af in asian: which noac to choose for particular patient ... in asian... · safety of noacs...
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AF in Asian: which NOAC to choose for particular patient and at what dose?
DEJIA HUANG
West China Hospital of Sichuan University, Chengdu, China
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Case report 64-year-old Chinese man with history of hypertension, COPD and
paroxysmal AF;
Persistent AF since 3 months ago;
No other underlying diseases.
BP: 136/82 mmHg. No chest pain;
No renal or liver dysfunction.
Medications: Perindopril 8mg daily, Verapamil 80mg tid
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What is the risk of stroke and major bleeding for this Chinese man
CHA2DS2-VASc
Score
Stroke rate (%
per year)
0 0
1 1.3%
2 2.2%
3 3.2%
4 4.0%
5 6.7%
6 9.8%
7 9.6%
8 6.7%
9 15.2%
Risk of Stroke
HAS-BLED
Score
Bleeding rate (%
per year)
0 1.13%
1 1.02%
2 1.88%
3 3.74%
4 8.7%
≥5 12.5%
Risk of Bleeding
——Am Heart J 2006; 151:713——Eur Heart J 2010; 31:2369
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What is the risk of stroke?According to a “real world” cohort of Chinese AF patients in Hong Kong (n=9727), the risk of stroke is 6.64% per year.
——Siu CW et al. Heart Rhythm 2014; 11:1401
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What is the risk of stroke?According to Taiwan AF cohort (n=186,570), the risk of stroke is 2.11% per year.
——Chao TF, et al. Heart Rhythm 2016; 13:46
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What is the risk of stroke?According to Taiwan BNHI database (n=7920),
the risk of stroke is 0.5% per year.
——Lin LY, et al. Atherosclerosis 2011; 217: 292
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What is the risk of stroke?According to Swedish National Register data (n=140,420), the risk of stroke is 0.7% per year.
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What is the really risk of stroke for this Chinese man?
1.3% per year (Euro Heart Survey 2006)
6.64% per year (Hong Kong Cohort 2014)
2.11% per year (Taiwan AF Cohort 2016)
0.50% per year (Taiwan BNHI database 2011)
0.70% per year (Swedish National Register data)
Which one do you choose?
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How do you predict the stroke risk for this patient?
The tricky part is that the risk of stroke for this patient with CHA2DS2-VASc score of 1 may range from 0.5% to 6.64% yearly according to different cohorts.
Everyone who take an anticoagulant incurs an increased risk of bleeding. If he was at low risk of stroke, he may get no net clinical benefit from the drug.
What is the threshold of stroke risk for net benefit of anticoagulation (Warfarin Vs. NOACs): 1% or 2%?
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Do you prescribe an anticoagulant for this patient?
Warfarin?
Risk of stroke: Hong Kong Cohort: 6.64%
Taiwan AF Cohort: 2.11%
Risk of bleeding: 1.88% (HAS-Bled)?
NOACs? If the risk of stroke for this patient is less than 2% per year: Euro Heart Survey 1.3%, Taiwan BNHI data 0.50%, and Swedish National Register data 0.70%.
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NOAC Vs. Warfarin
INR2-3
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Therapeutic window of dabigatran: not so broad
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NOACs Vs. WarfarinAll cause mortalityRisk ratio (95%CI)
Major bleedingRisk ratio (95%CI)
RE-LY (150mg) 0.88 (0.77-1.00) 0.94 (0.82-1.07)
ROCKET-AF 0.92 (0.82-1.03) 1.03 (0.90-1.18)
ARISTOTLE 0.89 (0.80-0.99) 0.71 (0.61-0.81)
ENGAGE-AF (60mg) 0.92 (0.83-1.01) 0.80 (0.71-0.90)
Combined(n=58,498)
0.90 (0.85-0.95)P=0.003
0.86 (0.73-1.00)P=0.06
——Ruff CT, et al. Lancet 2014; 383:955
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——Hori M et al. 2nd Asia Pacific Stroke Conference.
Rates of Major Bleeding in Asian Patients
in RE-LY Trial%
/
Ye
ar
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Which of the NOACs will you prescribe to our patient and at what dose?
A) Dabigatran (150mg or 110mg Bid)
B) Rivaroxaban (20mg or 15mg Qd)
C) Apixaban (5mg or 2.5mg Bid)
D) Edoxaban (60mg or 30mg Qd)
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Safety of NOACsDabigatran
Rivaroxaban ApixabanEdoxaban
110 150 60 30
Major bleeding
(% per year)2.71 3.11 3.6 2.13 2.75 1.61
Fatal bleeding
(% per year)1.22 1.45 0.2 — 0.21 0.13
Intracranial bleeding
(% per year)0.23 0.30 0.5 0.33 0.39 0.26
——Data from DE-LY, ROCKET-AF, ARISTOTLE and ENGAGE-AF trials
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Major bleeding in ENGAGE-AF trial
3.43%
2.75%
1.61%
0.0%
0.5%
1.0%
1.5%
2.0%
2.5%
3.0%
3.5%
4.0%
Warfarin Edoxaban 60mg Edoxaban 30mg
P<0.01P<0.01
——Giugliano RP, et al. NEJM 2013; 369:2093
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Reduced bleeding ≈ Reduced mortality: lower dose may be better
-100
-80
-60
-40
-20
0
Edoxaban 60mg—Warfarin
Edoxaban 30mg—Warfarin
Prior non-fatal bleeds
Bleeds contributed todeath
Fatal bleeds
-59
-88——Giugliano RP, et al. ESC 2014
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Low Vs. High dose
More ischemic events but less bleeding;
Preventing excess drug exposure in vulnerable patients.
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Dose reduction in NOAC trials RE-LY: 2-dose regimens: 110mg Vs. 150mg Bid;
ROCKET-AF: 20 15mg Qd for CrCl 30-49ml/min;
ARISTOTLE: 5 2.5mg Bid for any tow: age ≥ 80 years, body weight ≤ 60kg and serum creatinine ≥ 1.5mg/dL;
ENGAGE-AF: 60-30mg Qd or 30-15mg Qd for CrCl 30-50ml/min; body weight ≤ 60kg; use of Quinidine or Verapamil.
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——Heidbuchel H, et al. EHRA guideline Europace. 2013; 15: 625
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Dose reduction preserved efficacy: ENGAGE-AF trial
1.80%1.53%
2.68%
1.57%1.33%
2.32%
3.14%
0.0%
0.5%
1.0%
1.5%
2.0%
2.5%
3.0%
3.5%
WarfarinN=7036
WarfarinN=1787
WarfarinN=5249
All patients
EdoN=14059
Edo 60→30 and 30→15
N=3569
EdoN=10490
Edo 30→15N=1785
No Dose Reduction
Dose Reduction
P=0.97
SS
E (
% p
tsp
er
ye
ar)
SSE: Stroke or systematic embolism
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Dose reduction with better safety: ENGAGE-AF trial
3.43%3.02%
4.85%
2.75% 2.66%3.05%
1.50%
0.0%
1.0%
2.0%
3.0%
4.0%
5.0%
6.0%M
ajo
r b
lee
din
g (
% p
tsp
er
ye
ar)
All patients No Dose Reduction
Dose Reduction
EdoN=14059
Edo 60→30 and 30→15
N=3569
EdoN=10490
Edo 30→15N=1785
WarfarinN=7036
WarfarinN=1787
WarfarinN=5249
P=0.02
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Our patient: my choice 1) Apixaban 5mg or 2.5mg Bid;
2) Edoxaban 30mg Qd (Verapamil 53%);
3) Rivaroxaban 20mg or 15mg Qd;
4) Dabigatran 110 or 75mg Bid (Verapamil 12-180%)
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