dr.saifur prelunch sympo.pdf

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Anticoagulant in PCI for High Risk

Acute Coronary Syndrome

Mohammad Saifur RohmanDept Cardiology and Vascular Medicine

Faculty of Medicine, Brawijaya University/dr Saiful Anwar Hospital Malang


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ACS Subset and The Treatment

Conservative

Early Invasive

Conservative

Elective PCIPrimary PCI

NSTEACS STEACS

Anticoagulant ?


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Low-Molecular Weight Heparin in

Low Risk ACS patients

Lower risk ACS trials with conservative strategy

–ESSENCE (n~3,000) treated 2-8 days

–TIMI 11B (n~4,000)

–Significant reduction in death/MI compared to

unfractionated heparin


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Reperfusion Therapy for Patients with STEACS

*Patients with cardiogenic shock or severe heart failure initially seen at a non –PCI-capable hospital should be transferred for cardiaccatheterization and revascularization as soon as possible, irrespective of time delay from MI onset (Class I, LOE: B). †Angiography and

revascularization should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy.


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STEMI/NSTEMI Onset in dr. Saiful

Anwar Hospital Malang

ACS

Patients

Saiful

Anwar

Hospital

9.5% of samples

Self

Medication56% of sample

Other

facilities

4. 35±2.77 hours

4.08±4.63 hours

7.68±5.43 hours

5.33±2.78 hours

50% aware

16.7% Aware

34.3% Aware

70 % Aware

Rohman MS, Dwi Chya, Rahmawatus, Mefetika, Prsented at ASMIHA 2012

Late Onset


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Dr. Saiful Anwar:6.32 ± 5.37 hours

Harapan Kita: 5.78 ± 5.2 hours

ER-CVCU : 3.75±2.5 hours

American College of

Cardiology and American

Heart Association. 2004.

Guidelines for themanagement of patients with

STEMI


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INITIAL INVASIVE VS CONSERVATIVE STRATEGY

CLASS 1 RECOMMENDATIONS:

• Early invasive strategy for refractory angina, hemodynamicinstability (LOE B)

• Early invasive strategy for stabilised patients with elevated riskfor clinical events.

• High risk factors include:

• Recurrent angina, ischaemia at rest or minimal activity

• Elevated troponins

• New ST depression

• Signs of heart failure/worsening mitral regurg.

• Ventricular tachycardia

• Prior CABG

• PCI in last 6 months

• High TIMI/GRACE scores

• LVEF < 40%


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• Prior CABG• PCI in last 6 months

• High TIMI/GRACE scores

• LVEF < 40%

CLASS 2b RECOMMENDATIONS

• May opt for initial conservative strategy in stabilised high risk

patients – dependent on patient/physician preference (LOE B)

CLASS 3 RECOMMENDATIONS

• Invasive strategy -not recommended in patients with multiple co

morbidities, low risk patients, patients not consenting.(LOE C)

INITIAL INVASIVE VS CONSERVATIVE STRATEGY


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Procedure- and Non-Procedure-Related Bleeds

Associated With Increased 30-Day Mortality in NSTE

ACS

Procedure-related

GUSTO bleeds

Non-procedure-related

GUSTO bleeds

R i s k o f d e a t h ( H

R )

None

1.0

Mild

1.3

Severe

16.5

0

5

20

10

15

None

1.0

Mild

2.1

Moderate

2.5

Severe

10.9

Moderate

3.7

Rao SV, et al. Am J Card io l . 2005;96:1200-1206.


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Advantages of LMWH vs UFH

• No platelet activation

• Inhibits von Willebrand factor release

• Augments TFPI release

• Inhibits thrombin generation

• No rebound hypercoagulability


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Can we improve safety in PCI with

enoxaparin?


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FINESSE: Improved Safety and Efficacy in

Facilitated PCI

UFH

(40 U/kg , 3,000 U max)

“Main Study”

(N = 1,693)

Enoxapar in (0.5 mg /kg IV, 0.3 mg/kg SC)

“LMWH Substudy”

(N = 759)

R

Reteplase/abciximab-facilitated 1° PCI

(n = 258)

Abciximab-facilitated

1° PCI

(n = 255)

1°

PCI w/ in-lababciximab

(n = 246)

Reteplase/abciximab-

facilitated 1° PCI

(n = 570)

Abciximab-facilitated1° PCI

(n = 563)

1° PCI w/ in-lab

abciximab

(n = 560)

R

Montalescot G. TCT 2007.


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FINESSE: TIMI Major Bleeding

0

5

10

15

M a j o r b l

e e d i n g ( % )


2.9 2.51.6

5.74.4

5.2

P = 0.043P = 0.464P = 0.015

P = NS

2.9

4.6


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Can we improve safety and efficacyin primary PCI?


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FINESSE: Death, ReMI, Urgent Revasc, or

Refractory Ischemia Through Day 30


0

5

10

15

P e r c

e n t a g e

8.4

4.55.9

7.5

5.4

8.0

5.3

8.0

P = 0.016P = 0.047


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0

5

10

15

FINESSE: Death at 90 Days

D e a t h

( % )


5.4

2.4

4.7 5.6 4.35.9

3.85.6

P = 0.061P = 0.065


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FINESSE: Adjusted Odds Ratios for Efficacy

and Safety EndpointsLMWH vs. UFH

Endpoint OR 95% CI P

TIMI major bleeding 0.56 0.31 – 0.99 0.04

Death/complications of MI to day 90 ( °)* 0.73 0.52 – 1.03 0.07

Death to day 90 0.59 0.35 – 0.99 0.04

Death or MI to day 30 0.58 0.35 – 0.96 0.03

Death, MI, urg revasc or refr. ischemia to day 30 0.47 0.31 – 0.72 0.0005

Net benefit (death/MI/stroke/major bleeding) 0.64 0.45 – 0.91 0.01

*Hazard ratio (logistic regression model)


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ExTRACT –TIMI 25Improved Efficacy in 2° PCI

ExTRACT –TIMI 25

(N = 20,479)

PCI

by 30 days

(n = 2,272)

PCI

by 30 days

(n = 2,404)

Enoxaparin(n = 10,256)

UFH(n = 10,223)

RRR = 23%

P < 0.001

Enox 10.7%

UFH 13.8%

0

3

6

9

12

15

0 5 10 15 20 25 30

D e a t h / M I ( % )

Days

TIMI Major or Minor 4.6% vs.

4.0% P = 0.3

Antman EM, et al. N Engl J Med . 2006;354:1477-1488.Gibson CM, et al. J Am Col l Cardio l . 2007;49:2238-2246.


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ACOS (STEMI) Registry

6,299 STEMI patients 2,021 Lysis

2,371 1° PCI

2,683 No early reperfusion

10.2

16.6

8

4

14.8

22.5

13.8

9.8

0

5

10

15

20

25

All No reperf. Lysis 1° PCI

DeathorMI(%)

LMWH

UFH

*

*

*

*P < 0.05, univariate analysis

Death 10.0% UFH vs .

7.2% LMWH;

P < 0.05

Zeymer U, et al. Thromb Haemost . 2008;99:150-154.


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FAST –MI (STEMI) Registry

0

2

4

6

8

10

LMWH Other A/C

LMWH

Other A/C

0

1

2

3

4

LMWH Other A/C

LMWH

Other A/C

Death Major bleeding

Multivariate analysis: LMWH predicts survival

1,714 STEMI patients: 1,025 with reperfusion55% 1

PCI

45% lysis

P e r c e n t

Danchin N. ACC 2007.


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27Slide 27

Enoxaparin in the Cath. Lab. Replacing UFH

Is there enough evidence based trial ?


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ATOLL An international randomized study

comparing IV enoxaparin to IV UFH in primary PCI

G. Montalescot, M. Cohen, P. Goldstein,

K. Huber, C. Pollack, U. Zeymer, E. Vicaut

for the ATOLL investigators

G. MONTALESCOT, DISCLOSURE: Research Grants (to the Institution) from Abbott Vascular, Bristol Myers

Squibb, Boston Scientific, Centocor, Cordis, Eli-Lilly, Fédération Française de Cardiologie, Fondation de France,

Guerbet Medical, INSERM, Medtronic, Pfizer, Sanofi-Aventis Group, Société Française de Cardiologie;

Consulting or Lecture Fees from Accumetrics, Astra-Zeneca, Bayer, Biotronik, Boehringer-Ingelheim, Bristol-

Myers Squibb, Daichi-Sankyo, Eisai, Eli-Lilly, Menarini, MSD, Novartis, Portola, Sanofi-Aventis Group, Schering-Plough , Servier and The Medicines Company.

ATOLL : Acute STEMI Treated with primary PCI and intravenous enoxaparin Or UFH to

Lower ischemic and bleeding events at short- and Long-term follow-up

(Investigator -driven study)

E S C ,

S t o c k h o l m -

A u g u s t 3 0 ,

2 0 1 0 –

H o t l i n e s e s s i o n


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STEMI

planned for 1° PCI

ENOXAPARIN IV

0.5 mg/kg(± GP IIb/IIIa inhibitor)

UFH IV

50 – 70 IU/kg if GP IIb/IIIa

70 – 100 IU/kg if no GP IIb/IIIaDose adjusted to ACT

Randomization (N = 850)

1° PCI and stenting

1° EP: Death, complication of MI, procedure failure

or non-CABG major bleeding at 30 days

Main 2° EP: Death, MI, refractory ischemia, urgent revasc.

6-month follow-up

Patients who have already received UFH or LMWH or any other anticoagulant are excluded.All concomitant drugs accepted, except lytics; cross-over to other anticoagulant NOT accepted.

ATOLL: Study Design


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Primary EndpointDeath, Complication of MI, Procedure Failure or Major Bleeding

33.7

28

0

5

10

15

20

25

30

35

40

UFH

ENOX

RRR = 17%

P = 0.07

%

o f p a t i e

n t s

RRR: Relative Risk Reduction


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Death, Complication of MI or Major bleeding

Net clinical benefit

15

10,2

0

2

4

6

8

10

12

14

16

UFH

ENOX

RRR = 32%

P = 0.03

%

o f p a t i e

n t s


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Intravenous enoxaparin vs. UFH in PCI

57%

Major Bleeding

(p=0.004)

23%

Death or re-MI

(p


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ESC guidelines 2012


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ESC guidelines 2012

(AMI - STEMI)

35

Recommendations Class Level

An injectable anticoagulant must be used in primary PCI. I C

Enoxaparin (with or without routine GP IIb/IIIa blocker) may be preferred over UFH. IIb B

Fondaparinux is not recommended for primary PCI. III B

The use of fibrinolysis before planned primary PCI is not recommended. III A

Recommendations Class Level

The anticoagulant can be :

* Enoxaparin i.v. followed by s.c. (using the regimen described below) (preferred over UFH). I A

* UFH given as a weight-adjusted i.v. bolus & infusion. I C

In patients treated with streptokinase, fondaparinux i.v. bolus followed by s.c. dose 24 h later. IIa B

Antithrombin co-therapy with fibrinolysis

Tabel 12 :

Periprocedural antithrombotic medication in primary PCI

Anticoagulants

UFH with or without routine GP IIb/IIIa blocker must be used in patients not receiving bivalirudin or

enoxaparin.

I C

Tabel 13 :

Fibrinolytic therapy

Bivalirudin (with use of GP IIb/IIIa blocker restricted to bailout) is recommended over UHF & GP IIb/IIIa

blocker.I A

Anticoagulation is recommended in STEMI patients treated with lytics until revascularization (if

performed) or for the duration of hospital stay up to 8 days. I C

ESC idelines 2012


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ESC guidelines 2012

(AMI - STEMI)

36

Enoxaparin 0.5 mg/kg i.v. bolus.

In patients 75 years of age :

In patients with creatinine clearance of


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Conclusions

Efficacy and safety have been proven on theuse of enoxaparin (LOVENOX) not only in

conservative strategy of ACS but also in highrisk patient undergoing PCI

A proper dose should administered accordingthe guideline recommendation


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dr.saifur prelunch sympo.pdf

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