Prof. Dr. Wan Azman B.

Wan Ahmad
Head of Cardiology since 2001
Head of Department of Medicine 2004 - 2009
A council member of the National Heart
Association
Member of Malaysian Cardiovascular
Interventional Society
Member of Clinical Cardiology Asia Pacific
Society of Cardiology
Fellow 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 Ahmad
MRCP, 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 OR
SCORE 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 ; 284:835-842
For 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 ACS
Chest discomfort < 24 hours
Age>60, ST Segment , cardiac markers (any 2 of 3)
Fondaparinux
2.5 mg sc. OD up to 8 days or hospital
discharge
randomization
Enoxaparin
1 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
Exclude
Age < 21
Any contra-ind to heparin
Haemorrhagic 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
C
u
m
u
l
a
t
i
v
e

H
a
z
a
r
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
Fondaparinux
HR: 1.01
95% CI: 0.90-1.13
P
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 deaths
Enoxaparin: 352 deaths
Days
0 3 6 9 12 15 18 21 24 27 30
C
u
m
u
l
a
t
i
v
e

H
a
z
a
r
d
0.0
0.01
0.02
0.03
HR: 0.83
95% CI: 0.71-
0.97
p=0.02
Enoxaparin
Fondaparinux
0.04
3.5 %
2.9 %
OASIS 5 Investigators. N Engl J Med 2006;354:1464-76
Bassand JP Expert Rev Cardiovasc Ther 2007;5:1013-26
17 %
RRR
The reduction in mortality was
maintained at 6 months
Fondaparinux: 574 deaths
Enoxaparin: 638 deaths
OASIS 5 Investigators. N Engl J Med 2006;354:1464-76
Days
C
u
m
u
l
a
t
i
v
e

H
a
z
a
r
d
0.0
0.02
0.04
0.06
0 20 40 60 80 100 120
140
160
180
HR: 0.89
95% 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
C
u
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u
l
a
t
i
v
e

H
a
z
a
r
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
C
u
m
u
l
a
t
i
v
e

H
a
z
a
r
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-
0.72
p<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
C
u
m
u
l
a
t
i
v
e

H
a
z
a
r
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 months
HR: 0.72
95% CI: 0.64-
0.82
p<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.