43
I was born …
July 25th 1949
Semarang, Central Java, Indonesia
I am basically …
A Cardiologist
I am also …
A Professor
A Researcher
Studied in …
Faculty of Medicine, Airlangga University
Surabaya, East Java, Indonesia
…..
IRM Fellow in Cardiology
Philippine Heart Center for Asia, Manila
PhD in Health Science
Airlangga University, Surabaya
Resident of Cardiology and Vascular Medicine, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
(1976 – 1980)
Head of Cardiology & Vascular Medicine Outpatient Clinic, Dr. Soetomo General Hospital - Airlangga University, Surabaya, Indonesia
(1981 – present)
Head of Exercise Stress Test Division of Dr. Soetomo General Hospital - Airlangga University, Surabaya, Indonesia
(1983 – present)
Staff of Cardiology & Vascular Medicine Department, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
(1976 – present)
Members of Surabaya Heart Center, Dr. Soetomo General Hospital – Airlangga University, Surabaya, Indonesia
(1979 – present)
Member of
Indonesian Medical Association
The Indonesian Society of Internal Medicine
Indonesian Heart Association
Asia Pacific Society of Cardiology
Asean Federation of Cardiology
Scientific Publication & Research
…
Writer
145 Papers
• Co-Writer
– 100 Papers
Nice to meet you ….. Let’s begin …..
Prof.DR.dr.Djoko Soemantri,SpJP, (K) FIHA,FASCC
Faculty of Medicine, Airlangga University /
Dr. Soetomo General Hospital
Surabaya Indonesia
Percentage breakdown of deaths from cardiovascular diseases
(United States: 2006) Source: NCHS.
5117
7
7
414
Coronary HeartDisease
Stroke
HF*
High Blood Pressure
Diseases of theArteries
Other
CHD & Stroke are the largest contributor of all CVD.
Anti-platelet Therapy for Coronary Artery
Disease
Platelet aggregation
plays a central role in
thrombous formation
Antiplatelet therapy is
the main therapy for
patients with coronary
artery disease
Atherothrombotic Events (MI, Stroke, or CV Death)
Plaque
Rupture
Platelet
Adhesion,
Activation, and
Aggregation
Thrombus
Formation
MI Atherothrombotic
Stroke PAD Unstable Angina
Ness J, et al. J Am Geriatr Soc. 1999;47:1255-1256.
Schafer AI. Am J Med. 1996;101:199-209.
Common Underlying Atherothrombotic Disease Process
Atherothrombosis Significantly Shortens Life
Analysis of data from the Framingham Heart Study.
Peeters A, et al. Eur Heart J. 2002;23:458-466.
Average Remaining Life Expectancy at Age 60 (Men)
0
4
8
12
16
20
Healthy
Years
History of AMI
-9.2
years
History of Cardiovascular Disease
-7.4
years
History of Stroke
-12
years
Atherothrombosis reduces life expectancy by around
8-12 years in patients aged over 60 years
Clinical Manifestations of Atherothrombosis
Cerebral Ischemic stroke
Transient ischemic attack
Cardiac Myocardial infarction
Angina pectoris (stable, unstable)
Peripheral Arterial Disease
Critical limb ischemia, claudication
Oral administration
Suitable for chronic use
Potent anti-platelet activity leading to reductions in cardiovascular events and stroke
Not associated with excess bleeding
No hypersensitivity or drug resistance
Antiplatelet – what could be ideal?
UNMET NEEDS !
Prostaglandin Pathway and its Biological
Effects
Current issue on anti platelet
AHA 2012 - Antiplatelet Therapy and
PPI: Clinician Update
Aspirin causes direct damage to the gastric
epithelium and inhibits prostaglandin
production by the gastric mucosa
Leading to ulcerations and an estimated 2-
fold increased risk of GI bleeding with low-
dose aspirin alone
Circulation 2012, 125:375-380
Inhibition of TXA2-dependent platelet function by aspirin leaves other platelet pathway [ADP-P2Y, TPA receptor] largely unaffected, thus providing a rational for dual or triple antiplatelet therapy in high-risk settings.
Patrono, Eur Heart J, 2011
A valid option antiplatelet
Anti platelet – MOA
Antiplatelets Class Inhibit
Thromboxane
A2
Preserves
Prostacyclin
Inhibits
Phosphodiesterase
Triflusal New Generation Yes Yes Yes
Acetylsalicyclic
Acid
Throboxane A2
inhibitor
Yes No No
Clopidogrel ADP Receptor
Antagonist
No No No
Ticlopidine ADP Receptor
Antagonist
No No NO
Cilostazol Phosphodiesterase
Inhibitor
NO No Yes
Dipyridamole Phosphodiesterase
Inhibitor
No No Yes
Platelet and Thromboxane Pathway
VASCULAR
WALL
ENDOTHELIUM PLATELET
Membrane phospholipids Membrane phospholipids
Arachidonic acid Arachidonic acid
Endoperoxides PGG2-PGH2
Endoperoxides PGG2-PGH2
Thromboxane A2 (Aggregant)
Prostacyclin (Antiaggregant)
Phosphodiesterase Adenylcyclase
Phospholipase A2
Vascular cyclooxygenase
Phospholipase A2
Platelet cyclooxygenase
Prostacyclin-synthase
Thromboxane-synthase
ATP Platelet cAMP
5’ AMP
ADP ADP Clopidogrel
Ticlopidine
ASA
TRIFLUSAL
Cilostazol/
Dipyridamol
TRIFLUSAL
ASA
TRIFLUSAL
Triflusal an unique antiplatelet
Triflusal reduces
TxA2 production
and has
at least similar
efficacy to that
of aspirin with
less bleeding risk
Chemical structure: related to aspirin
but not derived from aspirin
HTB:
main metabolite also active as
antiplatelet
long half-life (35h)
Triflusal :
not a prodrug
quick onset of action
Triflusal in Myocardial Infarction
E u r H e a r t J 2 0 0 0 ; 2 1 : 4 5 7 - 4 6 5
TRIFLUSAL IN MYOCARDIAL INFARCTION:
A COMPARATIVE SEQUENTIAL ANALYSIS
VS. ASPIRIN
P r i m a r y : P r i m a r y : c o m b i n e d c o m b i n e d i n c i d e n c e o f d e a t h a n d n o n i n c i d e n c e o f d e a t h a n d n o n - - f a t a l f a t a l
r e i n f a r c t i o n r e i n f a r c t i o n a n d C V A a n d C V A
S e c o n d a r y : S e c o n d a r y : m o r t a l i t y , n o n m o r t a l i t y , n o n - - f a t a l r e f a t a l r e - - i n f a r c t i o n a n d C V A , i n f a r c t i o n a n d C V A ,
r e v a s c u l a r i z a t i o n , s a f e t y ( e s p e c i a l l y r e v a s c u l a r i z a t i o n , s a f e t y ( e s p e c i a l l y h a e m o r r h a g i c h a e m o r r h a g i c
a d v e r s e e v e n t s ) a d v e r s e e v e n t s )
Objectives
E u r H e a r t J 2 0 0 0 ; 2 1 : 4 5 7 - 4 6 5
Efficacy Analysis (endpoints)
Triflusal in Myocardial
Infarction
To compare the efficacy of Triflusal with Aspirin
in patients with AMI
Triflusal (n=1056) Triflusal (n=1056)
ASA (n=1068) ASA (n=1068)
0.5
1.3
Risk Reduction
63.6%*
5 14
0 0
1 1
2 2 In
cid
en
ce
% *
* Adjusted for sequential analysis
Non-Fatal CVA
Eur Heart J 2000; 21: 457-465
Sequential analysis
*p = 0.03
Triflusal in Myocardial
Infarction
Gastrointestinal*
Renal*
Skin*
CNS
Others*
Total hemorrhagic*
p= 0.03
*p= ns
1.5
0.3
0.9
1.0
0.3
3.6
0.9
0.2
0.6
0.3
0.5
2.4
1 2 3 4 5 0
%
Triflusal (n=1131)
ASA (n=1139)
Eur Heart J 2000; 21: 457-465
Hemorrhagic Adverse Events
Triflusal in Myocardial
Infarction
Treatment of triflusal in AMI has similar efficacy to aspirin
in the prevention of CV events (death, non-fatal MI,
cerebrovascular events).
Conclusions TIM Study
Triflusal is associated with a significantly lower
incidence of non-fatal cerebrovascular events and cerebral
hemorrhage.
E u r H e a r t J 2 0 0 0 ; 2 1 : 4 5 7 - 4 6 5
Triflusal currently appears to constitute a VALID alternative to Aspirin in AMI, particularly in patients at increased risk of stroke or hemorrhage.
Triflusal in Myocardial
Infarction
Triflusal in Unstable Angina
PROTECTIVE EFFECT OF TRIFLUSAL IN AMI IN
PATIENTS WITH UNSTABLE ANGINA:
RESULTS OF A SPANISH MULTICENTER TRIAL
Catheterization and Intervention
Cardiology: Cardiology 1993;82: 388-398
Non-fatal AMI
Triflusal: 300 mg/t.i.d. (n=143)
Placebo: (n=138)
Follow up: 6 months
Cardiology 1993; 82: 388-398
Triflusal in
Unstable Angina
0 40 80 120 160 200
Follow up (days)
0
5
10
15
20
25
30
Pati
en
ts
Control (12.3%)
Triflusal (4.2%)
p= 0.013 65.8%
Risk Reduction
PREVENTION OF AORTOCORONARY VEIN-GRAFT
ATTRITION WITH LOW-DOSE ASA AND TRIFLUSAL
BOTH ASSOCIATED WITH DIPYRIDAMOLE:
RANDOMIZED DOUBLE-BLIND,
PLACEBO CONTROLLED TRIAL
Guiteras. Eur Heart J 1989; 10: 159-67
Triflusal in Aortocoronary By-pass
Guiteras. Eur Heart J 1989; 10: 159-67
Objectives
To evaluate the efficacy of a low dose Aspirin (50 mg/tid)
plus Dipyridamole (75 mg/tid) or Triflusal (300 mg/tid) plus
Dipyridamole (75 mg/tid) in the prevention of
aortocoronary vein-graft occlusion over 6 months.
Design
Prospective, randomized, double-blind, placebo controlled trial
Triflusal in
Aortocoronary By-pass
Eur Heart J 1989; 10:159-67 (206 patients; 390 grafts)
0
5
10
15
20
25
30
35
40
45
50
%
Graft occluded Patients with
1 occlusion
Distal anastomoses
occluded
P=0.045
P=0.045
11.6 15.7
24.2
11.1 15.1
20.4
30.6
40.0
PLACEBO ASPIRIN TRIFLUSAL
Triflusal in
Aortocoronary By-pass
Occlusion Rate at 6 Months
P=0.045
24.4
P=0.02
P=0.02
P=0.02
P=0.027
P=0.027
P=0.027
Triflusal plus dipyridamole appeared superior to
low-dose aspirin plus dipyridamole in the
prevention of vein-graft occlusion and was
particularly effective in moderately to severely
atherosclerotic distal bed.
Guiteras. Eur Heart J 1989; 10: 159-67
Conclusion
Triflusal in
Aortocoronary By-pass
Pérez Gomez, et al. JACC 2004: 44:1557-66
NAtional Study for Prevention of Embolism
in Atrial Fibrillation
COMPARATIVE EFFECTS OF ANTIPLATELET,
ANTICOAGULANT OR COMBINED THERAPY IN
PATIENTS WITH ATRIAL FIBRILATION
NASPEAF Study
To evaluate the efficacy and safety of the combination of
an antiplatelet (triflusal) and moderate intensity
anticoagulation in patients with atrial fibrillation in
association with vascular risk factors or mitral stenosis
Prospective, multicentre, randomized, open label with blind
events and safety outcomes
Pérez Gomez, et al. JACC 2004: 44:1557-66
Objectives
Design
NASPEAF Study
P= 0.32
Reduced primary end-point in Intermediate Risk Group
Primary Outcome: vascular death, non-fatal stroke, TIA, embolism
Pérez Gomez, et al. JACC 2004: 44:1557-66
% p
atie
nts
/ ye
ar
0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
3.8
2.7
0.9
67% RRR
P= 0.02
3 2 1 0
100
95
90
85
80
%F
reed
om fr
om e
vent
years
Log-rank test, p= 0.004
Triflusal Anticoagulant Combined
NASPEAF Study
The combination of an antiplatelet (triflusal) and moderate
intensity anticoagulation therapy significantly decreased
the vascular events compared with anticoagulant alone
and proved to be safe in atrial fibrillation patients.
Pérez Gomez, et al. JACC 2004: 44:1557-66
Conclusion
NASPEAF Study
Triflusal-based triple antiplatelet
therapy achieved superior platelet
inhibition compared to the dual therapy
ex vivo & it could be applied after
complex intervention with DES (drug-
eluting-stent)
Triple antiplatelet therapy - Triflusal
Suh, Int Heart J 2009
AMI , Stroke/TIA: similar to aspirin in secondary
prevention of vascular events but with significantly lower
risk of severe hemorrhages
Atrial Fibrillation: combined with moderate-intensity
anticoagulation was better than standard anticoagulation
alone. No increase in bleeding
Gastric bleeding: lower risk than with low dose aspirin,
ticlopidine or clopidogrel
Potent antiplatelet action, particularly suited for patients
at risk of bleeding and those with aspirin intolerance or
hypersensitivity
TRIFLUSAL - SUMMARY
Thank You
