CardioLucca 2019 Cuore d'Autore Lucca, 7-9 febbraio 2019 Centro Congressi Auditorium San Francesco - Aristea
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13° Meeting
CardioLucca 2019
Cuore d’Autore Lucca, 7-9 febbraio 2019
Centro Congressi Auditorium San Francesco
Trattamento antiaggregante in CATH LAB: dalle
linee guida, ai registri e alla personalizzazione
delle scelte
Alberto Menozzi
Parma
Antiplatelet therapy in ACS
Early and Long-Term Risk of Ischemic Events
Peri-procedural MI Subacute stent
and acute thrombosis and Death or MI
stent thrombosis spontaneous MI
Within 48 hours Within 30 days 1 year
Incidence: 6-8% Incidence: 6.5-8.5% Incidence: 10-12%%
Complications of PCI / Stent Placement
Complications of Atherothrombotic Disease
ACS with persistent ST-segment elevation
Relevant issues 1) Choice of oral P2Y12 inhibitor 2) Timing of oral P2Y12 inhibitor 3) Role for parenteral antiplatelet agents 4) Choice of parenteral antiplatelet agent
The TRITON-TIMI 38 and PLATO trials
New P2Y12 Inhibitors in STEMI
HR 0.87; 95%CI 0.75-1.01; P=0.07
Primary endpoint benefit with ticagrelor was
consistent with the
overall PLATO trial results
The TRITON-TIMI 38 and PLATO trials
New P2Y12 Inhibitors in STEMI
Major Bleeding
Major Bleeding unrelated to CABG
Steg PG., et al. Circulation 2010;122:2131-41
Montalescot G., et al. Lancet 2009;373:723-31
Stent Thrombosis in STEMI patients
Reduction with Prasugrel and Ticagrelor versus Clopidogrel
Montalescot G., et al. Lancet 2009;373:723-31 Steg PG., et al. Circulation 2010;122:2131-41
Impaired Bioavailability of Clopidogrel
in STEMI patients
Comparison of changes in platelet aggregation after 600 mg clopidogrel
loading dose between STEMI patients and healthy controls
5 mmol/l ADP 20 mmol/l ADP
Heestermans A., et al. Thrombosis Research 2008;122:776-781
Clopidogrel in STEMI • Oral anticoagulation • Prior hemorrhagic stroke • Severe renal failure in hemodialysis • Severe hepatic dysfunction • Very high bleeding risk • Very elderly patients (>85 years)
Inibitori P2Y12 in pazienti con STEMI
in Emilia-Romagna – anno 2016
REGIONE ER
Romagna
Ferrara
Imola
Clopidogrel
Bologna Prasugrel
Ticagrelor
Modena
Reggio E
Parma
Piacenza
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
% calcolate su numero di giornate di terapiaRegistro GISE SCA-Diabete
Regione Lombardia (anno 2017)
Ferlini M et al. CAD 2018The PRAGUE-18 Study Ticagrelor vs Prasugrel in STEMI patients
Ticagrelor vs Prasugrel antiplatelet effects
in patients undergoing primary PCI
Alexopoulos D., et al. Circ Cardiov Interv 2012;5:797-804Morphine is associated with a delayed activity
of oral antiplatelet agents in STEMI
100
No Morphine
p= 0.030
80
Morphine
p= 0.0001 p= 0.0001
60
40
p= 0.029 p= 0.726
20
0
1 hr 2 hrs 2 hrs 4 hrs 8 hrs
(PRU cut-off 208)
The difference between the 2 groups persisted after excluding patients with vomit.
No difference between prasugrel and ticagrelor patients (39% vs 37%; p= 0.719).
Parodi G. et al., Circ Intv 2015Pretreatment with a P2Y12 inhibitor Sibbing D et al. EHJ 2016;37:1284-95.
The ATLANTIC trial
Primary Efficacy End-Points
1st Co‐primary endpoint 2nd Co‐primary endpoint
ST‐segment resolution (≥70%) TIMI 3 flow in infarct‐related artery
Montalescot G, et al. N Engl J Med 2014The ATLANTIC trial
Safety of Ticagrelor pretreatement
Non‐CABG‐related Bleeding Events
Montalescot G, et al. N Engl J Med 2014The ATLANTIC trial
Reduction in Stent Thrombosis
Definite Stent Thrombosis
Montalescot G, et al. N Engl J Med 2014No Benefit of Ticagrelor Pretreatement in P-PCI
The Swedeheart Registry
Koul S et al. Circ Card Intv 2018; 5: 268-77Documento di Indirizzo Emilia‐Romagna Terapia antitrombotica SCA
Oral Pretreatment in STEMI Ghobrial J, Gibson CM, Pinto DS. Journal of Invasive Cardiology 2015;27(5):E68-E69.
Is there still a role for intravenous
antiplatelet agents in primary PCI ?
Yousuf, O. & Bhatt, D. L. (2011) The evolution of antiplatelet therapy in cardiovascular disease
Nat. Rev. Cardiol. doi:10.1038/nrcardio.2011.96
Yousuf O, Bhatt DL. Nat Rev Cardiol 2011Ticagrelor vs Prasugrel antiplatelet effects
in patients undergoing primary PCI
How comfortable
would you feel if this
was your platelet
reactivity after a
freshly implanted
stent?
Alexopoulos D., et al. Circ Cardiov Interv 2012;5:797-804ESC STEMI Guidelines 2017
Impact of GPI in contemporary PCI for ACS
The National Cardiovascular Data Registry CathPCI Registry
970.865 patients included
326.283 receiving GPI (33.6%)
Safley DM, et al. JACC Cardiol Interv 2015;8:1574-82Inibitori GP IIb/IIIa e flusso TIMI pre-PCI in STEMI
Flusso TIMI 3 pre-PCI - 23% vs. 13.3%, pMajor Bleeding with GPI in STEMI Eur Heart J. 2009 Nov; 30(22): 2705–2713.
Uso dei GPI nello STEMI in Emilia‐Romagna
80
70
70
60
60
50
50
40 40
40
35
30 28
25 25
20
20
10
0
Piacenza Parma Reggio Emilia Modena Bo Magg Bo S.O Ferrara Forlì Ravenna RiminiGPI strategy optimization in 2018 • Carefully select patients • Use radial access • Carefully dose heparin • Use GPI’s provisionally after sheat inserction and coronary angiography • Do NOT wait for bailout use • Prefer reversible GPI’s and administer high‐ bolus alone or followed by short infusion
Cangrelor Parenteral ADP-P2Y12 receptor antagonist ATP analogue Molecular weight
Cangrelor Rationale for use
Champion-Phoenix study
Primary End-point
Death/ MI/ IDR/ Stent Thrombosis within 48h
clopidogrel 5.9%
Event Rate (%)
4.7%
cangrelor
Log Rank P Value = 0.006
Patient at Risk Hours from Randomization
Cangrelor: 5472 5233 5229 5225 5223 5221 5220 5217 5213
Clopidogrel: 5470 5162 5159 5155 5152 5151 5151 5147 5147
Bhatt DL, et al. N Engl J Med 2013; 368:1303-13The Champion Phoenix Trial
Stent thrombosis within 48 hours
Bhatt DL, et al. N Engl J Med 2013; 368:1303-13IPST in CHAMPION PHOENIX
10,939 pts assessed by a blinded core lab
Phoenix
Reduction of IPST with cangrelor
P Int =
0.77
2.5
Clopidogrel (n=5470)
2 Cangrelor (n=5469) OR 0.76
OR 0.75 [0.34,1.73]
OR 0.65 [0.38,1.50] p=0.52
IPST (%)
1.5 [0.42,0.99] p=0.42
p=0.04 OR 0.50
[0.24,1.05]
1
p=0.06
0.5 1.0 1.3 1.0 1.4 1.0
0.6 0.7
0.4
0
All Stable NSTE-ACS STEMI
Angina
Généreux P et al. JACC 2013.Bleeding Events
Champion trials pooled analysis
Franchi F. et al. Expert Opinion on Drug Safety 2016Propensity-Matched Analysis Comparing Cangrelor Alone
vs. Clopidogrel+GP IIb/IIIa Inhibitors in the CHAMPION
Trials
PS-Matched Cohort
Cangrelor Alone Clopi+GPI
OR (95% CI) P
(n=1,021) (n=1,021)
Composite death/MI/IDR/ST 2.6% 3.3% 0.79 (0.48-1.32) 0.37
Stent thrombosis 0.1.% 0.6% 0.17 (0.02-1.38) 0.1
GUSTO severe 0.3% 0.7% 0.43 (0.11-1.66) 0.22
Blood tranfusion 1.0% 2.1% 0.45 (0.20-0.99) 0.05
1:1 propensity-score matching based on 16 baseline clinical variables
Cangrelor alone was associated with similar ischemic risk and lower risk-
adjusted major bleeding risk compared with clopidogrel plus GPIs.
Vaduganathan M, Harrington RA, Stone GW,
et al. JAMA Cardiol 2017;2:127-135.Predictors of bail-out GPI use
in Champion Phoenix Trial
Variable Adjusted OR (95% CI) P value
Independent predictors of higher risk for bailout GPI
STEMI 4.97 (3.76, 6.57)CANTIC: Pharmacodynamic assessment measured by VerifyNow
P2Y12 (PRU) following administration of cangrelor versus placebo
PRU levels at 30 minutes (primary end point) were significantly lower with cangrelor compared with
placebo [63 (32-93) vs. 214 (183-245); mean difference: 152; 95% CI: 108-195; pCangrelor vs GPI: Key PK/PD differences
GPI CANGRELOR
Fast onset
(minutes)
Potent platelet Inhibition
Rapid offset
(How to deal in everyday clinical practice?
Cangrelor GPI’s
Prasugrel ‐ Ticagrelor – (Clopidogrel)Antiplatelet Therapy in the Cath-lab:
patient-oriented choiceQuale strategia nel paziente STEMI
Alto Rischio Emorragico Basso rischio emorragico
Basso rischio ischemico P2Y12 orali Cangrelor
Alto rischio ischemico
con basso burden Cangrelor (vs Orali) Cangrelor (vs Tirofiban)
trombotico
Alto rischio ischemico
con elevato burden Cangrelor (vs Tirofiban) Tirofiban (vs Cangrelor)
trombotico
Cangrelor
Uso in “bailout”
GPI’s
Tirofiban Tirofiban (vs Abciximab)
Prasugrel ‐ Ticagrelor – (Clopidogrel)
Ridotta compliance
all’assunzione di farmaci Cangrelor Cangrelor
oraliConclusions
Ticagrelor and Prasugrel should be preferred over clopidogrel in the large
majority of STEMI patients. Clopidogrel should be limited to patients with
high‐bleeding‐risk such as those receiving oral anticoagulation or very
elderly or with previous cerebral ischemic events
Preadministration of ticagrelor is safe and should be recommended in patients
admitted in spoke centers or once STEMI diagnosis is confirmed and
bleeding risk evaluated. Available data on oral pretreatement in STEMI do
not justify a routine in‐ambulance administration strategy
Use of parenteral agents seems clinically justified in the setting of primary or
urgent PCI as a bridge to oral antiplatelet therapy, at least in selected
patients at higher ischemic risk
GPI, especially tirofiban, should have a role in patients with high trombotic
burden and low bleeding risk especially if early presenter, or in bailout case
Cangrelor has a more safe profile then GPI and should be the agent of choice in
the setting of primary PCI or in high‐risk NSTEMI in patients not pretreated
with oral P2Y12You can also read
