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DAPT should be prolonged in patients with acute coronary syndrome ?
João Morais
Head of Cardiology Division
Leiria Hospital Centre
Chairman WG Thrombosis
João Morais Honoraria received from Astra Zeneca and Merck Sharp & Dhome Consulting activities and invited speaker National and international levels
Disclosures related with the current topic
DAPT
Antithrombin
Aspirin +
ticagrelor or prasugrel
UFH or LMWH/fondaparinux or bivalirudin
+
In hospital 12 months DAPT, dual antiplatelet therapy; LMWH, low molecular weight heparin; UFH, unfractionated heparin
Antithrombotic environment in patients with ACS
∕∕
P2Y12inhib
???? ????
Clopidogrel
Patient oriented strategy
Stent oriented strategy
DAPT post ACS Rationale for 12 months of treatment duration
Total death / AMI at 12 months Event rate
Revascularization (+) 5.2% Revascularization (-) 9.0%
Cu
mu
lati
ve s
urv
ival
(%
)
Revasc (+)
Revasc (-) Discharge
Morais J et al Unpublished data
Single centre (n=965)
0 3 6 9 12
CURE PLATO
TRITON
DAPT post ACS Rationale for 12 months of treatment duration
?
? ? ? ? ? ?
Stent oriented strategy
Time duration can be shorten ?
Capodanno D, Circulation. 2013;128:2785-2798
DAPT post stent implantation
Death Myocardial Infarction Stent Thrombosis Cerebrovascular Accident TIMI Major Bleeding
Odds Ration M-H Random 95% CI 1.15 |0.85, 1.54] 0.95 [0.66, 1.36] 0.88 [0.43, 1.81] 1.51 [0.92, 2.47] 2.64 [1.31, 5.30]
Extended Better Control Better
Clinical Impact of Extended DAPT after PCI A metanalysis of Randomized trials (n=8231)
N Engl J Med 2010;362:1374–1382 Circulation 2012;125:2015–2026 Circulation 2012;125:505–513. J Am Coll Cardiol. 2012 Oct 9;60(15):1340-8.
Cassese et al Eur Heart Journal 2012; 33: 3078-3087
DAPT post stent implantation Stent thrombosis – new generation of stents
Drug eluted stents 1st vs 2nd generation
Giustino G, et al. J Am Coll Cardiol 2015;65:1298–310
Patient oriented strategy
Outcomes in patients with atherosclerosis
0,6%
3,8%
8,9%
0,6%
3,3% 2,8%
7,8%
2,6%
7,2%
2,6%
7,2%
2,3%
Morte EAM Revasc. AVCAll death AMI Revasc Stroke
João Morais, 2016 to be published
Single centre N=965 12 months f-up
Global event rate 14,1%
Unstable angina
STEMI
NSTEMI
4,5% 2,9% 7,7% 2,1%
Outcomes in post ACS patients
PROSPECT: MACE M
AC
E (%
)
Time in Years 0 1 2 3
All Culprit lesion (CL) related Non culprit lesion (NCL) related Indeterminate
0
5
10
15
20
25
Number at risk
ALL 697 557 506 480
CL related 697 590 543 518
NCL related 697 595 553 521
Indeterminate 697 634 604 583
12.9%
20.4%
11.6%
2.7%
13.2%
7.9%
6.4%
0.9%
18.1%
11.4%
9.4%
1.9%
Extended DAPT
HR (95% CI) ≤ 1 Year:
0.99 (0.84, 1.16)
HR (95% CI) > 1 Year:
0.72 (0.54, 0.97)
Primary Efficacy Endpoint to 30 Months (Age < 75 years)
HR (95% CI):
0.91 (0.79, 1.05)
P = 0.21
Interaction P = 0.07
Prasugrel vs. Clopidogrel for Acute
Coronary Syndromes Patients Managed
without Revascularization
the TRILOGY ACS trial
Background – 1° Efficacy Evaluation Overall Population
CV Death, MI, or Stroke
9.3%
10.5%
Hazard Ratio 0.87
p < 0.001
N = 26449
Mean f/u: 2.5 years Placebo
Vorapaxar
GUSTO Mod/Sev at 3 yrs
4.2 v. 2.5%, HR 1.66, p<0.001
Morrow et al. N Engl J Med 2012
ClinicalTrials.gov NCT00526474c
0%
2%
4%
6%
8%
10%
12%
0 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080
Ev
en
t R
ate
(%
)
Days since randomization
Extended DAPT Udell’s meta-analysis
European Heart Journal doi:10.1093/eurheartj/ehv443
?
Final remarks - I
Appropriate patient selection is the key to handle the delicate balance between preventing thrombosis and
provoking bleeding
Patients with an established history of ACS and / or stent implantation may benefit of DAPT
prolongation. The exact time duration is unknown
Patient oriented approach should be preferred over a more simplistic way focusing only on the stent
Final remarks - II
Individual characteristics Thrombotic risk
Bleeding risk Associated co-factors
DAPT score
Stent characteristics Type of stent
(nr, length, location, diameter, overlap, dissection)
Coronary anatomy
Individualized therapy should be based on
Many thanks
João Morais
Head of Cardiology Division
Leiria Hospital Centre
Chairman WG Thrombosis
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