Αναστολείς GPIIb/IIIa (GPIs)static.livemedia.gr/hcs2/documents/al17320_us80... · 2016....
Transcript of Αναστολείς GPIIb/IIIa (GPIs)static.livemedia.gr/hcs2/documents/al17320_us80... · 2016....
Κωνσταντίνος Τριανταφύλλου,
Επιμελητής A´A´ Καρδιολογικό Τμήμα
Γ.Ν.Α. «Ευαγγελισμός»
Αναστολείς GPIIb/IIIa (GPIs) :
ποια είναι η θέση τους σήμερα.
Πιθανή σύγκρουση συμφερόντων
Ομιλητής: Κωνσταντίνος Τριανταφύλλου.
Δεν υπάρχει πιθανή σύγκρουση συμφερόντων σχετική
με την παρουσίαση αυτή.
Ανενεργό αιμοπετάλιο.
Αδρανείς υποδοχείς GPIIb/IIIa
Ενεργοποιημένο αιμοπετάλιο.
Ενεργοί υποδοχείς GPIIb/IIIa
Fibrinogen / Fibrin
GPIIb/IIIa inhibitor
GP IIb/IIIa υποδοχείς και αναστολείς
GPIIb/IIIa R:
integrin, heterodimer,
aIIβ & β3 subunits.
Αbciximab Eptifibatide Tirofiban
Molecule Fab 7E3 Synthetic peptide Nonpeptide mimetic
Binding Noncompetitive Competitive Competitive
Half-life
Plasma: 10 - 15 hr Plasma: 2 -2.5 hr Plasma: 2 -2.5 hr
Biologic: 12 - 24 hr Biologic = plasma Biologic = plasma
PCI dosing
Bolus: Bolus: Bolus:
0.25mg/kg 180µg/kg (10min) + 180µg/kg 25µg/kg
Infusion: Infusion: Infusion:
0.125µg/kg/min (12hr)
Max:10μg/min
2µg/kg/min (24 to 48 hr) 0.15µg/kg/min (18hrs)
*Renal adjustment No
Bolus: Bolus:
180µg/kg 12.5µg/kg
Infusion: Infusion:
1µg/kg/min (24 to 48 hr) 0.075 µg/kg/min (18hs)
Aναστολείς GP IIb/IIIa
2014 ESC/EACTS Guidelines on myocardial revascularization
Stable CAD
Recent trials did not demonstrate additional benefit from GPIs
after a clopidogrel loading dose of 600 mg.
Biondi-Zoccai et al. Am Heart J 2012;163:835 e1-7. (eptifibatide).
Kastrati et al. N Engl J Med 2004;350:232-8. (abciximab).
Valgimigli et al. J Am Coll Cardiol 2004;44:14-9. (tirofiban).
Windecker et al. Eur Heart J 2014;35:2541-619.
Tirofiban as adjunctive therapy for ACS and PCI:
a meta-analysis of RCTs
Valgimigli et al. Eur Heart J 2010;31:35-49.
14 RCTs, 3424 pts.
After pretreatment with clopidogrel.Does clopidogrel help tirofiban effect?
GPI use in contemporary ACS trials
NSTE ACS
Era before DAPT, patients undergoing PCI (POBA or with stents):
lower incidence of MACE in favour of UFH+GP IIb/IIIa treatment vs UFH alone,
primarily through a reduction in MI.
Boersma et al. Lancet 2002;359:189-98 (Metanalysis).
Era after DAPT, ISAR REACT 2 (Clopidogrel 600 mg LD)
Lower incidence of MACE in favour of UFH+GPIIb/IIIa (abciximab) vs UFH maintained:
- In NSTEMI (13.1% vs. 18.3%; RR 0.71, p = 0.02),
- Not in UA (4.6% vs. 4.6%, p= 0.98).
Kastrati et al. JAMA 2006;295:1531-8.
NSTE ACS - ACUITY study
Stone et al. N Engl J Med 2006;355:2203-16.
NSTE ACS – ISAR REACT 4
Kastrati et al. N Engl J Med 2011;365:1980-9.
NACE:NS Major bleeding:
bivalirudin safer
MACE: NS
NSTEMI patients undergoing PCI (n=1721).
All 600mg clopidogrel.
UFH+abciximab vs bivalirudin.
Early versus delayed, provisional eptifibatide in NSTE ACS.
Guiliano et al. N Engl J Med 2009;360:2176-90.
Pts in the early eptifibatide group :
significantly higher rates of bleeding and red-cell transfusion.
(TIMI major bleeding 2.6% vs 1.8%, OR 1.42, p=0.02).
NSTE ACS – EARLY ACS
Ticagrelor & Prasugrel
Wiviott et al. N Engl J Med 2007;357:2001-15.Wallentin et al. N Engl J Med 2009;361:1045-57.
PLATO TRITON -TIMI 38
NSTE ACS
TRITON -TIMI 38
O’ Donongue et al. J Am Coll Cardiol 2009;54:678-85.
- Prasugrel significantly reduces MACE in ACS pts after PCI regardless of GPI use.
- GPIs do not accentuate bleeding RR with prasugrel as compared with clopidogrel.
NSTE ACS – ISAR REACT 3
Stable or unstable angina (Tn - ) patients undergoing PCI. (n=4570).
All 600 mg clopidogrel, > 2hrs before.
UFH vs bivalirudin.
NACE:NS MACE:NS
Kastrati et al. N Engl J Med 2008;359:688-96.
- Bivalirudin did not provide a net clinical benefit compared to UFH.
- However, it reduced the incidence of major bleeding: 3.1 vs 4.6%, p=0.008.
2014 ESC/EACTS Guidelines on myocardial revascularization
NSTE ACS
Windecker et al. Eur Heart J 2014;35:2541-619.
De Luca et al. JAMA 2005;293:1759-65.
Abciximab in primary PCI metanalysis
- 8 RCTs, 3949 STEMI pts randomized
- Primary PCI (7 RCTs) or rescue PCI (1 RCT).
STEMI - pPCI
Era before
thienopyridine preloading
Vaglimili
EVA-AMI
MULTISTRATEGY
FATA
Gurm et al. Circ Cardiovasc Interv 2009;2:230-6.
STEMI pPCI: Abciximab vs small molecule GPIs metanalysis
STEMI - pPCI
No difference in outcome (mortality, NACE, MACE, bleeding).
STEMI - pPCI
Ellis et al. N Engl J Med 2008;358:2205-17.
“Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab
alone significantly improved the clinical outcomes, as compared with abciximab given at the
time of PCI, in patients with ST-segment elevation myocardial infarction.”
FINESSE study -2452 pts randomized
STEMI - pPCI
On-TIME study -1398 pts.
ASA/UFH/600mg clopidogrel.
Randomized to HBD tirofiban in ambulance - upstream vs provisional – downstream.
MACE at 30 days: 5.8% vs. 8.6%, p= 0.043.
Mortality 30d (2.2% vs. 4.1%, p=0.051) & 1-year (3.7% vs. 5.8%, p=0.08).
No clinically relevant difference in bleeding (3.4% vs 2.9%, p=0.58)
Ten Berg et al. J Am Coll Cardiol 2010;55:2446-55.
De Luca et al. J Thromb Haemost 2011;9:2361-70.
.
Early GPIs in primary angioplasty - abciximab long-term results
(EGYPT-ALT) cooperation: individual patient's data meta-analysis.
INFUSE-AMI:Intracoronary abciximab and aspiration thrombectomy
in patients with large anterior STEMI.
Stone et al. JAMA 2012;307:1817-26.
.
STEMI - pPCI
STEMI - pPCI
Thiele et al. Lancet 2012;379:923-31.
Death, MI, CHF Death
Reinfarction New CHF
AIDA STEMI: 2065 pts.
IC vs IV abciximab in STEMI < 12 hrs.
Stone et al. N Engl J Med 2008;358:2218-30.
HORIZONS-AMI:
Bivalirudin during primary PCI in acute myocardial infarction.
*But increased acute ST :
1.3% vs 0.3%, p<0.001).
STEMI - pPCI
STEMI - pPCI
EUROMAX (2218 pts).
STEMI transferred:
Bivalirudin vs UFH+provisional GPI (69.1%)
*Acute ST higher with bivalirudin (1.1% vs. 0.2%; RR, 6.11, P=0.007).
Death or non CABG major bleeding. Death, re-MI or non CABG major bleeding.
Steg et al. N Engl J Med 2013;369:2207-17.
STEMI - pPCI
Shahzad et al. Lancet 2014;384:1849-58
HEAT-PPCI1491 of 1812 pts did PCI,
1 center RCT, open label.
UFH vs bivalirudin in pPCI.
Contemporary practice:
-Restriction of GPIs for bail-out (15%)
- Novel P2Y12 inhibitors: 89%
- Radial approach: 81%
- DES implantation
Primary efficacy EP:
-Death, CVA, recurrent MI, TLR @ 28d: 5.7% vs 8.7%, p=0.01.
* ST: 0.9% vs 3.4%, p=0.001,
* Mortality: 4.3% vs 5.1%, p=NS.
Primary safety EP:
Major BARC 3-5 bleeding: 3.1% vs 3.5%, p=NS.
Bivalirudin vs heparin with or without tirofiban during pPCI in STEMI.
Han et al. JAMA 2015;313:1336-46.
NACE
MACCE Any BARC bleeding
STEMI - pPCI
BRIGHT RCT
Bivalirudin ctd 3hrs post PCI.
***No acute ST increase.
Bivalirudin versus heparin in patients planned for PCI: a meta-analysis of RCTs.
Bleeding decreased with bivalirudin only with routine GPI use in UFH arm.
No difference in mortality (contrast with HORIZONS – AMI).
Increased early ST/MI with bivalirudin.
Prolonged bivalirudin infusion (full dose) 4 hours post procedure may prevent ST.
Cavender MA, Sabatine MS. Lancet 2014;384:599-606.
STEMI - pPCI
Bivalirudin versus UFH with or without GPIs
in patients with STEMI undergoing pPCI
Stone et al. J Am Coll Cardiol 2015;65:27-38.
STEMI - pPCI
Comprehensive M/A of safety and efficacy of bivalirudin versus UFH with
or without routine GPI in ACS pts (study-level data).
Navarese et al. JACC Cardiovasc Interv 2015;8:201-13.
STEMI - pPCI
Bivalirudin or UFH in Acute Coronary Syndromes
7213 pts randomized.
MATRIX study
MACE and NACE:
not significantly lower with bivalirudin .
Urgent TVR/definite ST/ NACE:
not significantly lower with a post-PCI bivalirudin infusion.
MACE NACE
NACE/urgent TVR, definite ST
Valgimigli et al. N Engl J Med 2015;373:997-1009.
Death (any): 1.7% vs 2.3%, p=0.04.
Death (cardiac): 1.5% vs 2.2%, p=0.03.
Definite ST: 1% vs 0.6%, p=0.048.
Major bleeding (BARC 3-5): 1.4% vs 2.5%, p<0.001)
!
Use of GPIs as bail-out
on bivalirudin arms of RCTs :
~ 1:10 pts
STEMI - pPCI
2014 ESC/EACTS Guidelines on myocardial revascularization
Windecker et al. Eur Heart J 2014;35:2541-619.
Alexopoulos et al. Circ Cardiovasc Interv 2012;5:797-804.
Randomized assessment of ticagrelor versus prasugrel
antiplatelet effects in patients with STEMI.
STEMI - pPCI
FABOLUS PRO:
Prasugrel versus tirofiban bolus with or without short post-bolus infusion with or without
concomitant prasugrel administration in patients with myocardial infarction undergoing
coronary stenting.
Valgimigli et al. JACC Cardiovasc Interv 2012;5:268-77.
Prasugrel administration leads to a suboptimal IPA for at least 2 hrs in STEMI patients.
Prasugrel, given in association with a bolus only GPI obviates the need of post-bolus infusion and
almost abolishes residual variability of IPA after treatment.
Cangrelor ?
“Compared with control (clopidogrel or placebo), cangrelor reduced PCI periprocedural
thrombotic complications, at the expense of increased mild bleeding.”
Steg et al. Lancet 2013;382:1981-92.
24910 pts
STEMI – 11.6%
NSTEMI - 57.4%
SCAD – 31%
Death, MI, IDR, ST at 48hrs:
3.8% vs 4.7% (-19%)
*ST at 48hrs:
0.5 vs 0.8% (-42%)
*GUSTO maj/mod bleeding:
No difference
*GUSTO mild bleeding:
16.8% vs 13%
Safley et al. JACC Cardiovasc Interv 2015;8:1574-82.
Period : July 2009 and September 2011.
970,865 pts included - 326,283 (33.6%) received a GPI.
Multivariable logistic regression, propensity-matched and instrumental variable analysis.
Impact of Glycoprotein IIb/IIIa Inhibition in Contemporary PCI for ACS.
Insights From the National Cardiovascular Data Registry.
GPIs
Heavy thrombotic burden.
Intraprocedure thrombus formation.
Slow flow / no-reflow.
Threatened vessel closure.
? No preloading with P2Y12 antagonists.
? Complex lesions / High risk patients.
Prevent bleeding!
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