1. No category

Case presentation
Stroke prevention in patient with atrial
fibrillation—other than aspirin?
Reporter: Intern 陳欣伶
Supervisor: Attending 傅進華
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Patient
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Name: 范o霖, 79y/o male
ID: P101313429
Bed No.:1121-3
Admission date: 2006/10/14
Chief complaint: sudden onset of left side
weakness noted in this afternoon
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Present illness
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Underlying diseases: hypertension, atrial fibrillation,
COPD and CAD s/p PCI; past history of duodenal ulcer
s/p pyeloroplasty was noted.
Regular follow up in local clinics with medications of
isosorbide-dinitrate, aspirin, lasix and aldactone.
Left side weakness was noted at 5pm on 10/14, after
coming back from exercise and taking a shower. Cold
sweating and slurred speech were accompanied.
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Present illness (cont.)
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He was sent to our ER that conscious drowsy (GCS:
E2V3M5), BT 35.1^C, PR of 67bpm, RR 20/min and
BP 167/91 mmHg was noted.
PE: bilateral eyes deviation to right, left facial palsy,
pupil size : 3.0/3.0 mm with light reflex, muscle power
of upper: 5/2-3, lower : 5/3-4. Babinski sign of Rt/Lt: /+.
Brain CT without contrast: no ICH.
EKG: atrial fibrillation with RVR
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Brain CT
on 10/14
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EKG
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CXR
10/14
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Lab data
CBC & PL
0951014 WBC
RBC
Hb
Ht
MCV
PL
N.band
N.seg.
Lym.
Mono.
Eosin.
Baso.
PT
Control
INR
APTT
Control
7.28
4.26
14.1
42.6
100.0
191
53.5
37.9
7.1
1.2
0.3
9.7
10.0
1.0
23.9
28.5
*10^3/ul
*10^6/ul
g/dl
%
fl
*10^3/ul
%
%
%
%
%
%
sec
sec
sec
sec
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Blood
0951014 Na
134
K
4.52
GLU
99
BUN
26
CRE
1.3
GOT/AST27
0951015 U A
7.4
TCH
148
TG
39
HDL-C 66
LDL-C
99
mmol/L
mmol/L
mg/dl
mg/dl
mg/dl
IU/L
mg/dl
mg/dl
mg/dl
mg/dl
mg/dl
Blood
0951015 C K
111
CKMB(mass)
TnI
<0.1
IU/L
4.89ng/ml
ng/ml
Tentative diagnosis
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Cerebral infarction, might be right MCA
territory
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Bilateral eyes deviation to right, conjugate
Left side weakness with sensory impairment
Dysarthria or dysphasia
Conscious disturbance, but not totally coma
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TCD & CD on 10/20
intima-media thickening
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Plaque formation
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TCD & CD
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Trans-cranial Doppler:
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normal flow velocity in right MCA and bil. PCA
reduced flow velocity in bil. vertebral arteries.
may suggest atherosclerosis with high vascular resistance
in bil. PCA and hemodynamic dysfunction in bil.
vertebral arteries.
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The carotid duplex
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intima-media thickening, and plaques formation in bil.
bifurcation and left ICA
also reduced flow velocity in bil. vertebral arteries.
may suggest atherosclerosis with mild stenosis in left ICA
(25%), left bifurcation (27%) and right bifurcation (16%);
also hemodynamic dysfunction in bil. vertebral arteries.
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10/14
10/15
10/16
10/19
-admitted to MICU
-acute management of stroke:
Aspirin, Nootropil
-Af with RVR: Digoxin
Aspirin
100mg qd
-fever (BT 38^c), thick sputum: fever
survey: URI? UTI? Blood?
-tachycardia: with rate control (+ CCB)
-Sputum: WBC>25/HPF with bacteria
-Urine: pyuria and bacteriuria
-10/17 CBC: leukocytosis (WBC 13.2,
Seg 89%)
-10/18: U/A: coagulase-negative
staphylococci;
-Transferred to general ward: GCS
E3V3M4-5, and slurred speech, could
follow order. MP: R/L: 5/2.
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Augmentin
1200mg q8h
Aug.
10/16~
10/20
-10/20: sputum culture: K.P. ++
10/24
-change antiplatelet to Ticlopidine
due to past history of duodenal ulcer
10/25
-still complained of headache and
chest tightness, DC nitrate
-an episode of aspiration: Lab. CXR
-elevated cardiac enzyme was noted:
NTG IVD
10/26
-fever(+), aspiration pneumonia?
-headache: DC NTG, use Sigmart
-follow up cardiac enzyme
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Gentamycin
120mg qd
DC aspirin,
Ticlopidine
Re-start Abx
Current condition
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Conscious: E3V3-4M5
Vital sign: stable, fever subsided
PE: Left side motor and sensory impairment, muscle
power was 2; left facial palsy; eyes deviation to right;
easy choking(+); unwilling to express himself
Plan:
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recurrent stroke prevention: ticlopidine
For CHF and CAD: sigmart
control of aspiration pneumonia
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Discussion
Stroke prevention if patients with
atrial fibrillation: other than
aspirin?
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Q. stroke prevention in AF
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P: patients of non-valvular AF with/without
previous stroke nor TIA
I: anticoagulant (warfarin) or antiplatelet (other
than aspirin, ex.clopidogrel)
C: general aspirin use
O: prevention of stroke and risk of hemorrhage
or other side effect
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Method
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Database: PubMed, Cochrane
MesH term:
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atrial fibrillation & stroke
stroke & antiplatelet
atrial fibrillation & antiplatelet
Ticlopidine, clopidogrel, dipyridamole & stroke
Publish date: after 2000
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Current trend…… ASA or Warfarin?
1.
2.
3.
Class I: Administer antithrombotic therapy—oral anticoagulation: warfarin,
keep INR 2-3; or aspirin, 325mg/day to all patients with atrial fibrillation,
except those with lone atrial fibrillation, to prevent thromboembolism.
(Level of Evidence: A)
Individualized treatment.
Those under 60y/o or having low-risk of thromboembolism need no longterm anticoagulants. (Interpreted from Class III.)
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1. Two trials (EAFT and VASPINAF) involving 485 people
were included.
2. Follow-up time was 1.7 years in one trial and 2.3 years in
the other. Anticoagulants of warfarin reduced the odds of
recurrent stroke by two-thirds (odds ratio (OR) 0.36, 95%
confidence interval (CI) 0.22 to 0.58). The odds of all
vascular events was shown to be almost halved by
treatment (OR 0.55, 95% CI 0.37 to 0.82).
3. The odds of major extracranial haemorrhage was
increased (OR 4.32, 95%CI 1.55 to 12.10). No intracranial
bleeds were reported among people given anticoagulants.
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1. Five randomized trials (AFASAK I; BAATAF; CAFA;
SPAF I; SPINAF) comparing warfarin (mean INR:
2.0~2.6) with aspirin or placebo.
2. During 1.5 years mean follow up, warfarin was
associated with large, highly statistically significant
reductions in all strokes (OR 0.39, 95%, CI 0.26 to
0.59), ……and the combined endpoint of all stroke,
myocardial infarction or vascular death (OR 0.56, 95% CI
0.42 to 0.76).
3. The observed rates of intracranial and extracranial
hemorrhage were not significantly increased by OAC
therapy, but the confidence intervals were wide.
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1. Three trials (SPAF I, AFASAK I, LASAF) were included:
tested aspirin, ranging from 75 mg to 325 mg per day and
125 mg every other day vs warfarin or no treatment in 1965
AF patients without prior stroke or TIA.
2. Aspirin was associated with non-significant lower risks of all
stroke (odds ratio (OR) 0.70, 95% confidence interval (CI)
0.47 to 1.07) The combination of stroke, myocardial
infarction or vascular death was significantly reduced (OR
0.71, 95% CI 0.51 to 0.97 ).
3. No increase in intracranial hemorrhage or major
extracranial hemorrhage was observed.
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Controversial: Antiplatelet other than aspirin
-systemic review, meta-analysis study
-effects of antiplatelet therapy among patients at high risk
(included Af patients) of occlusive vascular events
-high dose aspirin vs low lose, other antiplatelet alone vs
aspirin, other antiplatelet in addition to aspirin vs aspirin
alone
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Proportional effects of antiplatelet on vascular events in 5 main
high risk categories.
-smaller effect in patients treated during acute stroke
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<Different dose of aspirin>
Direct comparison :
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Indirect comparison
(bias: when patients in the trials had different diseases)
-favor low dose aspirin (<75mg/day), but only few studies
-current suggestion: 75-150mg/day dose
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<antiplatelets other than aspirin>
Direct comparison:
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indirect comparison
-In patients with history of MI, stroke and perpheral arterial
diseases, clopidogrel, as well as ticlopidine, could reduce
serious vascular events compared with aspirin alone.
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<Other antiplatelet + aspirin>
direct comparison
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indirect comparison
-dipyridamole + aspirin and ticlopidine + aspirin have non-significant
reduction in serious vascular events
-GpIIb/IIIa + aspirin had significant reduction in serious vascular
event, but major extracranial bleeding was noted in 23/1000 patients.
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Summary
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How about
clopidogrel + aspirin?
Aspirin regimen: 150-300mg loading dose in acute
stage with following 75-150mg/day for prevention.
Clopidogral is an appropriate alternative for patients
with a contraindication to aspirin.
Gp IIb/IIIa in addition to aspirin has evidence-based
benefit in patients s/p PCI or with unstable angina,
but only available for short-term use due to side
effect of bleeding.
For patients of atrial fibrillation, aspirin could protect
against serious vascular effect.
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15,603 patients with either clinically evident cardiovascular disease
or multiple risk factors, randomized into 2 groups: clopidogrel 75
mg/day + low-dose aspirin (75 to 162 mg/day) vs placebo + low-dose
aspirin.
Follow up for 28 months. The primary efficacy end point was a
composite of myocardial infarction, stroke, or death from
cardiovascular causes.
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Conclusion:
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Clopidogrel plus aspirin was not significantly more
effective than aspirin alone in reducing the rate of
myocardial infarction, stroke, or death from
cardiovascular causes among patients with stable
cardiovascular disease or multiple cardiovascular
risk factors.
Furthermore, the risk of moderate-to severe
bleeding was increased.
Our findings do not support the use of dual
antiplatelet therapy across the broad population
tested.
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-Patients: atrial fibrillation plus one or more risk factor for stroke
-oral anticoagulation therapy (INR 2·0–3·0; n=3371)
or clopidogrel (75 mg per day) plus aspirin (75–100 mg per day
recommended; n=3335).
-Primary outcome: first occurrence of stroke, non-CNS systemic
embolus, myocardial infarction, or vascular death.
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Conclusion: Oral anticoagulation therapy is superior to clopidogrel plus aspirin
for prevention of vascular events in patients with atrial fibrillation at high risk of
stroke, especially in those already taking oral anticoagulation therapy. There exist
selection bias in this study. Study for clopidpgrel+ASA vs ASA is in ACTIVE A.
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Summary
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Aspirin or warfarin was still the trend, and no definite
result in the difference of hemorrhage events.
Antiplatelets other than aspirin had no significant effect
for stroke prevention if use alone. Addition to aspirin
may have non-significant effect.
For patients contraindicated to aspirin, clopidogrel was
an appropriate alternative for long term control.
Warfarin was applicable for those without active
bleeding or bleeding tendency.
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A study that is on going.
-lower levels of BP are associated with a lower risk of vascular events
-There is some evidence that ARBs reduce the recurrence of AF
-The prevalence of hypertension in patients with AF is very high, especially
in those considered candidates for aggressive antithrombotic therapy,
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Back to our patient
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Suggest warfarin or clopidogrel/ticlopidine
alone. The latter one afford better compliance.
Study on going in patients of AF: clopidogrel +
aspirin + ARB.
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Thanks for your attention!
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Cardiac enzyme and follow-ups
cardiac enzyme
CK-MB, TnI
4
253
4.04
3
2
1
0
0.45
184
2.47
2.75
2.67
2.87
1.12
0.47
97
0.76
90
0.88
2.41
63
0.96
300
250
3.4 200
150
100
52 50
0.69
0
00:00
6
30
42
48
54
78
CK-MB
4.04
2.47
2.75
2.67
2.87
2.41
3.4
TnI
0.45
0.47
0.76
1.12
0.88
0.96
0.69
CK
253
184
97
90
63
52
hours
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CK-MB
CK
5
TnI
CK
Ximelagatran vs Warfarin
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Anticoagulants
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Ximelagatran vs Warfarin
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phase III trials of Ximelagatran in AF, SPORTIF III and V,
found that a fixed oral dose of Ximelagatran (36mg twice
daily) was comparable to dose-adjusted warfarin (INR 2.0
to 3.0) in preventing stroke and systemic thromboembolic
complications among high-risk patients with AF.
combined rates for major and minor bleeding were
significantly lower with Ximelagatran
Ximelagatran may cause increased GPT and higher
incidence of CAD.
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VS comment
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Case Presentation的comment:
有review多篇經典paper的結論,只是應該進一步篩選,因為報告時
間只有十分鐘.
目前對於atrial fibrillation的病人發生stroke的處
理,warfarin或aspirin的使用在quideline上沒有明確的建議哪一
種較佳,不過在Cochrane的結論是使用warfarin.不過這位病人的
年齡已經快80歲,對於warfarin的使用有relative
contraindication,所以臨床上還是選擇aspirin.
aspirin的選擇劑量,guideline上是建議325mg的daily dose,不過
目前在國內好像沒有人用這個dose,關於這一點心內的醫師看法
是,aspirin用在ACS的預防上目前也沒有用到這個high dose,還是
選擇75mg~150mg的劑量.至於在有gastric ulcer history的病人,
也不會說因為有這樣的history就完全不用,而是會給予胃藥的使
用.針對這個問題,報告者指出在BMJ 2002的那篇paper裡review眾
多study後也是建議使用75~150mg的daily dose.
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