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Randomisation
Visit 2 Visit 3 Visit 4 Visit 5 Visit 6
*STEMI patients scheduled for primary PCI were randomised; however, they may not have received PCI.
Initial Treatment approaches †A loading dose of 300-mg clopidogrel was permitted in patients not previously treated with clopidogrel,
• Medically managed (n=5,216 — 28.0%) with an additional 300 mg allowed at the discretion of the investigator.
• Invasively managed (n=13,408 — 72.0%) ‡The PLATO study expanded the definition of major bleeding to be more inclusive compared with
previous studies in ACS patients. The primary safety endpoint was the first occurrence of any major
bleeding event.
12 11.7 Clopidogrel
11
Cumulative Incidence of
10 9.8 Ticagrelor
9 Clopidogrel
Stroke) %
8 5.4 at 12 months
7
6 at 1 month ARR=1.9% 54 NNT
5 ARR=0.6% RRR=16% ( primary composite
4 4.8 RRR=12% endpoint)
3 Ticagrelor
2 HR: 0.84 (95% CI, 0.77–0.92); P<0.001
1 HR: 0.88 (95% CI, 0.77−1.00); P=0.045
0
0 2 4 6 8 10 12
No. at risk Months After Randomization
Ticagrelor 9,333 8,628 8,460 8,219 6,743 5,161 4,147
Clopidogrel 9,291 8,521 8,362 8,124 6,650 5,096 4,047
10
Net Clinical Benefit was greater for ticagrelor compared with
clopidogrel and The greatest relative difference was observed after
30 days
PLATO Study: Net clinical benefit*1
Exploratory post hoc analysis using primary efficacy and safety endpoints (31 days –12 months)
14
Ticagrelor
12
Clopidogrel
Net Clinical Benefit (%)
p = 0.026
10
8 8,97
7,86
6
-
*Net clinical benefit was defined as the composite of CV death, MI, stroke and major bleeding (CABG or non-CABG related)1
†Net clinical benefit favoured ticagrelor both within the initial 30 days of treatment and after1
Diabetes
Endothelial dysfunction
NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PAI-1, plasminogen activator inhibitor-1; PKC, Jung JH et al. Diabetes Metab J. 2015;39:95-113
protein kinase C; RAGE, receptor for advanced glycation endproducts; VSMC, vascular smooth muscle cell
Diabetes among ACS in China Type 2 Diabetes and CV Disease
Zhou et al. Cardiovasc Diabetol (2018) 17:147 Cosentino F et al. European Heart Journal (2019) 00, 169
Ticagrelor, when compared with clopidogrel,
reduced ischaemic events in ACS patients
irrespective of diabetic status and glycaemic control,
without an increase in major bleeding events
East Asian Paradox
Curr Cardiol Rep 2014 May;16(5):485 Y. Huo et al. / Science Bulletin 64 (2019) 166–179
The effects of ticagrelor versus clopidogrel were not significantly different between Asians and non-Asians
with respect to the primary efficacy outcome
(hazard ratio for Asians vs non-Asians, 0.84 [95% CI 0.61-1.17] vs 0.85 [95% CI 0.77-0.93], P = .974)
Am Heart J 2015;169:899-905.e1
Outline
Antiplatelets in ACS
• The Need
• Choosing
• Sweet Spot
• Certain Populations : Diabetes & Asian
STEMI
• Guidelines ( PPCI, Fibrinolytic, Conservative)
• Evidence
• Switching
NSTE-ACS
• Guidelines (Risk Stratification, Ischemic Driven )
• Evidence
Take Home Messages
• Summary
• Future
ACS Spectrum
Ticagrelor Vs Clopidogrel in STEMI Intended for PPCI : PLATO Trial Subgroup Analysis
PPK PERKI SKA 2019
Fibrinolytic
Switch ±
Berwanger O et al. JAMA Cardiol 2018 doi:10.1001/jamacardio.2018.0612 European Heart Journal (2017) 00, 1–66
Explore safety of ticagrelor vs
clopidogrel after thrombolytic therapy
The TREAT study:
Multinational,*open-label, randomized, Phase III trial to assess safety and efficacy of ticagrelor vs
clopidogrel in patients aged 18–75 years, diagnosed with STEMI ≤24 hours prior to randomization, with
documented cardiac ischaemic symptoms due to atherosclerosis >10 minutes duration at rest and treated
with pharmacological thrombolysis† (N=~3794)1
2.5 Clopid
Ticagrelor ogrel P value
Cumulative incidence of primary outcome,
Difference
Endpoint (N=1913) (N=188 for non-
2 (95% CI)
n (%) 6) inferiority
TIMI major bleeding (KM%)
Ticagrelor
Clopidogrel
n (%)
1.5
TIMI major
1 0.04%
bleeding 13
14 (0.73%) (-0.49 to <0.001
(primary (0.69%)
0.58%)
0.5 endpoint)
1. Berwanger O et al. JAMA Cardiol 2018 doi:10.1001/jamacardio.2018.0612; 2. Berwanger O et al. JAMA Cardiol 2018 doi:10.1001/jamacardio.2018.0612
Supplementary Appendix
Among patients age <75 years with STEMI,
administration of ticagrelor after fibrinolytic therapy
did not significantly reduce the frequency of
cardiovascular events when compared with clopidogrel
ESC 2017 Focused Update DAPT in CAD :
Algorithm for switching between oral P2Y12 inhibitors
in ACUTE setting 1
Class I LOE B
Class Iib LOE C
32
Both NSTEMI and STEMI patients are at high risk of recurrent CV events, NSTEMI
is associated with greater long-term risk than STEMI
33
Ruff CT, Braunwald E. Nature Review Cardiology.2011;8: 140-147 European Heart Journal (2020) 00, 179
34
35
European Heart Journal (2016) 37, 267–315
36
European Heart Journal (2020) 00, 179
In specific clinical scenarios, DAPT duration can
be shortened (<12 months), extended (>12 months), or modified
37
European Heart Journal (2020) 00, 179
European Heart Journal (2020) 00, 179
[10.0 vs. 12.3%; hazard ratio (HR) 0.83; 95% 13.4 vs. 12.6%; HR1.07;95%CI ¼ 0.95–1.19 3.4 vs. 12.6%; HR 1.07;95%CI ¼ 0.95–1.19
confidence interval (CI) ( 0.74–0.93]
European Heart Journal (2020) 00, 179 Reference: Valgimigli M et al. European Heart Journal (2017) 0, 1–48
European Heart Journal (2020) 00, 179
European Heart Journal (2020) 00, 179
Outline
Antiplatelets in ACS
• The Need
• Choosing
• Sweet Spot
• Certain Populations : Diabetes & Asian
STEMI
• Guidelines ( PPCI, Fibrinolytic, Conservative)
• Evidence
• Switching
NSTE-ACS
• Guidelines (Risk Stratification, Ischemic Driven )
• Evidence
Take Home Messages
• Summary
• Future
STEMI
Take Home Messagess
• There is no such one DAPT combination fits all
• The efficacy to prevent CV Events and The safety from bleeding
should always be balanced, both eventually contributes to mortality
• ACS and Diabetes are two clinical entities that represents high
thrombotic burdens, nevertheless they carry substantial risk of
bleeding
• Guideline directed decision making, based on reliable trials, should
always be kept in mind