Akhtar Fajar Muzakkir New ESC NSTEMI Guideline Collet JP et al European Heart Journal 2020 00 179 What is NEW Collet JP et al European Heart Journal 2020 00 179 Major Changes in Recommendation ID: 931129
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Slide1
Expert Discussion on Antiplatelet for ACS Patients: Controversies for Asian Patients
Akhtar
Fajar
Muzakkir
Slide2New ESC NSTEMI Guideline
Collet JP et al European Heart Journal (2020) 00, 1-79
Slide3What is NEW?
Collet JP et al European Heart Journal (2020) 00, 1-79
Slide4Major Changes in Recommendation
Collet JP et al European Heart Journal (2020) 00, 1-79
Slide5Major Changes in Recommendation
An alternative to these scores may be the assessment of bleeding risk according to the
Academic Research Consortium for High Bleeding Risk (ARC-HBR).
ARC-HBR criteria may be difficult to apply in routine clinical practice as several of the criteria are quite detailed and so far, this score has not been validated.
In order to estimate bleeding risk in this setting,
scores such as the Can Rapid risk stratification of Unstable angina patients, CRUSADE and the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) bleeding risk scores have been developed.
CRUSADE bleeding risk score may be considered in patients undergoing coronary angiography to quantify bleeding risk.
Among HBR patients based on PRECISE-DAPT (i.e. PRECISE-DAPT score >_25), prolonged DAPT was associated with no ischaemic benefit but a
large bleeding burden
Collet JP et al European Heart Journal (2020) 00, 1-79
Slide6Acuity Score
Mehran R, et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol 2010;55:2556-2566
Slide7CRUSADE SCORE
CRUSADE Score for Post-MI Bleeding Risk, downloaded from
https://www.mdcalc.com/crusade-score-post-mi-bleeding-risk#use-cases
, accessed on 11 Sep 2020. Xi S. Thromb Haemost 2017;117:2186–2193.
Slide8Recommendations for post-interventional and maintenance treatment in patients with Non-ST-segment elevation acute coronary syndrome
Collet JP et al European Heart Journal (2020) 00, 1-79
Slide9P2Y12 Receptor Inhibitors in NSTEMI ESC 2020
Collet JP et al European Heart Journal (2020) 00, 1-79
Slide10Algorithm for antithrombotic therapy in non-ST-segment elevation acute coronary syndrome patients without AF undergoing PCI
Collet JP et al European Heart Journal (2020) 00, 1-79
Slide11ESC Guidelines (NSTEMI 2020;STEMI 2017)
Eur Heart J.201
7
;DOI: 10.1093/eurheartj/eh
x393, Collet JP et al European Heart Journal (2020) 00, 1-79
NSTEMI 2020
STEMI
2017
Recommendations for antithrombotic treatment in non-ST-segment elevation acute coronary syndrome patients without atrial fibrillation undergoing percutaneous coronary intervention
Slide12Recommendations (2017 ESC guideline DAPT)
Class
Level
Clopidogrel (300 mg loading dose in patients aged ≤ 75, 75 mg
o.d.
) is recommended on top of aspirin in STEMI patients receiving thrombolysis
IA
A
Valgimigli
M, et
al.Eur
Heart J.2018;39:213-54; Ibanez B, et
al.Eur
Heart J.2017;00:1-66.
Clopidogrel added to aspirin
reduces the risk
of cardiovascular events and overall mortality in patients treated with fibrinolysis
and should be added to aspirin as an adjunct to lytic therapy.
Prasugrel and ticagrelor
have not been studied
as adjuncts to Thrombolysis.
2017 ESC guidelines for STEMI
Slide13Duration of DAPT after fibrinolytic (without PCI)
Clopidogrel is recommended for
1 month
in patients treated with fibrinolysis without subsequent PCI.
Expanding the duration of DAPT
up to 12 months
should be considered in these patients.
2017 ESC guidelines for STEMI
Clopidogrel should be continued for a
minimum of 14 days (
Class I – A
) and ideally at least 12 months
. Expanding the duration of DAPT up to 12 months should be considered in these patients (
Class I – C-EO
)
In patients who have tolerated DAPT without bleeding complication and who are not at high bleeding risk
continuation of DAPT for longer than 12 months may be reasonable
(
Class IIb – A
)
2016 ACC/AHA guidelines for STEMI
Ibanez B, et
al.Eur
Heart J.2017;00:1-66; Levine GN, et al.Circulation.2016;133:000-000.
Slide14Antiplatelet effect vs Bleeding risk
“Use of more potent P2Y12 inhibitors
(
ticagrelor
or
prasugrel
)
in place of
clopidogrel
also results in
decreased
ischemic risk and
increased
bleeding risk”
–
Levine GN, et al 2016 ACC/AHA Guideline
Antithrombotic
Bleeding
Slide15INHIBITION OF PLATELET AGGREGATION
RISK OF ANY EVENT
“Sweet Spot”
Bleeding risk
Ischemic risk
Ferreiro
Jl
, et al.
Thromb
Haemost
2010; 103: 1128–1135
History of bleeding
Therapy OAC
Female
Advanced Age
Low body weight
CKD
Diabetes
Anemia
Chronic steroid or NSAID
High risk ischemic patient = high risk for bleeding
Factors Associated With Increased
Ischemic
And
Bleeding Risk
High Ischemic risk
Advanced age
ACS
Multiple prior MI
Extensive CAD
DM
CKD
High risk Stent Thrombosis
ACS
Diabetes
LVEF < 40%
DES 1
st
generation
Stent technique suboptimal
Stent Type
Slide16Clopidogrel is safer than ticagrelor in regard to bleeds : A closer look at the PLATO trial
“To compare hemorrhagic events between clopidogrel and ticagrelor in PLATO “
“Compared to
clopidogrel
,
ticagrelor
significantly increased spontaneous bleeds, major bleeds, major plus minor bleeds, and major plus minor plus minimal bleeds”
Major + minor bleeding (any bleeding requiring intervention
Non-procedural (spontaneous) major + minor bleeds
Di
Nicolantonio
JJ,
D’Ascenzo
F, Tomek A, et
al.Int
J Cardiol.2013;168:1739-44.
Slide17DiNicolantonio
JJ,
D’Ascenzo
F, Tomek A, et
al.Int
J Cardiol.2013;168:1739-44.
Clopidogrel is safer than ticagrelor in regard to bleeds : A closer look at the PLATO trial
“To compare hemorrhagic events between clopidogrel and ticagrelor in PLATO “
Slide18Summary from PLATO study
Choice between clopidogrel and ticagrelor :
Other things to consider for clinical practice
Keypoints
Description
Clopidogrel
loading dose
Only 19.6% of subjects randomized to
clopidogrel
received loading dose of
clopidogrel
as recommended by ESC guideline.
Drug compliance
Ticagrelor : 2x/day;
clopidogrel
1x/day
Premature discontinuation is
higher in
ticagrelor
arm (7.4% vs 6.0%; p<0.001)
Other
adverse event
Incidence
of dyspnea is higher in
ticagrelor
arm (13.8% vs 7.8%; p<0.001)
Wallentin
L, Becker RC,
Budaj
A, et
al.N
Eng
J Med.2009;361:1045-57.
Slide19De-escalation strategy
Slide20De-escalation strategy for ACS patients undergoing PCI
Slide21ESC 2020 NSTEMI GUIDELINE
Collet JP et al European Heart Journal (2020) 00, 1-79
Slide222018 ESC/EACTS Guidelines on Myocardial Revascularization
Recommendation
Class
Level
De-escalation of P2Y12 inhibitor treatment (e.g. with a switch from
ticagrelor
to
clopidogrel
) guided by platelet function testing may be considered as an alternative DAPT strategy, especially for ACS patients
deemed unsuitable
for 12-month potent platelet inhibition
IIb
B
DAPT scenario in the guideline
Duration of treatment
Shortened
(< 12 month)
Extended
(> 12 month)
P2Y12i switching
De-escalation
Escalation
‘ Triggers for DAPT de-escalation include clinical (bleeding events or presumed high bleeding risk) and socio-economic factors’
Neumann FJ, et
al.Eur
Heart J.2018;00:1-96.
Slide23|
23
TOPIC evaluated the effect of de-escalation from a new P2Y
12
inhibitor to clopidogrel on clinical outcomes and results were reported at
EuroPCR
in May 2017 and simultaneously published in the European Heart Journal
646 ACS patients
undergoing
PCI
Without
ischemic
events
or bleeding (BARC ≥2) at 1-month follow-up after PCI
Receiving DAPT with a new P2Y12 inhibitor + aspirin
Randomization
1:1
De-
escalation
DAPT group
Clopidogrel
+
aspirin
FDC
Composite
primary
endpoint
Death
, non fatal MI, stroke, all BARC
bleeding
Secondary
endpoints
Components of
primary
endpoint
Death
, MI, stroke, BARC
bleeding
≥2
TOPIC: T
iming
O
f
Platelet Inhibition after acute Coronary SyndromeFDC, fixed-dose combination; NCT02099422Cuisset T et al. Eur Heart J. 2017 May 16. doi
: 10.1093/
eurheartj
/ehx175. [
Epub
ahead of print]
Design
Interventions
Primary endpoint
Prospective, randomized trial in
646
ACS patients
Prasugrel or ticagrelor
Clopidogrel
Death, non-fatal MI, stroke, all BARC bleedings at 12 months
TOPIC: RCT study design
Unchanged
DAPT group
New P2Y
12
inhibitor
+
aspirin
1- year follow-up
1- year follow-up
Slide24Better
Prognosis
with
switched
DAPT (
aspirin+Clopidogrel
)
Cuisset
T, et
al.Eur
Heart J.2017;0:1-9
Primary
Endpoint
Death
, Urgent
revasc
., Stroke, BARC ≥ 2
TOPIC
(Timing Of Platelet Inhibition after acute Coronary Syndrome)
randomized study
To evaluate the benefit of switching DAPT from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS.
Slide25Cuisset T, et
al.Eur
Heart J.2017;0:1-9
No
difference
for
ischemic
events
Any
ischemic
endpoint
TOPIC
(Timing Of Platelet Inhibition after acute Coronary Syndrome)
randomized study
To evaluate the benefit of switching DAPT from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS.
Slide26Cuisset T, et
al.Eur
Heart J.2017;0:1-9
Higher
Rate of BARC
bleeding
≥ 2
with
Unchanged
DAPT
BARC
bleedings
≥ 2
TOPIC
(Timing Of Platelet Inhibition after acute Coronary Syndrome)
randomized study
To evaluate the benefit of switching DAPT from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS.
Slide27ENDPOINTS
Switched
DAPT
(n=322)
Unchanged
DAPT
(n=323)
HR (95%IC)
P-value
Net
clinical
benefit
43 (13.4%)
85 (26.3%)
0.48 (0.34 - 0.68)
<0.01
Any
ischaemic
event
30 (9.3%)
37 (11.5%)
0.48 (0.34 - 0.68
0.36
Cardiovascular Death
1 (0.3%)
4 (1.2%)
0.30 (0.05 - 1.73)
0.18
Unplanned
revascularization
28 (8.7%)
30 (9.3%)
0.93 (0.56 - 1.55)
0.78
Stent
Thrombosis
4 (1.2%)
3 (0.9%)
1.34
(0.30 – 6.0)
0.72
Stroke
1 (0.3%)
3 (0.9%)
0.37 (0.05 – 2.60)
0.32
All
Bleedings
30 (9.3%)
76 (23.5%)
0.39 (0.27 - 0.57)
<0.01
BARC
Bleedings
≥ 2
13 (4%)
48 (14.9%)
0.30 (0.18 - 0.50)
<0.01
TIMI Major
1 (0.3%)
4 (1.2%)
0.30 (0.05 - 1.73)
0.18
TIMI
Minor
9 (2.8%)
26 (8%)
0.37 (0.19 - 0.71)
<0.01
TIMI Minimal
20 (6.2%)
46 (14.2%)
0.44 (0.27 - 0.71)
<0.01
Cuisset
T, et
al.Eur
Heart J.2017;0:1-9
TOPIC
(Timing Of Platelet Inhibition after acute Coronary Syndrome)
randomized study
To evaluate the benefit of switching DAPT from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS.
Slide28East Asian Paradox
Slide29A New Phenomenon : ‘East Asian Paradox’
Unique Characteristics of East Asians
Compared to their Caucasian counterparts, East Asian patients treated with dual antiplatelet therapy have a similar or lower rate of post-PCI
ischaemic
events in spite of having a higher level of platelet reactivity
Huo
Y, et
al.Science
Bulletin.2019;64:166-79.
Slide30World Heart Federation Expert Consensus :
Large, phase III, randomized, controlled trials of the P2Y12 inhibitors (
clopidogrel
, ticagrelor,
prasugrel
) only included few East Asian patients.
Data suggests that East Asian patients have DIFFERENT risk profiles for both thrombophilia and bleeding compared with white patients
different ‘therapeutic window
’ of on-treatment
platelet reactivity (
see figure
)
Levine GN, et al. Nat Rev Cardiol.2014. doi:10.1038/nrcardio.2014.104;
Huo
Y, et
al.Science
Bulletin.2019;64:166-79.
A New Phenomenon : ‘
East Asian Paradox’
Slide312018 World Heart Federation Expert Consensus Statement
East Asian Paradox
: East Asian patients show a similar or even a lower rate of ischemic event occurrence and higher bleeding risk compared with Caucasian patients
Consensus statement :
Clopidogrel in combination with aspirin is
a reasonable DAPT choice
for elective PCI or ACS (during the chronic phase) in East Asian population.
Use of standard-dose potent P2Y12 inhibitors needs attention to the
increased risk of bleeding
when used in East Asian ACS population (e.g., prior stroke, old age, low body weight, and recurrent episodes of nuisance bleeding).
After considering the risk-benefit profile, a reduced-dose strategy of potent P2Y12 receptor inhibitors (especially, prasugrel) may be a considerable choice in East Asian population with ACS.
Huo
Y, et
al.Science
Bulletin.2019;64:166-79.
Slide32“
The PLATO and PHILO randomized trials did not show efficacy superiority of ticagrelor vs clopidogrel in East Asian Patient
”
– 2018 WHF Consensus
Kang HJ, et al Ticagrelor versus clopidogrel in Asian patients with acute coronary syndrome: A retrospective analysis from PLATO
trial.Am
Heart J.2015;169:899-905.e1.
1,106 patients out of 18,621 (5.9%) of PLATO study population were Asian
Slide33Comparison of short-term clinical outcomes between ticagrelor versus clopidogrel in patients with acute myocardial infarction undergoing successful revascularization; from Korea Acute Myocardial Infarction Registry—National Institute of Health
Efficacy and safety comparison between
ticagrelor
and
clopidogrel
in AMI patients without increased bleeding risk among East Asian patients.
Result
:
No difference in the composite of cardiac death, MI, stroke, or target vessel revascularization at 6 months (
tica
vs
clopid
: 4.2% vs 4.9%; p=0.499)
Higher TIMI major bleeding in
ticagrelor
arm (2.6% vs 1.2%; p=0.008)In hospital mortality was higher in patients with major bleeding (11.3% vs 0.9%; p<0.001)
Conclusions
: Our study shows that ticagrelor did not reduce ischemic events
yet, however, was associated with increased risk of bleeding complications compared with clopidogrel. Further large-scale, long-term, randomized trials should be required to assess the outcomes of ticagrelor for East Asian patients with AMIPark KH,
Jeong
MH,
Ahn
Y, et
al.International
Journal of Cardiology.2016;215:193-200.
Slide34Safety and Effectiveness of Contemporary P2Y12 Inhibitors in an East Asian Population With Acute Coronary Syndrome: A Nationwide Population-Based Cohort Study’
An observational cohort study comparing safety and efficacy of P2Y12inh in 70,715 patients with ACS (mostly undergoing PCI). Median follow-up : 18.0
mo
Safety endpoint
Yun JE, Kim YJ, Park
JJ,et
al.J
Am Heart Assoc.2019;8:e012078.
Slide35Efficacy endpoint
“Compared with clopidogrel, ticagrelor was associated with an increased risk of bleeding but a decreased risk of mortality in East Asian patients.”
Safety and Effectiveness of Contemporary P2Y12 Inhibitors in an East Asian Population With Acute Coronary Syndrome: A Nationwide Population-Based Cohort Study’
An observational cohort study comparing safety and efficacy of P2Y12inh in 70,715 patients with ACS (mostly undergoing PCI). Median follow-up : 18.0
mo
Yun JE, Kim YJ, Park
JJ,et
al.J
Am Heart Assoc.2019;8:e012078.
Slide36TICAKOREA
Number of sample: 800 Korean patients with ACS (STEMI and N-STEMI)
Method: multicenter, open-label, randomized, controlled trial
Drug: 1:1 ratio
ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) OR clopidogrel (600 mg loading dose, 75 mg daily thereafter).
Primary End Point: clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months.
Result:
At 12 months, the incidence of clinically
significant bleeding Ticagrelor 11.7% vs Clopidogrel 5.3%
(p=0.002; higher in the ticagrelor).
The incidence of death from cardiovascular causes, myocardial infarction, or stroke was
not significantly different (Ticagrelor 9.2% vs Clopidogrel 5.8%, p=0.07)
Park DW, et al. Circulation.
2019;140:00–00
Slide37Ticagrelor cause higher
bleeding
compared to Clopidogrel in Asian
Park DW, et al. Circulation.
2019;140:00–00
TICAKOREA Result
Slide38No difference of MACE between Ticagrelor and Clopidogrel in Asian
Park DW, et al. Circulation.
2019;140:00–00
TICAKOREA Result
Slide39Lower
bleeding criteria with
Clopidogrel
Park DW, et al. Circulation.
2019;140:00–00
TICAKOREA Result
Slide40Park DW, et al. Circulation.
2019;140:00–00
Slide41Loading Dose Clopidogrel in PCI Patients
Slide42CURRENT OASIS 7:
A 2X2 Factorial Randomized Trial of Optimal Clopidogrel and Aspirin Dosing in Patients with ACS Undergoing an Early Invasive Strategy with Intent For PCI
Clopidogrel
Clopidogrel 300 mg followed by 75 mg daily reduces major CV events across the spectrum of ACS and PCI
Recent data suggest that
doubling
the loading and maintenance doses of clopidogrel results in a higher and more rapid antiplatelet effect
Aspirin
Dose of ASA varies between Europe and North America
No large-scale RCT’s have compared high (300-325 mg) versus low (75-100) dose aspirin in patients with ACS undergoing PCI
Mehta SR, et al. Lancet 2010; 376: 1233–43
Slide43Relative Risk Reduction
PCI
No PCI
CURE: Clopidogrel 300/75 mg v Placebo (CVD/MI)
30%
1
19
%
2
STEMI: Clopidogrel 300/75 mg v Placebo (CVD/MI)
46%
3
9%
4
TRITON: Prasugrel v clopidogrel 300/75mg (CVD/MI/Stroke)
19%
5
Not evaluated
Benefits of Antiplatelet Therapy in ACS are Greater in Patients Undergoing PCI
1. Mehta SR, et al. Lancet 2001; 358(9281):527-33.
2. Fox KAA, et al. Circulation 2004;110:1202-8
3.
Sabatine
MS, et al. JAMA 2005; 294(10):1224-32.
4. Chen ZM Lancet 2005;366:1607-21
4. Boersma E et al. Lancet 2002; 359:189
5.
Wiviott
S et al. N
Engl
J Med 2007; 357: 2001–15.
Slide44Study Design, Flow and Compliance
25,086 ACS Patients
(UA/NSTEMI 70.8%, STEMI 29.2%)
Planned Early (<24 h) Invasive Management with
intended PCI
Ischemic ECG
Δ
(80.8%)
or ↑cardiac biomarker (42%)
PCI 17,232
(70%)
Angio 24,769
(99%)
No PCI 7,855 (30%)
No Sig. CAD 3,616
CABG 1,809
CAD 2,430
Randomized to receive (2 X 2 factorial):
CLOPIDOGREL:
Double-dose
(600 mg then150 mg/d x 7d then 75 mg/d)
vs
Standard dose
(300 mg then 75 mg/d)
ASA:
High Dose
(300-325 mg/d)
vs
Low dose
(75-100 mg/d)
Efficacy Outcomes:
CV Death, MI or stroke at day 30
Stent Thrombosis at day 30
Safety Outcomes:
Bleeding (CURRENT defined Major/Severe and TIMI Major)
Key Subgroup:
PCI v No PCI
Clop in 1st 7d (median) 7d 7 d 2 d 7d
Complete Follow up 99.8%
Compliance:
Mehta SR, et al. Lancet 2010; 376: 1233–43
Slide45Kaplan-Meier curves for the primary outcome of CV death, MCI, or stroke, for the clopidogrel dose comparison
This benefit was mainly attributable to a lower rate of myocardial infarction; rates of cardiovascular death and stroke in the two groups were similar
Mehta SR, et al. Lancet 2010; 376: 1233–43
Slide46Kaplan-Meier curves for clopidogrel dose comparison for definite stent thrombosis in patients receiving a drug-eluting stent
The rate of definite or probable stent thrombosis was 31% lower and that of definite (angiographically confirmed) stent thrombosis was 46% lower with the double-dose than with the standard-dose clopidogrel regimen.
Mehta SR, et al. Lancet 2010; 376: 1233–43
Slide47Clopidogrel Dose Comparison
Compared with the standard dose, double-dose clopidogrel reduced the rate of the primary outcome (330 events [3·9%]
vs
392 events [4·5%]; adjusted hazard ratio 0·86, 95% CI 0·74–0·99, p=0·039) and definite stent thrombosis (58 [0·7%]
vs
111 [1·3%]; 0·54 [0·39–0·74], p=0·0001).
High-dose and low-dose aspirin did not differ for the primary outcome (356 [4·1%] vs 366 [4·2%]; 0·98, 0·84–1·13, p=0·76).
Major bleeding was more common with double-dose than with standard-dose clopidogrel (139 [1·6%] vs 99 [1·1%]; 1·41, 1·09–1·83, p=0·009)
Mehta SR, et al. Lancet 2010; 376: 1233–43
Slide48CASE ILLUSTRATION
A 79
y.o
. Hypertensive Javanese female , presented to the E.R. with a chief complain of recurrent chest pain which was previously attributed as another dyspepsia since she had a
history of peptic ulcer disease
She had no routine medication except for occasional use of
meloxicam
for her backache
Physical examination
BP 180 / 90 mmHg, otherwise unremarkable
As she presented in Non-PCI capable Hospital, prompt Thrombolytic was prepared
The fellow nurse asked:
“What regiment of loading antiplatelets would you advise to be given in this patient?”
Slide49CASE ILLUSTRATION
Antiplatelet loading rationale:
Loading dose of Aspirin
mandatory
Loading dose of P2Y12i
Potent
P2Y12i or Clopidogrel?
Lets consider the Potential Bleeding risk and Ischemic Risk :
Old age (>75y.o.)
Female
Poorly Controlled Hypertension
Chronic use of NSAID
Treated with Thrombolytic
High bleeding risk profile!
Clopidogrel has been proven effective in Thrombolytic settings
Potent P2Y12i
has not been studied
as an
Adjunct to Thrombolytic
(ESC STEMI, 2017)
No clear benefit over ischemic risk
An addition of clopidogrel 300mg LD is suitable for this patient
Slide50CASE ILLUSTRATION
A 68
y.o
. Male, presented to the E.R. with a prolonged chest pain since 2 hours prior to admission
History DVT a year ago
with routine medication of Rivaroxaban
Vital signs BP 130/70mmHg, HR 98 bpm, O2 Sat 98% on Room air, other physical findings unremarkable
Bedside Echocardiography no clinical signs of PE, RWMA (+)
Cardiac marker came back positive which prompt for Cath-lab Activation.
He was treated with 1 DES implantation in mid LAD.
What is the best antithrombotic treatment for this patient?
Slide51CASE ILLUSTRATION
Our Considerations :
Anticoagulant use
Raise the Bleeding risk
PCI treated ACS Risk of early stent thrombosis if no effective antithrombotic management
“Practically, in NVAF patient with chronic anticoagulant use who underwent PCI, the recommended P2Y12i is clopidogrel as a combination therapy with NOAC (As part of triple antithrombotic or dual antithrombotic)”
Slide52THANK YOU