Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post...

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Post SCA: Percezione e realtà del rischio residuo Marco Ferlini, MD, FESC, FANMCO, FSICI-GISE

Transcript of Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post...

Page 1: Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post Discharge Fox KAA et al Eur Heart J 2010. Recurrent Cardiovascular Events following ACS

Post SCA: Percezione e realtà del rischio residuo

Marco Ferlini, MD,

FESC, FANMCO, FSICI-GISE

Page 2: Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post Discharge Fox KAA et al Eur Heart J 2010. Recurrent Cardiovascular Events following ACS

Disclosures

Honoraria as consultant, advisory board or speaker from:

Astra Zeneca, Eli Lilly Chiesi Sanofi Bayer Boheringer

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30 days mortality according to reperfusion therapy (STEMI)

Danchin M et al. Arch Mal Coeur Vass 2005Danchi N et al Circulation 2008

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Trends in Management of STEMI in GRACE Registry

Fox KAA et al JAMA 2007

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In-Hospital and 6-month outcomes in Patients with STEMI or LBBB

Fox KAA et al JAMA 2007

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The SwedesHeart/Risk-HIA Data

Jernberg T et al. JAMA 2011

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The SwedesHeart/Risk-HIA Data

Jernberg T et al. JAMA 2011

Page 8: Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post Discharge Fox KAA et al Eur Heart J 2010. Recurrent Cardiovascular Events following ACS

The SwedesHeart/Risk-HIA Data

Jernberg T et al. JAMA 2011

Page 9: Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post Discharge Fox KAA et al Eur Heart J 2010. Recurrent Cardiovascular Events following ACS

Overall Risk of Death in H, from H-admission to 6 months and from H-discharge to 6 months after ACS

Fox KAA et al BMJ 2006

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Post ACS events are often fatals!

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5-years death rates post ACS

0

5

10

15

20

25

STEMI NSTEMI UA

Total Post Discharge

Fox KAA et al Eur Heart J 2010

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Recurrent Cardiovascular Events following ACS

Fox KAA et al Eur Heart J 2010

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MA

CE

cum

ula

tive

rat

e

years

N Eng J Med 2011; 364: 26-35

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Residual Risk in established cardiovascular disease

Kalbacher D et al. Ann Transl Med 2018

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JACC 2004; 44: 720-32

Residual cholesterol risk

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Proportions of patients achieving cLDL target by statin class

Reiner Z et al. Atherosclerosis 2016; 246: 243-50

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Terapia Ipolimemizzante Registro Post-PCI: Dimissione vs 12 mesi

0

10

20

30

40

50

60

Statina Alta Dose Statina/Ezetimibe Statina Alta Dose + Ezetimibe

Dimissione 12 mesi

%

All p value < 0.001

The Post PCI registry was supported by SICI-GISE; unrestricted grant: Astra Zeneca

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Evolocumab Outcomes Trial:

Study Design OverviewFOURIER: Further cardiovascular OUtcomes Research with PCSK9 Inhibition

in subjects with Elevated Risk

Screening

• Age 40–85 years

• MI, stroke, or PAD

• Additional risk factors (one

major or two minor)

• Optimal background lipid

therapy (including effective dose

of statin ± ezetimibe)

• LDL-C ≥ 70 mg/dL or

non–HDL-C ≥ 100 mg/dL

Evolocumab SC 140 mg Q2W or 420 mg QM

(per subject preference)

n ~ 13,750

Placebo SCQ2W or QM

(per subject preference)

n ~ 13,750

Ra

nd

om

iza

tio

n 1

:1

En

d o

f S

tud

y (

EO

S)

Maximum approximately 15 weeks D1 W4 W12 W24 Q24W Number of

key 20

endpoints

achieved

D = day; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol;

MI = myocardial infarction; PAD = peripheral artery disease; Q2W = every 2 weeks; Q24W = every 24 weeks; QM = every month; SC = subcutaneous;

W = week.

Sabatine MS, et al. Am Heart J. 2016;173:94-101. Sabatine MS, et al . NEJM. [published online ahead of print March 17, 2017]. doi: 10.1056/NEJMoa1615664

n = 27,564

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Primary Endpoint: Composite of CV Death, MI, Stroke,

Hospitalization for UA, or Coronary Revascularization

HR 0.85 (95% CI 0.79 to 0.92); P < 0.001

CV = Cardiovascular; MI = Myocardial infarction; UA = Unstable angina; HR = Hazard ratio

Sabatine MS, et al . NEJM. [published online ahead of print March 17, 2017]. doi: 10.1056/NEJMoa1615664

6.0

10.7

14.6

5.3

9.1

12.6

No. at RiskPlacebo 13,780 13,278 12,825 11,871 7,610 3,690 686Evolocumab 13,784 13,351 12,939 12,070 7,771 3,746 689

Cu

mu

lati

ve I

ncid

en

ce (

%) Placebo

Evolocumab

0

2

4

6

8

10

12

14

16

0 6 1812 24 3630Months

15%

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Residual Risk: the inflammatory patway

Reiner Z et al Atherosclerosis 2016

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Variable CANTOS

n 10061

Population h/o MI, hs-CRP>2 mg/l

FU-time 3.7 years (median)

Concept Anti-inflammatory

Substance/dosage Canakinumab 50, 150, 300 mg vs placebo

Adverse Effect Neutropenia, thrombocytopenia,infection

RRR (mortality) ns

NNT (mortality) ns

RRR (PEP: MACCE) 12.4%

NNT (PEP) 50

Treatment cost per year 54160 eur

Treatment cost per avoidance of PEP

2,708,005 eur

Modified, Ann Transl Med 2018; 6: 323

• Dose dependent reduction in hsCRP leveles• Best outcome for 150 mg: HR 0.85, 95% CI 0.74-0.98, p=0.021)• Greater risk reduction for hsCRP > 2 median• Significant increase of fatal infections• Cancer significantly reduced

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Perceived risk for cLDL or hsCRP

It’s easy…..just look at the value

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The risk for antithrombotic therapy

thrombotic risk haemorragic risk

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Antithrombotic therapy in CAD

choiche, combination, time point of initiation and duration depends on:

Patients’s characteristics Comorbidities

Clinical setting(SCAD vs ACS)

Mode of revascularization(PCI vs CABG)

Ischemic/Bleeding risk

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ESC Guidelines

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Co

ag

ula

tio

nP

late

let

ac

tiva

tio

n &

ag

gre

ga

tio

n

Thrombin

PAR-1PAR-4

Inactive

platelet

Activated

platelet

Rivaroxaban

Factor Xa

inhibition1

Antithrombotic therapy: a synergistic approach

Clot

Low dose aspirin2Thromboxane A2

COX-1

1. Adapted from Angiolillo DJ et al. Eur Heart J 2010;31:17–28;

2. 2. Adapted from Mitchell JRA. BMJ 1981;282:590–594

Fibrin

Other inactive

platelets

Aggregated

active platelets

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Long-term Ischaemic al bleeding risk according to MI status

0

1

2

3

4

5

6

ST MACCE Death GUSTO MI MI-ST rel MI -no ST rel

MI no MI

%

J Am Coll Cardiol 2015; 65: 2211-21

*

*

*

*p<0.05

*

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Does coronary anatomy matter?

Palmerini T et al. JACC Int 2014; 7: 1117-27

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Does coronary anatomy matter?

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Does coronary anatomy matter?

JACC 2017; 70: 2213-23

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Does PCI matter?

• 3 vessels treated• 3 stent

implanted• 3 lesions

treated• Bifurcation with

2 stentimplanted

• Total stentlenght > 60 mm

• CTO

Cardiac death, MI, ST

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Complex coronary anatomy and complex PCI help us in detection

of ischemic risk but NOT of bleeding risk!

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Bonaca M presented at ACC 2016

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Bleeding-MI-Mortality

Eur Heart J 2017; 38: 804-810

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Perceived or calculated risk?

Circ Cardiovasc Qual Outcomes 2013; 6: 299-308

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Iscehmic/Bleeding risk score

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Popolazione derivazione

P2Y12 Popolazionevalidazione

Timing evento emorragico

C-statistic

CRUSADE NSTEMI NA SCA-NSTEMI intraospedaliero 0.70

PARIS Stable/ACS clopidogrel(94%)

Stable/ACS 24 mesi 0.64

Mehran ACS NA NA 30 giorni NA

PRECISE-DAPT Stable/ACS clopidogrel(88%)

ACS 12 mesi 0.70/0.66

DAPT Stable/ACS clopidogrel(65%)

Stable/ACS dal 12 mese 0.64

BleeMACS ACS NA ACS 12 mesi 0.65

Ferlini M et al GIC 2018

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0

10

20

30

40

50

CRUSADE PARIS ACUITY-HORIZON PRECISE-DAPT

Perceived Calculated all differences, p < 0.001

%

Comparison between rate of patients at high bleeding risk

perceived vs calculated

Data from Post PCI registry Supported by SICI-GISE with unrestricetd grant of Astra ZenecaFerlini M et al. Circulation CV Int in press

Page 39: Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post Discharge Fox KAA et al Eur Heart J 2010. Recurrent Cardiovascular Events following ACS

The DAPT Score

39

Variable

Point

s

Patient Characteristic

Age

≥ 75 -2

65 - <75 -1

< 65 0

Diabetes Mellitus 1

Current Cigarette

Smoker1

Prior PCI or Prior MI 1

CHF or LVEF < 30% 2

Index Procedure

Characteristic

MI at Presentation 1

Vein Graft PCI 2

Stent Diameter < 3mm 1

Distribution of DAPT Scores among all

randomized subjects in the DAPT Study

HighLow

Page 40: Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post Discharge Fox KAA et al Eur Heart J 2010. Recurrent Cardiovascular Events following ACS

JACC 2018; 72: 1069-78

Page 41: Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post Discharge Fox KAA et al Eur Heart J 2010. Recurrent Cardiovascular Events following ACS

Variable COMPASS PEGASUS

n 27395 21162

Population Stable CAD Prior MI 1-3 year + additional risk

Median time form MI *79% 2 yrs 1.7 yrs

FU-time 23 months 33 months

Concept Anti-thrombotic Anti-platelet

Substance/dosage Riv 5 mg bid mono vs Riv 2.5 mg bid + ASA vs ASA mono

Tic 60 or 90 mb bid vs placebo

Adverse Effect ISTH bleed (HR 1.7; 95% CI 1.4-2.05, p<0.001) TIMI maj (HR 2.32, 95% CI 1.68-3.21, p<0.001)

NNH 83 80

RRR (mortality) 17.4% ns

NNT (mortality) 139 212

RRR (PEP) 23.8% 15.5%

NNT (PEP) 77 78

Treatment cost per year 1298 eur 943 eur

Treatment cost per avoidance of PEP

99,87 eur 74.48 eur

Modified, Ann Transl Med 2018; 6: 323*69% ha histroty of prior MI

Page 42: Post SCA: Percezione e realtà del rischio residuo Marco ... · STEMI NSTEMI UA Total Post Discharge Fox KAA et al Eur Heart J 2010. Recurrent Cardiovascular Events following ACS