CAPRI CARDIOVASCULAR CONFERENCE 2016 Capri, april 15 – 16. 2016

UPDATE SULLA DOPPIA ANTIAGGREGAZIONE PIASTRINICA

NELLA SINDROME CORONARICA ACUTA ALLA LUCE DELLE

NUONE LINEE GUIDA EUROPEE

Pasquale Perrone Filardi

Università Federico II Napoli

K-M estimate of time to first primary efficacy event (Composite of CV death, MI or stroke)

No. at risk

Clopidogrel

Ticagrelor

9,291

9,333

8,521

8,628

8,362

8,460

8,124

Days after randomisation

6,743

6,743

5,096

5,161

4,047

4,147

0 60 120 180 240 300 360

12

11

10

9

8

7

6

5

4

3

2

1

0

13 C

um

ula

tive i

ncid

en

ce (

%)

9.8

11.7

8,219

HR 0.84 (95% CI 0.77–0.92), p=0.0003

Clopidogrel

Ticagrelor

Completeness of follow-up 99.97% = five patients lost to follow-up

K-M = Kaplan-Meier; HR = hazard ratio; CI = confidence interval

Wallentin L et al. N Engl J Med. 2009 Sep 10;361(11):1045-57

4

~1 in 5 patients will suffer a MI, stroke or CV death within the first year after a MI

APOLLO HELICON Sweden analysis

CV, cardiovascular; MI, myocardial infarction.

Jernberg T, et al. ESC poster 2014: In press.

700 pts with ACS UA (with ECGΔ) or NSTEMI or STEMI >24º

undergoing PCI of 1 or 2 major coronary arteries

at up to 40 sites in the U.S. and Europe

PCI of culprit lesion(s)

Successful and uncomplicated

Formally enrolled

Metabolic S.

• Waist circum

• Fast lipids

• Fast glu

• HgbA1C

• Fast insulin

• Creatinine

Biomarkers

• Hs CRP

• IL-6

• sCD40L

• MPO

• TNFα

• MMP9

• Lp-PLA2

• others

PI: Gregg W. Stone

Sponsor: Abbott Vascular; Partner: Volcano

The PROSPECT Trial

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%

PROSPECT: VH-TCFA and Non

Culprit Lesion Related Events

Lesion HR 3.84 (2.22, 6.65) 6.41 (3.35, 12.24) 10.77 (5.53, 21.00) 10.81 (4.30, 27.22)

P value <0.0001 <0.0001 <0.0001 <0.0001

Prevalence* 51.2% 17.4% 11.0% 4.6%

*Likelihood of one or more such lesions being present per patient. PB = plaque burden at the MLA

Tricoci P et al. N Engl J Med 2012;366:20-33.

PROTEASE ACTIVATOR RECEPTOR 1 (PAR1) INHIBITION IN ACS

ALMOST

SIGNIFICANT

SIGNIFICANT

MAJOR

BLEEDINGS

12

Up to a third of patients who are event free for the first year post-MI, will suffer a MI, stroke or

death within 3 years

APOLLO 4-country analysis : Observed Incidence

*US sample restricted to patients aged ≥65 years. MI, myocardial infarction.

Rapsomaniki E, et al. ESC Late Breaking Registry presentation 2014: In press.

13

14

15

EFFICACY AND SAFETY OF PROLONGED DUAL ANTIPLATELET THERAPY

A META-ANALYSIS OF 15 RANDOMIZED TRIALS ENROLLING 85,265 PATIENTS

Udell JA et al. Eur Heart J 2015

Recommendations for platelet inhibition in non-ST-elevation acute coronary syndromes

Eur Heart J. 2015 Aug 29. pii: ehv320

a) Class of recommendation. b) Level of evidence. c) References supporting level of evidence. d) Non-enteric coated formulation; 75–150 mg intravenously if oral ingestion is not possible. e) Contraindications for ticagrelor: previous intracranial haemorrhage or ongoing bleeds. Contraindications for prasugrel: previous intracranial haemorrhage, previous ischaemic stroke or transient ischaemic attack or ongoing bleeds; prasugrel is generally not recommended for patients ≥75 years of age or with a bodyweight <60 kg. f) Recommendations for cardiac surgery are listed in section 5.6.6.2.

Reduction in Ischemic Events with Ticagrelor in

Diabetic Patients from the PEGASUS-TIMI 54 Trial

Deepak L. Bhatt, MD, MPH, Marc P. Bonaca, MD, MPH,

Sameer Bansilal, MD, MS, Dominick J. Angiolillo,

MD, PhD, Marc Cohen, MD, Robert F. Storey, MD,

Kyungah Im, PhD, Sabina A. Murphy, MPH, Peter

Held, MD, PhD, Eugene Braunwald, MD, Marc S.

Sabatine, MD, MPH, Ph.

Gabriel Steg MD, on behalf of the PEGASUS-TIMI 54

Steering Committee and Investigators

NCT00526474

REACH Registry - Diabetes

Cavender MA, Steg PG, Smith SC, et al. Bhatt DL. Circulation. 2015. An Academic Research Organization of

Brigham and Women’s Hospital and Harvard Medical

School

Primary Endpoint - MACE C

V D

eath

, M

I, S

tro

ke

(%

) 11.6%

10.1%

7.8%

6.7%

Benefit in Diabetic vs. Non-Diabetic Patients:

Interaction P=0.99

Ticagrelor in Non-Diabetic Patients

HR 0.84 (95% CI 0.74 – 0.96)

ARR 1.1%; P=0.01

Ticagrelor in Diabetic Patients

HR 0.84 (95% CI 0.72 – 0.99)

ARR 1.5%; P=0.03

Ticagrelor (doses pooled)

Placebo

Days from Randomization An Academic Research Organization of

Brigham and Women’s Hospital and Harvard Medical

School

Cardiovascular Death C

ard

iovasc

ula

r D

eath

(%

)

3.9%

Benefit in Diabetic vs. Non-Diabetic Patients: Interaction P=0.38

2.6%

2.4%

Ticagrelor in Non-Diabetic Patients

HR 0.91 (95% CI 0.72 – 1.15)

ARR 0.2%; P=0.42

Ticagrelor in Diabetic Patients

HR 0.78 (95% CI 0.61 – 0.99)

ARR 1.1%; P=0.0495

5.0%

Ticagrelor (doses pooled)

Placebo

Days from Randomization An Academic Research Organization of

Brigham and Women’s Hospital and Harvard Medical

School

Efficacy and Safety of Ticagrelor as Long-Term

Secondary Prevention in Patients with Peripheral

Artery Disease and Prior Myocardial Infarction

Marc P. Bonaca, MD, MPH

on behalf of the PEGASUS-TIMI 54 Executive &

Steering Committees and Investigators

NCT00526474

Baseline Characteristics by PAD

An Academic Research Organization of

Brigham and Women’s Hospital and Harvard Medical

School All p-values < 0.001 except gender (p=0.17)

Background ASA >99%, statin>93%, beta blocker 83% no

significant difference by baseline PAD

No PAD

N=20,017

PAD

N=1,143

Age, median (IQR) 65 (59, 71) 66 (60, 73)

Gender (female) 24 22

History Hypertension 77 85 Risk

Factors History of Hypercholesterolemia 77 81

Current Smoker 16 30

History of COPD 7 68

eGFR < 60 (MDRD) 23 31 History of Diabetes 32 42

History of CHF 19 30 CV

Disease History of Second Prior MI 16 26

Multivessel Coronary Artery Disease 59 64

Prior CABG 4 13

ABI <=0.90 0 19 Limb

Disease Peripheral Revascularization 0 34

History of claudication 0 65

0 %

0

5%

10%

15%

20%

25%

90 180 270 360 450 540 630 720 810 900 990 108

CV

Death

, M

I, o

r S

tro

ke

(%

)

PAD Patients

N=404

19.3%

Patients without

PAD

N=6663

8.4%

Number at Risk

PAD

No PAD

404

6663 384

6508

367

6394

P<0.001

MACE in Patients* by PAD

1080

An Academic Research Organization of

Brigham and Women’s Hospital and Harvard Medical

School

*randomized to placebo Days from Randomization

344 309 223 104

6159 5567 4120 1924

An Academic Research Organization of

1.0 0.1 PAD

Better

PAD

Worse

1.84

1.33

2.31

2.05

1.57

CVD / MI / Stroke

CV Death

Myocardial Infarction

Stroke

Mortality

TIMI Major Bleeding

0.0013 (1.20 – 2.13)

Adjusted* Hazard

Ratio

1.60

Brigham and Women’s Hospital and Harvard Medical

School CABG, PCI with stenting, time from P2Y12 withdrawal, eGFR, region

3 Yr KM Rt %

PAD No PAD

19.3 8.4

(95% CI) P-value

9.6 3.0 (1.16 – 2.94) 0.0102

9.5 5.0 (0.91 – 1.94) 0.14

0.0071 4.0 1.8 (1.26 – 4.25)

<0.001 4.6 (1.43 – 2.94) 14.0

0.46 1.6 1.0 (0.47 – 5.22)

*Adjusted for age, race, MI type, second prior MI, diabetes, multivessel disease,

hypertension, hypercholesterolemia, smoking, CHF, COPD, prior stroke/TIA, angina,

Adjusted Risk for Events in Placebo

Patients by PAD

An Academic Research Organization of

CV

Death

, M

I, o

r S

tro

ke

(%

)

Days from Randomization

0%

5%

10%

15%

20%

25%

0 90 180 270 360 450 540 630 720 810 900 990 1080

19.3%

15.2%

8.4%

7.4%

PAD

HR 0.75 95% (CI 0.55 – 1.01)

ARR 4.1%

NNT 25

No PAD HR

0.86 95% (CI 0.77 –

0.96)

P-interaction 0.41 Placebo

Ticagrelor

(pooled doses)

ARR 1.0%

NNT 100

MACE with Ticagrelor by PAD at Baseline

Brigham and Women’s Hospital and Harvard Medical

School

Ac

ute

Lim

b I

sch

em

ia o

r

Pe

rip

hera

l R

evascu

lari

za

tio

n f

or

Isch

em

ia (

%)

0.0%

Number at Risk

0.2%

0.8%

0.71%

0.6%

0.46%

0.4%

1.0%

0 180

6988

13929 An Academic Research Organization of

Brigham and Women’s Hospital and Harvard Medical

School Days from Randomization

360

6912

13789

540

6701

13425

720

6077

12186

900

4518

9154

1080

2123

4296

HR 0.65

95% CI (0.44 – 0.95)

P=0.026

Placebo Ticagrelor

7067

14095

Major Adverse Limb Events with Ticagrelor