首都醫(yī)科大學附屬北京安貞醫(yī)院馬長生華法林在房顫治療中的應用及INR的監(jiān)測目目的的

了解中國目前心房顫動(房顫)

患病率、并發(fā)癥以及服藥情況,為進一步研究奠定基礎(chǔ)。方方法法 選取14

個自然人群進行整群抽樣調(diào)查,采用國際通用的標準化調(diào)查方法,在人群中進行以房顫為主要內(nèi)容的心血管流行病學調(diào)查并統(tǒng)計結(jié)果。結(jié)結(jié)果果 中國房顫患病率總患病率0177

%

,標準化率為0161

%。年齡分組顯示患病率有隨年齡增加的趨勢。男性病人房顫患病率高于女性(019%比017%

,

P

=

01013)

。所有房顫病人中瓣膜型、非瓣膜型及孤立性房顫所占比例分別為1219

%

,6512

%和2119

%。房顫病人中腦卒中以缺血性腦卒中為主,房顫病人腦卒中率明顯高于非房顫人群(1211

%比213%

,

P

<

0101)

。服藥情況華法林為117%

,阿司匹林為3719

%

,洋地黃為3719

%

,β受體阻滯劑為2416

%。結(jié)結(jié)論論

中國房顫患病率,年齡、性別、病因分組等均和國外相關(guān)資料趨勢接近,腦卒中發(fā)病率高,但服藥情況十分不理想,需要加強對房顫的控制。中國約有1000萬AF患者周自強,胡大一.中華內(nèi)科雜志.2004:49中國AF患病率數(shù)據(jù)來源于National

Registry

of

Atrial

Fibrillation（NRAF)?；颊邽榉秋L濕性AF，年齡65-95歲，出院時未服用華法林。Newmethod

of

predicting

stroke

in

heart

patientsSt.

Louis,

June

13,

2001

—

Researchers

atWashington

University

School

ofMedicine

in

St.

Louis

have

developed

a

formula

topredict

the

risk

of

stroke

in

patients

with

an

irregular

heart

rhythmcalled

atrial

fibrillation.“Our

hope

is

that

this

newclassification

scheme

will

help

physicians

select

the

appropriate

course

of

treatment

for

patients

withatrial

fibrillation,”

says

Brian

F.

Gage,

M.D.,

who

led

the

study.

Gage

is

assistant

professor

ofmedicine

atthe

School

ofMedicineand

medical

director

of

Barnes-Jewish

Hospital’s

blood

thinner

clinic.

The

results

are

published

in

the

June

13

issue

of

the

Journalof

the

American

Medical

Association.Patients

with

atrial

fibrillation,

an

irregular,

uncoordinated

contraction

of

heart

muscles,

are

estimated

to

have

a

fivefold

increasedrisk

of

stroke.

A

blood

thinner

called

warfarinsodium(sold

as

Coumadin?

and

others)

often

is

used

to

reduce

this

risk,

but

the

drugitself

can

cause

hemorrhage

and

other

side

effects.

It

also

is

more

expensive

and

more

difficult

to

administer

and

monitor

than

thealternative

treatment,

aspirin.To

help

predict

when

the

benefits

of

warfarinoutweigh

the

risks,

two

earlier

studies

completed

by

two

other

research

groupsdetermined

independent

factors

that

significantly

increase

the

risk

of

stroke.

However,

the

studies

reached

somewhat

differentconclusions:

The

Atrial

Fibrillation

Investigators

(AFI)

found

that

stroke

risk

correlated

withprior

stroke,

advanced

age,hypertensionanddiabetes;

the

Stroke

PreventionandAtrial

Fibrillation(SPAF)

teamfound

that

priorstroke,

blood

pressure,recentheart

failure

and

the

combination

ofbeing

over

75

years

old

and

female

increased

the

risk

of

stroke.“The

two

predictor

models

were

helpful,

but

discrepancies

between

themsometimes

led

to

confusion,”

says

Gage.

“We

needed

asimple,

uniformsystemto

help

select

warfarinfor

patients

at

moderate

or

high

risk

ofstroke,

while

avoiding

this

potentiallydangerous

blood

thinner

in

low-risk

patients.”So

Gage

and

colleagues

combined

the

factors

fromboth

models

and

developed

a

points

systemcalledCHADS2,

an

acronymfor

thefive

factors:

Congestive

heart

failure,

Hypertension,

Age,

Diabetes

and

Stroke.

Since

both

the

AFI

andSPAFfound

thata

history

of

stroke

is

the

best

predictive

factor,

it

was

given

a

value

of

two

points,

delineated

by

the

“2”at

the

end

of

the

mnemonic.

The

other

factors

each

are

allocated

one

point.

Patients

therefore

are

assigned

a

score

ranging

from

0

to

6.

In

general,

the

researcherssuggest

prescribing

warfarinto

patients

with

a

CHADS2

rating

of

one

or

greater,

depending

on

the

patient’s

preferences

and

risk

ofhemorrhage.In

collaboration

with

Peer

Review

Organizations

representing

seven

states,

the

teamobtained

data

from

1,733

Medicarebeneficiaries

aged

65

to

95

years.

They

followed

each

patient

for

an

average

of

1.2

years

and

assembled

a

National

Registry

ofAtrial

Fibrillation

(NRAF).

They

then

compared

the

predictive

value

ofeach

of

the

three

models

—

CHADS2,

AFI

and

SPAF.The

AFI

and

SPAF

schemes

both

predicted

stroke

better

than

chance,

but

CHADS2

yielded

significantly

more

accurate

results

thaneither

of

these

models.

In

addition,

the

risk

ofstroke

as

estimated

using

CHADS2

ranges

fromless

than

two

percent

to

roughly

18percent.

Both

AFI

andSPAFinclude

only

three

categories

—

low,

moderate

and

high

risk

—

with

stroke

risk

ranging

fromroughlyone

percent

to

ten

percent.“Havinga

wider

range

ofscores

provides

a

more

quantitative

approach

to

predicting

stroke,

which

is

very

helpful,”

explains

Gage.“For

example,

even

for

high-risk

patients,

it’s

important

to

know

how

high

their

score

is

so

that

you

can

take

extra

precautions

if近期心衰史CHF高血壓病史HP≥

75歲

AGE糖尿病

DM腦卒中TIA

Stroke2危險因素記分1111CHADS

2

計分Gage

BF.

JAMA.2001:

2864年卒中率(%)卒中危險分層：CHADS2

計分(NVAF)栓塞率/年60～70％心房顫動的抗凝治療一篇“Why

Do

Patients

WithAtrial

FibrillationNot

Receive

Warfarin?”綜綜述述的的圖圖表表Atrial

fibrillation

(AF)

is

a

growing

public

health

problemassociated

with

significantmorbidity

and

mortality.

Numerous

randomized

controlled

trials

of

warfarin

have

conclusivelydemonstrated

that

long-termanticoagulationtherapy

canreduce

the

risk

forstroke

by

approximately

68%

per

year

in

patients

withnonvalvularAF,

and

even

more

in

patients

with

valvular

AF.

However,

available

data

showthat

ofthose

patients

withAF

and

nocontraindication

to

warfarin

therapy,

only

15%

to

44%

are

prescribed

warfarin.

Our

literature

reviewhas

identified

patient-,

physician-,

and

health

care

system–related

barriers

to

warfarin

prescription.However,

the

relative

importance

of

these

specific

barriers

remains

unknown.

Furtherwork

is

needed

to

understand

the

discrepancy

between

the

randomized

controlled

trial

evidenceandclinical

practice

patterns.

Arch

Intern

Med.

2000;160:41-46周自強,胡大一.中華內(nèi)科雜志.2004:491Bungard

TJ.Arch

Intern

Med.2000:4華法林的使用情況第一篇：OBJECTIVES:

The

purpose

of

this

study

was

to

determine

both

treatment

gaps

and

predictors

of

warfarin

use

in

atrial

fibrillation

(AF)

patientsenrolled

ina

nationalmulticenter

study.

BACKGROUND:

The

NationalAnticoagulation

Benchmark

Outcomes

Report

(NABOR)

isa

performance

improvement

programdesigned

to

benchmark

anticoagulation

prophylaxis,

treatment,

and

outcomes

among

participating

hospitals.METHODS:

A

retrospective

cohort

study

of

inpatients

was

performed

at

21

teaching,

13

community,

and

4

Veterans

Administrationhospitals

inthe

U.S.

Patients

with

an

ICD-9-CM

code

for

AF

(427.31)

were

randomlyselected.

RESULTS:Among

the

945

patients

studied,

the

meanagewas

71.5

(+/-

13.5)

years;

43%

were

>75

yearsof

age,

54.5%

were

men,

and

67%

hada

history

of

hypertension.

Most

(86%)

had

factors

thatstratified

themas

at

high

risk

of

stroke,

and

only55%of

those

received

warfarin.

Neither

warfarin

nor

aspirin

were

prescribed

in

21%ofhigh-riskpatients,

including

18%

of

those

with

aprevious

stroke,

transient

ischemic

attack,

orsystemic

embolic

event.

Age

>80

years

(p

=

0.008)

andperceived

bleeding

risk

(p

=

0.022)

were

negative

predictors

of

warfarin

use.

Persistent/permanent

AF

(p

<

0.001)

and

history

of

stroke,

transient

ischemic

attack,

or

systemic

embolus

(p

=

0.014)

were

positive

predictors

of

warfarin

use,

whereas

high-risk

stratification

was

not.CONCLUSIONS:

This

study

confirms

the

under-use

of

warfarin,

but

also

adds

to

published

reports

in

several

regards.

It

showed

that

riskstratification,

the

guidepost

for

treatment

in

international

guidelines,

had

little

effect

on

warfarin

use,

and

that

age

>80

years

and

AF

classification(permanent/persistent)

are

factors

that

influence

warfarin

use.第二篇：ACKGROUND:

We

studied

the

prevalence

of

atrial

fibrillation

within

a

large

Italianinpatient

population,

and

evaluated

the

use

of

antithrombotictherapy

among

these

individuals.

METHODS:

Aprospective

cross

sectional

study

(Phase

1)

with

a

1-year

follow-up

period

(Phase

2)

wasconducted

at

a

single

Italian

centre.

During

Phase

1,

we

conducted

achart

review

of

all

inpatients

on

5

separate

days,

each

1

month

apart,between

January

and

May

1999.

During

Phase

2,

at

1-year

of

follow-up,

patients

or

their

families

were

contacted

to

document

the

occurrence

ofnew

clinical

events,

as

well

as

current

antithrombotic

therapy

use.

RESULTS:

A

total

of

3121

patient

charts

were

reviewed.

The

prevalence

ofatrial

fibrillation

was

7.2%.

Of

these

224

patients,

21.3%

were

on

oral

anticoagulants,

29.7%

on

antiplatelets,

while

49%received

neither.Patients

on

oral

anticoagulants

were

significantly

younger

(mean

age

72.3

years)

than

those

on

antiplatelets

(mean

age

80.6

years;

p<0.001)

orneither

therapy

(mean

age

80.7

years;

p<0.001).

At

1

year

follow

up,

an

acute

ischaemic

stroke

occurred

among

7.4%

of

the

121

contactedpatients.

Among

patients

with

chronic

atrial

fibrillation

[98],

25.5%were

receiving

an

oral

anticoagulant.

CONCLUSIONS:

Despite

clearevidence

fromclinical

trials,

oralanticoagulants

are

significantly

underused

among

patients

with

chronic

atrial

fibrillation.

Methods

shouldbedeveloped

to

improve

both

physician

and

patient

knowledge

about

the

overall

benefits

of

anti-thrombotic

therapy

among

these

individuals.第三篇美國：只有55%的高危住院AF患者使用華法林治療意大利：只有21%住院AF患者使用華法林治療華法林的使用情況Waldo

AL

.

J

Am

Coll

Card

2005:1729Ageno

W.

J

Thromb

Thromboly

2001:225OAT0

Oral

Anticoagulant

Therapy治療范圍窄受食物，酒精，精神壓力和其他藥物的影響不可預測的個體間差異治療窗INR臨床事件抗凝

出血↑藥物藥物↓2.0

to

3.02.5

to

3.5INR最佳范圍1.81.71.61.51.41.31.21.11.0PT比值ISI

2.44.03.02.01.0INR不同研究INR的目標范圍AFASAK

CAFA

SPAFI指南推薦INR：2-3BAATAFSPINAF華法林發(fā)生“缺血性卒中”時的INR1.81.71.61.51.41.31.21.11.0PT比值ISI

2.44.03.02.01.0INRAFASAKCAFASPAF

IIBAATAFSPINAF指南推薦INR：2-3不同研究INR的目標范圍華法林發(fā)生“出血性卒中”時的INROptimal

intensity

of

warfarin

therapy

for

secondary

prevention

of

stroke

in

patients

with

nonvalvular

atrial

fibrillation

:

amulticenter,

prospective,

randomized

trial.

Japanese

Nonvalvular

Atrial

Fibrillation-Embolism

Secondary

Prevention

CooperativeStudy

Group.Yamaguchi

T.National

Cardiovascular

Center,

Osaka,

Japan.

tyamaguc@hsp.ncvc.go.jpBACKGROUND

AND

PURPOSE:The

optimal

intensity

of

warfarin

therapy

for

secondarypreventionof

stroke

in

nonvalvular

atrial

fibrillation(NVAF)

remains

unclear.

We

studied

the

efficacyand

safety

of

conventional-

and

low-intensity

warfarin

therapy

in

a

prospective,

randomized,multicenter

trial.

METHODS:

The

study

population

consisted

of

patients

withNVAF

(<80

years

old)

who

had

a

stroke

or

transient

ischemicattack.

The

patients

were

randomly

allocated

into

a

conventional-intensity

group

(internationalnormalized

ratio

[INR]

2.2

to

3.5)

and

a

low-intensity

group

(INR

1.5

to

2.1).

They

were

carefullymonitored,

and

the

annual

rate

of

recurrent

ischemic

stroke

and

major

hemorrhagiccomplications

were

compared

between

the

groups.

RESULTS:

We

enrolled

115

patients

(mean

age

66.7+/-6.5

years)

into

the

study.

Fifty-fiveand

60

patients

were

allocated

into

the

conventional-

and

low-intensity

groups,

respectively.

The

trial

was

stopped

after

afollow-up

of

658+/-

423

days,

whenmajor

hemorrhagic

complications

occurred

in

6

patients

of

the

conventional-intensitygroup

and

the

frequency

(6.6%

per

year)was

significantly

higher

than

that

in

the

low-intensity

group

(0%

per

year,

P=0.01,

Fisher"s

exact

test).

All

of

the

6

patients

with

major

bleedingwere

elderly

(mean

age

74

years),

and

their

meanINR

before

the

major

hemorrhage

was

2.8.

The

annual

rate

ofischemic

stroke

was

lowin

bothgroups

(1.1%

per

year

in

the

conventional-intensity

group

and

1.7%

per

year

in

the

low-intensity

groups)

and

did

not

differ

significantly.CONCLUSIONS:

For

secondary

prevention

of

stroke

in

persons

withNVAF,

especially

in

old

patients,

the

low-intensity

warfarin(INR

1.5

to2.

1)

treatment

seems

to

be

safer

than

the

conventional-intensity

(INR

2.2

to

3.5)

treatment.嚴重出血指顱內(nèi)出血、視網(wǎng)膜出血、需要輸血或住院的大出血Yamaguchi

T.

Stroke

2000:817日本房顫卒中二級預防試驗美國的研究，1995-2000年入選了18867名NVAF患者進行回顧性研究OBJECTIVES:This

study

was

designed

to

studyracial/ethnic

differences

in

the

risk

for

intracranial

hemorrhage

(ICH)

and

the

effect

of

warfarinon

ICH

risk

among

patients

withatrial

fibrillation

(AF).

BACKGROUND:Nonwhites

are

at

greater

risk

for

ICH

than

whites

in

the

generalpopulation.

Whether

this

applies

to

patients

with

AF

and

whether

warfarintherapy

is

associated

withcomparable

risk

of

ICH

in

nonwhites

areunknown.

METHODS:

We

retrospectively

identified

a

multiethnic

stroke-free

cohort

hospitalized

with

nonrheumatic

AF.

Warfarin

use

andanticoagulation

intensity

were

assessed

bysearchingpharmacy

and

laboratory

records.

Crude

ICHevent

rates

were

calculated

by

Poissonregression.

Cox

proportional

hazard

models

were

constructed

to

assess

the

independent

effect

of

race/ethnicityon

ICHafter

adjustingfor

age,gender,

hypertension,

diabetes,

heart

failure,

and

warfarinexposure.

RESULTS:

Between

1995

and

2000,

we

identified

18,867

qualifying

AFhospitalizations

(78.5%

white,

8%black,

9.5%

Hispanic,

and

3.9%

Asian)

and

173

qualifying

ICH

events

over

3.3

years

follow-up.

Achievedanticoagulationintensitywas

lower

among

blacks

but

not

different

between

the

other

groups.

Warfarinwas

associated

with

increased

ICHrisk

inall

races,

but

the

magnitude

of

risk

was

greater

among

nonwhites.

There

were

no

gender

differences.

The

hazard

ratio

for

ICH

with

whites

asreferent

was

4.06

for

Asians

(95%

confidence

interval

[CI]

2.47

to

6.65),

2.06

for

Hispanics

(95%

CI

1.31

to

3.24),

and

2.04

(95%

CI

1.25

to3.35)

for

blacks.

CONCLUSIONS:

Nonwhites

with

AF

were

at

greater

risk

for

warfarin-related

ICH.

Blacks,

Hispanics,

and

Asians

were

atsuccessively

greater

ICHrisk

than

whites.ICH風險亞裔是白人的4.06倍Shen

AY.JACC.2007:309亞裔應用華法林顱內(nèi)出血風險增加Figure

1.

Cumulative

incidence

of

major

bleedingamongpatients

aged

80

years

and

80

years

(n472).

Numbersbelow

graph

are

the

number

of

patients

without

bleeding

whocontinued

onwarfarinat

that

time

point

(P0.009,

log-ranktest).Major

hemorrhage

was

defined

as

fatal,

hospitalizationwith

transfusionof

2

units

of

packed

red

blood

cells,

or

involvement

of

acritical

site

(ie,

intracranial,

retroperitoneal,

intraspinal,

intraocular,pericardial,

or

atraumatic

intra-articular

hemorrhage).Hylek

EM.

Circulation.

2007:213.1%4.7%高齡患者應用華發(fā)林第1年嚴重出血率高

華法林初始劑量5-10mg,隨后根據(jù)INR調(diào)整

首次服用華法林后2-3天查INR

INR值穩(wěn)定的患者，至少

4周查一次INR監(jiān)測頻率：抗血栓治療指南華法林初始劑量5-10mg,隨后根據(jù)INR調(diào)整住院患者1次/天，直至

INR值穩(wěn)定后2天，此后

2-3次/周。門診患者數(shù)天1次INR值穩(wěn)定的患者，至少

4周查一次ACCP7thACCP8th男性79歲，體檢時發(fā)現(xiàn)房顫第一位醫(yī)生建議他應用華法林抗凝治療，3mg

QN，并告之3天后查INR該患者遵醫(yī)囑服藥，3天后INR為2.3患者請另外一個醫(yī)生幫他看了化驗單，醫(yī)生看到INR在治療范圍后，告之繼續(xù)按原來的方案服藥，每月復查一次INR半個月后，患者出現(xiàn)昏迷，磁共振檢查證實為顱內(nèi)出血，當時INR為13.8，昏迷10天后，患者死亡升高速度反應敏感性，達標指穩(wěn)定在目標值，而不是到達病例病例

67歲男性患者，AF術(shù)后服用華法林治療

服用2mg/d的第5天及第10天INR均為2.31個月后患者出現(xiàn)左下腹疼痛，超聲示腹膜后血(10×10×14cm)。INR5.65

患者1個月內(nèi)無服用藥物的增減,無特殊飲食改變4周查一次INR是否合適？監(jiān)測INR的間隔天數(shù)和INR位于目標值范圍內(nèi)的百分數(shù)Should

obtain

2

consecutive

therapeutic

INRs

before

increasinginterval

between

tests.In

Germany,

70%

of

patients

on

PSM

test

themselves

weekly

(1)100

strips

are

reimbursed

per

year

(MHV

mostly)HQACM:

High

Quality

Anticoagulation

Manangement

(Ansell,

2007)Horton,

J.

et

al.

(1999);

Ansell,

J.A.

(2004);

(1)

Bernardo,

A.

et

al.

(2001)監(jiān)測頻率和INR位于靶目標范圍比例盡量多地提高檢測頻率每周檢測能保證85%的INR處于靶目標范圍內(nèi)每月檢測僅50%的的INR處于靶目標范圍內(nèi)HeneghanC.Lancet

2006:

404Bernardo

A.DtschMed

Wochenschr.

2001:346INR測測量量中中位位于于目目標標范范圍圍內(nèi)內(nèi)的的百百分分數(shù)數(shù)和和臨臨床床事事件件的的關(guān)關(guān)系系，，控控制制好好的的患患者者83%處處于于目目標標值值范范圍圍內(nèi)內(nèi)，，同同時時事事件件發(fā)發(fā)生生率率最最低低Background:

Warfarin

sodiumreduces

stroke

risk

in

patients

with

atrialfibrillation,

but

international

normalizedratio

(INR)

monitoring

is

required.

TargetINRs

are

frequently

not

achieved,

and

the

risk

of

death,bleeding,

myocardial

infarction

(MI),

and

stroke

orsystemic

embolismevent

(SEE)

may

be

related

to

INRcontrol.Methods:

We

analyzed

the

relationship

between

INRcontrol

and

the

rates

of

death,

bleeding,

MI,

and

strokeor

SEE

among

3587

patients

with

atrial

fibrillation

randomizedto

receive

warfarintreatment

in

the

SPORTIF(Stroke

PreventionUsing

an

Oral

Thrombin

Inhibitorin

Atrial

Fibrillation)

III

and

V

trials.

The

mean±SDfollow-up

was

16.6±6.3

months.

Patients

were

dividedinto

3

equal

groups

(those

withgood

control

[75%],those

with

moderate

control

[60%-75%],

or

those

withpoor

control

[60%])

according

to

the

percentage

timewith

an

INR

of

2.0

to

3.0.

Outcomes

were

comparedaccording

to

INR

control.

The

mainoutcome

measureswere

death,

bleeding,

MI,

and

strokeor

SEE.Results:

The

poor

control

group

had

higher

ratesof

annualmortality

(4.20%)

and

major

bleeding

(3.85%)

comparedwith

the

moderate

control

group

(1.84%

and

1.96%,respectively)

and

the

good

control

group

(1.69%

and1.58%,

respectively)

(P.01

for

all).

Compared

with

thegood

control

group,

the

poor

control

group

had

higherrates

of

MI

(1.38%

vs

0.62%,

P=.04)

and

of

strokeor

SEE(2.10%

vs

1.07%,

P=.02).Conclusions:

In

patients

with

atrial

fibrillation

takingwarfarin,

the

risksof

death,

MI,

major

bleeding,

and

strokeorSEE

are

related

to

INR

control.

Good

INR

control

isimportant

to

improve

patient

outcomes.Arch

Intern

Med.

2007;167:239-245控制好：83%INR處于2-3控制可：68%INR處于2-3控制差：48%INR處于2-3White

HD.

Arch

Intern

Med.

2007:239INR控制情況和臨床事件發(fā)生率PROTECT-AF研究，左心耳封堵術(shù)研究RELY:dabigatran和華法林的隨機對照研究安貞醫(yī)院門診INR目標范圍為1.8-2.5，其余為2-3Connolly

SJ.NEJM.2009:1Du. Chin

Med

J.

2005:1206/Reynolds

MW

.

Chest.

2004

1938.INR達標情況兩兩組組監(jiān)監(jiān)測測INR的的頻頻率率相相同同Background—Pharmacogenetic-guided

dosing

ofwarfarin

is

a

promising

applicationof“personalized

medicine”

but

hasnot

been

adequately

tested

in

randomized

trials.Methods

and

Results—Consenting

patients

(n206)

being

initiated

on

warfarinwere

randomized

to

pharmacogeneticguidedorstandard

dosing.

Buccal

swab

DNAwas

genotyped

for

CYP2C9

*2

and

CYP2C9

*3

and

VKORC1

C1173Twith

a

rapid

assay.

Standard

dosing

followed

an

empirical

protocol,

whereas

pharmacogenetic-guided

dosingfollowedaregression

equation

including

the

3

genetic

variants

and

age,

sex,

and

weight.

Prothrombin

time

internationalnormalized

ratio

(INR)

was

measured

routinely

on

days0,

3,

5,

8,

21,

60,

and

90.

A

research

pharmacist

unblinded

totreatment

strategy

managed

dose

adjustments.

Patients

were

followed

up

for

up

to

3

months.

Pharmacogenetic-guidedpredicted

doses

more

accuratelyapproximated

stable

doses

(P0.001),

resulting

in

smaller

(P0.002)

and

fewer

(P0.03)

dosingchanges

and

INRs

(P0.06).

However,

percent

out-of-range

INRs

(pharmacogenetic30.7%,standard33.1%),

the

primary

end

point,

did

not

differ

significantly

between

arms.

Despite

this,

when

restricted

towild-type

patients

(who

required

larger

doses;

P0.001)

and

multiple

variant

carriers

(who

required

smaller

doses;P0.001)

inexploratoryanalyses,

results

(pharmacogenetic29%,

standard39%)

achieved

nominal

significance(P0.03).

Multiple

variant

allele

carriers

were

atincreased

risk

of

an

INR

of

4

(P0.03).Conclusions—An

algorithm

guided

by

pharmacogenetic

and

clinicalfactors

improved

the

accuracyand

efficiency

ofwarfarin

dose

initiation.

Despite

this,

the

primaryend

point

of

a

reduction

in

out-of-range

INRs

was

not

achieved.

Insubset

analyses,

pharmacogenetic

guidance

showed

promise

for

wild-type

and

multiple

variant

genotypes.

(Circulation.2007;116:2563-2570.)基因測定結(jié)果結(jié)合年齡、性別、體重決定患者初始華法林劑量ACCP8th不推薦使用藥物基因測定指導華法林劑量選擇二者無統(tǒng)計學差異Anderson

JL.

Circulation.2007:25基因測試指導華法林劑量選擇IT:患患者者到到醫(yī)醫(yī)院院或或抗抗凝凝中中心心測測量量INR后后，，電電話話聯(lián)聯(lián)系系醫(yī)醫(yī)生生調(diào)調(diào)整整華華法法林林劑劑量量,AMS:傳傳統(tǒng)統(tǒng)的的醫(yī)醫(yī)院院檢檢查查醫(yī)醫(yī)生生面面對對面面調(diào)調(diào)整整劑劑量量Background:

Studies

demonstrate

the

effectiveness

of

anticoagulationmanagement

service

(AMS)

inproviding

antithrombotictherapy

for

eligible

patients.

We

sought

toextend

this

concept

by

determining

whether

an

interimtelephone

model

(IT)

is

comparable

to

our

current

AMSmodel

at

achieving

optimal

therapeutic

outcomes.Methods:

The

36-month

trial

(24-month

study

plus

12-month

extension)

enrolled

192

eligible

patients

receivinglong-termwarfarin

therapy

at

a

Veterans

Affairs

hospital.Consenting

participants

were

randomly

assignedto

either

our

current

face-to-face

clinic

model

(AMS),

orour

ITmodel.

The

primary

outcome

was

the

percentageof

time

individuals’

international

normalized

ratios

(INRs)were

maintained

within

their

target

INRrange

(2.0-3.0

or

2.5-3.5).

Secondaryoutcomes

included

the

numberof

adverse

events

(eg,

thromboembolismor

hemorrhage)experienced

during

the

study.Results:

We

found

no

statistically

significant

differencebetween

the

2

groups

in

the

percentage

of

timemaintained

within

INR

target

range

overall

(55.1%

forAMS;

57.8%

for

IT;

P=.28)

nor

over

the

courseof

thestudy.

There

were

no

statistically

significant

differencesin

the

rate

ofthromboembolic

or

serious

bleedingevents

between

IT

and

AMS

participants.

Nevertheless,we

did

note

differences

related

to

intensity

ofanticoagulation.

The

IT

group

receiving

treatment

at

ahigher

intensity

(INR,

2.5-3.5)

experienced

greateranticoagulation

control

(P=.04)

and

fewer

complicationsthan

the

AMS

group.

The

IT

participants,

however,reported

a

significantly

higher

rate

of

minor

bleedingevents,

experienced

mainly

by

those

at

an

INR

range

of

2.0

to

3.0.Conclusion:

Our

IT

model

is

a

viable

modification

ofour

AMS

model

for

the

management

of

patients

undergoing標范圍的時間百分數(shù)IT:患者通過24小時電話取得服務AMS：患者到醫(yī)院接受醫(yī)生面對面服務二者無統(tǒng)計學的差別Staresinic

AG.

Arch

Intern

Med.

2006:9924小時服務電話指導華法林使用加加拿拿大大的的研研究究，，抗抗凝凝門門診診：：接接受受抗抗凝凝培培訓訓的的專專業(yè)業(yè)人人員員組組成成，，提提供供一一站站式式服服務務，，快快速速監(jiān)監(jiān)測測和和同同事事調(diào)調(diào)整整劑劑量量，，家家庭庭醫(yī)醫(yī)生生：：家家庭庭醫(yī)醫(yī)生生決決定定患患者者何何時時監(jiān)監(jiān)測測及及如如何何調(diào)調(diào)整整劑劑量量

Background:There

is

growingevidence

that

better

outcomes

areachieved

when

anticoagulation

is

managed

by

anticoagulationclinics

rather

than

by

familyphysicians.

We

carried

out

a

randomizedcontrolled

trial

to

evaluate

these

2

models

of

anticoagulantcare.Methods:

We

randomlyallocated

patients

who

were

expected