This document summarizes information about various oral anticoagulants including warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban. It discusses their pharmacokinetic properties, dosing, indications for preventing thromboembolic events in atrial fibrillation and venous thromboembolism, efficacy and safety based on clinical trials, and considerations for use in Asian populations and perioperative settings. Meta-analyses found NOACs reduce stroke, mortality, and intracranial hemorrhage compared to warfarin, though increase gastrointestinal bleeding. Guidelines recommend NOACs over warfarin for non-valvular atrial fibrillation in Asians.

3. Coagulation cascade
12 12a
11 11a
9 9a
10 10a
77a
8a
5a
Prothrombin Thrombin
Fibrinogen
13a
Fibrin
KK
K
K
K K
VKOR
Warfarin

4. Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban
Cofarin®
Onset 24-72 hr 1-2 hr 2-4 hr 3-4 hr 1-2 hr
t1/2 40 hr 12-17 hr 5-9 hr 12 hr 10-14 hr
BA 100% 6% 80% 60% 62%
Food - - +39% - +6-22%
92% 80% 35% 27% 50%
2C9 3A4 3A4 3A4
1 & 5 mg 110 & 150 mg 10 15 20 mg 5 mg 60 mg
Dose adjustment
tailored to
patient digestion
110 mg for
Age ≥ 75
BW < 50 kg
Previous GI Bleed
Ccr 30-50 mL/min
CHADS2 ≥ 3
15 mg for
Ccr 30-50 mL/min
(Age ≥ 65 by BEER)
(Asian by J-ROCKET)
2.5 mg for
2 risks:
Age ≥ 80
BW < 60 kg
Cre ≥ 1.5 mg/dL
30 mg for
Ccr 30-50 mL/min
(Age ≥ 65 by BEER)
Strong p-gp inhibitor

5. Indications: preventing thrombo-embolic events
• Non-valvular atrial fibrillation
• Deep vein thrombosis
• Pulmonary embolism
• Prevention of DVT after hip and knee replacement
surgery

6. Non-valvular atrial fibrillation
• Valvular atrial fibrillation is associated with more
thromboembolic risks
• Severe mitral stenosis
• Mechanical valve replacement
• RE-ALIGN: high dose dabigatran (150-330 mg) in mechanical valve
• RIVER: rivaroxaban for VHD & Afib (MS)
• RAMV: rivaroxaban & apixaban in mechanical valve
• Bio-prosthetic valve replacement (?)
• Valvuloplasty with/without rings (?)
• MR, MVP, AS, AR (?)

7. NOAC (Trial) Dose
Inclusion
(CHADS2)
Exclusion TTR
Stroke
+SEE
ICH
Major
bleeding
GI
bleeding
Bleeding
of any
cause
(RE-LY)
150 mg
BID
CHADS-VASc ≥1
(mean 2.1)
History of heart
valve disorder
(including
MS/MR/AS/AR)
* Ccr < 30 mL/min
64%
(ROCKET-AF)
20 mg
QD
CHADS2 ≥2
(mean 3.5)
Hemodynamically
significant MS &
prosthetic valve
* Ccr < 30 mL/min
55%
(ARISTOTLE)
5mg
BID
CHADS2 ≥1
(mean 2.1)
Clinically significant
MS
& mechanical valve
* Ccr < 25 mL/min
Scr > 2.5 mg/dL
62%
(ENGAGE-AF)
60 mg
QD
CHADS2 ≥2
(mean 2.8)
Clinically significant
MS
& mechanical valve
* Ccr < 25 mL/min
65%
*
SEE: Systemic embolic event

8. Meta-analysis of pivotal trials
• Standard dose
• Reduce stroke & SEE, mainly by hemorrhagic stroke
• Reduce all-cause mortality & ICH
• Increased in GI bleeding
• Greater reduction in major bleeding in TTR <66%
(warfarin with poor controlled INR)
• Low dose regimen
• Similar efficacy with warfarin
• Increased ischemic stroke & MI with reduced hemorrhagic
stroke

10. Asian sub-analysis
GI bleeding
All bleeding

11. Asian sub-analysis
Stroke+SEE Hemorrhagic strokeIschemic stroke

12. Asian sub-analysis

13. Taiwan Afib guideline 2016

14. Patient with ACS & oral anticoagulant
• DC OAC at presentation
• Keep DAPT + OAC for 1 months for elective PCI
for 3-6 months for ACS/PCI
* low dose NOAC or warfarin INR 2-2.5 is preferred
• Keep Plavix + OAC till 1 year
till 3-6 months for high bleeding risk
• OAC alone after 1 year

15. For elective surgery

16. For elective surgery
• aPTT & PT are not indicator of NOACs’ efficacy &
safety
• aPTT can be used to assess the presence of the
anticoagulant effect of dabigatran
• PT (but INR) can be used to assess the presence of
the anticoagulant effect of rivaroxaban
• Anti-Xa assay for all Xa inhibitors

17. DVT
NOAC (Trial)
Bridge or
LD
Dose Dose adjustment TTR
VTE or
related
death
ICH
Major
bleeding
GI
bleeding
Bleeding
of any
cause
(RE-COVER)
LMWH SC
X 5-10 day
150 mg
BID
110 mg for
Age ≥ 80 +
BW < 50 kg
Previous GI Bleed
Ccr 30-50 mL/min
CHADS2 ≥ 3
60%
2.4%
vs 2.1%
(non-sig)
(EINSTEIN
-DVT/-PE)
15 mg BID
X 21 day
20 mg
QD
10 mg BID then
15 mg QD
in J-EINSTEIN
10 mgQD for
non-extended Tx
58% DVT 2.1%
vs 3.0%
PE 2.1%
vs 1.8% (Pooled
result)
(AMPLIFY)
10 mg BID
X 7 day
5mg
BID
2.5 mg BID for
reduced risk
61%
2.3%
vs 2.7%
(HOKUSAI-VTE)
LMWH SC
X 5-10 day
60 mg
QD
30 mg for
BW > 60
Ccr 30-50 mL/min
64%
1.6%
vs 1.9%

18. RECOVER: efficacy
EINSTEIN-VTE: efficacy
AMPLIFY: efficacy
HOKUSAI-VTE: efficacy

19. EKOS
• No comparative studies in selection of anticoagulants
after EKOS catheterization.
• Current recommendations suggest therapy based on VTE
stratification.
• Warfarin with INR goal 2.5-3.5 is recommended after
successful thrombolysis.
• Case series(n=5) reports effective use of rivaroxaban
after EKOS catheterization.
• A loading dose/bridging LMWH might still warranted

20. NOACs are preferred in Asian with non-valvular afib
Warfarin is chosen for patients with renal
impairment (Ccr < 30 mL/min) & valvular heart
disease
Anticipating data regarding NOACs use in patients
with MS or with mechanical valve are ongoing.
NOACs use in patient with DVT is effective & safe.