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Curriculum Vitae• Name : Prof. DR. Dr. Idrus Alwi SpPD, K-KV, FACC, FESC, FAPSIC,
FINASIM, FACP.
• Current Position : Professor of Internal Medicine, Faculty of Medicine,
University of Indonesia.
• Medical Student : Faculty of Medicine University of Indonesia 1986
• Internist : Faculty of Medicine University of Indonesia 1996
• Cardiovascular Consultant : The Indonesian Society of Internal Medicine , 2001
• PhD : Faculty of Medicine University of Indonesia, 2006
• FACC : American College of Cardiology, 2006
• FESC : European Society of Cardiology, 2008
• FAPSIC : Asia Pacific Society of Interventional Cardiology, 2009
• FINASIM : Indonesian Society of Internal Medicine, 2009
• FACP : American Colleague of Physician, 2013
• Advanced Course in Cardiology, Melbourne 1997
• Advanced Course on Echocardiography and Others Non Invasive Cardiology, Melbourne 1997
• Stem cell NOGA course, Cincinnatti, Ohio, 2009
• ASAN Interventional Cardiology Course, Seoul, 2011
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Division of Cardiology, Department of Internal Medicine, Faculty of Medicine , University of Indonesia,
Jakarta , Indonesia
Prof. Idrus Alwi MD, PhD, FINASIM, FACP, FACC, FESC, FAPSIC
The Role of Anticoagulant in ACS Management
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Outline
Spectrum of ACS, Therapy, Risk Stratification, Target of Anticoagulant
OASIS 5, Registry Data, OASIS 8
Recommendation of Anticoagulants
Conclusion
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Outline
Spectrum of ACS, Therapy, Risk Stratification, Target of Anticoagulant
OASIS 5, Registry Data, OASIS 8
Recommendation of Anticoagulants
Conclusion
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The spectrum of ACS
European Heart Journal (2011) 32, 2999–3054
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STEMI
1. Revascularisation
2. Anti - Thrombotic
3. Anti - Ischemia
NSTEMI
1. Anti - Ischemia
2. Anti - Thrombotic
3. Revascularisation
Therapy of Choice
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It is recommended to use established risk scores for prognosis and bleeding (e.g. GRACE, CRUSADE)
European Heart Journal (2011) 32, 2999–3054
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European Heart Journal (2011) 32, 2999–3054
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Fondaparinux Mechanism of Action
1. Olson et al. Role of the antithrombin-binding Pentasaccharide in heparin acceleration of antithrombin-proteinase reaction
J Biol Chem 1992;267:12528-38
2. Turpie et al. A synthetic Pentasaccharide for the Prevention of deep-vein trombosis after total hip replacement.
N Engl J Med 2001;344:619-25
Thrombin
Fibrinogen
Extrinsic pathway
Intrinsicpathway
AT
Fondaparinux
XaAT
Antithrombin
Fibrin clot
Xa
Pro-thrombin
Reutilized
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Outline
Spectrum of ACS, Therapy, Risk Stratification, Target of Anticoagulant
OASIS 5, Registry Data, OASIS 8
Recommendation of Anticoagulants
Conclusion
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OASIS 5: An International, Multicenter, Randomized, Double-Blind, Double-Dummy
Trial in 41 Countries
1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76.
20,078 patients with UA/NSTEMI20,078 patients with UA/NSTEMI
Fondaparinux2.5 mg s.c. od up to 8 days
Aspirin, Clopidogrel, anti-GPIIb/IIIa, planned Cath/PCI as per local practice
Randomization
Enoxaparin1 mg/kg s.c. bid for 2-8 days
1 mg/kg s.c. od if ClCr<30mL/min
Vital status ascertained in 20,066 (99.9%) Lost to follow-up at day 9: fondaparinux: n=7 and enoxaparin: n=5
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Study Objectives and OutcomesObjectives
Primary efficacy objective: To demonstrate non-inferiority of fondaparinuxcompared with enoxaparin
Primary safety objective: To determine whether fondaparinux was superior to enoxaparin in preventing major bleeding
Objectives
Primary efficacy objective: To demonstrate non-inferiority of fondaparinuxcompared with enoxaparin
Primary safety objective: To determine whether fondaparinux was superior to enoxaparin in preventing major bleeding
Outcomes (centrally adjudicated)
Primary efficacy: 1st occurrence of the composite of death, MI, or refractory ischemia (RI) up to day 9
Primary safety: Major bleeding up to day 9
Risk benefit: Death, MI, refractory ischemia, major bleeds up to day 9
Secondary: Above & each component separately at days 30 and 180
1. ArixtraTM PI BPOM 4 October 2010, GDS04/IPI04 (23 January 2007).2. Salim Yusuf, et al. Comparison of Fondaparinux and Enoxaprine in Acute Coronary Syndrome.
The fifth organization to assess strategies in Acute Ischemic Syndrome investigator. N Egl J Med 2006:354:1446-76.
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Cumulative Risk through Day 9
Yusuf et al. N Engl J Med 2006;354:1464-76
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Cumulative Risk through Day 180
Yusuf et al. N Engl J Med 2006;354:1464-76
Death through Day 180 Death, Myocardial Infarction, or Stroke through Day 180
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Results of Subgroup Analyses of Efficacy
Yusuf et al. N Engl J Med 2006;354:1464-76
Primary Efficacy at 9 Days Major Bleeding at 9 Days
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Treatments, Complications, and Outcomes among Patients Undergoing PCI within the First Eight Days after Randomization
Yusuf et al. N Engl J Med 2006;354:1464-76
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Summary of OASIS 5
• Fondaparinux at a dose of 2.5 mg daily is similar to enoxaparin in the short term in preventing ischemic events among patients with acute coronary syndromes without ST-segment elevation, but it is associated with substantially less bleeding — an effect that translates into lower long-term mortality and morbidity
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Brazilian Registry Data
de Matos Soeiro et al. Arq Bras Cardiol. 2016; 107(3):239-244
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SWEDEHEART Registry
Szummer et al. JAMA. 2015;313(7):707-716
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Mehta et al. J Am Coll Cardiol 2007;50:1742–51
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Is fo
nd
apar
inu
x sa
fer
than
en
oxap
arin
for
pat
ient
s u
nd
ergo
ing
P
CI?
Antman EM. Nat Clin Prac Cardiovasc Med. 2007Mehta et al. J Am Coll Cardiol 2007;50:1742–51
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Study Design OASIS 8
NSTEACSFonda
2.5 mg sc
AngioNo PCI
30 Day Follow-Up
Angiowith PCI R
Std Dose UFH
(85 U/kg or 60 U/kg with GP IIb/IIIa)
ACT guided*
30 Day Follow-Up
Low Dose UFH
(50 U/kg irrespective of GP IIb/IIIa) –
without ACT
30 Day Follow-Up
With at least 2 of following:
• Age>60
• elevated biomarkers
• ECG changes
Patients were not eligible if
required urgent coronary
angiography (<120 min) due
to clinical instability
Adjunctive therapy
during PCI
Double
Blind
Registry
*ACT Targets consistent with current guidelines
Coronary Angiography/PCI to be
performed within 72 hours
Jolly et al. JAMA. 2010;304(12):1339-1349
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Study Outcome DefinitionsMajor Bleeding (OASIS 5)
• Fatal
• Symptomatic ICH
• Retroperitoneal hemorrhage
• Intraocular bleeding leading to significant vision loss
• Requiring surgical intervention
• Hb drop of ≥3 g/dL
• Blood transfusion of > two units RBCs
Minor Bleeding Any other significant bleeding leading to transfusion of one unit of blood or discontinuation of antithrombotic therapy.
Major Vascular Access Site Complications
• Large hematoma (≥5 cm or requiring intervention)
• Pseudoaneurysm requiring treatment
• Arterio-venous fistula
• Other vascular surgery related to the access site
Jolly et al. JAMA. 2010;304(12):1339-1349
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Results
Jolly et al. JAMA. 2010;304(12):1339-1349
Death, myocardial infarction, or target vessel revascularisationMajor Bleeding
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Treatment Effect for Primary Outcome
Jolly et al. JAMA. 2010;304(12):1339-1349
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Treatment Effect for Death, Myocardial Infarction, or Target Vessel Revascularization
Jolly et al. JAMA. 2010;304(12):1339-1349
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Outline
Spectrum of ACS, Therapy, Risk Stratification, Target of Anticoagulant
OASIS 5, Registry Data, OASIS 8
Recommendation of Anticoagulants
Conclusion
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Recommendations for anticoagulants
Eur Heart J.2015
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Recommendations for anticoagulants
Eur Heart J.2015
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Recommendations for anticoagulants
Eur Heart J.2015
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Recommendations for anticoagulants
Eur Heart J.2015
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Recommendations for anticoagulants
Eur Heart J.2015
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Recommendations for anticoagulants in patients with normal and impaired renal function
Eur Heart J.2015
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Outline
Spectrum of ACS, Therapy, Risk Stratification, Target of Anticoagulant
OASIS 5, Registry Data, OASIS 8
Recommendation of Anticoagulants
Conclusion
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In management of ACS, the efficacy and safety of antithrombotic are
primary concern
Anticoagulant options in management of UA/NSTEMI: UFH, LMWH &
Fondaparinux
Based on OASIS 5, fondaparinux is a selective factor Xa inhibitor which
offers similar efficacy with less bleeding risk compared to enoxaparin for
management UA/NSTEMI
Fondaparinux 2.5 mg SC once daily is preferable than enoxaparin as
recommended by ESC guideline for UA/NSTEMI patients
Adding UFH during PCI to fondaparinux preserves the benefits and safety
of fondaparinux (ie. reduced bleeding) while minimizing catheter thrombus
Conclusion
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