ORAL FIBRINOLYTIC

A CHALLENGING
OPPORTUNITY

Riki Sukiandra
Neurology Department
Faculty of Medicine
Riau University

Pekanbaru, October 24th, 2015

Definition:

Stroke is a clinical syndrome

characterized by RAPIDLY developing
symptom and/or sign of focal and at
times global loss of cerebral functions,
with symptoms lasting more than 24
hours or leading to death, with no
apparent cause other than that of
vascular origin (WHO,1986)
Faktor Risiko Stroke
Non modifiable Modifiable
 Umur  Hipertensi
 Gender  Diabetes Melitus
 Ras  Merokok
 Herediter  Hiperlipidemia
 Alkoholisme
 Peny. jantung (AF)
 Kontrasepsi hormonal
 Hiperkoagulabilitas
Causes
 Ischemic
Injury
Apoptotic
Cell Death
Necrotic
Cell Death

-
Ischemic Stroke Infarct
 When a stroke
occurs, it kills brain
cells in that
immediate area
 This area of dead
cells is called an
infarct
 These cells usually
die within minutes to
a few hours after the
stroke starts
Definition of Ischemic Stroke
• Almost 80% of strokes are from an emboli or a
thrombus
• Embolic & Thrombotic strokes are ISCHEMIC
• < 15% of strokes are from hemorrhage, with an
even smaller percentage caused by hypoperfusion
CELULAR CHANGES DURING ISCHAEMIC
 Pembentukan Plak Aterosklerotik
1. Akumulasi lipoprotein pd tunika intima 2. Stres oksidatif
3. Aktivasi Citokine 4. Penetrasi Monocyte
5. Migrasi makrofag  foam cell 6. Muscle Cell Smooth
7. Akumulasi matriks ekstraseluler 8. Kalsifikasi dan fibrosis
Aliran Darah Vaskuler Normal
 Progresivitas Aterotrombosis

Trombosis

Unstable
angina
MI
ACS
Ischemic
stroke
Critical leg
ischemia
Aterosklerosis Intermitent
claudication
CV death

Stable angina/
Intermittent claudication
Aterotrombosis: Trombus Superimposed
pada Plak Aterosklerotik

Adapted from Falk E, et al. Circulation. 1995;92:657-671.

Plak yg keluar → pembentukan
aterotrombosis
Agregasi platelet
Aliran
darah Fibrin

Macrophage Tissue factor

Adapted from: Falk E et al. Circulation 1995; 92: 657–71.

 Faktor Risiko Ruptur Plak
Faktor Lokal Faktor Sistemik
Kelelahan Smoking

Cholesterol
Atheromatous Core
(size/consistency)
Diabetes
Mellitus Fibrinogen
Ketebalan /
konsistensi
Homocysteine
Inflamasi Impaired
Fibrinolysis

Plaque
Rupture
Fuster V, et al. N Engl J Med. 1992;326:310-318.
Falk E, et al. Circulation. 1995:92:657-671.
Adhesi dan aktivasi Platelet
Platelets adhering menuju
endotelium yg rusak Agregasi platelet
Platelet normal
dan melalui proses aktivasi kedalam trombus
pd aliran darah
A B C

Platelet
thrombus
Platelets adhering
to subendothelial
Platelets space

Endothelial cells
Subendothelial space

Adapted from: Ferguson JJ. The Physiology of Normal Platelet Function. In: Ferguson JJ, Chronos N,
Harrington RA (Eds). Antiplatelet Therapy in Clinical Practice. London: Martin Dunitz; 2000: pp.15–35.
Vascular Thrombogenesis Process
AUTOLYTIC
Manifestasi Klinik Mayor oleh karena
aterotrombosis

Ischemic Transient
stroke ischemic attack

Myocardial Angina:
infarction • Stable
• Unstable

Peripheral arterial
disease:
• Intermittent claudication
• Rest Pain
• Gangrene
• Necrosis

Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6.

Acute stroke care-General
management
 The mainstay of acute treatment (A,B,C)
 Treatment and stabilisation of general condition
 Specific therapy
– Recanalisation of a vessel occlusion
– Preventive of mecanism leading to neuronal death in
the ischhemic brain
 Early secondary prevention
 Early rehabilitation
 Prophylaxis and treatment of complications
(Lamsudin, 2004)
 Secondary prevention
•Rehabilitation CBF •Neuroprotectan
•Antitrombotic •Ca chanel blocker
•Heparin,nadroprin
•Free radical scavenger
•Antiplatelet
•GABA agonist
•aspirin
•Glutamate antagonist
•Fibrinogen depleting
•Phosphatidylcholine precussor
•ancrod
•NMDA antagonist
•Improve capillary flow
•Serotonin agonist
•pentoxifylline
•Comp.NMDA antagonist
•Trombolitic
AIMS OF SECONDARY STROKE PREVENTION
 TO PREVENT RECURRENCE STROKE
 TO PREVENT THE DEVELOPMENT OF VASCULAR
DEMENTIA
 TO IMPROVE QOL OF STROKE VICTIM
 INDIRECTLY PREVENT OTHER SERIOUS VASCULAR
EVENTS

STRATEGIES FOR SECONDARY STROKE PREVENTION

PROMOTION OF HEALTHY LIFE STYLE TREATMENT WITH

ANTIPLATELET AGENTS, ADEQUATE AND OPTIMAL
CONTROL OF STROKE RISK FACTORS, ADEQUATE
CONTROL TO PREVENT VASCULAR DEMENTIA
 CURRENTLY AVAILABLE
ANTITHROMBOTIC DRUGS

ANTIPLATELET AGENTS ANTICOAGULANTS THROMBOLYTIC

AGENTS

ORAL PARENTERAL ORAL PARENTERAL -PARENTERAL

GPIIb/IIIa -STREPTOKINASE
Aspirin Coumarin
antagonists Heparin -UROKINASE
Dipyridamol LMWH -tPA
Ticlopidin melagatran
Hirudin
Clopidogrel Argatroban
Cilostazol Fondaparinux
 Atherothrombosis* is a
Leading Cause of Death Worldwide1†
AIDS 5.1

Pulmonary disease 6

Injuries 9.1

Cancer 12.6

Infectious disease 17.8

Atherothrombosis* 28.7

0 5 10 15 20 25 30

Mortality (%)

* Ischemic heart disease, cerebrovascular disease, inflammatory heart disease and hypertensive heart disease
† Worldwide defined as Member States by WHO Region (Africa, Americas, Eastern Mediterranean, European,
South-East Asia and Western Pacific)

1. The World Health Report, 2002, WHO Geneva, 2002

 Common sense of Daily Practices
1. Vascular Thrombosis Obstruction can’t be open
automatically  Insufficiency of Autolytic activity

2. Neither Anticoagulant oral nor anti pletelet increase

Autolytic activity  Different mechanism

3. Fibrinolytic oral is needed to increase Autolytic activity 

common sense
“Lumbrokinase ( Fibrinolytic oral ) has opportunity for
these cases
Lumbrokinase Oral Function
 Fibrinolytic
Being an exogenous t-PA
Stimulating the vascular endothelial cells to secrete endogenous t-PA
 Indirect Thrombolysis
Being an exogenous plasmin
 Direct Thrombolysis
 Anticoagulation
Specific binding to fibrinogen (specific affinity with fibrinogen)
Hydrolyze fibrinogen (generate soluble degraded products)
 Decrease concentration of fibrinogen
 Antiplatelet
It decreases significantly the levels of Gmp-140, TXB2 and S-HT
 Inhibiting platelet activation and vasoconstriction
Plus (+) Endothelin ↓
 Lumbrokinase berasal dari sumber alami

 Compendium of Materia Medica : cacing tanah

(Lumbricus rubellus) dapat membuka sumbatan
pembuluh darah
 Observasi cairan digestif cacing tanah yang dapat
melarutkan fibrin.
 Mihara et al. (1991), melarutkan fibrin dgn enzim yg
diekstraksi dari cacing Lumbricus rubellus, enzim tsb
terdiri dari 6 enzim proteolitik yang lumbrokinase
 lumbrokinase digunakan secara luas di Cina sebagai
trombolitik
 Lumbrokinase dapat meningkatkan aktivitas fibrinolitik.
 Mechanism of Actions
Anti-platelet
aggregation

Anti-thrombosis
Fibrinogenolytic
DLBS
DLBS1033
1033 Clot lysis

Thrombolytic
Fibrinolytic

In addition, DLBS1033 also has Positive Pleiotropic Effects via Down

regulate expression of genes related to vascular remodeling
• Anti inflammatory activities: (NF-KB, P-Selectin, TNF-α, & VCAM-1)
• Plaque stabilization: MMP9
• VSMC inhibition of proliferation & migration: JAK1/STAT1
 Fibrinolysis Activity

Plasminogen

t-PA

DLBS
Plasmin
1033

Fibrin Fibrin Degradation Product

 Adhesion Molecules – Anti inflamation
Attach to EC
P-selectin is a cell adhesion molecule on the
endothelial cells that plays role on initial
recruitment of leukocytes during inflammation.
And in the arterial wall, it can induce the
atherosclerotic plaque formation
Kurnia and Tjandrawinata. Medicinus 24(1):18-24, 2011
VCAM
VCAM-1 mediates the adhesion of
lymphocytes, monocytes, eosinophils and
basophils to vascular endothelium.
The activated VCAM-1 can recruite the
leukocytes to arterial wall and trigger
atherosclerotic plaque formation
 Antiinflamation
NFKB

TNF α

Kurnia and Tjandrawinata. Medicinus 24(1):18-24, 2011

Inhibition of VSMC proliferation & migration

JAK 1

STAT 1

JAK 1

Kurnia and Tjandrawinata. Medicinus 24(1):18-24, 2011

Plaque Stabilization MMP9

MMP9 is a protease that degrades extracellular matrix proteins including gelatin,

collagen, elastin and laminin.
The activated MMP9 will degrade the tissue, including the plaque on the arterial
vessel, which could lead to plaque rupture

Kurnia and Tjandrawinata. Medicinus 24(1):18-24, 2011

 Double Blind Randomized clinical trial on Bleeding
Profile and Clinical Outcome - Ischemic stroke patients
2012

Neurology FK UGM Yogyakarta - DR. Dr. Ismail Setyopranoto Sp.S(K)

OBJECTIVE :
To Determine differences in bleeding profile and clinical outcome of
acute ischemic stroke patients by administering l DLBS 1033, aspirin
and clopidogrel

METHODS :
• Subject : 126, ischemic stroke patients.
• Randomized double blind clinical trials
• DLBS 1033 - 490 mg vs Aspirin - 80 mg vs Clopidogrel - 75 mg
• Hemostasis Examination used : PTT, APTT, INR
• Clinical outcome : Gadjah Mada Stroke Scale Score and Barthel
Index Score
 Jalannya Penelitian
 Subjek tetap diberikan terapi standar stroke akut
 Subjek yang sudah boleh pulang tetap diberikan obat-obat untuk
mengendalikan faktor risiko.
 Aspirin, clopidogrel dan DLBS1033 dengan sistem acak buta ganda
diberikan selama 3 bulan.
 Pada bulan ke-2, subjek diberi pengantar untuk pemeriksaan INR, PTT
dan APTT dan pemeriksaan dilakukan pada 2 hari sebelum kontrol pada
bulan ke-3.
 Pada kontrol hari ke-90 (3 bulan), subjek dilakukan pemeriksaan Indeks
Barthel dan SSGM.
 Dimonitor dan dicatat adanya keluhan atau kejadian yang tidak
diinginkan setelah pemberian obat-obat tersebut.
 Setelah selesai penelitian , pasien melanjutkan terapi standar untuk
stroke iskemik.
 Analisis Statistik
 Karena outcome dalam penelitian ini nilai INR,
PTT, APTT, Indeks Barthel dan SSGM merupakan
data kontinyu, maka digunakan t-test (jika
distribusi data masing-masing kelompok normal).
 Untuk karakteristik demografi baseline antara
kedua kelompok dianalisis dengan X2 (Chi-
square), terutama untuk variabel kategorikal
seperti status jender.
 Tingkat kemaknaan yang digunakan adalah 0,05
atau tingkat kepercayaan 95% (p<0,05), dengan
power 80%, analisis statistik digunakan program
statistik SPSS for Window versi 10.
 Hasil Penelitian
 Penelitian ini dilakukan di Unit Stroke dan Bangsal
Saraf RSUP Dr Sardjito Yogyakarta sejak bulan Juni
2011 sampai dengan September 2013.
 Besar sampel yang terkumpul dalam penelitian ini
sebanyak 129 subjek, yang terdiri
 43 subjek diberi aspirin,
 43 subjek diberi clopidogrel
 43 subjek diberi DLBS1033,
 Namun demikian pada masing-masing perlakuan
terdapat 1 subjek yang tidak melanjutkan penelitian,
sehingga jumlah total subjek adalah 126.
 Demography and Basic Characteristics of Subjects

Variables (mean) Aspirin Clopidogrel DLBS1033 p

Sex:
- Male 31 (73,8%) 29 (69,0%) 31 (73,8%) 0,854
- Female 11 (26,2%) 13 (31,0%) 11 (26,2%)
Age (year) 58,81 + 9,40 62,45 + 10,54 61,29 + 8,73 0,210
Initial Blood Pressure (mmHg):
- Systolic 166,90 + 35,97 162,74 + 26,09 168,45 + 29,39 0,570
- Diastolic 98,69 + 18,45 93,93 + 11,77 95,60 + 13,58 0,356
Initial Barthel Index Score 81,43 + 23,07 73,57 + 28,14 71,55 + 27,42 0,262
Initial SSGM Score 32,05 + 5,66 29,64 + 7,37 28,52 + 6,67 0,030
Laboratories:
- Fasting Blood Glucose 143,36 + 68,44 144,36 + 80,23 141,74 + 69,03 0,927
- Hemoglobin 14,58 + 1,52 13,88 + 1,76 14,28 + 1,57 0,365
- Cholesterol Total 226,21 + 43,84 217,69 + 48,02 214,28 + 45,61 0,222
- HDL 42,81 + 9,36 43,71 + 11,96 44,41 + 9,99 0,876
- LDL 160,08 + 36,74 140,79 + 35,63 142,24 + 32,03 0,044
- Triglyceride 173,40 + 90,83 154,17 + 80,92 147,27 + 61,66 0,559
- BUN 13,10 + 3,93 12,55 + 3,18 12,80 + 3,07 0,908
- Creatinin 1,23 + 0,70 1,17 + 0,41 1,09 + 0,51 0,766
- Uric Acid 6,48 + 1,42 6,20 + 1,72 6,50 + 1,50 0,748
- PTT 12,98 + 1,22 13,07 + 1,15 13,09 + 1,29 0,866
- APTT 29,65 + 1,22 29,39 + 3,39 29,65 + 4,73 0,978
- INR 0,93 + 0,16 0,93 + 0,13 0,96 + 0,15 0,545
 BLEEDING PROFILE – SAFETY ASPECTS

Mean change of parameters P

Bleeding profile
Aspirin Clopidogrel DLBS1033 ( Anova) *
- PTT 12,36 12,53 12,67 0,788
- APTT 29,59 29,96 30,54 0,619
- INR 0,94 0,96 0,99 0,154

Note : * Analysis on log transformed data

Results :
Not Significant Difference between Aspirin, Clopidogrel and DLBS1033 on
PTT, APTT, and INR  Relatively safe for the patients
Safety

• Within 3 months of treatment, DLBS1033 was

as safe as aspirin or clopidogrel in terms of
bleeding risk as measured by INR, PTT and
aPTT :
– No difference in INR, PTT and aPTT between groups, at
baseline and after 3 months of treatment
 CLINICAL OUTCOME RESULTS ON DAY-90

Clinical Outcome Baseline Day-90 Delta p

Barthel Index Score:
- Aspirin 81,43 96,55 15,12
- Clopidogrel 73,57 91,55 17,98 0,098
- DLBS1033 71,55 94,64 23,09
SSGM :
- Aspirin 32,05 35,79 3,74
- Clopidogrel 29,64 33,90 4,26 0,002
- DLBS1033 28,52 35,50 6,98

Results :
• Aspirin, Clopidogrel and DLBS 1033 showed Significant statistical difference
to improve clinical outcome on stroke patients, based on Barthel Index Score
and SSGM after 90 days of administration.
 Efficacy: Barthel Index

• After 3 months of post-acute treatment, aspirin, clopidogrel and DLBS1033

significantly increased (i.e. improved) the BI in ischemic stroke subjects.
• The improvement resulted in Aspirin, Clopidogrel and DLBS1033 Group were
equivalent, but seems greater in DLBS1033 Group
 Efficacy: SSGM

• After 3 months of post-acute treatment, aspirin, clopidogrel and DLBS1033 significantly

increased (i.e. improved) the SSGM in ischemic stroke subjects.
• The improvement resulted in DLBS1033 Group was significantly greater than that in
Aspirin or Clopidogrel Group.
 Other CV parameters: Systolic BP

• The SBP in Aspirin, Clopidogrel and DLBS1033 Group were equivalently well
controlled
o Note: anti-hypertensive agents used (for HT patients) during study conduct :
Valsartan 80/160 mg and/or Furosemid 40 mg or Amlodipin 5/10 mg, daily
 Other CV parameters: Diastolic BP

• The DBP in Aspirin, Clopidogrel and DLBS1033 Group were equivalently well
controlled
o Note: anti-hypertensive agents used (for HT patients) during study conduct :
Valsartan 80/160 mg and/or Furosemid 40 mg or Amlodipin 5/10 mg, daily
 Conclusion
This Study concluded that:
 DLBS1033 significantly improved the clinical outcome of
ischemic stroke treatment as measured by SSGM (Stroke Scale
Gadjah Mada).
 The improvement given by DLBS1033 was significantly greater
than that of aspirin or clopidogrel
 In terms of safety:
• Treatment with aspirin, clopidogrel and DLBS1033 for 90 days in ischemic
stroke subjects demonstrated no significant differences of hemostatic
profile, as measured by PTT, APTT dan INR.
 The safety of DLBS1033 in ischemic stroke subjects was similar
with that of aspirin or clopidogrel.
Berdasarkan mekanismenya maka
target terapi dari DLBS1033 dapat
diberikan pada kasus:
1. Stroke iskemik
2. Atherosclerosis
3. Acute Limb Ischemia
4. VTE (DVT dan Emboli Paru)
5. Jantung ( Angina pectoris,
NSTEMI,STEMI )
 DISOLF affected CIMT Reduction
Open study of DLBS1033 on the progression of CCA-IMT
in atheroscrelotic subjects (n = 18): DLBS1033
significantly reduced CIMT

Gunawan H, 2012. The effect of DLBS1033 on the progression of CIMT in subjects with atherosclerosis. Jakarta
 DLBS1033-CIMT case study
(Dr. Gunawan) Efficacy RESULT
Significant reduction in CCA-IMT from baseline to Week 2 and 4
of treatment
Parameters Baseline Week 2 Week 4

CIMT left (mm) 1.9 ± 0.52 1.3 ± 0.25 1.1 ± 0.30*

* p < 0.05 ver *
CIMT right 1.3 ± 0.32 -- 1.1 ± 0.37*
(mm)
Biggest CIMT CIMT 1.3 ± 0.32 1.2 ± 0.30*
(mm) (left)
 Significant improvement in MEDT (mitral E wave
deceleration time) by DISOLF

MEDT (mitral E wave deceleration time  an indicator of

diastolic dysfunction)
Parameters Baseline Week 2 Week 4

MEDT (msec) 140.6 ± 41.59 178.5 ± 21.92* 172.1 ± 20.45*

p (vs baseline) 0.005 0.010

Note : normal MEDT 140 – 240 msec

Gunawan H, 2012. The effect of DLBS1033 on the progression of CIMT in subjects with atherosclerosis. Jakarta
 Deep Vein Thrombosis

Mrs YF, 47 yrs

16 Mei 2011: Underwent coronary angiography at Hosp F
27 Mei 2011: Edema of right leg
30 Mei 2011: Doppler Diagnosis: DVT. Th/ Simarc
3 Jun 2011: Came to Harapan Kita Hosp.

Diagnosis: DVT. Totally occluded Right Com Fem Vein

Therapy : - Lumbrokinase 3x3
- Ardium 3x1
6 Juni 2011 10 Juni 2011 17 Juni 2011
 THROMBOEMBOLI
Mr S, 62 yrs
Diagnosis :
Acute Limb Ischemia, stage Iib
Mitral Stenosis, moderate
Atrial fibrilation
DM
Hypertension
Therapy :
Lumbrokinase 3x2
Cilostazol 100 2x1
Digoxin 0.25 1x1
Metformin 500 2x1
Irbesartan 150 1x1
ISDN 10 3x1
 CT Angio Day 1

Mr S, 62 yrs

23 Sept 2008

Right side :
Femoralis Superficialis Artery
tandem occlusion 3.5 cm and 13 cm
respectively.
Poplitea Artery totally occluded

Left side :
Iliaca Communis Artery occluded
7.4 cm
Poplitea Artery totally occluded
CT Angio Day 15 CT Angio Day 50
 Pain and numbness of both legs disappear
Day-4 Patient only felt stiffness on dorsum pedis and toes
Physical examination: weak pulsation of tibialis anterior and dorsalis pedis arteries
CT angiography: better contrast flow on bothn legs
Day-15 After 2 weeks of treatment with Lumbrokinase
 discharged with good conditions

Day-50 CT angiography: normal contrast flow on both legs

Mr N 69 y.o
Shortness of breath within 10 days
Diabetes Mellitus
Normal blood pressure

Pulmonary Embolism
•ECG:
S1Q3T3

• Chest X-ray :
within normal limit

• Echocardiography:
Mc Connel Sign

• D-dimer assay test: 2100

• Lung Perfusion Scanning:

V/Q mismatch

• CTA Filling defect RPA

 Pulmonary Embolism
Day 2

Lung Perfusion Scanning

CTA PULMONARY ARTERY
 Treatments:
Aspilet, 1 X 80mg
Lumbrokinase, 3 X 3 capsule
 After 10 days of Treatment

• Short of breath  Getting better

• D-dimer  Decrease
• CT Scan  Improvement
• Ultrasound  Improvement
• Lung Perfusion Scan  Improvement
 CT PA
Day 2 Day 10
Day 1
Day 10
day 30 day 10 day 0
 THE EFFECT OF DLBS1033
IN PERIPHERAL ARTERY DISEASE

Randomized Clinical Controlled Trial, 20

number of subject , mean age of all 55,4
years old , for 2 weeks evaluation

Ndraha S et al. Depart of Intern Med UKRIDA Christian

University, Jakarta-indonesia 2013
68
Baseline characteristic of patients with intermittent claudication in Koja Hospital (n=20)
Baseline Characteristic DLBS 1033 (n:10) Control ( n:10 )
n % n %
1. Age
a. < 60 years old 6 30 8 40
B. 60-80 years old 4 20 2 10
C. > 80 years old 0 0 0 0
d. Mean age (years old) 55.8 7.8 53.2 6.8
2. Sex
Female 9 45 9 45
Male 1 5 1 5
3. Subjective complaint
a. Pain
b. Numbness
7
3
35
15
5
1
25
5
Jakarta , April – Aug 2013
c. Leg heaviness 0 0 4 20
4. Smoker
a. Non Smoker
b. Ex-smoker
7
2
35
10
9
0
45
0
Measurement :
c. Smoker 1 5 1 5 ABI ( Ankle Brachial Index )
d. > 10 cigarettes per day 0 0 0 0
5. Exercise
a. Never 7 35 9 45
b. Once a month 1 5 1 5 Dose :
c. Once a week 2 10 0 0
d. 2-3 times a week 0 0 0 0 DISOLF 3 x 1
6. Body mass index (BMI)
a. Underweight (BMI < 18.5 kg/m2) 2 10 2 10 Versus Placebo
b. Normoweight (BMI 18.5 – 25 kg/m2) 5 25 5 25
c. Overweight (BMI > 25 – 29.9 kg/m2) 3 15 3 15
e. Obese (IMT ≥ 30 kg/m2) 0 0 0 0
7. Hypertension
a. Yes 8 40 6 30
b. No 2 10 4 20
8. Diabetes mellitus (DM)
a. Yes 7 35 5 25
b. No 5 25 3 15
9. Dyslipidemia
a. Yes 6 30 6 30
b. No 4 20 4 20
10. Ankle Brachial Index (ABI)
a. Mild – moderate 0.41 – 0.9) 10 50 10 50
b. Severe (0.00 – 0.40) 0 0 0 0
Results after 2 weeks

Figure 1. Ankle-Brachial Index (ABI) values in DLBS1033 and

Control group, pre- and post-treatment
 Improvement after 2 weeks

Figure 2. Improvement of Ankle-Brachial Index (ABI) values from baseline.

Improvement of Ankle-Brachial Index (ABI) values in DLBS1033 group was significantly
higher than that in Control group (p < 0.01)
CONCLUSION
 Almost all PAD subjects were females,
mean age of all subjects was 55.4 years
old.
 The most prevalent independent risk
factors for PAD observed in the study were
hypertension, diabetes, dyslipidemia, and
lack of exercise.
 DBLS1033 showed to improve ABI in
patients with intermittent claudication.
Mr. OW 55 y.o

ACUTE STEMI ANTERIOR

onset 36 hours

Treatments:
Aspirin, Clopidogrel, Arixtra
Maintate
Discharge:
+ Lumbrokinase 3x 1 tablet
MPI – Gamma Camera
 MPI : Summed Stress Score ( SSS )
STEMI

PRE

POST
25/11/2010 - PRE STEMI
SSS 33 SRS 26 SDS 7

28/12/2010 – POST Lumbrokinase 3 x 1 tab 1 mo

SSS 23 SRS 23 SDS 0
Mrs S 75 y.o

ACUTE NSTEMI

Treatments:
Aspirin, Clopidogrel, Arixtra
Maintate
Discharge:
+ Lumbrokinase 3x 1 tablet
Acute NSTEMI Discharge standard treatment
Mrs. S /75
+ Lumbrokinase 3 x 1 tablet

1 Week

SSS 26 SRS 22 SDS 4

Acute NSTEMI Standard treatment
Mrs. S /75 + Lumbrokinase 3 x 1 tablet

1 Month
 SSS SRS SDS

Discharge

25 22 4
Acute After Tx
NSTEMI Lumbro 30
days
Mrs. S / 75
1 1
1

1 Month
EF 34% Acute EF 64%
NSTEMI
Mrs. S /75

55 % 1%

After Tx
EF 35% Lumbro
30 days EF 58%

51 % 3%
 Improved Myocardial Perfusion in Stable
Angina Pectoris by Oral Lumbrokinase:
A Pilot Study

M. Kasim, A. A. Kiat, M. S. Rohman, Y. Hanifah, and H. Kiat,

Improved myocardial perfusion in stable angina pectoris by
oral lumbrokinase: a pilot study, Journal of Alternative and
Complementary Medicine, vol. 15, no. 5, pp. 539–544, 2009.

10 stable angina pectoris patients were randomly selected

from proved CAD population in National Cardiovascular
Center Harapan Kita.

Diagnosis of CAD confirmed by MSCT or coronary

angiography examination.
 Methods

They were given additional 2 capsules of 250 mg

lumbrokinase three times daily (3 x 2 Capsule) for 30 days
to a standard therapy including nitrate, ß blocker, statin
and aspirin.

Perfusion imaging 99mTc-Sestimibi was used to evaluate

the perfusion and viability of myocardium before and after
treatment using DSX rectangular gamma Sophy camera.
 Results

70% of total sample receiving oral lumbrokinase

revealed a significant decrease summed stress score of
perfusion imaging suggesting a better perfusion in
viable myocardium after 30 day oral lumbrokinase
treatment.
 MPI
Improved Perfusion after 1 month lumbrokinase in APS

Pre Treatment Post Treatment Pre Treatment Post Treatment

Patient # 6 : SSS 33  12
- 39%
SSS <4 normal scan
4-8 mild
9-13 moderate
>13 severe abnormal scan
- 37%
SDS = (SSS – SRS)
<2 no ischemia
2-7 mild to moderate
>7 severe ischemia
 Conclusion

This pilot study represents the first description of the use of oral
lumbrokinase in the treatment of chronic CAD with objective
assessment using MPI.

Lumbrokinase effects a reduction in the degree and extent of

inducible myocardial ischemia with amelioration of anginal
symptoms in patients with CAD with stable angina, after one
month treatment without bleeding complication