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
NOAC Evidence in AFBridging the Gap Between Scientific Knowledge and Clinical Experience
Workshop objective
• Balancing safety benefit and efficacy in vulnerable patient for SPAF• Elderly
• Renal impairment
• Prior stroke
• With ACS/CAD after PCI
• Selecting NOAC based on trial results and real world evidence in Asian patient
Case illustration
• Female, 78 years old, 70 kg
• Creatinine clearance 45 mL/min
• Hypertension for 12 years (blood pressure 165/85 mmHg)
• Diagnosis of AF (asymptomatic) 5 years ago
• Now admitted to the hospital with a minor ischaemic stroke
• Current Medications• Enalapril 10 mg +
Hydrochlorothiazide 12.5 mg
• Aspirin 100 mg
AF, atrial fibrillation
CHADS2 = ...... points; CHA2DS2-VASc = ..... points; annual stroke risk ≈ ......
#1
Case illustration
• Female, 78 years old, 70 kg
• Creatinine clearance 45 mL/min
• Hypertension for 12 years (blood pressure 165/85 mmHg)
• Diagnosis of AF (asymptomatic) 5 years ago
• Now admitted to the hospital with a minor ischaemic stroke
• Current Medications• Enalapril 10 mg +
Hydrochlorothiazide 12.5 mg
• Aspirin 100 mg
AF, atrial fibrillation
CHADS2 = 4 points; CHA2DS2-VASc = 6 points; annual stroke risk ≈ 10%
#1
European Society of Cardiology Guidelines2
1. Lip GY et al, Chest. 2010;137(2):263-72; 2. Camm AJ et al, Eur Heart J. 2010;31:2369–2429
0%
3%
6%
9%
12%
15%
18%
0.0%
1.3%2.2%
3.2%4.0%
6.7%
9.8% 9.6%
6.7%
15.2%
0 1 2 3 4 5 6 7 8 9
Annual Risk of Stroke
CHA2DS2VASc Score
Ris
k o
f St
roke
CHA2DS2 – VASc risk criteria Score
Cardiac failure 1
Hypertension 1
Age >75 yrs 2
Diabetes mellitus 1
Prior Stroke or TIA 2
Vascular disease (MI, PAD, aortic atherosclerosis)
1
Age 65-74 yrs 1
Sex category (female) 1
Newer Stroke Risk Scoring System In AF: CHA2DS2VASc Score
2016 ESC Guidelines Added Edoxaban among NOACs for Stroke Prevention in Patients with AF1:
AF = atrial fibrillation; ESC = European Society of Cardiology; NOACs = novel oral anticoagulants; VKA = vitamin K antagonist; INR = international normalized ratio
1. Kirchhof P et al. Eur Heart J. 2016 Oct 7;37(38):2893-2962
Edoxaban
Apixaban
Dabigatran
Rivaroxaban
Considering this high bleeding risk patient, what would you recommend to prevent the 2nd stroke?
A. Stay with Aspirin and combine with Clopidogrel (DAPT)
B. Change to Warfarin (INR 2-3)
C. Change to NOAC
D. Change to parenteral anticoagulant first, then OAC
#1
HASBLED risk criteria Score
Hypertension 1
Abnormal renal or liver function (1 point each)
1 or 2
Stroke 1
Bleeding 1
Labile INR’s 1
Elderly (> 65 yrs old) 2
Drugs or alcohol (1 point each)
1 or 2
Bleeding Risk Assessment With HASBLED
Risk Factors/Score N
Number of Bleeds
Bleeds per 100 Patient-Years
0 798 9 1.13
1 1286 13 1.02
2 744 14 1.88
3† 187 7 3.74
4 46 4 8.70
5 8 1 12.50
Any score 3071 48 1.56
P value for trend .007
Camm AJ, et al. Eur Heart J. 2010;31(19):2369-429. Pisters R. Chest. 2010;138:1093-100. Lip GY, et al. Am J Med. 2010;123(6):484-8.
Risk of major bleeding in patients with AF in the Euro Heart Survey
†Score of ≥3 indicates ‘high risk,’
Unfortunately, a high CHADS score often correlates with a high HAS-BLED score & these patients do not receive anticoagulation due to the high bleeding risk
Singapore
Thailand Malaysia East Asia Myanmar Global VietnamTimor-Leste
LaosCambodi
aSEA Indonesia
Philippines
Incident -49.6% -18.3% -16.8% 4.9% -16.9% -8.1% -21.1% -7.9% -13.1% -13.0% -7.1% 8.8% 15.0%
Deaths -73.8% -51.5% -46.0% -42.3% -36.8% -36.2% -33.0% -32.2% -27.6% -24.4% -22.0% 6.3% 14.1%
Disability (DALYS) -74.5% -47.3% -46.5% -41.0% -38.9% -34.2% -34.6% -36.9% -32.2% -28.4% -20.1% 6.0% 15.7%
Singapore
Thailand
Malaysia
East Asia
Myanmar
Global
Vietnam
Timor-Leste
Laos
Cambodia ASEAN
Indonesia
Philippines
-100%
-80%
-60%
-40%
-20%
0%
20%
40%
60%
80%
% Change since 1990 to 2016Incident Deaths Disability (DALYS)
Unlike the rest of the world, stroke burden in Indonesia keep increasing in
last 26 years
(ie. incidence, mortality, and morbidity), second to Phillipines in Southeast Asia region
Lancet Neurol. 2019 Mar 11;16(11):877–97.
Steinberg BA. Am Heart J 017;194:132-40
In real world, the use of NOAC is increasing
But, there is still significant percentage (20-30%) of patient that received
antiplatelet only or no anticoagulation at all
Since 1993, Aspirin doesn’t have proven efficacy for secondary
prevention of ischaemic stroke in patients with AF
EAFT: 1007 patients with non-rheumatic AF and recent TIA or minor ischemic stroke (mean follow-up 2.3 years)
EAFT Study Group. Lancet 1993;342:1255–62
AF, atrial fibrillation; OAC, oral anticoagulant; INR, international normalised ratio;
TIA, transient ischaemic attack
P=0.31
66
14
0
10
20
30
40
50
60
70
Str
ok
e r
isk
re
du
cti
on
vs
. p
lac
eb
o (
%)
Warfarin (INR 2.5–4.0)
Aspirin (300 mg/day)
P<0.001
12
6 Trials of Warfarin vs. Placebo
1989-1993
RE-LY
(Dabigatran)
2009
ROCKET AF
(Rivaroxaban)
2010
ARISTOTLE
(Apixaban)
2011
ENGAGE AF-TIMI 48
(Edoxaban)
2013
Warfarin vs. Placebo
2,900 Patients
NOACs vs. Warfarin
71,683 Patients
Pivotal Trials for Stroke Prevention in AF
Hart RG. Ann Intern Med 2007;146:857-867 Ruff CT. Lancet 2014;383:955-962
Warfarin is a good anticoagulant, but NOAC is better
1414
Risk factors for intracranial haemorrhage under warfarin
● Intensity of oral anticoagulation
●History of TIA or stroke
●Age (≥75 years)
●Hypertension (especially systolic BP >160 mmHg)
●Concomitant use of aspirin
Hart RG et al. Stroke 2005;36:1588-93
Hart RG et al. Stroke 2012;43:1511-17.BP, blood pressure; TIA, transient ischaemic attack
Physician tends to treat patient with subtherapeutic INR (<2)
1515
Out of range INR will cost more than in range INR, and the highest cost is associated with suboptimal INR (<2).
Schein et al. Thrombosis Journal (2016) 14:14
Major Bleeding per Year in the 4 Major SPAF trials on NOACs vs VKA
Not only efficacy, some NOACs offer better safety!
What we already know about Edoxaban?
• Edoxaban, the new kid on the block, in SPAF management, have several unique features – Once daily dosing that has been proven, safer than BID dosing– Highly selective for and potently inhibits Factor Xa– Rapidly absorbed with good bioavailability after oral dosing– Is not highly dependent on renal elimination– Does not induce CYP450 isozymes – Can be taken with or without food– Is affected by P-gp inhibition and body weight– Safe to be use with low dose ASA
• Edoxaban have clear guidance for dose reduction (60 to 30 mg)– CrCl <50 ml/min– BW <60 kg– Concomitant with strong PgP Inh
ENGAGE AF: Summary of key outcomes – Edoxaban 60/30 mg QD
Edoxaban 60 mg QD
Edoxaban better Warfarin better
0.50 1.50
Stroke, SEE, major bleed, death: ITT0.89
Cardiovascular death: ITT0.86
Death: ITT0.92
CRNM bleed: safety cohort0.86
Major bleed: safety cohort0.80
Stroke and SEE: ITT0.87
Stroke and SEE: mITT on-treatment0.79
1.00Ischaemic stroke: ITT
Hemorrhagic stroke: ITT0.54
1.000.00
Giugliano RP et al. N Engl J Med 2013;363:2093-104.
CRNM, clinically relevant non-major bleed; ITT, intention to treat;
mITT, modified ITT; QD, once daily; SEE, systemic embolic event
If this patient have mild mitral regurgitation, which anticoagulant will you choose?A. Warfarin
B. NOAC
#1
In real world, acceptance of NOAC is low in Asian
(GLORIA-AF Registry)
Mazurek M. Thromb Haemost 2017;117:2376–2388
NOAC has been dominating for SPAF treatment, except for Asia
Remaining question
Was it because more valvular AF than “non valvular”?
Why the acceptance for NOAC is still low in Asian countries?
Clinicians were often confused with “Valvular” term in SPAF trials
Valvular Atrial Fibrillation: Changing Definitions in Guidelines
ACC/AHA/ESC 2001: Non Valvular means absence of rheumatic mitral stenosis or a prosthetic heart valve.
ACC/AHA/ESC 2006: absence of rheumatic mitral valve disease, a prosthetic heart valve, or mitral valve repair.’
ESC 2012: Valvular AF includes rheumatic valvular disease and prosthetic valves
ESC 2016 / ACC/AHA 2019: Non valvular means absence of mechanical prosthetic heart valves and moderate to severe mitral stenosis.
• Other valvular problems is defined as ‘non-valvular’
• Biological valves or after valve repair included in some trials on ‘non-valvular AF’, including Edoxaban
Definition of “Valvular AF” in all NOACs trials
RELY ROCKET-AF ARISTOTLE ENGAGE-AF
Total Sample size 18,113 14,264 18,201 21,105
Exclusion criteria
regarding VHD
1. Prosthetic valve
2. Hemodynamically
relevant valve
disease
1. Hemodynamically
significant mitral
valve stenosis
2. Prosthetic heart
valve
1. Valvular disease
requiring surgery
2. Prosthetic
mechanical heart
valve,
3. Moderate or severe
mitral stenosis
1. Moderate or severe
mitral stenosis,
2. Unresected atrial
myxoma,
3. A mechanical heart
valve
Patients with VHD,
n (%)
3,950 (22%) 2,003 (14%) 4,808 (26%) 2,824 (13%)
De Caterina R. et al. JACC 2017
NOACs efficacy and safety were remain consistent in VHD, except in ROCKET trial
Question for the audience
If you were to treat the patient with a NOAC, which NOAC would you choose and at what dose?
A. Edoxaban 60mg once daily
B. Edoxaban 30mg once daily
C. Rivaroxaban 15mg once daily with food
D. Apixaban 5mg twice daily
E. Apixaban 2.5mg twice daily
F. Dabigatran 150mg twice daily
G. Dabigatran 110mg twice daily
NOAC, non vitamin-K antagonist oral anticoagulant
Female 78 years old 70 kg
Creatinine clearance 45
mL/minHypertension
Ischaemic stroke
#1
Treatment
choice
Age
Comorbidity
Renal
Function
Efficacy
Real clinical
practice
Safety
NOAC, non vitamin-K antagonist oral anticoagulant
Which NOAC should I select for my patient?
Safety in Elderly Population
28Ref) Kato ET, et al.:J Am Heart Assoc 2016 (doi:10.1161/JAHA.116.003432)
4.6
6.2
0
2
4
6
8
10
12
4.0 4.8
0
2
4
6
8
10
12
5.0
8.8
0
2
4
6
8
10
12
■ Edoxaban 60/30 mg ■ Warfarin (TTR=69.6% in >75 years, 69.5% in >80 years, 68.4% in >85 years)
>80 years (n=3,591)〔60mg⇒30mg in 53%〕
> 85years (n=899)〔60mg⇒30mg in 67%〕
Inci
den
ce r
ate
of
Maj
or
Ble
edin
g (%
/yea
r)
>75 years (n=8,474)〔60mg⇒30mg in 41%〕
HR=0.7595% CI [0.58-0.98]
HR=0.5895% CI [0.35-0.94]
HR=0.8395% CI [0.70-0.99]
“Edoxaban reduced major bleeding compared to warfarin in elderly patients over 75 years old, 80 years old, or even 85 years old.”
Korean real world evidence –
Edoxaban vs Warfarin outcome by renal function
Yu TH et al. Stroke. 2018;49:2421-9
In real-world practice, edoxaban 60 mg were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin.
The first head-to-head comparison of the effectiveness and safety between
the two once-daily NOAC regimens (rivaroxaban, edoxaban) in a nationwide
Asian cohort with NVAF.
Lee S, et al. Sci Rep 2019;9:6690
Edoxaban vs Rivaroxaban in real world setting
after introduction of edoxaban to Asian market
Among patients with available CrCl value and body weight information, 93% on rivaroxaban and 44% on
edoxaban received inappropriate dose reduction.
Lee S, et al. Sci Rep 2019;9:6690
Lee S et al. Stroke. 2019;50:00-00. DOI: 10.1161/STROKEAHA.119.025536
Patient case
• 83 year old man, permanent AF
• Receiving stable oral anticoagulation
• Warfarin: Aiming at an INR 2.0–3.0
• Admitted with a non-ST-segment elevation myocardial Infarction
• Hypertension • Treated with an ACE inhibitor +
calcium antagonist
• Hypercholesterolemia • Treated with a statin
• Former smoker
• Chronic renal failure: eGFR 52 ml/kg/1.73m² (at admission)
• Haemoglobin level: 10.8g/dl
• White blood cell count 7.2*109/L
AF, atrial fibrillation; INR, international normalised ratio; ACE, angiotensin-converting enzyme; AF, atrial fibrillation; eGFR, etimated glomerular filtration rate
#2
What’s this patient profile?
A. High stroke risk, low bleeding risk
B. High ischemic risk, low bleeding risk
C. High stroke risk, ischemic risk, and bleeding risk
D. Low stroke risk, high ischemic and bleeding risk
#2
Risk stratification
• Adjusted stroke rate (%/year): 4.8% (Moderate-High)
CHA2DS2-VASc:
4
• Bleeds / 100 patient years: 8.7 (High)
HAS-BLED:
3
• TIMI major or minor bleeding (12 months): >4.14% (High)
Precise-DAPT:
39
83 y.o man with a history of permanent atrial fibrillation on
stable oral anticoagulation (‘warfarin’ aiming at an INR 2.0–
3.0) admitted with a NSTEMI. Hypertension and Moderate
Renal Impairment.
Patient underwent PCI with Single stent technique (bifurcation Medina 1-0-1), Endeavour
resolute stent 3.0*18 mm (DES)
CABG, coronary artery bypass graft; DAPT, dual antiplatelet therapy; INR, international normalised ratio; PCI, percutaneous coronary intervention; TIMI, thrombosis in myocardial infarction; Precise-DAPT, PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy
European Society of Cardiology Guidelines2
1. Lip GY et al, Chest. 2010;137(2):263-72; 2. Camm AJ et al, Eur Heart J. 2010;31:2369–2429
0%
3%
6%
9%
12%
15%
18%
0.0%
1.3%2.2%
3.2%4.0%
6.7%
9.8% 9.6%
6.7%
15.2%
0 1 2 3 4 5 6 7 8 9
Annual Risk of Stroke
CHA2DS2VASc Score
Ris
k o
f St
roke
CHA2DS2 – VASc risk criteria Score
Cardiac failure 1
Hypertension 1
Age >75 yrs 2
Diabetes mellitus 1
Prior Stroke or TIA 2
Vascular disease (MI, PAD, aortic atherosclerosis)
1
Age 65-74 yrs 1
Sex category (female) 1
Newer Stroke Risk Scoring System In AF: CHA2DS2VASc Score
HASBLED risk criteria Score
Hypertension 1
Abnormal renal or liver function (1 point each)
1 or 2
Stroke 1
Bleeding 1
Labile INR’s 1
Elderly (> 65 yrs old) 2
Drugs or alcohol (1 point each)
1 or 2
Bleeding Risk Assessment With HASBLED
Risk Factors/Score N
Number of Bleeds
Bleeds per 100 Patient-Years
0 798 9 1.13
1 1286 13 1.02
2 744 14 1.88
3† 187 7 3.74
4 46 4 8.70
5 8 1 12.50
Any score 3071 48 1.56
P value for trend .007
Camm AJ, et al. Eur Heart J. 2010;31(19):2369-429. Pisters R. Chest. 2010;138:1093-100. Lip GY, et al. Am J Med. 2010;123(6):484-8.
Risk of major bleeding in patients with AF in the Euro Heart Survey
†Score of ≥3 indicates ‘high risk,’
Unfortunately, a high CHADS score often correlates with a high HAS-BLED score & these patients do not receive anticoagulation due to the high bleeding risk
Precise DAPT score
Bleeding score
Points
Hb
WBC
Age
Cr CI
Prior bleed
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
≥12 11.5 ≤1011 10.5
≥5 8 ≤2012 1610 14 18
≥50 ≤9060 70 80
≥100 080 60 40 20
NoYes
Web score calculator: http://www.precisedaptscore.com/predapt/webcalculator.html CrCl, creatinine clearance; DAPT, dual antiplatelet therapy; Hb, haemoglobin;
TIMI, thrombolysis in myocardial infarction; WBC, white blood cell count;
10.8 9
7.2 2
83 16
52 12
Precise DAPT score
Effect of Long (12-24 months) vs. short (3-6 months) DAPT
Absolu
te r
isk d
iffe
rence
(%
)
4
3
2
1
0
1
2
3
4
Very low Low Moderate High
Harm
Benefit
NET BENEFIT OF LONG DAPTIschemia= −1.53% p=0.007 NNT=65
Bleeding= +0.14% p=0.45
Ischemia= +1.41% p=0.48
Bleeding= +2.59% p=0.005 NNT=38NET HARM
LONG DAPT
PRECISE DAPT <25 >25
DAPT, dual antiplatelet therapy; MI,
myocardial infarction; TIMI, thrombolysis in
myocardial infarction; TVR, target vessel
revascularisation
Web score calculator: http://www.precisedaptscore.com/predapt/webcalculator.html
Ischemic (MI, Def. ST, stroke, TVR)
Bleeding (TIMI major or minor)
Net Effect
Question for audience
After successful PCI, how would you treat this patient?
A. DAPT only
B. OAC only
C. OAC plus DAPT for 12 months
D. OAC plus DAPT for 1 month followed by OAC and clopidogrel
E. Other
DAPT, dual antiplatelet therapy; OAC, oral anticoagulation
#2
Wang TY et al. Am Heart J. 2008;155(2):361-8.
42Capodanno D, Huber K, Mehran R, et al. Management of Antithrombotic Therapy in Atrial Fibrillation
Patients Undergoing PCI: JACC State-of-the-Art Review. J Am Coll Cardiol 2019; 74(1): 83-99.
Approximately 15% of patients with AF
may require PCI with stent placement to
treat obstructive coronary artery disease.
Anti-coagulant therapy
Thrombus in the left atrium
Low shear stress
Antiplatelet therapy (additive benefit
oral anticoagulant?)
Thrombus,platelet mediated in the
coronary artery
High shear stress
43
TF/VIIa
IX*
IXaVIIIa
X*
Xa
II*
IIa
Fibrinogen Fibrin
Thrombus
Platelet Aggregation
Conformational Activation of GPIIb/IIIa
Collagen
Thromboxane A2
ADP
Aspirin
ClopidogrelPrasugrelTicagrelor
Initiation
Propagation
Fibrin Formation
RivaroxabanApixabanEdoxaban
Dabigatran Etexilate
VII*
Anticoagulants and their targets in the
coagulation pathway
Weitz JI, et al. J Thromb Haemost 2005;3:1843–53.
44
Bleeding is bad…
CI, confidence interval; HR, hazard ratio
44.4%
19.4%
WOEST trial - Combined antiplatelet and NOAC therapy after
acute coronary syndrome: Three is a crowd!
DeWilde et al. Lancet. 2013;381:1107–15
NOAC in AF after PCI and/or ACS (1)
PIONEER-AF PCI• VKA+DAPT vs
• Rivaroxaban 2.5 mg* BID + DAPT vs
• Rivaroxaban 15 mg* QD + P2Y12
RE-DUAL PCI
• VKA+DAPT vs
• Dabigatran 110 mg BID + P2Y12
• Dabigatran 150 mg BID + P2Y12
*Rivaroxaban dose is not designed for adequate SPAF in pivotal trial
NOAC in AF after PCI and/or ACS (2)
ClinicalTrials.gov Identifier: NCT02415400
AUGUSTUS
Overall, the PIONEER-AF, RE-DUAL PCI and AUGUSTUS study validated with greater power the WOEST hypothesis (i.e.
less bleeding with the drop of ASA)
and cumulatively add strength to the concept that abandoning ASA might improve safety towards bleeding in stented patients on DAPT with a NOAC and a P2Y12 inhibitor.
PIONEER-AF PCI
RE-DUAL PCIAUGUSTUS
Patients with AF Undergoing PCIMeta Analysis –
3 NOACs vs VKA
Better safety with similar efficacy
signal?
Edoxaban- vs vitamin-K-antagonist-based anti-thrombotic regimen after successful coronary stenting
in patients with atrial fibrillation (ENTRUST-AF PCI): A randomised, open-label, phase 3b trial
Andreas Goette, Marco Valgimigli, Lars Eckardt, Jan Tijssen, Thorsten Lewalter, Giuseppe Gargiulo, Valerii Batushkin, Gianluca Campo, Zoreslava Lysak, Igor Vakaliuk, Krzysztof Milewski, Petra Laeis, Paul-Egbert Reimitz, Rüdiger Smolnik, Wolfgang Zierhut, Pascal Vranckx
ENTRUST-AF PCI: Study design
ClinicalTrials.gov Identifier: NCT02866175
*** VKA pre-defined by country, target INR 2–3
****ASA 100 mg OD for 1–12 months guided by
clinical presentation (ACS or stable CAD),
CHA2DS2-VASc and HAS-BLED
4 hours – 5 days
after sheath removal
Inclusion criteria:
• OAC indication
for AF for at
least 12 months
• Successful PCI
with stent
placement
(goal of at least
25% ACS)
**Clopidogrel 75 mg OD or if
documented need prasugrel
5 or 10 mg OD or ticagrelor
90 mg BID
Declared at randomisation
P2Y12 antagonist** (without ASA)
Edoxaban 60 mg QD*
P2Y12 antagonist (ASA 1 - 12 months)****
Vitamin K Antagonist***
*Edoxaban dose reduction to
30 mg QD if:
• CrCL ≤50 ml/min
• BW ≤60 kg
• Certain concomitant P-gp
inhibitors• Primary outcome: ISTH major and clinically relevant non-major
bleeding
AF, atrial fibrillation; ACS, acute coronary syndrome; ASA, aspirin; BID, twice daily; BW, body weight; CAD, coronary artery
disease; CrCl, creatinine clearance; INR, international normalised ratio; ISTH, International Society on Thrombosis and
Haemostasis; OAC, oral anticoagulation; PCI, percutaneous coronary intervention; QD, once-daily; .VKA, vitamin K antagonist
R12 months: end
of treatment
N=1500
Key differentiation features of
ENTRUST-AF-PCI (Based on Study Design)
Relative to RE-DUAL, ENTRUST-AF PCI study allows greater flexibility in aspirin use in the comparator arm of 1 to 12 months (based on investigator’s decision and according to ESC guidelines)
The endpoint for AUGUSTUS is 6 months; ENTRUST-AF PCI assesses bleeding events over a 12-month period
The doses of rivaroxaban used in PIONEER-AF PCI are 25% and 75% lower than the approved 20 mg QD dose for stroke prevention in patients with AF; the doses used in ENTRUST-AF PCI were assessed globally in large, prospective, randomized trials
Primary Study EndpointITT Analysis (N=1506), overall study period
Cu
mu
lati
ve in
cid
ence
in o
utc
om
es
0.25
0.20
0.15
0.10
0.05
0.00
0
Days from randomization
360
Number at risk
330300270240210180150120906030
751 506
755 485
Edoxaban
VKA
565575584590600609618629646665688
538543552561568578588603625648678
Number of events:Edoxaban: 128/751VKA: 152/755
HR (95% CI): 0.83 (0.65; 1.05)P-value (noninferiority): 0.0010P-value (superiority); 0.1154
Post Hoc Landmark Kaplan Meier Analysis Primary Study Endpoint
Cu
mu
lati
ve r
ate
of
even
ts
0.25
0.00
0
Days from randomization
360
Number at risk
751 506
755 485
Edoxaban
VKA0.20
0.15
0.10
0.05
14 30 60 90 120 150 180 210 240 270 300 330
565575584590600609618629646665688
538543552561568578588603625648678
707
721
Phase 1 (≤day 14) HR (95% CI): 2.42 (1.27; 4.63)Phase 2 (>day 14) HR (95% CI): 0.68 (0.53; 0.88)Interaction P-value: <0.0001
Time from PCI toRandomisation: • shortest – 0.2 h• median – 45 h
94%
69%
42%37% 37% 39%
5%
23%
34% 40% 44% 44%
1%
8%
24% 22% 19% 17%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
≤Day 1 Day 2 to 7 Day 8 to 14 Day 15 to 21 Day 22 to 28 Day 29 to 35
Mean INR <2 Mean INR 2–3 Mean INR > 3
INR in VKA regimen in first 5 weeksOverall study period: median TTR = 63.1%
Should we abandon aspirin completely for AF patient after PCI?
Yes No
#2
Goette A. et al. ESC Congress 2019. FP 6044; Vrancks P. et al. Lancet. 2019. pii:S0140-6736(19)31872-0
Key takeaways for AF after PCI
Since all NOAC have published data for AF after PCI, which NOAC will you choose?A. Dabigatran
B. Rivaroxaban
C. Apixaban
D. Edoxaban
#2
Selecting NOACs in AF
after PCI
CYP450 PgP Inh
c
c
Take home message
NOACs are clearly more beneficial compare to VKA or antiplatelet in SPAF, including for vulnerable patients
Real world evidence for Asian patient strengthen the safety benefit and convenience of Edoxaban relative to VKA and other NOACs
There is no one drug fits all!
• In AF patient after successful PCI, only Dabigatran and Edoxaban have enough evidence for 12 months treatment using approved full dose for SPAF
• The use of aspirin after PCI in AF patient is still beneficial in the first 14 days due to high risk for stent thrombosis, before switching to OAC+P2Y12
• ENTRUST-AF PCI adds to the evidence of NOACs in post PCI AF patients that dual antithrombotic therapy with edoxaban plus a P2Y12 antagonist, is an alternative to VKA plus a P2Y12 antagonist, and aspirin (ASA) risk based for 1 month or more (triple therapy)
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