Dayi Hu Peking University
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Transcript of Dayi Hu Peking University
Dayi Hu
Peking University
PREVENTION OF STROKE IN PATIENTS WITH AF IN
CHINA
Atrial Fibrillation (AF)
The most common significant heart rhythm The most common significant heart rhythm disturbancedisturbance Incidence increases with age and the Incidence increases with age and the development of structural heart diseasedevelopment of structural heart diseaseCommon cause of stroke (10-15% of all strokes)Common cause of stroke (10-15% of all strokes)Associated with significant cardiovascular Associated with significant cardiovascular morbidity and mortality morbidity and mortality Tends to recur in at least half the patients being Tends to recur in at least half the patients being treated with antiarrhythmic drug therapytreated with antiarrhythmic drug therapy
Per
cent
of s
ubje
ct d
ied
in fo
llow
-up
years
Higher Mortality Rate In Patients With AF
Benjamin EJ, Circulation 1998; 946-952
10%
30%
50%
0 1 3 4 652 7 8 9 10
70%
Women, No AF
Men, AF
Women, AF
Men, No AF
men women
Odds Ratio for Death
1.2-1.8 1.5-2.2
The epidemiology of atrial fibrillation
Go: JAMA, 2001Go: JAMA, 2001
Prevalence Prevalence of AF(millioof AF(millio
n)n)
YearYear1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
ATRIA StudyATRIA Study
ATRIAL FIBRILLATION AND STROKE
Thrombembolic stroke
• High Incidence
• Multi-focal and severe
• Prone to hemorrhage
• High mortality
0
10
20
30
Wolf et al. Stroke 1991;22:983-988.
50–59 60–69 70–79 80–89
The Framingham Study: Attributable Risk of Stroke
%
AF prevalence Strokes attributable to AF
Age Range (years)
Ryder KM, et al. Am J Cardiol 1999; 84: 131R-138R.
Prevalence of AF in different countries
5.5%5.4%
≥ 50 yrs, USA (CHS), single ECG≥ 65 yrs, UK, single ECG≥ 60 yrs, Netherlands, single ECG & medical record ≥ 50 yrs, UK, single ECG ≥ 55 yrs, Netherlands, single ECG
≥ 35 yrs, USA, medical record≥ 50 yrs, UK, single ECG Review results≥ 60 yrs, Australia, triennial survey≥ 40 yrs, Japan, single ECG ≥ 60 yrs, Hong Kong, single ECG≥ 35 yrs, Denmark, single ECG25 - 64 yrs, west German, single ECG≥ 15 yrs, India, single ECG0.1%
5.1%3.7%
3.0%2.8%
2.4%1.5%
1.3%1.3%
0.60%0.28%
Estimate of prevalence of AF vary based on the characteristics of population studied and how AF is ascertained.
Atrial Fibrillation Demographics by Age
Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-473.
U.S. population
Population withatrial fibrillation
Age, yr
<5 5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85-89
90-94
>95
U.S. populationx 1000
Population with AFx 1000
30,000
20,000
10,000
0
500
400
300
200
100
0
Prevalence of AF is increasing in USA N
umbe
r (×
10,0
00)
1984 19940
5.0
10.0
15.0
20.0
25.0
30.0
11.1
27.0
NEJM 1997 337:1360-1369
% o
f hos
pita
lizat
ion
7.65%7.90%
8.16%
1999 2000 20016.0%
6.5%
7.0%
7.5%
8.0%
9.0%
Qi W, et al. Chinese J Cardiol, 2003 ; 31 : 913-916
Percent of Hospitalization in Patients with AF Is Increasing in China
Average
7.90%
The Epidemical Investigation of AF in China Fourteen Natural Populations, 13 Different Provinces
Incidence of AF Stratified by Age and Sex in Chinese Population
0
1
2
3
4
5
6
7
8
Age Group, yAge Group, y
Rat
e pe
r 100
Rat
e pe
r 100
30-3930-39 40-4940-49 50-5950-59 60-6960-69 OverallOverall
Men (n=13358)Men (n=13358)
Women (n=15521)Women (n=15521)
0.30.3 0.20.20.50.5 0.60.6
1.41.4 1.11.1
3.63.62.62.6
7.57.5 7.47.4
70-7970-79 ≥≥8080
0.90.9 0.70.7
Data collected from 13 natural populations from 14 different provinces across China
Hu D, et al. 2004 Chin J Intern Med; in press.
Prevalence of AF in China and other countries
5.5%5.4%
≥ 50 yrs, USA (CHS), single ECG≥ 65 yrs, UK, single ECG≥ 60 yrs, Netherlands, single ECG & medical record ≥ 50 yrs, UK, single ECG ≥ 55 yrs, Netherlands, single ECG
≥ 35 yrs, USA, medical record≥ 50 yrs, UK, single ECG Review results≥ 60 yrs, Australia, triennial survey≥ 40 yrs, Japan, single ECG ≥ 60 yrs, Hong Kong, single ECG≥ 35 yrs, main land, China, single ECG≥ 35 yrs, Denmark, single ECG25 - 64 yrs, west German, single ECG≥ 15 yrs, India, single ECG0.1%
5.1%3.7%
3.0%2.8%
2.4%1.5%
1.3%1.3%0.77%0.60%
0.28%
Patients with AF In China 8 million
Hospitalized Patients with AF in China: Causes and Associated Condition
Idiopathic AF
RVD
CHF
CAD
Advanced age
0 40% 50% 60%30%20%10%
58.1%
40.3%Hypertension
caidiomyopathy
34.8%
33.1%
23.9%
7.4%
5.4%
4.1%Diabetes
CAD: coronary artery disease; CHF: congestive heart failure; RVD: rheumatic valve disease
Chinese J Cardiol, 2003 ; 31 : 913-916
Prevalence of Stroke in Chinese Patients with AF
%
12.95%
24.81%
17.5%
Hu D, 2004 Qi W, 20030
5%
10%
15%
20%
25%
Hu D, 2004Hu D, et al. 2004 Chin J Intern Med; in press. Random sample of population
Qi W, et al. 2003 Chin J Cardiol; 31: 913-916. Case-control study. Hospitalized patients
Hu D, et al. 2003 Chin J Intern Med; 42: 157-161. Case-control study. Hospitalized patients
Prevalence of Stroke in Patients with None Valve AF Stratified by Age
years0
5
10
15
20
25
Prev
alen
ce (
%)
30
>40 40 ~49
60 ~ 6950-59 70 ~79
>80
HU D, et al. Chin J Intern Med, 2003; 42: 157-161
Framingham Heart Study: Significant Multivariable Risk for developing AF
Prior MI
HTN
DM
VHD
CHF
AGE
0 4 5 6321 7 8 9
Male
Female2.1 (1.8-2.5)
2.2 (1.9-2.6) 4.5 (3.1-
6.6)
4.2 (4.2-8.4)1.8 (1.2-
2.5)
3.4 (2.5-4.5)1.4 (1.0-
2.0)1.5 (1.2-2.0)
1.4 (1.1-1.8)1.4 (1.0-
2.0)
1.6 (1.1-2.2)
Benjamin EJ, et al. JAMA, 1994; 271: 840-844
Risk Factors for Stroke in Chinese with Non Vascular AF: A Case-control Study
AGE >76 yrs
Hypertension
Diabetes
LA thrombi
SBP
1.76 (1.08-2.89)
1.52 (1.28-1.80)
1.39 (1.11-1.76)
1.71 (1.21-2.28)
1 2 3 4 5
2.77 (1.25-6.13)
HU D, et al. Chin J Intern Med, 2003; 42: 157-161
0
2
4
6
8
AFASAK58%7– 81
SPAF67%
27– 85
BAATAF86%
51– 96
CAFA42%
- 68– 80
SPINAF79%
52– 90
TOTAL68%
50–79Risk reduction
AF Investigators. Arch Intern Med 1994;154:1449-1457.Atwood et al. Herz 1993;18:27-38.
St ro
ke I n
cid e
n ce
(%)
95% CI
AF Investigators: Meta-analysis
Warfarin for Stroke Prevention
p < 0.03
p < 0.01
p < 0.02
p > 0.2p < 0.002
p < 0.001
Controls Warfarin
Antiplatetet and Anticoagulation showed Significant Lower Stroke in Chinese Hospitalized Patients with AF
Number of Strokes Prevented
Qi W, et al. Chinese J Cardiol, 2003 ; 31 : 913-916
0 5% 10% 15% 20% 25%
No Therapy
Anticoagulation
Antiplatetet
5.5%
6.7%
24.2%
P<0.001
P<0.001
stroke rate
Prevalence of Antiplatetet and Anticoagulation in Chinese Hospitalized Patients with AF
None35%
Aspirin58%
Warfarin7%
Qi W, et al. Chinese J Cardiol, 2003 ; 31 : 913-916
Prevalence of Antiplatelet and Anticoagulation in Patients with AF in Chinese Natural Population
None60%
Aspirin38%
Warfarin2%
Hu D, et al. 2004 Chin J Intern Med; in press
Is Warfarin Better than Aspirin?
If So
What is the Optimal INR?
For Chinese,
Is Warfarin Better than Aspirin?
If So
What is the Optimal INR?
For Chinese,
The Randomized Prospective Trial compared aspirin with adjusted –dose warfarin in NVAF Patients
18 hospitals from 7 provinces in China
• Age 40-80Age 40-80
ASPIRIN150-160mg
WARFARININR 2.0-3.0
Secondary endpoit: lacunar infarction, peripheral arteries embolism, TIA, silent stroke, acute myocardial infarction,serious bl
eeding
NVAF Patients
RandomizeRandomize(n =704 )(n =704 )
Primary endpoint: Death or IS
Study Design
Results—Study Patients
828 randomized704 included in ITT analysis
414 assigned to aspirin
369 in efficacy analysis
414 assigned to warfarin
335 in efficacy analysis
Results— Baseline Characteristics
Age, years(SD) 63.85(9.71 ) 62.60 (10.26) 0.55
Male gender 216(58.5) 204(60.9) 0.524
Age>=75 40(10.8) 42(12.5) 0.483
History of hypertension 163(44.2) 135(40.3) 0.229
History of dyslipidemia 55(15) 60(18) 0.280
Diabetes 52(14.1) 55(16.4) 0.391
CAD 137(37.4) 112(33.6) 0.295
Prior MI 42(11.4) 23(6.9) 0.041
Prior STROKE 80(21.7) 57(17) 0.118
Prior HF 122(33.1) 109(32.5) 0.882
DM 20(5.4) 23(6.9) 0.424
> = 1 risk factor 225 (61) 221(66.2)0.153
aspirin(n=369)
warfarin(n=335) P value*
*Analysis of variance *Analysis of variance PP value. value. ††Canadian Cardiovascular Society Class 4.Canadian Cardiovascular Society Class 4.
*Analysis of variance *Analysis of variance PP value. value.
Beta-blockers 186(50.4) 151(45.1) 0.157
ACEIs 185(50.1) 147(43.9) 0.097
CCBs 48(13) 58(17.3) 0.111
Diuretics 105(28.5) 79(23.6) 0.142
Digoxin 145(39.3) 115(34.3) 0.173
Statins 63(17.1) 49(14.6) 0.375
nitrates 89(24.1) 65(19.4) 0.131
Prior aspirin 159(43.1) 128(38.2) 0.188
Prior warfarin 27(7.3) 28(8.4) 0.607
AspirinN=369
WarfarinN=335 P value*
Results --Treatments Received and Concomitant Medications
Full Target Dosage 100% 68.3%
Mean (SD) Dose Received, mg 150-160 3.19±0.69
Treatments Received
Concomitant Medications (Percentage of Patients)
ResultsPrimary Endpoints
2.7%
6.0%p=0.03
WARFARIN ASPIRIN
RRR 56%
7
6
5
4
3
2
1
Death and Ischem
ic Stroke
(%
)
ResultsAll-Cause Death
Ischemic Stroke 2 1 Hemorrhage 0 2Neoplasia 2 1 AMI 1 0HF 1 0
SD 2 0 Total 8 4 P=NS
AspirinN=369
WarfarinN=335
ResultsIschemic stroke
1.8%
4.6%
p=0.04
WARFARIN ASPIRIN
62%Event rate (%
)
5
4
3
2
1
Results Total Embolic Events
5,4%
10.6%p=0.01
WARFARIN ASPIRIN
52%12
10
8
6
4
2
Event rate
(%
)
Results Secondary Endpoints
5.67 %
7.05 %
p=0.457
WARFARIN ASPIRIN
10
8
6
4
2
Event rate
(%
)
Secondary endpoit: lacunar infarction, peripheral arteries embolism, TIA, silent stroke, acute myocardial infarction,serious bleeding
Results Adverse Events-- Hemorrhage
0
5
10
15
aspirinWarfarin
Even
t Rat
e (%
)Ev
ent R
ate
(% )
MajorMajorBleedingBleeding
Major + MinorMajor + MinorBleedingBleeding
P<0.05P<0.05
6.86%6.86%2.44%2.44%
0.0%0.0%1.49%1.49%0.0%0.0% 0.89%0.89%
ICHICH
Results: combined end points联合
终点事件
联合
终点事件
(%)
(%)
月0 6 12 18 240
20
15
10
5
Aspirin ( 150-160mg )Warfarin ( INR 2-3 )
RRR
36 %
13.0%
8.4%
非瓣膜房颤 717 例,平均随访 19 个月。
Conclusions
• Compared to aspirin, adjusted-dosed warfarin (INR 2.0-3.0) can significantly reduce: -- primary endpoints by 44% 56% -- thromboembolism events by 52% -- combined endpoints by 36%39%• For Chinese NVAF patients, most of which (63.5% ) have at least one risk factor, warfarin is more effective than aspirin(150-160mg)• Warfarin is associated with increased risk of hemorrhage.
Is Warfarin Better than Aspirin?
If So
What is the Optimal INR?
For Chinese,
Distribution of 3482 INRs during follow-up
INR
0 1.0-1.4<1.0 1.5-1.9 2.0-2.4 2.5-2.9 3.0-3.4 3.5-3.9 >4.0
70
60
50
40
30
20
10
%
2378 ( 68.3% )
• Follow-up period :median 19m ( 2 ~ 24m )• Mean dose of warfarin: 3.19±0.69 mg ( 1.5-5mg )
Thromboembolic event in WarfarinC
ombi
ned
Endp
oint
C
ombi
ned
Endp
oint
O
ccur
renc
e (%
)O
ccur
renc
e (%
)
0
2.0
1.5
1.0
0.5
2.5
3.0
INR0 1.0-1.4<1.0 1.5-1.9 2.0-2.4 2.5-2.9 >3.0
N=15 N=4
There were 19 cases of thromboembolic events, most of them occurred in INR <2.0.
Hemorrhage events in warfarin
10
8
6
4
2
%
INR0 1.0-1.9<1.0 2.0-2.9 3.0-3.9 4.0-4.9 5.0-5.9
Minor bleeding
Major bleeding INRs of 5 major bleeding :
4.75 , 4.98, 5.76, 5.24, 3.85
The optimal intensity of anticoagulation
<1.5 1,5-1.9 2.0-2.4 2.5-2.9 3.0-3.4 3.5-3.9 >4.0
INR
Embolic
Hemorrhage
4
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
LOWEST EFFECTIVE ANTICOAGULATION INTENSITY FOR WARFARIN
INRINR
1.0 1.5 3.0 4.02.0
Rat
e fo
r em
bolic
Eve
ntR
ate
for e
mbo
lic E
vent
0.6
0.5
0.4
0.3
0.2
0.1
Rat
e fo
r em
bolic
Eve
ntR
ate
for e
mbo
lic E
vent4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Conclusions
• INR >3.0 should be avoided to minimize the bleeding complications.• Under intense monitoring, adjusted-dose warfarin (INR 2.0-3.0) is effective and safe for the moderate to high risk atrial fibrillation patients.
Atrial fibrillation in China:
A Long Way to Go!
Difference in Trend between Paroxysmal AF and Persistent AF
0%1%2%3%4%5%6%7%8%
30~ 40~ 50~ 60~ 70~ 80~
persi stent AFparoxysmal AF
Hu D, et al. 2004 Chin J Intern Med; in press.
Similar trends and relatively lower prevalence of AF in China compared with USA, Australia and UK
0
2
4
6
8
10
12
14
30 40 50 60 70 80 90
ChinaFHS, USAAustraliaUK
FHS: the Framingham study. Wolf PA et al. Sroke 1991; 22: 983-988
Australia: Lake FR, et al. Aust NZ Med 1989; 19: 321-326
UK: Hill JD et al. J R Coll Gen Pract 1987; 37: 172-173
%
years
Risk of Stroke: Case-control Study
HU D, et al. Chin J Intern Med, 2003; 42: 157-161
%
Lone AF
PersistenceAF
Control of heart rate
Stroke Control
5.6
62.4
75.2
2.3
94.4
97.7 P<0.001
0
25
66.9
37.6
Paroxymal AF
Conversion
50
75
24.8
51.9
P=0.21
100
None valve AF
P=0.009
21.218.8
• Control the ventricular rate• Restore/maintain sinus rhythm• Prevent embolic complications
AF Treatment – Possible Objectives
No therapy24%
Control ofVenticular Rate
20% Cardioversion56%
Treatment of Chinese Hospitalized patients with paroxymal AF
Qi W, et al. Chinese J Cardiol, 2003 ; 31 : 913-916
Amiodarone 31.0%
Cedilanid 29.6%
β-Blocker 18.3%
Propafenone 14.3%
None3%
Control ofVenticular Rate
83%
Cardioversion14%
Treatment of Chinese Hospitalized patients with persistent AF
Qi W, et al. Chinese J Cardiol, 2003 ; 31 : 913-916
Amiodarone
Digoxin
β-Blocker
CCB