24 RIVAL S Jolly et al Lancet 2011; 377:

25 RIFLE STEAACS 30-day NACE rate p = 0.003 N=1001 21.0% p = 0.029
13.6% 12.2% 11.4% 7.2% 7.8% 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 25

26 RIFLE STEAACS 30-day bleeding rate N=1001 p = 0.026 p = 1.000
12.2% 7.8% 6.8% 5.4% 5.2% 2.6% 30-day bleeding rate 26

27 HORIZON MI Transradial:n=200!!!

28 2-Year Stent Thrombosis (ARC Definite/Probable)
6 Bivalirudin alone (n=1800) Heparin + GPIIb/IIIa (n=1802) 5 4.6% 4.3% 4 Stent Thrombosis (%) 3 HR [95%CI]= 2 0.94 [0.67, 1.32] p= 0.73 1 3 6 9 12 15 18 21 24 Months Number at risk Bivalirudin alone 1611 1509 1475 1444 1206 Heparin+GPIIb/IIIa 1591 1482 1449 1386 1153

29 Thrombose de stent 3.0% 2.2% P = 0.06 HR [95%CI] = 1.73 [0.47-1.13]
Bivalirudin monotherapy Heparin + GPIIb/IIIa inhibitor 3.5 HR [95%CI] = 5.93 [ ] P = 3.0% 3.0 2.5 2.2% 2.0 Def/Prob Stent Thrombosis (%) 1.5% 1.5 HR [95%CI] = 1.73 [ ] P = 0.06 1.0 0.5 0.3% 0.0 1 30 90 180 270 365 Time in Days Number at risk Bivalirudin 1611 1600 1562 1525 1506 1485 1355 UFH+GPIIb/IIIa 1591 1587 1521 1495 1476 1457 1315