Prof. Dr. Wan Azman B. Wan Ahmad

Head of Cardiology since 2001Head of Department of Medicine 2004 - 2009A council member of the National Heart

AssociationMember of Malaysian Cardiovascular

Interventional SocietyMember of Clinical Cardiology Asia Pacific

Society of CardiologyFellow of the Royal College of Physicians (MRCP)

Glasgow (1988)MBBS from University of Malaya (1983)

Pengalaman Dalam Pemilihan

Ubat-ubat Halal Dan Tidak

Halal Kepada Pesakit

Wan Azman Wan AhmadMRCP, FRCP, FAMM, FNHAM, FCAPS, FAsCC, FAPSIC, FSCAI, FACC, FESC

Professor of Medicine and Cardiology

Head Cardiology Unit

70 year old Muslim man was admitted with chest pain. Patient is known to have IHD and had undergo PCI before. His cardiovascular risk factors are hypertension, diabetes mellitus and hypercholesterolemia. 12 lead ECG showed dynamic ST changes and CardiacTroponin was positive. He was given Aspirin and plavix at A&E. At CCU a chinese doctor who is looking after the patient want to start him on S/C Clexane.

The family came to consult you regarding this matter

* What advice will you give to the family

* If you are the doctor in charge how do you manage his

anticoagulant

Case Scenario 1

Lima perkara perlu dipatuhi untuk mengharuskan penggunaan ubat-ubatan dari sumber yang tidak halal :-

* Tidak ada bahan lain daripada sumber suci yang boleh digunakan

* Rawatan haruslah bersifat kritikal dan diperlukan demi kesejahteraan pesakit

* Hanya doktor muslim yang fasih mengenai hukum ini sahaja yang boleh memperskrib ubat-ubatan ini.

* Pesakit/waris terdekat haruslah diberikan penerangan sejelas-jelasnya oleh doktor mengenai perkara ini.

* Ubat ini hanya boleh digunakan untuk jangkamasa yang tertentu sahaja mengikut rawatan yang disyorkan oleh doktor.

Classification of recommendations and

level of evidence – ACC/AHA format

Class I Conditions for which there is evidence for and/or general agreement that that

the procedure or treatment is beneficial, useful or effective

Benefit >>> Risk (SHOULD)

Class II Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment

IIa : Weight of evidence/opinion is in favour of usefulness/efficacy

Benefit >> Risk (REASONABLE)

IIb : Usefulness/efficacy is less well established by evidence/opinion

Benefit ≥ Risk (± CONSIDERED)

Class III Conditions for which there is evidence and/or general agreement that the

procedure/treatment is not useful/effective and in some cases may be harmful

Risk ≥ Benefit (NOT)

Weight of evidence

Level of Evidence A:

Data derived from multiple randomized clinical

trials

Level of Evidence B:

Data derived from a single randomized trial or

non-randomized studies

Level of Evidence C:

Only consensus opinion of experts, case

studies, or standard care

HISTORICAL

POINTS

Age 65 1

3 CAD risk factors 1

(FHx, HTN, chol, DM, active smoker)

Known CAD (stenosis 50%) 1

ASA use in past 7 days 1

PRESENTATION

Recent ( 24H) severe angina 1

cardiac markers 1

ST deviation 0.5 mm 1

RISK SCORE = Total Points (0-7)

TIMI RISK SCORE for UA/NSTEMI

RISK OF CARDIAC EVENTS (%)

BY 14 DAYS IN TIMI 11B *

RISK DEATH DEATH, MI ORSCORE OR MI URGENT REVASC

0/1 3 5

2 3 8

3 5 13

4 7 20

5 12 26

6/7 19 41

* Entry criteria: UA or NSTEMI defined as

ischemic pain at rest within past 24H, with

evidence of CAD

(ST segment deviation or + marker)

Antman et al JAMA 2000 ; 284:835-842For more information, go to www.timi.tv

8.2 ANTICOAGULANTS

Enoxaparin(Clexane)

• The ESSENCE and TIMI IIB(circulation

1999) showed Enoxaparin is superior to

UFH resulting in 15 to 20% fewer MACEs

• Malaysia CPG UA/NSTEMI 2011-1A

Fondaparinux(Arixtra)

• QASIS-5 Trial ( J Am Coll Cardio 2007)

• Malaysia CPG UA/NSTEMI 2011-1A

• ESC Guideline favour Fondaparinux

unless patient is planned for early

intervention

• ACC/AHA Guideline-1B

OASIS 5: A randomized, double-blind,

double-dummy, non inferiority trial

20,078 Patients with NSTE ACSChest discomfort < 24 hours

Age>60, ST Segment Δ, cardiac markers (any 2 of 3)

Fondaparinux2.5 mg sc. OD up to 8 days or hospital

discharge

randomization

Enoxaparin1 mg/kg sc bid for 2-8 days

1 mg/kg sc OD if CrCl<30mL/min

OASIS 5 Investigators. N Engl J Med2006;354: 1464-76

Mean treatment : 5.5 days

ExcludeAge < 21Any contra-ind to heparinHaemorrhagic stroke< 12 mo.Creat> 265 umol/L

Mean treatment : 5.2 days

Fondaparinux is non-inferior to Enoxaparin

at Day 9 (primary efficacy outcome)

Days

Cu

mu

lati

ve H

azar

d

0.0

0.01

0.02

0.03

0.04

0.05

0.06

0 1 2 3 4 5 6 7 8 9

Enoxaparin

FondaparinuxHR: 1.01 95% CI: 0.90-1.13P non-inferiority: 0.007

Death / MI / RI

OASIS 5 Investigators. N Engl J Med 2006;354:1464-76

Fondaparinux significantly reduced mortality at

Day 30

Fondaparinux: 295 deathsEnoxaparin: 352 deaths

Days

0 3 6 9 12 15 18 21 24 27 30

Cu

mu

lati

ve H

azar

d

0.0

0.01

0.02

0.03

HR: 0.83 95% CI: 0.71-0.97p=0.02

Enoxaparin

Fondaparinux

0.04

3.5 %

2.9 %

OASIS 5 Investigators. N Engl J Med 2006;354:1464-76Bassand JP Expert Rev Cardiovasc Ther 2007;5:1013-26

17 % RRR

The reduction in mortality was

maintained at 6 months

Fondaparinux: 574 deathsEnoxaparin: 638 deaths OASIS 5 Investigators. N Engl J Med 2006;354:1464-76

Days

Cu

mu

lati

ve H

azar

d

0.0

0.02

0.04

0.06

0 20 40 60 80 100 120 140 160 180

HR: 0.8995% CI: 0.80-1.00 p=0.05

Enoxaparin

Fondaparinux

0.08

6.5 %

5.8 %

Significant early major bleeding reduction

with Fondaparinux

OASIS 5 Investigators. N Engl J Med 2006;354:1464-76

*Am J Cardiovasc Drugs 2008; 8 (1):in press

48%

RRR

Days

Cu

mu

lati

ve H

azar

d

0.0

0.01

0.02

0.03

0.04

0 1 2 3 4 5 6 7 8 9

HR: 0.52 95% CI: 0.44-0.61 p<0.0001

Enoxaparin

Fondaparinux

4.1 %

2.2 %

*At day 5, the reduction was already significant, p=0.048

*

Major bleeding was significantly

reduced at Day 30

OASIS 5 Investigators. N Engl J Med 2006;354:1464-76

Days

Cu

mu

lati

ve H

azar

d

0.0

0.01

0.02

0.03

0.04

0.05

0 3 6 9 12 15 18 21 24 27 30

HR: 0.62 95% CI: 0.54-0.72p<0.001

Enoxaparin

Fondaparinux

5.0%

3.1%

38%RRR

Significant Reduction in Major Bleeding

Maintained at 6 Months

OASIS 5 Investigators. N Engl J Med 2006;354:1464-76

Days

Cu

mu

lati

ve H

azar

d

0.0

0.01

0.02

0.03

0.04

0.05

0.06

0 20 40 60 80 100 120 140 160 180

At 6 monthsHR: 0.7295% CI: 0.64-0.82p<0.001

Enoxaparin

Fondaparinux

5.8%

4.3%

Can Enoxaparin still be used

• Fondaparinux is contraindicated if

creatinine clearance is less than 30ml/min

• -the risk of bleeding increases with

impaired renal function or very low body

weight

• Other high risk medical condition

-Pulmonary embolism

-Prosthetic valve that require conversion

from warfarin to heparin

SOP di PPUM bagi penggunaan ubat dari

sumber yang tidak halal

1. Doktor merawat memastikan hanya ubat itu

sahaja yang boleh digunakan berdasarkan

kepda prinsip berikut :-

1.1 Rawatan haruslah bersifat kritikal dan

diperlukan demi kesejahteraan pesakit

1.2 Tidak ada bahan lain daripada sumber suci

yang boleh digunakan

1.3 Ubat ini hanya boleh digunakan untuk

jangkamasa yang tertentu sahaja mengikut

rawatan

2. Doktor merawat hendaklah merujuk dan

berbincang dengan seorang doktor Muslim

3. Doktor Muslim berbincang dan memberitahu

pesakit atau waris pesakit terdekat mengenai

penggunaan ubat ini.

4. Pesakit menandatangani borang keizinan untuk

menggunakan ubat tersebut

5. Ubat dituliskan di atas slip prekripsi

6. Satu nota yang mengesahkan bahawa pesakit telah

memberikan keizinan dicatitkan di ats slip perskripsi

ubat

7. Staf Farmasi mengulangi lagi pengesahan ini daripada

pesakit dan mendispens ubat.