Anticoagulant Therapy in nstemi patients alwi - The Role of Anticoagula… · Szummer et al. JAMA. 2015;313(7):707-716. Mehta et al. J Am Coll Cardiol 2007;50:1742–51. n ? Mehta

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

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

Outline

Spectrum of ACS, Therapy, Risk Stratification, Target of Anticoagulant

OASIS 5, Registry Data, OASIS 8

Recommendation of Anticoagulants

Conclusion

Outline




Conclusion

The spectrum of ACS

European Heart Journal (2011) 32, 2999–3054

STEMI

1. Revascularisation

2. Anti - Thrombotic

3. Anti - Ischemia

NSTEMI

1. Anti - Ischemia

2. Anti - Thrombotic

3. Revascularisation

Therapy of Choice

It is recommended to use established risk scores for prognosis and bleeding (e.g. GRACE, CRUSADE)



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

Outline




Conclusion

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

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.

Cumulative Risk through Day 9

Yusuf et al. N Engl J Med 2006;354:1464-76

Cumulative Risk through Day 180


Death through Day 180 Death, Myocardial Infarction, or Stroke through Day 180

Results of Subgroup Analyses of Efficacy


Primary Efficacy at 9 Days Major Bleeding at 9 Days

Treatments, Complications, and Outcomes among Patients Undergoing PCI within the First Eight Days after Randomization


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

Brazilian Registry Data

de Matos Soeiro et al. Arq Bras Cardiol. 2016; 107(3):239-244

SWEDEHEART Registry

Szummer et al. JAMA. 2015;313(7):707-716

Mehta et al. J Am Coll Cardiol 2007;50:1742–51

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

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

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

Results

Jolly et al. JAMA. 2010;304(12):1339-1349

Death, myocardial infarction, or target vessel revascularisationMajor Bleeding

Treatment Effect for Primary Outcome

Jolly et al. JAMA. 2010;304(12):1339-1349

Treatment Effect for Death, Myocardial Infarction, or Target Vessel Revascularization

Jolly et al. JAMA. 2010;304(12):1339-1349

Outline




Conclusion

Recommendations for anticoagulants

Eur Heart J.2015


Eur Heart J.2015


Eur Heart J.2015


Eur Heart J.2015


Eur Heart J.2015

Recommendations for anticoagulants in patients with normal and impaired renal function

Eur Heart J.2015

Outline




Conclusion

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

Documents

Anticoagulant Therapy in nstemi patients alwi - The Role of Anticoagula… · Szummer et al. JAMA. 2015;313(7):707-716. Mehta et al. J Am Coll Cardiol 2007;50:1742–51. n ? Mehta