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Morais J et al Unpublished data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