Verlängerte antithrombozytäre Therapie nach ACS: …...Falk et al. Circulation, 1995 Patients with MI (n) 0 Ambrose 1988 10 20 30 40 50 60 70 80 90 100 0 40 80 120 160 200 Little

Verlängerte antithrombozytäre Therapie nach ACS: welcher Patient profitiert?

Meinrad GawazInnere Medizin III, Kardiologie und Kreislauferkrankungen

Eberhard Karls Universität Tübingen

7. Thromboseforum, Stuttgart 2017

Koronare Herzerkrankung(stabile KHK, PCI, ACS)

Vorhofflimmern(Kunstklappen, TVT, LE)

Antithrombotische Therapie

Indikationen in der Herzmedizin

Akutes Koronarsyndrom (NSTEMI/ STEMI)

Plaque Ruptur und Thrombose

Davies, 2001

Koronare Thrombose –

Akutes Koronarsyndrom und Stentthrombose

Stentthrombose

GPIb

GPIbGPVI

GPIb GPVIGPIIb/IIIa

TxA2 ADP

FXa Thrombin Fibrin

Orale Antithrombotische Therapie

Antikoagulation Antithrombozytäre Therapie

2008

Vitamin K-Antagonisten

(Marcumar®)

2017

Acetylsalicylsäure (Aspirin®)

Clopidogrel (Plavix®, (Iscover®)

Rivaroxaban (Xarelto®)

Dabigatran (Pradaxa®)

Apixaban (Eliquis®)

Edoxaban (Lixiana®)

Prasugrel (Efient®)

Ticagrelor (Brillique®)

Vorapaxar (Zontivity®)

ESC Guideline NSTE-ACS

Roffi M, ESC Guidelines

Roffi M et al., Eur Heart J, August 2015, doi:10.1093/eurheartj/ehv320,

http://eurheartj.oxfordjournals.org/content/ehj/33/20/2569.full.pdf

Recommendations for platelet inhibition

Oral antiplatelet therapy Class Level

A P2Y12 inhibitor is recommended, in addition to aspirin, for 12 months unless there are

contraindications such as excessive risk of bleeds.I A

• Ticagrelor (180 mg loading dose, 90 mg twice daily) is recommended, in the absence of

contraindications,e for all patients at moderate-to-high risk of ischemic events (e.g. elevated cardiac

troponins), regardless of initial treatment strategy and including those pretreated with clopidogrel (which

should be discontinued when ticagrelor is started).

I B

• Prasugrel (60 mg loading dose, 10 mg daily dose) is recommended in patients who are proceeding to

PCI if no contraindication.eI B

• Clopidogrel (600 mg loading dose, 75 mg daily dose) is recommended for patients who cannot receive

ticagrelor or prasugrel or who require oral anticoagulation.I B

P2Y12 inhibitor administration for a shorter duration of 3–6 months after DES implantation may be

considered in patients deemed at high bleeding riskIIb A

It is not recommended to administer prasugrel in patients in whom coronary anatomy is not known. III B

Long-term P2Y12 inhibition

P2Y12 inhibitor administration in addition to aspirin beyond 1 year may be considered after careful

assessment of the ischemic and bleeding risks of the patient.IIb A


Krumholz et a. JAMA 2009

„short term risk“ - Myokardinfarkt

30-Tage Mortalität

(n=2.7 Mio)

Puymirat et a. JAMA 2012

French Registry FAST-MI (n=6707, 1995-2010)

„short term risk“ - STEMI

Nauta et al. PlosOne 2011

Netherlands (n>6820, 1985-2008)

„long term risk“ - STEMI

„short term“ „long term“

approx. 1 of 8 will die after STEMI

Mortality Survival

Nauta et al. PlosOne 2011

Netherlands (n>7614, 1985-2008)

„long term risk“ – N-STEMI

approx. 1 of 8 will die after N-STEMI

„short term“ „long term“

Mortality Survival

Duale Antithrombozytäre Therapie

• 12 Monate bei NSTEMI/STEMI

• bei allen?

Stentthrombose

Komplikationen nach PCI

Komplikationen der Koronaren Herzerkrankung/Atherosklerose

Frühes und spätes ischämisches Risiko und Blutungsrisiko

Risikoadjustierte DAPT

Duale Antiplättchen Therapie (DAPT)

Tod und Myokardinfarkt

„fibrous cap“-Atherom („Fibröse Kappe“)

„Plaque rupture healing“

StenoseInsuli W, Am J Med 2009

Plaque characteristics:

• thin, fibrous cap (<65µm)

• large, lipid rich pool

• increased macrophage activity

• T-cells, old hemorrhage, calcium

H.C. Stary, 1993MacNeill et al.; ATVB 2003

Predisposing cellular mechanisms:

• reduced collagen synthesis

• overexpression of collagenase

• smooth muscle cell apoptosis

• inflammatory cytokines

Contributing factors: local shear stress, systemic inflammation (CRP )

Vulnerable Plaque

„Trigger Event“

Angiographic & angioscopic images in a 58-year-old man

with anterior MI[Asakura 2001]

.

Asakura M et al. J Am Coll Cardiol 2001

Multiple vulnerable Plaques bei Patienten mitAkutem Koronarsyndrom

Falk et al. Circulation, 1995

Patients

with MI (n)

0Ambrose

1988

10

20

30

40

50

60

70

80

90

100

0

40

80

120

160

200

Little

1988Nobuyoshi

1991TotalGiroud

1992

>70% hochgradig

50%-70% mittelgradig

<50% leicht

68%

18%

Stenosegrad der vulnerablen Plaquebei Myokardinfarkt

14%

Insuli W, Am J Med 2009

Koronare “Plaquelast” in Abhängigkeit des kardiovaskulären Risikoprofils und des Alters

Hohes CV-Risiko Niedriges CV-Risiko

Alter Alter

Ndrepepa et al., Am Heart J 2016

Association of Progression or Regression of Coronary Artery Atherosclerosis

with Long-term Prognosis

Gjin Ndrepepa MD, Raisuke Iijima MD, Sebastian Kufner MD, Sieg-

mund Braun MD, Salvatore Cassese MD, Robert A. Byrne MD, Jonas Sorges,

Stefanie Schulz-Schupke MD, Petra Hoppmann MD, Massimiliano Fussaro

MD, Karl-Ludwig Laugwitz MD, Heribert Schunkert MD, Adnan Kastrati MD

PII: S0002-8703(16)30020-5

DOI: doi: 10.1016/j.ahj.2016.03.016

Reference: YMHJ 5157

To appear in: American Heart Journal

Received date: 30 October 2015

Accepted date: 29 March 2016

Please cite this art icle as: Ndrepepa Gjin, I ij ima Raisuke, Kufner Sebast ian, Braun Sieg-

mund, CasseseSalvatore, ByrneRobert A., SorgesJonas, Schulz-SchupkeStefanie, Hopp-

mann Petra, Fussaro Massimiliano, Laugwitz Karl-Ludwig, Schunkert Heribert , Kastrat i

Adnan, Associat ion of Progression or Regression of Coronary Artery Atherosclerosiswith

Long-term Prognosis, American Heart Journal (2016), doi: 10.1016/ j.ahj.2016.03.016

This is a PDF file of an unedited manuscript that has been accepted for publicat ion.

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Progression der Koronaren Herzerkrankung undMortalität

Stent-Thrombose

Restenose

Progression

der KHK

Koronare Determinanten des Langzeitrisikos nach Myokardinfarkt

Anhaltender „Entzündungsprozess“

.....................................................................................................................................................................................

.....................................................................................................................................................................................

CLIN ICAL RESEARCHVascular medicine

Long-term prognosis of pat ients with peripheral

arter ial disease with or without polyvascular

atherosclerot ic disease

Jan-Peter van Kuijk1, W illem-Jan Flu2, Gijs M.J.M. W elten1, Sanne E. Hoeks2,

Michel Chonchol 3, Radosav Vidakovic1, Hence J.M. Verhagen1, Jeroen J. Bax4,

and Don Poldermans1*

1Department of Vascular Surgery, Erasmus Medical Center, ‘s Gravendijkwal 230, Room H-805, Rotterdam 3015 CE, The Netherlands; 2Department of Anesthesiology, Erasmus

Medical Center, Rotterdam, The Netherlands; 3Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, CO, USA; and 4Department

of Cardiology, Leiden University Medical Center, Leiden, The Netherlands

Received 11 August 2009; revised 9 October 2009; accepted 3 November 2009; online publish-ahead-of-print 27 December 2009

A im s Patients with peripheral atherosclerotic disease often have multiple affected vascular beds (AVB), however, data on

long-term follow-up and medical therapy are scarce. We assessed the prevalence and prognostic implicationsof poly-

vascular disease on long-term outcome in symptomatic peripheral arterial disease (PAD) patients.

Met hods

and r esult s

Two thousand nine hundred and thirty-three consecutive patients were screened prior to surgery for concomitant

documented cerebrovascular disease and coronary artery disease. The number of AVB was determined. Cardiovas-

cular medication as recommended by guidelines wasnoted at discharge. Single, two, and three AVBwere detected in

1369 (46%), 1249 (43%), and 315 (11%) patients, respectively. During a median follow-up of 6 years, 1398 (48%)

patients died, of which 54% secondary to cardiovascular cause. After adjustment for baseline cardiac risk factors

and discharge-medication, the presence of 2-AVB or 3-AVB was associated with all-cause mortality (HR 1.3 95%

CI 1.2–1.5; HR 1.8 95% CI 1.5–2.2) and cardiovascular mortality (HR 1.5 95% CI 1.2–1.7; HR 2.0 95% CI 1.6–

2.5) during long-term follow-up, respectively. Patients with 2- and 3-AVB received extended medical treatment com-

pared with 1-AVB at the time of discharge.

Conclusion Polyvascular atherosclerotic disease in PAD patients is independently associated with an increased risk for all-cause

and cardiovascular mortality during long-term follow-up.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywor ds Peripheral arterial disease † Atherosclerosis † Polyvascular disease † Long-term † Prognosis

Int roduct ion

Peripheral arterial disease (PAD) is a multifactorial syndrome that

most commonly affects people over 60 years of age.1 As popu-

lation age increases, the prevalence of atherosclerotic disease

and its associated adverse outcomes will increase. Cardiovascular

risk profiles have been established in several large studies,

showing an equal risk factor distribution among all populations

and across age groups and gender.2,3 It has to be noted that the

process of established atherothrombosis is not limited to a single

arterial location. The Reduction of Atherothrombosis for

Continued Health (REACH) registry showed that one of six

patients with PAD, cerebrovascular disease (CVD), or coronary

artery disease (CAD) had involvement of one or two other arterial

beds.1,4 The REACH registry also demonstrated a substantial gap

between recommended clinical guidelines and actual clinical prac-

tices in the care of patients with or at risk for atherothrombosis.

A pattern of underutilization of established medical therapies and

lifestyle interventions was shown throughout all geographic

regions studies and vascular disease subtypes.1 Consequently,

patients with PAD have a three- to six-fold increased risk for the

occurrence of cardiovascular mortality compared with patients

* Corresponding author. Tel: þ 31 10 703 4613, Fax: þ 31 10 703 4957, Email: [email protected]

Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2009. For permissions please email: journals.per [email protected].

European Heart Journal (2010) 31, 992–999

doi:10.1093/eurheartj/ehp553

by

gu

est on

April 2

7, 2

01

6h

ttp://e

urh

eartj.o

xfo

rdjo

urn

als.org

/D

ow

nlo

ad

ed fro

m

Van Kuijik et al., Eur H J 2010

N= 2933

Kaplan–Meier estimates for long-term all-cause mortality, stratified

according to the number of affected vascular beds.

Nakatani et al. Circ J 2013; 77:439-446

Trip et al. New Engl J Med 1990

Hohe individuelle Variabilität nach PCI

Geisler, Gawaz et al.; Heart 2008

9060300days

cum

ula

tive h

azard

for

event-

free s

urv

ival

1.00

0.95

0.90

0.85

0.80

0.75

0

P<0.001

n=341

n=22

HR: 3.7

Geisler T. & Gawaz M. Eur Heart J 2006

clopidogrel

responder

clopidogrel

low-responder

(RPA ≥ 70%)

Low response to Clopidogrel measured by residual platelet

aggregation is associated with clinical prognosis

(MI,C

V-d

eath

, S

tro

ke)

Thromb & Hemostasis 2015

N=739

Droppa, Geisler et al., PlosOne 2015

Reny et al., TH 2016

Beurteilung des

Langzeitrisikos nach ACS?

Zeit

ACS Initialereignis

Akute Phase Langzeit Phase

Unterschiedliche Schwerpunkte antithrombozytärer Therapien im zeitlichen

Verlauf

Effektive Hemmung der

Plättchenaggregation Inhibition der

Thrombozyten

abhängigen

Inflammation

Niedrig dosierte Thrombin

Inhibition

Reduktion von

Blutungen

Geisler T, Eur Heart J.

2010;31(1):59-66.

Reduktion von nicht

stentbezogenen Ereignissen

Schulz, Kastrati, Rev Esp Cardiol.

2015;68(10):827–829

REACH Registry 1

1 Bhatt et al. JAMA 2010; 304 (12):1350-1357

Erhöhtes Risiko vs. Allgemeinbevölkerung (%)

Erstereignis Myokardinfarkt Schlaganfall

Myokardinfarkt

Schlaganfall

pAVK

5–7 x größeres Risiko

(einschließlich Tod)1


(einschließlich TIA)2


(einschließlich Angina und

plötzlicher Tod*)2

9 x größeres Risiko

4 x größeres Risiko

(einschl. tödl. MI und anderer

KHK-Tod †)3


(einschließlich TIA)4

Einfluss der Atherothrombose auf weitere kardiovaskuläre Ereignisse

* innerhalb einer Stunde dokumentierter, auf eine KHK zurückzuführender Tod; † ausschließlich nicht-tödlicher MI

TIA: Transitorische ischämische Attacke; MI: Myokardinfarkt; KHK: koronare Herzkrankheit

1. Adult Treatment Panel II. Circulation 1994; 89: 1333–1363; 2. Kannel WB. J Cardiovasc Risk 1994; 1: 333–339; 3. Criqui MH et al. N Engl J Med 1992; 326: 381–

386; 4. Wilterdink JI et al. Arch Neurol 1992; 49: 857–863

Patienten mit einer atherothrombotischen Erkrankung in einem Gefäßbett haben ein erhöhtes

Risiko für kardiovaskuläre Folgeereignisse, die jedoch auch andere Gefäßbetten betreffen

können.

Chronische NI erhöht kardiovaskuläres Risiko

*Grad 3; **keine CKD*, Z.n. MI vs. CKD*, kein MI

CKD: Chronic Kidney Disease; ARIC: Atherosclerosis Risk In Communities; eGFR: geschätzte glomeruläre Filtrationsrate;

MI: Myokardinfarkt; ACS: Akutes Koronarsyndrom

Mod. nach Wattanakit K et al. J Am Coll Cardiol 2008;48(6):1183-1189

Eine chronische Niereninsuffizienz alleine erhöht das ACS-Risiko im Gegensatz zum Z.n.

Myokardinfarkt kaum. Tritt die CKD allerdings als Komorbidität zum Z.n. Myokardinfarkt auf,

steigt das Risiko für weitere akute Koronarereignisse erheblich.

• Daten von über 12.000

Nicht-Diabetikern der ARIC-

Studie

• Kategorisierung der

Teilnehmer nach

Nierenfunktion

(eGFR ≥ 60 ml/min vs.

30-59 ml/min)

Z.n. Myokardinfarkt

(Ja oder Nein)

• Follow-Up: 10 Jahre

Persistierende Gerinnungsaktivierung / gesteigerte Thrombin Generierung in der

Langzeitphase nach ACS

Ardissino D, Blood 2003

Was sagen die Leitlinien zur verlängerten

Thrombozytenfunktionshemmung nach ACS?













I B












Tri

log

yD

AP

T

PE

GA

SU

S

TR

A 2

P

Yeh et al,JACC 2015 Bhatt DL et al, JACC 2007

Wiviott SR et al, Lancet 2013 Scirica B et al, Lancet 2013

Hinweise aus RCTs für eine Vorteil einer prolongierten antithrombotischen TX

bei ausgewählten Patienten nach ACS

AT

LA

S-T

IMI

51

CH

AR

ISM

A

Bonaca MP et al, NEJM 2015

Mega JL, NEJM 2012

38

38

Mauri, Kereiakes et al. AHJ. 2010;160(6): 1035-41.

38

DAPT Study - Design

Thienopyridine+Aspirin12-Month

Observa onalPeriod:Open-Label

Thienopyridine+AspirinRequired Placebo+Aspirin

3-MonthObserva onalPeriod:Off

Thienopyridine,OnAspirin

Randomiza onStudyDrug

TreatmentEnds

0(mos) 12 30 33

PrimaryAnalysisPeriod

Results – MACCE

DAPT– Subanalysis for history of MI

Cu

mu

lati

ve

in

cid

en

ce

of

MA

CC

E

Patients presenting without myocardial infarction

Thienopyridine

Placebo

Thienopyridine vs. placebo, 4.4% vs. 5.3%;

HR 0.83, p=0.08

0 3 6 9 12 15 18

8%

6%

4%

2%

0%

Months after randomization

Thienopyridine

Placebo

4050

4008

4020

3982

3951

3893

3900

3830

3851

3772

3786

3705

3718

3660

Patients presenting with myocardial infarction Thienopyridine vs. placebo, 3.9% vs. 6.8%;

HR 0.56, p<0.001Thienopyridine

Placebo

Months after randomizationCu

mu

lati

ve

in

cid

en

ce

of

MA

CC

E

Thienopyridine

Placebo

1802

1766

0 3 6 9 12 15 18

8%

6%

4%

2%

0%

1791

1749

1761

1706

1737

1676

1704

1632

1676

1592

1649

1553

Yeh R, J Am Coll Cardiol. 2015;65(20):2211-21.

Predictors of Combined Treatment

Effect

40

Characteristics

Impact on

Combined

Treatment Effect

% of Variation

Explained DAPT Score

Age ≥ 75

Age 65 - < 75

Age < 65 (reference)

-1.2%

-0.5%

-

6.0%

2.2%

-

-2

-1

0

Prior PCI or MI 1.1% 14.6% 1

Stent Diameter < 3 mm 0.9% 10.1% 1

CHF or LVEF < 30% 1.9% 9.9% 2

MI at Presentation 1.0% 9.6% 1

Paclitaxel-Eluting Stent 1.0% 8.8% 1

Cigarette Smoker 0.7% 4.3% 1

Diabetes 0.6% 4.3% 1

Vein Graft PCI 1.6% 3.7% 2

Hypertension 0.2% 0.4%

Renal Insufficiency 0.4% 0.3%

PAD -0.1% 0.04%

Yeh et al. JAMA 2016

41

Continued Thienopyridine vs. Placebo DAPT Score

<2 (Low); N=5731

1.7% vs.

2.3%

P=0.07

Continued Thienopyridine

Placebo

10%

8%

6%

4%

2%

0%

Cu

mu

lative

In

cid

en

ce

of

ST

/MI

12 15 18 21 24 27 30

Months After Enrollment

3.7% vs.

3.8%

P=0.73


Placebo

10%

8%

6%

4%

2%

0%

Cu

mu

lative

In

cid

en

ce

of

MA

CC

E

12 15 18 21 24 27 30


3.0% vs.

1.4%

P<0.001


Placebo

10%

8%

6%

4%

2%

0%

Cu

mu

lative

In

cid

en

ce

of

GU

ST

O M

od

era

te/

Se

ve

re B

lee

d

12 15 18 21 24 27 30


Stent Thrombosis or MI MACCE

GUSTO

Moderate/

Severe

Bleeding


42

Continued Thienopyridine vs. Placebo DAPT Score ≥

2 (High); N=5917

2.7% vs.

5.7%

P<0.001


Placebo

10%

8%

6%

4%

2%

0%

Cu

mu

lative

In

cid

en

ce

of

ST

/MI

12 15 18 21 24 27 30


4.9% vs.

7.6%

P<0.001


Placebo

10%

8%

6%

4%

2%

0%

Cu

mu

lative

In

cid

en

ce

of

MA

CC

E

12 15 18 21 24 27 30


1.8% vs.

1.4%

P=0.26


Placebo

10%

8%

6%

4%

2%

0%

Cu

mu

lative

In

cid

en

ce

of

GU

ST

O M

od

era

te/

Se

ve

re B

lee

d

12 15 18 21 24 27 30


Stent Thrombosis or MI MACCE

GUSTO

Moderate/

Severe

Bleeding


43

NNT

192

NNT

53

NNH

70

NNH

264

NNH

97

NNT

60

P=0.06 P=0.07 P=0.003

-0,52%

1,44%

1,03%

-1,90%

0,38%

-1,67%

-4,0%

-3,0%

-2,0%

-1,0%

0,0%

1,0%

2,0%

3,0%

4,0%

DAPT Score < 2

DAPT Score ≥ 2

Continued Thienopyridine vs. Placebo,

by DAPT Score, Excluding Paclitaxel-Eluting Stent

Stent Thrombosis or MI

GUSTO Moderate Or Severe Bleed

Net AdverseEvents

Ris

k D

iffe

ren

ce (

Con

tin

ued

Th

ien

op

yri

din

e –

Pla

ceb

o),

12

-30

M


PEGASUS-TIMI 54: Study Design

Patients aged ≥50 years with a history of spontaneous MI 1–3 years prior to enrolment AND at

least one additional atherothrombosis risk factor*

(N=21,162)

Ticagrelor 60 mg bid

+ ASA 75–150 mg/day

Minimum of 12 months’ follow up:

Every 4 months in Year 1,

then semi-annually

Primary efficacy endpoint: CV death, MI or stroke

Primary safety endpoint: TIMI-defined major bleeding

Placebo

+ ASA 75–150 mg/dayTicagrelor 90 mg bid

+ ASA 75–150 mg/day

*Age ≥65 years, diabetes mellitus, second prior MI, multivessel CAD or chronic non-end stage renal disease

bid, twice daily; CAD, coronary artery disease; TIMI, Thrombolysis in Myocardial Infarction

Bonaca MP et al. Am Heart J 2014;167:437–444

Bonaca MP et al. N Engl J Med 2015 [Epub ahead of print] 44

PEGASUS-TIMI 54: Primary Endpoint

45

CI, confidence interval; HR, hazard ratio

Bonaca MP et al. N Engl J Med 2015 [Epub ahead of print]

No. at risk

Placebo

90 mg bid

60 mg bid

7067

7050

7045

6979

6973

6969

6892

6899

6905

6823

6827

6842

6761

6769

6784

6681

6719

6733

6508

6550

6557

6236

6272

6270

5876

5921

5904

5157

5243

5222

4343

4401

4424

3360

3368

3392

2028

2038

2055

Eve

nt

rate

(%

)

Months from randomisation

Ticagrelor 60 mg vs placebo

HR 0.84 (95% CI 0.74–0.95) P=0.004

Ticagrelor 90 mg vs placebo

HR 0.85 (95% CI 0.75–0.96) P=0.008

9.04% Placebo

7.85% 90 mg bid

7.77% 60 mg bid

Placebo



0 3 6 9 12 15 18 21 24 27 30 33 36

0

1

2

3

4

5

6

7

8

9

10

PEGASUS renal function: results by therapy

Magnani G, Antithrombotic Drugs – an ongoing story, 3032

HR 95% CI

0.81 (0.68-0.96)

ARR = 2.70%

HR 95% CI

0.88 (0.77-1.00)

ARR = 0.63%

Primary Endpoint: CV death, MI, stroke

Months since randomization

eGFR < 60 Placebo (N=1,649)

eGFR < 60 Ticagrelor Pooled (N=3,200)

eGFR ≥ 60 Placebo (N=5,336)

eGFR ≥ 60 Ticagrelor Pooled (N=10,713)

13.99%

11.29%

7.43%

6.80%

3-y

r K

M %

6

12

10

8

16

14

4

0 12 24 36

2

0

PEGASUS-TIMI 54: Bleeding3-y

ear

KM

event ra

te

2.6

2.3

1.11.3

1.2

0.4

0.6 0.70.6 0.6 0.6

0.5

0.10.3 0.3

Rates are presented as 3-year Kaplan-Meier estimates

P<0.026 indicates statistical significance

Bonaca MP et al. N Engl J Med 2015 [Epub ahead of print]

P<0.001

P<0.001

P=NS P=NS P=NS













I B












EPICOR

Aim: to describe current international patterns of the use of DAPT after discharge

in patients surviving hospitalization for ACS using data from the EPICOR study

Background

Bueno H et al., AHA 2014

Modified after: Bueno H et al., Am Heart J 2013;165:8-14

49

Index event Inclusion

Pre-hospital In-hospital Post-discharge

Day 0Phone call FU at 6 w and quarterly

24 months

after index event

Acute phase Long-term FU

• Basline data

• Short-term medical management from

symptoms onset: antithrombotics (dose

+ timing), invasive procedure

• Early clinical outcomes

• Economic evalutation

• Long-term medical management

• Post-discharge clinical outcomes

• QoL-assessment

• Persistence on antithrombotic treatment:

planned + unplanned interruptions

• Economic evaluation

Admission Discharge

EPICORResults – changes in DAPT over time in patients

discharged on DAPT

Bueno H et al., AHA 2014 50

0 6

Months since discharge

10 14 22

8000

6000

4000

2000

0

Num

ber

of patients

20181612842

DAPT Aspirin only Other antiplatelet only None Died Lost to FU

EPICORResults – persistence on DAPT at the end of FU by

country in patients discharged on DAPT

Bueno H et al., AHA 2014 51

Eastern Europe

P<0.001

Latin America

P<0.001

Northern Europe

P<0.001

Southern Europe

P<0.001

Pe

rcen

tage o

f p

atie

nts

rem

ain

ing o

n D

AP

T

%

62.9% 66.6% 63.0%

55.5%

Secondary prophylaxis after MI -

individualized therapeutic concept

Balancing ischaemic versus

bleeding risk:

bleeding risk ↑ ?

platelet function guided

adjustment of DAPT, Therapeutic

Window? Clinically / Genetic Risk

Factors (Scores)

Biomarkers (hsTNT, hsCRP,

other?)

1month 12 months indefinite??

ideal candidates: patients

with low bleeding risk and

high ischaemic risk

Vessel Disease in multiple

locations, heart failure

ischemic risk ↓ ?

individual patient

selection

Verlängerte antithrombozytäre Therapie nach ACS: welcher Patient profitiert?

Meinrad GawazInnere Medizin III, Kardiologie und Kreislauferkrankungen

Eberhard Karls Universität Tübingen

7. Thromboseforum, Stuttgart 2017

Analysis of UK and Belgian patients with ACS enrolled in the GRACE study

ACS, acute coronary syndromes; GRACE, Global Registry of Acute Coronary Events; MI, myocardial infarction.

Fox KA, et al. Eur Heart J 2010;31:2755–2764.

A residual risk of mortality is observed in ACS patients post-6-month survival

Risikoscores: GRACE UK–Belgian Study:

Mortality in patients with prior MI

1.00

0.00

0

Su

rviv

al

dis

trib

uti

on

fun

cti

on

(%

) 0.75

0.50

0.25

500 1000 2000 2500 3500 4000

Time (days)

1500 3000

Cox proportional hazard p<0.0001

High risk

Intermediate risk

Low risk

Documents

Verlängerte antithrombozytäre Therapie nach ACS: …...Falk et al. Circulation, 1995 Patients with MI (n) 0 Ambrose 1988 10 20 30 40 50 60 70 80 90 100 0 40 80 120 160 200 Little