The role of Prasugrel in the management of the ACS-PCI patient · The role of Prasugrel in the management of the ACS-PCI patient Professor Gilles Montalescot This symposium has been

1

The role of Prasugrel in the management of the ACS-PCI patient

Professor Gilles Montalescot

This symposium has been sponsored by the Alliance of Daiichi Sankyo and Eli Lilly and Company. The speaker has been selected, briefed and paid an honorarium by the Alliance. Prescribing Information can be found on the last slide.

UKEFF01023a Date of Preparation Jan 2014

2

Disclosures of Interest

• Pr G. Montalescot reports receiving research grants to the institution or consulting/lecture fees

from Abbott Vascular, AstraZeneca, Biotronik, Daiichi-Sankyo, Eli Lilly, Fédération Française de

Cardiologie, Fondation de France, INSERM, Institut de France, Medtronic, Nanospheres, Pfizer,

Roche, Sanofi-Aventis, Stentys, Société Française de Cardiologie, The Medicines Company,

BMS, Menarini, Accumetrics, Bayer, Boehringer-Ingelheim, Duke Institute, Europa, GSK, Iroko,

Lead-Up, Novartis, Springer, TIMI group, WebMD, Wolters.

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Licensed indication

1. Efient SPC (EF9M). eMC. http://www.medicines.org.uk/emc/ (document last updated on the eMC: 02/01/2014; date of first authorisation: 25 February 2009).

Efient® (prasugrel) therapeutic indications1

Efient, co-administered with acetylsalicylic acid (ASA), is indicated

for the prevention of atherothrombotic events in adult patients with

acute coronary syndrome (i.e. unstable angina, non-ST segment

elevation myocardial infarction [UA/NSTEMI] or ST segment

elevation myocardial infarction [STEMI]) undergoing primary or

delayed percutaneous coronary intervention (PCI)

A treatment of up to 12 months is recommended, unless the

discontinuation of prasugrel is clinically indicated.1

4

All patients (n=13,608)

• UA/NSTEMI (n=10,074)

• STEMI (n=3534)

Clopidogrel 300 mg LD

+ ASA

n=6795

Prasugrel 60 mg LD

+ ASA

n=6813

PCI

A loading dose of

study drug was

administered any time

between

randomisation and

1 hour after leaving

the cardiac

catheterisation

laboratory

PCI

Coronary angiography

Clopidogrel 75 mg MD

+ASA

Prasugrel 10 mg MD

+ASA

A treatment of up to 12 months is

recommended unless the

discontinuation of prasugrel is clinically

indicated 2

Duration of follow-up: 6-15 months

TRITON-TIMI 38: Study design1

Primary efficacy endpoint: Death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke1

Primary safety endpoint: Non-CABG-related TIMI major bleeding 1

1. Wiviott S et al. Prasugrel versus clopidogrel in patients with acute coronary syndrome. N Engl J M 2007; 357(20): 2001-2015.


LD: loading dose MD: maintenance dose

5

TRITON-TIMI 38: all ACS-PCI (n=13,608)

Please note

The “overall cohort” of TRITON-TIMI 38 is referred to as “all ACS-PCI “ in this presentation1.


6

Prasugrel + ASA

(n=6,813)

Adapted from reference 1 and 2


2. DoF0007TT38PrasEffic365dy Data on file, Daiichi Sankyo, Inc. and Eli Lilly and Company and/or one of its subsidiaries.

TRITON-TIMI 38 All ACS-PCI: primary efficacy endpoint (12 months)

Primary efficacy endpoint: death from cardiovascular causes,

nonfatal myocardial infarction or nonfatal stroke1,2

ARR: 2% RRR: 19% NNT: 50 HR: 0.81 ( 0.73 - 0.90) p=0.0001

365 180 90 60 30 0

Days from randomisation

Prim

ary

Eff

icacy E

nd

po

int (%

)

14

12

10

8

6

4

2

0

Clopidogrel + ASA

(n=6,795)

11.4%

9.4%

7 1. Wiviott S et al. Prasugrel versus clopidogrel in patients with acute coronary syndrome. N Engl J M 2007; 357(20): 2001-2015.

TRITON-TIMI 38 All ACS-PCI: primary efficacy endpoint (3 days)

0 1 2 3

5.6

4.7

Days after randomisation

0

2

4

6

8

Prasugrel

Clopidogrel

ARR: 0.9%

HR: 0.82

(0.71-0.96)

p=0.01

1

3

5

7

Prim

ary

Eff

icacy E

nd

po

int (%

)

Timing of benefit at 3 days: primary end point of death from

cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke1-2

8

0 5 10 15 20 25 30

7.4

5.7

Days

0

2

4

6

8

Prasugrel

Clopidogrel

TRITON-TIMI 38 All ACS-PCI: primary efficacy endpoint (30 days)

Timing of benefit at 30 days: primary end point of death from

cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke1,2

Adapted from reference 1.and 2

NB: Trial not powered for the 30-day landmark analyses

ARR: 2.3%

HR: 0.77

(0.67–0.88)

p=0.0001

1. Antman E. 40th Annual NY Symposium December 2007. New York


Prim

ary

Eff

icacy E

nd

po

int (%

)

9

All ACS-PCI, N=13,457

Event

Through 12 months Through study end (15 months)

Prasugrel

+ASA

Clopidogrel

+ASA

Prasugrel

+ASA

Clopidogrel

+ASA

(n=6741) (n=6716) HR (95% CI) p value (n=6741) (n=6716) HR (95% CI) p value

TIMI major

bleeding (primary) 2 1.6

1.24

(0.96, 1.59) 0.098 2.2 1.7

1.32

(1.03, 1.68) 0.029

Life-threatening 1.1 0.8 1.38

(0.97, 1.95) 0.068 1.3 0.8

1.52

(1.08, 2.13) 0.015

– Fatal 0.3 0.1 4.48

(1.52, 13.2) 0.003 0.3 0.1

4.19

(1.58, 11.1) 0.002

–- Symptomatic

ICH 0.2 0.2

0.94

(0.46, 1.89) 0.853 0.3 0.3

1.12

(0.58, 2.15) 0.737

TIMI minor

bleeding 2.3 1.8

1.29

(1.02, 1.64) 0.035 2.4 1.9

1.31

(1.04, 1.66) 0.022


2. EMEA Assessment Report for Efient 117561/2009.

3. DOF009TT38PrasSftBl365-450dy Data on file, Daiichi Sankyo, Inc. and Eli Lilly and Company and/or one of its subsidiaries..

TRITON-TIMI 38 All ACS-PCI: safety endpoints (12 and 15 months)

Observed Event Rates of Non-CABG-related bleeding at 12 and 15 months (% patients)1-3

A treatment of up to 12 months is recommended unless the discontinuation of prasugrel is clinically indicated 1

10

TRITON-TIMI 38: STEMI-PCI (n=3,534)

Please note: TRITON-TIMI 38 was not prospectively designed or powered to show superiority of prasugrel over clopidogrel in the STEMI cohort alone.1

1. Montalescot G et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial

infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009; 373(9665): 723-731.

11

Prasugrel + ASA

(n=1,769)

Adapted from reference 1 and 2

TRITON-TIMI 38 STEMI-PCI: primary efficacy endpoint (12 months)

Death from cardiovascular causes, nonfatal myocardial infarction

or nonfatal stroke1,2

ARR: 2.5% RRR: 23% NNT: 40 HR: 0.77 (0.63 - 0.95) p=0.013

365 180 90 60 30 0


14

12

10

8

6

4

2

0

Clopidogrel + ASA

(n=1,765)

12.1

9.6

1. DoF0007TT38PrasEffic365dy Data on file, Daiichi Sankyo, Inc. and Eli Lilly and Company and/or one of its subsidiaries. .

2. Montalescot G et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial

infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009; 373(9665): 723-731.

Prim

ary

Eff

icacy E

nd

po

int (%

)

12



TRITON-TIMI 38 STEMI-PCI and All ACS-PCI: CV mortality (30 and 365 days)

STEMI-PCI: CV mortality at 30 and 365 days1,2

2.4

3.2

1.4

2.3

0

1

2

3

4

5

30 days 365 days

Pa

tie

nts

(%

)

ARR: 1% RRR: 39% HR: 0.61 (0.37 -1.00) p=0.047

p=0.097

STEMI-PCI

Prasugrel +

ASA (n=1,769)

Clopidogrel +

ASA (n=1,765)

1.2

2.2

0.9

1.9

0

1

2

3

4

5

30 days 365 days

Pa

tie

nts

(%

)

p=0.169

p=0.210

All ACS-PCI

Prasugrel + ASA

(n=6,813)

Clopidogrel +

ASA (n=6,795)

All ACS-PCI: CV mortality at 30 and 365 days1,2

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2. EfientDOF009TT38PrasSftBl365-450dy Data on file, Daiichi Sankyo, Inc. and Eli Lilly and Company and/or one of its subsidiaries. .

Observed Event Rates of Non-CABG-related bleeding at 12 and 15 months (% patients)1,2

STEMI-PCI, N=3476

Event


Prasugrel

+ASA

Clopidogrel

+ASA

Prasugrel

+ASA

Clopidogrel

+ASA


TIMI major

bleeding (primary) 2.1 2.0

1.06

(0.66, 1.69) 0.82 2.2 2.0 1.11

(0.70, 1.77) 0.645

Life-threatening 1.0 1.0 0.94

(0.49, 1.83) 0.861 1.2 1.0 1.11

(0.59, 2.10) 0.75

– Fatal 0.3 0.1 NE NE 0.4 0.1 NE NE

–- Symptomatic

ICH 0.1 0.2 NE NE 0.2 0.2 NE NE

TIMI minor

bleeding 2.6 2.5

1.07

(0.70, 1.62) 0.764 2.7 2.6 1.04

(0.69, 1.57) 0.849

NE = not evaluated due to insufficient sample size

TRITON-TIMI 38 STEMI-PCI: safety endpoints (12 and 15 months)


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TRITON-TIMI 38: Diabetic ACS-PCI (n=3,146)

1. Wiviott S et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement

in therapeutic outcomes by optimizing platelet inhibition with prasugrel thrombolysis in mycocardial infarction 38 Circulation 2008;118(16): 1626-1636.

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1. DoF0008TT38PrasEfficDiabet365dy Data on file, Daiichi Sankyo, Inc. and Eli Lilly and Company and/or one of its subsidiaries.

2. Wiviott S et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement

in therapeutic outcomes by optimizing platelet inhibition with prasugrel thrombolysis in mycocardial infarction 38 Circulation 2008;118(16): 1626-1636.

TRITON-TIMI 38 Diabetic ACS-PCI: primary efficacy endpoint (12 months)

Death from cardiovascular causes, non-fatal myocardial infarction or

non fatal stroke in diabetic ACS-PCI cohort1,2

ARR: 4.1% RRR: 29% NNT: 24 HR: 0.71 (0.58 - 0.86) p=0.0006

365 180 90 60 30 0


Pa

tie

nts

(%

)

18

16

14

10

8

6

2

0

15.5

11.4

Prasugrel + ASA

(n=1,576)

Clopidogrel + ASA

(n=1,570)

Adapted from reference 2

12

4

16

TRITON-TIMI 38 Diabetic ACS-PCI: primary efficacy endpoint (30 and 365 days)

Death from cardiovascular causes, non-fatal myocardial infarction or

non fatal stroke at 30 and 365 days1,2

1. DoF0011TT38PrasEfficDiabet30dy Data on file, Daiichi Sankyo, Inc. and Eli Lilly and Company and/or one of its subsidiaries.

2. DoF0008TT38PrasEfficDiabet365dy Data on file, Daiichi Sankyo, Inc. and Eli Lilly and Company and/or one of its subsidiaries

8.2

15.5

5.0

11.4

0

2

4

6

8

10

12

14

16

18

30 days 365 days

Pa

tie

nts

(%

) ARR: 3.2%

RRR: 40%

NNT: 31

HR: 0.60

(0.45 – 0.79)

p=0.0003

ARR: 4.1%

RRR: 29%

NNT: 24

HR: 0.71

(0.58 – 0.86)

p=0.0006 Prasugrel + ASA

(n=1,576)

Clopidogrel + ASA

(n=1,570)

17 1. DOF0010TT38PrasSftBlDiabet365-450dy Data on file, Daiichi Sankyo, Inc. and Eli Lilly and Company and/or one of its subsidiaries..

TRITON-TIMI 38 Diabetic ACS-PCI: safety endpoints (12 and 15 months)

Observed event rates of Non-CABG-related bleeding at 12 and 15 months (% patients)1

Diabetic ACS-PCI, N=3,108

Event


Prasugrel

+ASA

Clopidogrel

+ASA

Prasugrel

+ASA

Clopidogrel

+ASA


TIMI major

bleeding (primary) 2.2 2.1

1.03 (0.64, 1.66)

0.9 2.3 2.2 1.06 (0.66,

1.69) 0.807

Life-threatening 1.5 1.2 1.21 (0.66,

2.23) 0.533 1.6 1.3

1.25 (0.70, 2.26)

0.450

– Fatal 0.5 0.1 NE NE 0.5 0.2 2.36 (0.61,

9.11) 0.2

– Symptomatic

ICH 0.3 0.5

0.57 (0.17, 1.94)

0.360 0.3 0.5 0.62 (0.20,

1.90) 0.401

TIMI minor

bleeding 2.7 1.9

1.46 (0.91, 2.34)

0.116 2.8 1.9 1.53 (0.96,

2.45) 0.073

NE = not evaluated due to insufficient sample size


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DOSING

• A treatment of up to 12 months is recommended, unless the discontinuation of prasugrel is clinically indicated.

• In UA/NSTEMI patients, where coronary angiography is performed within 48 hours after admission, the loading

dose should only be given at the time of PCI.1


Appropriate use of prasugrel1

< 60kg 60mg 5mg

≥ 60kg and < 75 years 60mg 10mg

Loading dose Maintenance

dose

After careful risk-benefit evaluation

≥ 75 years Generally not recommended 60mg 5mg

Hypersensitivity to the active substance, or to any of the excipients

History of stroke or TIA

Severe hepatic impairment (Child-Pugh class C)

Active pathological bleeding CONTRAINDICATED

Please see the full Summary of Product Characteristics before prescribing

Documents

The role of Prasugrel in the management of the ACS-PCI patient · The role of Prasugrel in the management of the ACS-PCI patient Professor Gilles Montalescot This symposium has been