R2 Patcharee Seesongsom R2 Sirada Phojai Advisor AJ T a chawan J iratiwanon Scope Overview Introduction of NOACs Rivaroxaban Xarelto Dabigatran Pradaxa ID: 571148
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Slide1
New Oral Anticoagulant
R2 Patcharee Seesongsom
R2
Sirada
Phojai
Advisor AJ
T
a
chawan
J
iratiwanonSlide2
Scope
Overview
Introduction of NOACs
Rivaroxaban ( Xarelto )Dabigatran ( Pradaxa )Anesthetic implicationSlide3
Hemostasis
http://www.thrombosisadviser.com/en/understanding-thrombosis/haemostasis/
Primary hemostasis
Secondary hemostasisSlide4Slide5
NEW FUNDAMENTALS IN HEMOSTASIS
Physiol
Rev93: 327–358,
2013doi:10.1152/physrev.00016.2011Slide6
NEW FUNDAMENTALS IN HEMOSTASIS
Physiol
Rev93: 327–358,
2013doi:10.1152/physrev.00016.2011Slide7
Various Phases of Coagulation
Initiation
phase
Extrinsic pathway of coagulation. Disrupted vasculature. FVII, TF ( Tissue factor ). Amplification phaseThrombin.
Propagation phase
NEW FUNDAMENTALS IN HEMOSTASIS
Physiol
Rev93: 327–358,
2013doi:10.1152/physrev.00016.2011Slide8Slide9
Oral Anticoagulant Drug
Current anticoagulants
Vitamin K antagonists : warfarinNovel anticoagulantsDirect Factor Xa
inhibitors : rivaroxaban, apixaban
Direct
thrombin
inhibitors :
Ximelagatran
,
Melagatran
,
dabigatranSlide10
Do you know mechanism of action of warfarin
?Slide11
Warfarin >> Vitamin K Antagonist Slide12
Disadvantage of Warfarin
Narrow
therapeutic
range.Slow onset of action.Slow offset of action (long duration of action,long elimination
half life) Multiple drug and dietary interactions.
Monitoring
required to maintain
in therapeutic range.
Thromb
Haemost
2010;103:34-39Slide13
Oral Anticoagulant drug
Novel anticoagulants
Direct Factor
Xa inhibitors : rivaroxaban ( Xarelto )
Direct thrombin
inhibitors :
dabigatran
(
Pradaxa
)Slide14
Action of Anticoagulant Drug
Rivaroxaban
Dabigatran
Rivaroxaban
: An oral direct inhibitor of factor
Xa
,
American
Society of Health-System
Pharma
-cists
,
Inc. All rights reserved.
1079-2082/08/0802-1520$06.00.DOI
10.2146/ajhp070624Slide15
RivaroxabanSlide16
Rivaroxaban
Managing
New Oral Anticoagulants in the Perioperative
and Intensive Care Unit Setting
,the American Society of Anesthesiologists
, Inc. Lippincott
Williams
& Wilkins. Anesthesiology 2013; 118:1466-74
Direct
FXa
inhibitorSlide17
Pharmacokinetic of Rivaroxaban
Managing
New Oral Anticoagulants in the Perioperative
and
Intensive Care Unit
Setting
,
the
American
Society of Anesthesiologists
, Inc. Lippincott
Williams
& Wilkins. Anesthesiology 2013; 118:1466-74Slide18
Drug Interaction
New Drug
Review
Rivaroxaban
: An Oral Factor Xa
Inhibitor
(
Clin
Ther.2013;35:427) © 2013 Published by Elsevier HS
Journals, Inc
.Slide19
Not Recommended
Avoid in patients with mod-severe hepatic impairment
Avoid in pregnancy women
New Drug Review Rivaroxaban: An Oral Factor
Xa InhibitorClin
Ther.2013;35:427
.Slide20
Monitoring
Rivaroxaban
prolongs the
prothrombin time (PT) and this might be used as a rough estimate of an anticoagulation effect.A better estimate for an anticoagulant effect for the oral Factor Xa inhibitors is
an anti-Xa assay.
Managing
New Oral Anticoagulants in the Perioperative
and
Intensive Care Unit
Setting
,
the
American
Society of Anesthesiologists
, Inc. Lippincott
Williams
& Wilkins. Anesthesiology 2013; 118:1466-74Slide21
n engl j med 358;26 www.nejm.org june 26, 2008Slide22Slide23
RECORD1 clinical trials
.Slide24
RECORD1 clinical trials
.Slide25
Conclusion
Rivaroxaban
was
superior to enoxaparin for thromboprophylaxis
after total hip arthroplasty,
with
similar rates of
bleeding.
10-mg
oral
of
rivaroxaban
VS
40-mg
SC of enoxaparin.
RECORD1 clinical trials
.Slide26
n engl j med 358;26 www.nejm.org june 26, 2008Slide27Slide28
RECORD3 clinical trials
.Slide29
RECORD3 clinical trials
.Slide30
Conclusion
Rivaroxaban
was
superior to enoxaparin for thromboprophylaxis
after total knee arthroplasty, with
similar rates of bleeding
.
10-mg oral of
rivaroxaban
VS 40-mg SC of enoxaparin.
RECORD3 clinical trials
.Slide31
n
engl
j med 365;10 nejm.org
september 8, 2011Slide32Slide33Slide34Slide35
Conclusion
In patients with
AF,
rivaroxaban was equal to warfarin for the prevention
of stroke or systemic embolism. There
was no significant between-group
difference
in the risk of major bleeding, although
intracranial and fatal bleeding
occurred
less
frequently in the
rivaroxaban
group.
ROCKET
AF
Clinical Trials.Slide36
Approval
Approved by
FDA,
EMA ( European Medicines Agency ) & ACCP ( American College of Chest Physicians )
VTE prophylaxis after hip or knee replacement surgery.Stroke
prevention in patients
with
non-
valvular
AF.Slide37
Dosing Guidelines
Managing
New Oral Anticoagulants in the Perioperative
and
Intensive Care Unit
Setting
,
the
American
Society of Anesthesiologists
, Inc. Lippincott
Williams
& Wilkins. Anesthesiology 2013; 118:1466-74Slide38
Dabigatran
Slide39
Dabigatran
Managing
New Oral Anticoagulants in the Perioperative
and
Intensive Care Unit Setting,the American
Society of Anesthesiologists
, Inc. Lippincott
Williams
& Wilkins. Anesthesiology 2013; 118:1466-74
Direct thrombin inhibitorSlide40
Pharmacokinetic of Dabigatran
Managing
New Oral Anticoagulants in the Perioperative
and
Intensive Care Unit Setting,the American
Society of Anesthesiologists
, Inc. Lippincott
Williams
& Wilkins. Anesthesiology 2013; 118:1466-74Slide41
Drug interaction
Ketoconazole
Quinidine
AmiodaroneVerapamil Slide42
Monitoring
Prolong
aPTT
( exclude if normal value)Prolong thrombin time Prolong of ECT ( ecarin clotting time ) is directly and linearly to the plasmatic levels of
dabigatran. Slide43
Ecarin Clotting Time Slide44
RE-LYSlide45
Procedure >> 18,113 patients Slide46
RE-LY clinical trails.
Stroke and
systemic embolismSlide47
RE-LY clinical trails.Slide48
Major bleedingSlide49
Stroke or Systemic embolism
Dabigatran
110 mg VS
warfarin
(Relative risk)
Dabigatran
150 mg VS
warfarin
(Relative risk)
Stroke or Systemic embolism
0.91
(0.74-1.11)
P-value < 0.001
0.66 (0.53-0.82)
P-value < 0.001
Major bleeding
0.80(0.69– 0.93)
P-value 0.003
0.93(0.81-1.07)
P-value
0.31Slide50
Conclusion
P
atients with AF,
dabigatran 110 mg oral bid VS warfarin treatmentSimilar rate of stroke and systemic embolism
lower rates of major hemorrhage.
Patients with AF,
dabigatran
150 mg oral bid
VS
warfarin
treatment
lower
rate of stroke and systemic embolism
similar
rates of major
hemorrhage. Slide51Slide52Slide53Slide54
Conclusion
Meta-analysis of RE-MODEL and RE-NOVATE and RE-MOBILIZE
Dabigatran
etexilate is non-inferior to enoxaparin 40 mg
od, with a similar
safety
profile.
No significant
difference between
dabigatran
and
enoxaparin
in any of the end-points
analysed
Total VTE
All cause of mortalitySlide55
Approval
Stroke
prevention in patients
with non-valvular AF.Approved by FDA & EMA ( European Medicines Agency ),Canada,Japan and United statesVTE
prophylaxis after hip or knee replacement surgery.Approved in Europe and Canada
Not approved ,yet in United statesSlide56
Dosing Guidelines
Managing
New Oral Anticoagulants in the Perioperative
and
Intensive Care Unit Setting,the
American
Society of Anesthesiologists
, Inc. Lippincott
Williams
& Wilkins. Anesthesiology 2013; 118:1466-74Slide57
Anesthetic Implication
Elective surgery
Emergency surgerySlide58
Preoperative Discontinuation of
Dabigatran
Managing
New Oral Anticoagulants in the Perioperative
and Intensive Care Unit Setting,
the
American
Society of Anesthesiologists
,
Anesthesiology
2013; 118:1466-74Slide59
Interruption of Target-Specific Oral Anticoagulant Therapy for
Invasive
Procedures and Surgery
Oral anticoagulant therapies: Balancing the
risks,Am
J Health-
Syst
Pharm—Vol
70 May 15, 2013 Slide60
Recommended time intervals before and
after puncture
or catheter removal
Time
before puncture/cathetermanipulation or removal
Time
after
puncture/catheter
manipulation or removal
Rivaroxaban
(for
prophylaxis, 10 mg OD)
22–26 h
4–6 h
Dabigatran
(for prophylaxis, 150–220 mg)
Contraindicated according
to the manufacturer
6 h
Guideline Regional
anaesthesia
and antithrombotic
agents
:
recommendations
of the European
Society of
Anaesthesiology
,
Eur
J
Anaesthesiol
2010;27:999–1015Slide61
Emergency caseSlide62
Managing
New Oral Anticoagulants in the Perioperative
and
Intensive Care Unit
Setting,the American
Society of Anesthesiologists
, Inc. Lippincott
Williams
& Wilkins. Anesthesiology 2013; 118:1466-74Slide63
Managing
New Oral Anticoagulants in the Perioperative
and
Intensive Care Unit
Setting,the American
Society of Anesthesiologists
, Inc. Lippincott
Williams
& Wilkins. Anesthesiology 2013; 118:1466-74Slide64
Take Home Message
New oral anticoagulants have approved for
thromboprophylaxis
after hip & knee arthroplasty
and stroke prevention in non-
valvular
AF patient
.
Rivaroxaban
> Direct
Fxa
inhibitor.
Dabigatran
> Direct thrombin inhibitor.
No antidote
available now.
If abnormal bleeding >> Supportive & symptomatic treatment.Slide65
THANK YOUSlide66
new
E
ngland
Jounal med 361;24 nejm.org december 10, 2009Slide67Slide68
Conclusion
A
fixed dose of
dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin for treatment of venous thromboembolism.Slide69
Recommended time intervals before and after puncture or catheter removalSlide70
2012 focused update of the ESC Guidelines for the management of atrial fibrillation
,
European Heart Journal (2012)33, 2719–2747 doi:10.1093/
eurheartj
/ehs253Slide71
2012 focused update of the ESC Guidelines for the management of atrial
fibrillation
,European
Heart Journal (2012)33, 2719–2747 doi:10.1093/
eurheartj
/ehs253Slide72Slide73Slide74Slide75Slide76Slide77Slide78Slide79Slide80